LTF induces senescence and degeneration in the meniscus via the NF-κB signaling pathway: A study based on integrated bioinformatics analysis and experimental validation

Background: The functional integrity of the meniscus continually decreases with age, leading to meniscal degeneration and gradually developing into osteoarthritis (OA). In this study, we identified diagnostic markers and potential mechanisms of action in aging-related meniscal degeneration through bioinformatics and experimental verification.Methods: Based on the GSE98918 dataset, common differentially expressed genes (co-DEGs) were screened using differential expression analysis and the WGCNA algorithm, and enrichment analyses based on Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were further performed. Next, the co-DEGs were imported into the STRING database and Cytoscape to construct a protein‒protein interaction (PPI) network and further validated by three algorithms in cytoHubba, receiver operating characteristic (ROC) curve analysis and the external GSE45233 dataset. Moreover, the diagnostic marker lactotransferrin (LTF) was verified in rat models of senescence and replicative cellular senescence via RT‒qPCR, WB, immunohistochemistry and immunofluorescence, and then the potential molecular mechanism was explored by loss of function and overexpression of LTF.Results: According to the analysis of the GSE98918 dataset, we identified 52 co-DEGs (42 upregulated genes and 10 downregulated genes) in the OA meniscus. LTF, screened out by Cytoscape, ROC curve analysis in the GSE98918 dataset and another external GSE45233 dataset, might have good predictive power in meniscal degeneration. Our experimental results showed that LTF expression was statistically increased in the meniscal tissue of aged rats (24 months) and senescent passage 5th (P5) meniscal cells. In P5 meniscal cells, LTF knockdown inhibited the NF-κB signaling pathway and alleviated senescence. LTF overexpression in passage 0 (P0) meniscal cells increased the expression of senescence-associated secretory phenotype (SASP) and induced senescence by activating the NF-κB signaling pathway. However, the senescence phenomenon caused by LTF overexpression could be reversed by the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC).Conclusion: For the first time, we found that increased expression of LTF was observed in the aging meniscus and could induce meniscal senescence and degeneration by activating the NF-κB signaling pathway. These results revealed that LTF could be a potential diagnostic marker and therapeutic target for age-related meniscal degeneration

Survival predictors associated with signet ring cell carcinoma of the esophagus (SRCCE): A population-based retrospective cohort study.

Signet ring cell carcinoma of the esophagus (SRCCE) is an uncommon tumor associated with significant morbidity and mortality. There is still no consensus regarding cut-off values for tumor size, age and optimal treatment for SRCCE. Thus, we elucidated the current survival outcomes of patients with SRCCE and analyzed factors associated with prognosis.A retrospective cohort study based on the SEER (The Surveillance, Epidemiology, and End Results) program database was conducted. We identified 537 patients (461 men and 76 women) newly diagnosed with SRCCE between January 2004 and December 2014. A multivariate Cox proportional hazards model was utilized to measure the mortality-associated risk factors in patients with SRCCE after adjusting for various variables.The 1-, 2- and 5-year disease-specific mortalities (DSM) were 51.6%, 67.6%, and 78.4%, respectively, and the median survival time was 12.0 months. The factors correlated with mortality hazard were marital status (unmarried versus married, Hazard Ratio (HR) = 1.443), tumor size (≥ 5 cm versus < 5 cm, HR = 1.444), tumor grade (high grade versus low grade, HR = 3.001), condition of primary tumor (T4 versus T1, HR = 2.178), regional lymph node metastasis (N1 versus N0, HR = 1.739), further metastasis (M1 versus M0, HR = 1.951) and chemotherapy (receiving chemotherapy versus no chemotherapy, HR = 0.464).The contemporary 5-year DSM was 78.4%. Being unmarried, having a tumor size ≥ 5 cm, a high tumor grade, a score of T4 for tumor invasion of adjacent organs, a score of N1 for regional lymph node metastasis, a score of M1 for distant metastasis and no chemotherapy were independent predictors of high DSM

Dendrobine Alleviates Cellular Senescence and Osteoarthritis via the ROS/NF-κB Axis

Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and cartilage degradation. Dendrobine (DEN) is reported to inhibit inflammation and oxidative stress in some diseases, but its role in chondrocyte senescence and OA progress has not yet been elucidated. Our study aimed to explore the protective effects of DEN on OA both in vitro and in vivo. We found that DEN inhibited extracellular matrix (ECM) degradation and promoted ECM synthesis. Meanwhile, DEN inhibited senescence-associated secretory phenotype (SASP) factors expression and senescence phenotype in IL-1β-treated chondrocytes. Furthermore, DEN improved mitochondrial function and reduced the production of intracellular reactive oxygen species (ROS). Also, DEN suppressed IL-1β-induced activation of the NF-κB pathway. Further, using NAC (ROS inhibitor), we found that DEN might inhibit NF-κB cascades by reducing ROS. Additionally, X-ray, micro-CT, and histological analyses in vivo demonstrated that DEN significantly alleviated cartilage inflammation, ECM degradation, and subchondral alterations in OA progression. In conclusion, DEN inhibits SASP factors expression and senescence phenotype in chondrocytes and alleviated the progression of OA via the ROS/NF-κB axis, which provides innovative strategies for the treatment of OA

Single-bundle versus double-bundle autologous anterior cruciate ligament reconstruction: a meta-analysis of randomized controlled trials at 5-year minimum follow-up

Abstract Background Both single-bundle (SB) and double-bundle (DB) techniques were widely used in anterior cruciate ligament (ACL) reconstruction recently. Nevertheless, up to now, no consensus has been reached on whether the DB technique was superior to the SB technique. Moreover, follow-up of the included studies in the published meta-analyses is mostly short term. Our study aims to compare the mid- to long-term outcome of SB and DB ACL reconstruction concerning knee stability, clinical function, graft failure rate, and osteoarthritis (OA) changes. Methods This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Embase, and the Cochrane Library were searched from inception to October 2017. The study included only a randomized controlled trial (RCT) that compared SB and DB ACL reconstruction and that had a minimum of 5-year follow-up. The Cochrane Collaboration’s risk of bias tool was used to assess the risk of bias for all included studies. Stata/SE 12.0 was used to perform a meta-analysis of the clinical outcome. Results Five RCTs were included, with a total of 294 patients: 150 patients and 144 patients in the DB group and the SB group, respectively. Assessing knee stability, there was no statistical difference in side-to-side difference and negative rate of the pivot-shift test. Considering functional outcome, no significant difference was found in proportion with International Knee Documentation Committee (IKDC) grade A, IKDC score, Lysholm scores, and Tegner scores. As for graft failure rate and OA changes, no significant difference was found between the DB group and the SB group. Conclusion The DB technique was not superior to the SB technique in autologous ACL reconstruction regarding knee stability, clinical function, graft failure rate, and OA changes with a mid- to long-term follow-up

Zoledronic Acid Enhanced the Antitumor Effect of Cisplatin on Orthotopic Osteosarcoma by ROS-PI3K/AKT Signaling and Attenuated Osteolysis

Osteoclasts can interact with osteosarcoma to promote the growth of osteosarcoma. Cisplatin is common in adjuvant chemotherapy of osteosarcoma. However, due to chemoresistance, the efficacy is profoundly limited. Previous studies have found that zoledronic acid (ZA) has osteoclast activation inhibition and antitumor effect. However, the combined effect of ZA and cisplatin on osteosarcoma remains unclear. In vitro, the effects of ZA and cisplatin alone or in combination on 143B cell activity, proliferation, apoptosis, and ROS-PI3K/AKT signaling were detected. At the same time, the effect of ZA and cisplatin on osteoclast formation, survival, and activity was detected by TRAP staining and bone plate absorption test. These were further verified in mice. The results showed that in vitro, compared with the single treatment and control, the combination of ZA and cisplatin could significantly inhibit the activity and proliferation of 143B cells and induced their apoptosis and further promoted the generation of ROS and inhibited the phosphorylation of PI3K and AKT. ROS scavenger and the agonist of the PI3K/AKT pathway could reverse these results. In addition, cisplatin in synergy with ZA could significantly inhibit osteoclast formation and survival to reduce bone plate absorption. In vivo, compared with the single group, the tumor volume and cell proliferation were significantly reduced, apoptosis and necrosis of tumor cells increased, and TRAP+ osteoclasts and osteolysis destruction decreased in the combined group. In conclusion, ZA enhanced the antitumor effect of cisplatin on osteosarcoma by ROS-PI3K/AKT signaling, reducing the chemoresistance and osteoclast activation to enhance chemotherapy and inhibit osteolysis. And this present study raised the possibility that combining ZA and cisplatin may represent a novel strategy against osteosarcoma

Anteromedial versus transtibial technique in single-bundle autologous hamstring ACL reconstruction: a meta-analysis of prospective randomized controlled trials

Abstract Background The aim of this study was to compare the clinical outcome and postoperative complication between single-bundle anterior cruciate ligament (ACL) reconstruction with an anteromedial (AM) technique and a transtibial (TT) technique. Methods The study includes clinical randomized controlled trials comparing the clinical outcomes of ACL reconstruction using the autologous hamstring tendon with an AM method and a TT method published up to September 2017 were retrieved from PubMed, Cochrane Library, and Embase databases. Relevant data were extracted and the Physiotherapy Evidence Database (PEDro) scale was used to assess the methodological quality. Stata/SE 12.0 was used to perform a meta-analysis of the clinical outcome. Results Five RCTs were included, with a total of 479 patients: 239 patients and 240 patients in the AM group and the TT group, respectively. Assessing postoperative stability, better results were found in the AM group for the negative rate of the Lachman test (P  0.05). In terms of postoperative complication, no significant difference was found between the AM group and the TT group (P > 0.05). Conclusions The outcome of single-bundle ACL reconstruction with the AM technique is better than that with the TT technique in terms of postoperative stability and functional recovery of the knee

Cox model with hazard ratios and 95% confidence intervals of mortality associated with covariates in patients with signet ring cell carcinoma of the esophagus.

<p>Cox model with hazard ratios and 95% confidence intervals of mortality associated with covariates in patients with signet ring cell carcinoma of the esophagus.</p

Kaplan—Meier survival curves of all patients and patients stratified by various factors.

<p>Kaplan—Meier survival curves of all patients and patients stratified by various factors.</p

Three-dimensional CT study on the anatomy of vertebral artery at atlantoaxial and intracranial segment

Xiamen City's Scientific & Technical Program [3502Z 20064008]; Xiamen board of health's Medical Research Program, Xiamen, China [WSK 0622]The atlantoaxial and intracranial segments of vertebral artery (V(3-4)) are winding around their peripheral structures. Their panorama is not easy to be observed in surgery. CT angiography (CTA) shows some advantages in this aspect. So, the aim of this study is to reveal the three-dimensional (3D) anatomy related to V(3-4) and prepare ground for clinical diagnosis and treatment. Ninety-eight cases without the pathologies of V(3-4) were selected from the head-neck CTA examination. All the 3D images were formed with multiplanar reconstruction, volume rendering and volume rendering together with separating, fusing, opacifying and false-coloring. On the 3D images, the courses and branch of V(3-4) were observed and measured, as well as their peripheral venous vascular plexus (VVP). V(3-4) with typical five curves was found in 85 cases and with variations in 13. The left V(3-4) is larger than right (P 0.05). The anatomy and variations of V(3-4) can be clearly and directly shown by 3DCTA. The understanding of vertebral artery and bony structures around there can provide anatomic basis for surgery and radiological diagnosis