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Objectives: TANK-binding kinase 1 (TBK1) is pivotal in autoimmune and inflammatory diseases, yet its role in osteoarthritis (OA) remains elusive. This study sought to elucidate the effect of the TBK1 inhibitor BX795 on OA and to delineate the underlying mechanism by which it mitigates OA. Methods: Interleukin-1 Beta (IL-1ß) was utilized to simulate inflammatory responses and extracellular matrix degradation in vitro. In vivo, OA was induced in 8-week-old mice through destabilization of the medial meniscus surgery. The impact of BX795 on OA was evaluated using histological analysis, X-ray, micro-CT, and the von Frey test. Additionally, Western blot, RT-qPCR, and immunofluorescence assays were conducted to investigate the underlying mechanisms of BX795. Results: Phosphorylated TBK1 (P-TBK1) levels were found to be elevated in OA knee cartilage of both human and mice. Furthermore, intra-articular injection of BX795 ameliorated cartilage degeneration and alleviated OA-associated pain. BX795 also counteracted the suppression of anabolic processes and the augmentation of catabolic activity, inflammation, and senescence observed in the OA mice. In vitro studies revealed that BX795 reduced P-TBK1 levels and reversed the effects of anabolism inhibition, catabolism promotion, and senescence induction triggered by IL-1ß. Mechanistically, BX795 inhibited the IL-1ß-induced activation of the cGAS-STING and TLR3-TRIF signaling pathways in chondrocytes. Conclusions: Pharmacological inhibition of TBK1 with BX795 protects articular cartilage by inhibiting the activation of the cGAS-STING and TLR3-TRIF signaling pathways. This action attenuates inflammatory responses and cellular senescence, positioning BX795 as a promising therapeutic candidate for OA treatment. The translational potential of this article: This study furnishes experimental evidence and offers a potential mechanistic explanation supporting the efficacy of BX795 as a promising candidate for OA treatment.
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The journal retracts the article "Inhibition of SDF-1α/CXCR4 Signalling in Subchondral Bone Attenuates Post-Traumatic Osteoarthritis" [...].
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This investigation employs femtosecond laser-induced breakdown spectroscopy (fs-LIBS) to measure the concentrations of chromium (Cr), lead (Pb), and copper (Cu) in flowing aqueous solutions. The fs pulsed laser excites the water, generating plasma in a dynamic setting that prevents liquid splashing-a notable advantage over static methods. The flowing water column maintains a stable liquid level, circumventing the laser focus irregularities due to liquid-level fluctuations. Calibration curves, based on a linear function, reveal limits of detection (LODs) as low as 0.0179 µg/mL for Cr, 0.1301 µg/mL for Pb, and 0.0120 µg/mL for Cu. The reliability of the experiment is confirmed by R2 values exceeding 0.99. These findings offer valuable insights for the analysis of trace heavy metals in flowing aqueous solutions using fs-LIBS, demonstrating the technique's potential for environmental monitoring.
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Despite advances in surgery and chemotherapy, the survival of patients with osteosarcoma (OS) has not been fundamentally improved over the last two decades. Microvesicles (MVs) have a high cargo-loading capacity and are emerging as a promising drug delivery nanoplatform. The aim of this study was to develop MVs as specifically designed vehicles to enable OS-specific targeting and efficient treatment of OS. Herein, we designed and constructed a nanoplatform (YSA-SPION-MV/MTX) consisting of methotrexate (MTX)-loaded MVs coated with surface-carboxyl Fe3O4 superparamagnetic nanoparticles (SPIONs) conjugated with ephrin alpha 2 (EphA2)-targeted peptides (YSAYPDSVPMMS, YSA). YSA-SPION-MV/MTX showed an effective targeting effect on OS cells, which was depended on the binding of the YSA peptide to EphA2. In the orthotopic OS mouse model, YSA-SPION-MV/MTX effectively delivered drugs to tumor sites with specific targeting, resulting in superior anti-tumor activity compared to MTX or MV/MTX. And YSA-SPION-MV/MTX also reduced the side effects of high-dose MTX. Taken together, this strategy opens up a new avenue for OS therapy. And we expect this MV-based therapy to serve as a promising platform for the next generation of precision cancer nanomedicines.
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Neoplasias Óseas , Micropartículas Derivadas de Células , Osteosarcoma , Animales , Humanos , Ratones , Neoplasias Óseas/tratamiento farmacológico , Efrinas , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Osteosarcoma/tratamiento farmacológicoRESUMEN
We experimentally studied the supercontinuum induced by femtosecond filamentation in different liquid media. Using a Mach-Zehnder interferometer, we determined the relative filamentation thresholds (Pth) of these media. Research has shown that the value of the filamentation threshold is greater than that of Pcr (critical power for self-focusing), which can mainly be attributed to the strong dispersion effect. Changing the focal length of the focusing lens affects filamentation dynamics, thereby affecting the measured results regarding the filamentation threshold. With shorter focal lengths, the linear focusing (i.e., geometrical focusing) regime dominates, and the measured values of Pth for different liquid media are almost the same; as the focal length becomes larger, self-focusing starts to play a role, making the values of Pth for different media different from each other. This study presents an efficient method for investigating the femtosecond filamentation phenomenon in liquid media, helpful to provide further insights into the physical mechanism of supercontinuum generation via femtosecond filamentation in liquid media.
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Cyromazine, when used as an insect growth regulator and low-toxicity insecticide, may degrade into melamine and pose a potential threat to the environment and soil health, which has thus attracted extensive research on eliminating such a harmful effect. In this paper, density functional theory (DFT)/LC-BLYP/6-311G(d,p) is used to optimize the geometric structure and analyze the vibration of cyromazine. The DFT/LC-BLYP/def2-SVP is used for the cyromazine-Au complex optimization and vibration analysis. The molecular electrostatic potential (MEP), frontier molecular orbitals (FMOs), vibration frequency, electrophilicity-based charge transfer (ECT) descriptor, binding energy (BE), polarizability, normal Raman spectroscopy (NRS), and surface-enhanced Raman spectroscopy (SERS) of cyromazine adsorbing on Au6 and Au20 are calculated. The study of the chemical enhancement mechanism of SERS of cyromazine at different adsorption sites of Au6 or Au20 confirms the existence of a charge transfer between cyclopromazine and Au6 and Au20, which can adsorb and form stable cyromazine-Au complexes. The results show that N2, H13, and N4 are the adsorption sites of Au6 and Au20. The Raman spectra of the cyromazine-Au complex can be selectively enhanced with a factor up to 9.07. Compared with those of cyromazine-Au6, the Raman spectra of cyromazine-Au20 are enhanced more significantly.
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Osteoarthritis (OA) is a chronic progressive articular illness which commonly affects olderaged adults, presenting with cartilage inflammation and degradation. Rutaecarpine (RUT) has been shown to exert promising antiinï¬ammatory effects; however, the efficacy of RUT in the treatment of OA is debatable. The present study investigated the potential of RUT in alleviating OA in a mouse model. Treatment with RUT inhibited the inï¬ammatory response and extracellular matrix degradation by suppressing process regulators in interleukin (IL)1ßstimulated chondrocytes. Moreover, treatment with RUT in vitro upregulated the gene expression of anabolic agents, such as collagen type II, aggrecan and SRYbox transcription factor 9, indicating that RUT contributed to cartilage repair. Additionally, flow cytometric assays, and the measurement of ßgalactosidase levels, autophagic flux and related protein expression revealed that RUT effectively attenuated IL1ßinduced chondrocyte apoptosis, senescence and autophagy impairment. In addition, bioinformatics analysis and in vitro experiments demonstrated that RUT protected cartilage by mediating the phosphoinositide3kinase (PI3K)/Akt/nuclear factorκB (NFκB) and mitogenactivated protein kinase (MAPK) pathways. The ameliorative effects of RUT on IL1ßstimulated chondrocytes were abrogated when siRNA was used to knock down integrin αVß3. Furthermore, the results of immunohistochemical analysis and microcomputed tomography confirmed the in vivo therapeutic effects of RUT in mice with OA. On the whole, the present study demonstrates that RUT attenuates the inflammatory response and cartilage degradation in mice with OA by suppressing the activation of the PI3K/AKT/NFκB and MAPK pathways. Integrin αVß3 may play a pivotal role in these effects.
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FN-kappa B , Osteoartritis , Animales , Ratones , Proteínas Quinasas Activadas por Mitógenos , Integrina alfaVbeta3 , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Microtomografía por Rayos X , Osteoartritis/tratamiento farmacológicoRESUMEN
Osteoarthritis (OA) is a common degenerative joint disease urgently needing effective treatments. Bone marrow mesenchymal stromal cell-derived exosomes (Exo) are considered good drug carriers whereas they have limitations such as fast clearance and low retention. This study aimed to overcome the limitations of Exo in drug delivery using multiple strategies. Novel photocrosslinking spherical gelatin methacryloyl hydrogel (GelMA)-encapsulated cartilage affinity WYRGRL (W) peptide-modified engineered Exo were developed for OA treatment and the performance of the engineered Exo (W-Exo@GelMA) loaded with a small inhibitor LRRK2-IN-1 (W-Exo-L@GelMA) was investigated in vitro and in vivo. The W-Exo-L@GelMA showed an effective targeting effect on chondrocytes and a pronounced action on suppressing catabolism and promoting anabolism in vitro. Moreover, W-Exo-L@GelMA remarkably inhibited OA-related inflammation and immune gene expression, rescuing the IL-1ß-induced transcriptomic responses. With enhanced retention in the joint, W-Exo-L@GelMA demonstrated superior anti-OA activity and cartilage repair ability in the OA murine model. The therapeutic effect was validated in the cultured human OA cartilage. In conclusion, photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered Exo exhibit notable potential in OA therapy. Engineering Exo by a series of strategies enhanced the targeting ability and retention and cartilage-targeting and Exo-mediated drug delivery may offer a novel strategy for OA treatment.Clinical trial registration: Not applciable.
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Exosomas , Osteoartritis , Humanos , Animales , Ratones , Hidrogeles , Sistemas de Liberación de Medicamentos , Péptidos , Osteoartritis/tratamiento farmacológicoRESUMEN
Aims: Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism. Methods: In vitro, interleukin-1 beta (IL-1ß) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results: DHCA prevented iNOS and IL-6 from being upregulated by IL-1ß. Moreover, the IL-1ß-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1ß-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion: We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment.
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Osteoarthritis (OA) is a common, progressive, and chronic disorder of the joints that is characterized by the inflammation and degradation of articular cartilage and is known to significantly impair quality of daily life. Stevioside (SVS) is a natural diterpenoid glycoside that has anti-inflammatory benefits. Hence, in the current research, it was hypothesized that SVS might exert anti-inflammatory effects on articular chondrocytes and alleviate cartilage degradation in mice with OA. The expression of inflammatory cytokines, like inducible nitric oxide synthase (iNOS), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), and cyclooxygenase-2 (COX-2) in chondrocytes after interleukin-1ß (IL-1ß) exposure, was inhibited by the pretreatment of SVS. As well, SVS inhibited the reduction of collagen II and sry-box transcription factor 9 (SOX9) in chondrocytes stimulated by IL-1ß and suppressed the expression of MMP3 and MMP13. Further, after treatment with SVS, cell cytometry, autophagy flux, and related protein expression showed diminished cell apoptosis and reduced autophagy impairment. Moreover, SVS blocked the activation of phosphoinositide-3-kinase/Akt/nuclear factor-kappa beta (PI3K/Akt/NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways stimulated by IL-1ß. This resulted in decreased cellular inflammation. In vivo experiments with intra-articular injections of SVS in mice with the DMM mouse model demonstrated a decrease in cartilage degradation and an improvement in subchondral bone remodeling. After the integrin αVß3-related knockdown using siRNA, a reversed effect was observed on the anti-inflammatory, anabolic promoting, catabolic blocking, and NF-κB and MAPK signaling pathway inhibition of SVS on chondrocytes treated with IL-1ß. The above findings highlighted that SVS blocked IL-1ß, triggered an inflammatory response in mice chondrocytes, and prevented cartilage degradation in vivo through integrin αVß3. This suggested that SVS might serve as a novel therapeutic option for OA.
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Cartílago Articular , Osteoartritis , Animales , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Cartílago Articular/metabolismo , Células Cultivadas , Condrocitos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Integrina alfaVbeta3/metabolismo , Interleucina-1beta/farmacología , FN-kappa B/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Background: Intracerebral hemorrhage (ICH) is one of the most serious complications in patients with chronic kidney disease undergoing long-term hemodialysis. It has high mortality and disability rates and imposes a serious economic burden on the patient's family and society. An early prediction of ICH is essential for timely intervention and improving prognosis. This study aims to build an interpretable machine learning-based model to predict the risk of ICH in patients undergoing hemodialysis. Methods: The clinical data of 393 patients with end-stage kidney disease undergoing hemodialysis at three different centers between August 2014 and August 2022 were retrospectively analyzed. A total of 70% of the samples were randomly selected as the training set, and the remaining 30% were used as the validation set. Five machine learning (ML) algorithms, namely, support vector machine (SVM), extreme gradient boosting (XGB), complement Naïve Bayes (CNB), K-nearest neighbor (KNN), and logistic regression (LR), were used to develop a model to predict the risk of ICH in patients with uremia undergoing long-term hemodialysis. In addition, the area under the curve (AUC) values were evaluated to compare the performance of each algorithmic model. Global and individual interpretive analyses of the model were performed using importance ranking and Shapley additive explanations (SHAP) in the training set. Results: A total of 73 patients undergoing hemodialysis developed spontaneous ICH among the 393 patients included in the study. The AUC of SVM, CNB, KNN, LR, and XGB models in the validation dataset were 0.725 (95% CI: 0.610 ~ 0.841), 0.797 (95% CI: 0.690 ~ 0.905), 0.675 (95% CI: 0.560 ~ 0.789), 0.922 (95% CI: 0.862 ~ 0.981), and 0.979 (95% CI: 0.953 ~ 1.000), respectively. Therefore, the XGBoost model had the best performance among the five algorithms. SHAP analysis revealed that the levels of LDL, HDL, CRP, and HGB and pre-hemodialysis blood pressure were the most important factors. Conclusion: The XGB model developed in this study can efficiently predict the risk of a cerebral hemorrhage in patients with uremia undergoing long-term hemodialysis and can help clinicians to make more individualized and rational clinical decisions. ICH events in patients undergoing maintenance hemodialysis (MHD) are associated with serum LDL, HDL, CRP, HGB, and pre-hemodialysis SBP levels.
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Background: The incidence of intervertebral disc degeneration (IVDD) is a common degenerative disease with inflammation, decreased autophagy, and progression of fibrosis as its possible pathogenesis. Physalin A (PA) is a widely studied anti-inflammatory drug. However, its therapeutic effects on IVDD remain unexplored. Therefore, we aimed to explore the therapeutic potential of PA in IVDD progression. Materials and methods: In vivo, we investigated PA bioactivity using a puncture-induced IVDD rat model. IVDD signals and height changes were detected using X-ray, micro-CT, and MRI, and structural and molecular lesions using histological staining and immunohistochemistry of intervertebral disc sections. In vivo, interleukin-1 beta (IL-1ß) and TGF-ß1 were employed to establish inflammation fibrotic nucleus pulposus (NP) cells. The PA effect duration, concentration, influence pathways, and pathological changes in IVDD treatment were elucidated using western blotting, real-time PCR, and immunofluorescence. Results: PA exerted significant effects on IVDD remission due to anti-inflammation, fibrosis reduction, and autophagy enhancement. In vitro, PA improved inflammation by blocking the NF-κB and MAPK pathways, whereas it promoted autophagy via the PI3K/AKT/mTOR pathway and affected fibrotic progression by regulating the SMAD2/3 pathway. Moreover, PA improved the disc degeneration process in IVDD model. Conclusions: PA exhibited significant anti-inflammatory and anti-fibrotic effects and improved autophagy in vivo and in vitro IVDD models, thus effectively relieving IVDD progression, indicating it is a promising agent for IVDD treatment. The translational potential of this article: This study successfully reveals that PA, a natural bioactive withanolide, effectively relieved IVDD progression via inflammation inhibition, fibrosis reduction, and autophagy enhancement, indicating it is a promising agent for IVDD treatment.
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This study used a femtosecond laser to ablate a Cu sample, forming a micro/nanostructural layer on the surface. And the effect of this structural layer on nanosecond laser-induced breakdown spectroscopy (LIBS) was discussed. Firstly, the effect of the micro/nanostructural layer on the intensity of laser-induced Cu plasma spectra was investigated. The micro/nanostructure could significantly enhance the spectral intensity of the Cu plasma by 82.5 times at 13.3 mJ laser energy. Secondly, the Cu plasma temperature and electron density were calculated. The micro/nanostructures could significantly increase Cu plasma temperature and electron density. Finally, the effect of micro/nanostructure surface on the spectral intensities of Pb and Cr elements in water was investigated for LIBS analysis. It was found that the detection limit of Pb and Cr trace metal elements in water was 1.85 ng/mL and 0.51 ng/mL at a lower laser energy (13.3 mJ), which was significantly better than other LIBS methods reported so far. The results show that the micro/nanostructure enhanced LIBS is a more sensitive method for detecting trace metal elements in the water.
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Osteoarthritis (OA) is a trauma-/age-related degenerative disease characterized by chronic inflammation as one of its pathogenic mechanisms. Mulberroside A (MA), a natural bioactive withanolide, demonstrates anti-inflammatory properties in various diseases; however, little is known about the effect of MA on OA. We aim to examine the role of MA on OA and to identify the potential mechanisms through which it protects articular cartilage. In vitro, MA improved inflammatory response, anabolism, and catabolism in IL-1ß-induced OA chondrocytes. The chondroprotective effects of MA were attributed to suppressing the MAPK, NF-κB, and PI3K-AKT-mTOR signaling pathways, as well as promoting the autophagy process. In vivo, intra-articular injection of MA reduced the cartilage destruction and reversed the change of anabolic and catabolic-related proteins in destabilized medial meniscus (DMM)-induced OA models. Thus, the study indicates that MA exhibits a chondroprotective effect and might be a promising agent for OA treatment.
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AIMS: Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. METHODS: After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1ß was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry. RESULTS: In chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF-κB signalling pathways. We found that in macrophages, knockdown of Peli1 can inhibit M1-type polarization of macrophages. In addition, the corresponding conditioned culture medium of macrophages applied to chondrocytes can also produce an anti-apoptotic effect. During in vivo experiments, the results have also shown that knockdown Peli1 reduces cartilage destruction and synovial inflammation. CONCLUSION: Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA.Cite this article: Bone Joint Res 2023;12(2):121-132.
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Background: Hand osteoarthritis (OA) is a chronic progressive disease characterized by disabling pain in the hand, with a high clinical burden. This study is designed to assess the epidemiological patterns of hand OA from 1990 to 2019 and analyze its secular trends based on sex, age, and socio-demographic index (SDI) at global, regional, and national levels. Methods: Data on the incidence and disability-adjusted life years (DALYs) of hand OA were extracted from the 2019 Global Burden of Disease (GBD), and their respective age-standardized rates (ASRs) were calculated. The estimated annual percentage changes (EAPCs) in ASR were calculated to assess the prevalent trends of the incidence and DALYs of hand OA over the recent three decades. The relationship between ASR and SDI was analyzed by Pearson's correlation analysis. Results: The incidence of hand OA increased from 371.30 million in 1990 to 676.02 million in 2019, increasing by 82.07%, whereas its age-standardized incidence rate (ASIR) decreased, with a downward trend [EAPC = -0.34; 95% confidence interval: -0.39--0.28]. With the changes in age, the incidence of hand OA exhibited a unimodal distribution before 70 years of age, peaking at 50-54 years, while its incidence had an upward trend in the >70 years age groups. Overall, hand OA-related DALYs increased in the recent 30 years. Meanwhile, its annual age-standardized DALY rate decreased, with EAPCs of -0.35 (95% CI, -0.38 --0.32). The DALYs increased with age. In 2019, the ASIR and age-standardized DALY rate were positively associated with the SDI regions. The incidence and DALYs presented predominance in female patients. The burden of hand OA over the recent three decades displayed obvious geographical diversity. Conclusion: The incident cases of hand OA increased globally from 1990 to 2019, while the ASIR and age-standardized DALY rate decreased. However, in many countries and regions, there was a rising trend of ASR related to incidence and DALYs. In addition, the prevalence revealed geographical, sex, and age diversity. Thus, governments and medical institutions should reallocate medical resources based on the epidemiological characteristics of hand OA.
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Background: Osteoarthritis (OA) is a common aging-related degenerative joint disease with chronic inflammation as its possible pathogenesis. Oroxin B (OB), a flavonoid isolated from traditional Chinese herbal medicine, possesses anti-inflammation properties which may be involved in regulating the pathogenesis of OA, but its mechanism has not been elucidated. Our study was the first to explore the potential chondroprotective effect and elucidate the underlying mechanism of OB in OA. Methods: In vitro, primary mice chondrocytes were stimulated with IL-1ß along with or without the administration of OB or autophagy inhibitor 3-methyladenine (3-MA). Cell viability assay was measured with a cell counting kit-8 (CCK-8). The phenotypes of anabolic-related (Aggrecan and Collagen II), catabolic-related (MMP3, MMP13, and ADAMTS5), inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1ß), and markers of related signaling pathways in chondrocytes with different treatment were detected through western blot, RT-qPCR, and immunofluorescent staining. In vivo, the destabilized medial meniscus (DMM) operation was performed to establish the OA mice model. After knee intra-articular injection with OB for 8 weeks, the mice's knee joints were obtained for subsequent histological staining and analysis. Results: OB reversed the expression level of anabolic-related proteins (Aggrecan and Collagen II) and catabolic-related (MMP3, MMP13, and ADAMTS5) in IL-1ß-induced chondrocytes. Mechanistically, OB suppressed the inflammatory response stimulated by IL-1ß, as the inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1ß) markers were downregulated after the administration of OB in IL-1ß-induced chondrocytes. Besides, the activation of PI3K/AKT/mTOR signaling pathway induced by IL-1ß could be inhibited by OB. Additionally, the autophagy process impaired by IL-1ß could be rescued by OB. What's more, the introduction of 3-MA to specifically inhibit the autophagic process impairs the protective effect of OB on cartilage. In vivo, histological staining revealed that intra-articular injection of OB attenuated the cartilage degradation, as well as reversed the expression level of anabolic and catabolic-related proteins such as Aggrecan, Collagen II, and MMP13 induced in DMM-induced OA models. Conclusions: The study verified that OB exhibited the chondroprotective effect by anti-inflammatory, inhibiting the PI3K/AKT/mTOR signaling pathway, and enhancing the autophagy process, indicating that OB might be a promising agent for the treatment of OA.
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Osteoartritis , Fosfatidilinositol 3-Quinasas , Ratones , Animales , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/farmacología , Metaloproteinasa 3 de la Matriz/uso terapéutico , Agrecanos/metabolismo , Agrecanos/farmacología , Agrecanos/uso terapéutico , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/farmacología , Ciclooxigenasa 2/uso terapéutico , Osteoartritis/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , FN-kappa B/metabolismo , Interleucina-6 , Condrocitos , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Antiinflamatorios/uso terapéutico , Autofagia/fisiología , Colágeno/metabolismoRESUMEN
It is well known that Bessel beams have non-diffractive characteristics, which can be generated by Gaussian beams focused by an ideal axicon. In general, the length of filament generated by Bessel beams is longer than that by Gaussian beams and the electron density in the filament generated by Bessel beams is more uniform. This paper experimentally studied the propagation distance-resolved characteristics of copper plasma emission induced by axicon-focused femtosecond laser filamentation in the air. The evolution of the spectral intensity, plasma temperature, and electron density with the filament propagation path was obtained. The experiment results showed that when the base angle of the axicon was 5.0°, the spectral intensity along with the filament propagation path was more stable than that the base angle of the axicon was 0.5°. The changes in the plasma temperature and electron density along the filament propagation path were consistent with the change in the spectral intensity. This work provides a demonstration for the applications of filament-induced breakdown spectroscopy (FIBS), such as long-distance detection.
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This study has investigated the microscopic mechanisms of ultralow lattice thermal conductivity by the first-principles density functional theory. By solving the phonon Boltzmann equation iteratively, we find that the thermal conductivity of the lattice is abnormally low and that glass like heat transfer behavior occurs. Therefore, in addition to the contribution about the particle-like propagation to heat transport, the off-diagonal elements of the heat-flux operator through wave-like interbranch tunneling of phonon modes are also considered. The results provided new insights into the minimum thermal conductivity (κL) for Cs2SnBr6 (0.17 W m-1 K-1 at 450 K). It was also found that polar optical phonon scattering severely affects carrier lifetime. In addition, an impressive thermoelectric figure of merit of 0.55 at 450 K for Cs2SnBr6 was obtained in the case of doping p-type carriers. The study helps us understand the ultralow κL in complex crystals with strong anharmonicity and find that Cs2SnBr6 is a new and promising thermoelectric material.
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Cancer is one of the primary causes of death worldwide, and its morbidity and mortality rates are increasing rapidly. However, standard treatment modalities (surgery, radiotherapy, chemotherapy, and immunotherapy) often fail to achieve a satisfactory therapeutic effect. Extracellular vesicles (EVs) are natural nano-sized lipid bilayer vesicles secreted from cells. Owing to their advantages of low toxicity, high biocompatibility, low immunogenicity, and inherent targeting, EVs can be exploited as drug delivery vectors for cancer treatment. In this review, we summarize the research progress of EV-based drug delivery systems in cancer treatment by focusing on four aspects: sources, cargo types, cargo loading methods and modification strategies. Finally, current challenges and future perspectives are discussed.