The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the onset of osteoarthritis (OA). Hydrogen sulfide (H2S), a gaseous signalling ...molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H2S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H2S in the pathogenesis of OA and its protective effects on interleukin (IL)‐1β‐induced chondrocytes were identified. Our data revealed decreased H2S expression in both human degenerative OA cartilage tissue and IL‐1β‐induced chondrocytes. Pretreatment with the H2S donor sodium hydrosulfide (NaHS) dramatically attenuated IL‐1β‐induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K/AKT pathway‐mediated inhibition of nuclear factor kappa B (NF‐κB). Moreover, mitochondrial dysfunction‐related apoptosis was significantly reversed by NaHS in IL‐1β‐stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL‐1β‐induced phosphorylation of the mitogen‐activated protein kinase (MAPK) cascades. Furthermore, in the destabilization of the medial meniscus mouse model, OA progression was ameliorated by NaHS administration. Taken together, these results suggest that H2S may antagonize IL‐1β‐induced inflammation and mitochondrial dysfunction‐related apoptosis via selective suppression of the PI3K/Akt/NF‐κB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA.
Graphical
Hydrogen sulfide protects against interleukin‐1β‐induced inflammation and mitochondrial dysfunction‐related apoptosis in chondrocytes via selective suppression of the PI3K/Akt/nuclear factor kappa B and mitogen‐activated protein kinase signalling pathways; also it effeciently ameliorates osteoarthritis.
Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain. Polydatin (PD) has been shown to exert multiple pharmacological effects on different diseases; here, we test the ...therapeutic potential of PD for IVDD. In in‐vitro experiments, we confirmed PD is nontoxic to nucleus pulposus cells (NPCs) under the concentration of 400 μmol/L. Furthermore, PD was able to decrease the level of senescence in TNF‐α‐treated NPCs, as indicated by β‐gal staining as well as senescence markers p53 and p16 expression. In the aspect of extracellular matrix (ECM), PD not only reduced metalloproteinase 3 (MMP‐3), metalloproteinase 13 (MMP‐13) and a disintegrin‐like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS‐4) expression, but also increased aggrecan and collagen II levels. Mitochondrion is closely related to cellular senescence and ECM homeostasis; mechanistically, we found PD may rescue TNF‐α‐induced mitochondrial dysfunction, and it may also promote Nrf2 expression and activity. Silencing Nrf2 partly abolished the protective effects of PD on mitochondrial homeostasis, senescence and ECM homeostasis in TNF‐α‐treated NPCs. Correspondingly, PD ameliorated IVDD in rat model by promoting Nrf2 activity, preserving ECM and inhibiting senescence in nucleus pulposus cells. To sum up, our study suggests that PD exerts protective effects in NPCs against IVDD and reveals the underlying mechanism of PD on Nrf2 activation in NPCs.
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.
Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, ...is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD. We assessed SIRT3 expression in degenerative nucleus pulposus (NP) tissues and oxidative stress-induced nucleus pulposus cells (NPCs). SIRT3 was knocked down by lentivirus and activated by honokiol to determine its role in oxidative stress-induced NPCs. The mechanism by which honokiol affected SIRT3 regulation was investigated in vitro, and the therapeutic potential of honokiol was assessed in vitro and in vivo. We found that the expression of SIRT3 decreased with IVDD, and SIRT3 knockdown reduced the tolerance of NPCs to oxidative stress. Honokiol (10 μM) improved the viability of NPCs under oxidative stress and promoted their properties of anti-oxidation, mitochondrial dynamics and mitophagy in a SIRT3-dependent manner. Furthermore, honokiol activated SIRT3 through the AMPK-PGC-1α signaling pathway. Moreover, honokiol treatment ameliorated IVDD in rats. Our study indicated that SIRT3 is involved in IVDD and showed the potential of the SIRT3 agonist honokiol for the treatment of IVDD.
Background: Early dysphagia is a frequent complication of anterior cervical (AC) spine surgery. However, there are no reports that have discussed the correlation between early dysphagia and the ...positional relationship between thyroid cartilage and the surgical level.
Methods: We retrospectively enrolled 82 patients in our hospital who underwent single-level AC discectomy performed by the same surgeon using the same internal fixation apparatus from 2015 to 2017. Swallowing difficulty was rated during the first five postoperative days using a 10-point scoring system. The positional relationship between the thyroid cartilage and the surgical level was defined as discectomy within the thyroid cartilage (IN group) or outside the thyroid cartilage (OUT group) using preoperative computed tomography (CT) images. The confounding factors such as gender, age, body mass index (BMI), hypertension, diabetes mellitus, drinking, smoking, operative level, operative time, and blood loss were analyzed by a binomial logistic regression.
Results: The thyroid cartilage was most commonly located above the C5 level (65.1%). Early dysphagia developed in 47.6% of the patients during the first five postoperative days. The IN and OUT groups each contained 41 cases. The difference in the cumulative postoperative early dysphagia score between the IN and OUT groups was statistically significant (p < .05). The factors of gender, age, BMI, hypertension, diabetes mellitus, drinking, smoking, operative level, operative time, blood loss did not significantly influence the incidence of postoperative early dysphagia.
Conclusions: We found that early dysphagia, which is a self-limiting complication, was correlated with surgery performed at levels outside the thyroid cartilage region. Preoperative review of the positional relationship between the thyroid cartilage and the surgical level can predict the incidence of postoperative transient dysphagia.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This paper proposes an efficient bandwidth allocation scheme to fully utilize the multi-access ability of multimode terminals in heterogeneous networks. To model the fact that the suitability of ...different networks to different traffics varies, which is seldom considered in previous literature, the term "Match-Degree" is introduced and calculated using grey relational analysis. Afterwards, two methods, namely weighted bandwidth factor and cumulative utility function are proposed to integrate the influence of "Match-Degree" into the conventional utility-functions. Moreover, energy consumption and network price are also considered to make our model more comprehensive. The bandwidth allocation problem is formulated as maximizing the overall utility by adjusting the bandwidth allocated to each user. Based on optimization theory, an iterative algorithm is constructed to solve this problem. And numerical results validate the performance enhancement of our scheme compared with the existing ones.
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-1β. The results showed that IF blocked IL-1β-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-1β-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.
•Isofraxidin is a coumarin compound which has not been reported to have effective for treating osteoarthritis.•Isofraxidin inhibited the IL-1β-induced inflammatory mediators in human osteoarthritis chondrocytes.•Isofraxidin inhibited IL-1β-induced inflammatory response through suppressing NF-κB activation
To retrospectively explore the effect of a half-dose buprenorphine transdermal patch for analgesia after arthroscopic rotator cuff repair (ARCR).
This analysis was performed with clinical data from ...patients who received unilateral ARCR in our hospital between October 2017 and December 2020. The patients were divided into three groups (30 cases each). In group A (control group), 100 mg flurbiprofen axetil (FA) was administered twice a day for 5 days after surgery. In group B (experimental group), 100 mg FA was administered twice a day for 5 days and half (2.5 mg) of a buprenorphine transdermal patch was applied after surgery; an additional half (2.5 mg) patch was applied 3 days later. In group C (condition control group), 100 mg FA was administered twice a day for 5 days and a 5-mg patch was applied directly after surgery. The visual analog scale (VAS) was administered repeatedly 1 day before surgery and 1, 2, 3, 5, and 14 days after surgery in each group. The simple shoulder test (SST) score, range of shoulder forward elevation (FE), and external rotation (ER) were recorded preoperatively and 12 weeks postoperatively.
VAS scores on postoperative days 3 and 5 were significantly lower in groups B and C than in group A (p < 0.05). The VAS score on postoperative day 14 was significantly lower in group C than in group A (p < 0.05). The difference in VAS score between groups B and C was not significant (p > 0.05). All patients had significantly improved VAS scores, SST scores, FE, and ER at 12 weeks postoperatively.
The half-dose buprenorphine transdermal patch had a good analgesic effect with minimal side effects after ARCR and did not delay the recovery of shoulder joint function.
Keywords: apoptosis; chondrocytes; hydrogen sulfide; inflammation; osteoarthritis The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the ...onset of osteoarthritis (OA). Hydrogen sulfide (H.sub.2S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H.sub.2S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H.sub.2S in the pathogenesis of OA and its protective effects on interleukin (IL)-1beta-induced chondrocytes were identified. Our data revealed decreased H.sub.2S expression in both human degenerative OA cartilage tissue and IL-1beta-induced chondrocytes. Pretreatment with the H.sub.2S donor sodium hydrosulfide (NaHS) dramatically attenuated IL-1beta-induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K/AKT pathway-mediated inhibition of nuclear factor kappa B (NF-PHIB). Moreover, mitochondrial dysfunction-related apoptosis was significantly reversed by NaHS in IL-1beta-stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL-1beta-induced phosphorylation of the mitogen-activated protein kinase (MAPK) cascades. Furthermore, in the destabilization of the medial meniscus mouse model, OA progression was ameliorated by NaHS administration. Taken together, these results suggest that H.sub.2S may antagonize IL-1beta-induced inflammation and mitochondrial dysfunction-related apoptosis via selective suppression of the PI3K/Akt/NF-PHIB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA. Article Note: Ben Wang and Zhenxuan Shao contributed equally to this work. CAPTION(S): Supplementary information. Supplementary information. Byline: Ben Wang, Zhenxuan Shao, Mingbao Gu, Libin Ni, Yifeng Shi, Yingzhao Yan, Aimin Wu, Haiming Jin, Jiaoxiang Chen, Xiaoyun Pan, Daoliang Xu
Inflammation and extracellular matrix (ECM) degradation have been implicated in the pathological process of osteoarthritis (OA). α-Cyperone is the main active component of the traditional Chinese ...medicine
Cyperus rotundus L
. In this study, we found that α-Cyperone abolished the IL-1β-induced production of inflammatory cytokines in isolated rat chondrocytes, such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), in a dose-dependent manner (0.75, 1.5 or 3 μM). Also, the results showed that α-Cyperone downregulated the expression of metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS5), and upregulated the expression of type-2 collagen. Mechanistically, molecular docking tests revealed that α-Cyperone stably and effectively binds to p65, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). α-Cyperone inhibited NF-κB activation by blocking its nuclear transfer, and decreasing the phosphorylation of mitogen-activated protein kinase (MAPKs). In addition,
in vivo
studies based on a mouse model of arthritis showed that α-Cyperone prevented the development of osteoarthritis. Therefore, α-Cyperone may be a potential anti-OA drug.
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