Lung cancer is a major public health problem worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. Autophagy has recently sparked great interest, and it is thought to participate in a variety of diseases, including lung cancer. Uncoordinated (Unc) 51-like kinase 1 (Ulk1), a serine/threonine kinase, plays a central role in the autophagy pathway. However, the role of Ulk1 in NSCLC remains unclear. We report that NSCLC cell lines exhibited high expression of Ulk1 and that Ulk1 was negatively correlated with prognosis in lung cancer patients. Knockdown of Ulk1 or the inhibition of Ulk1 by the selective inhibitor SBI0206965, inhibited cell proliferation, induced cell apoptosis and enhanced the sensitivity of cisplatin against NSCLC cells. Moreover, we demonstrated that Ulk1 exerted oncogenic activity in NSCLC by modulating both autophagy and apoptosis pathways. Inhibition of autophagy by SBI0206965 sensitized NSCLC cells to cisplatin by inhibiting cisplatin induced cell-protective autophagy to promote apoptosis. Furthermore, SBI0206965 promoted apoptosis in NSCLC cells independent of autophagy, which was partly mediated by destabilization of Bcl2/Bclxl. In summary, our results show that inhibition of Ulk1 suppresses NSCLC cell growth and sensitizes NSCLC cells to cisplatin by modulating both autophagy and apoptosis pathways, and that Ulk1 might be a promising target for NSCLC treatment.

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The aim of the present study was to investigate the anti-cancer effects of the natural plant flavonoid, taxifolin, on human osteosarcoma cancer cells. Taxifolin was demonstrated to exhibit anti‑cancer effects on U2OS and Saos‑2 osteosarcoma cell lines. Treatment of cells with taxifolin inhibited proliferation and diminished colony formation in soft agar in a dose‑dependent manner. In vivo, intraperitoneal administration of taxifolin in nude mice bearing U2OS xenograft tumors, significantly inhibited tumor growth. In addition, taxifolin treatment was demonstrated to promote G1 cell cycle arrest and cell apoptosis in U2OS and Saos‑2 cell lines, as demonstrated by flow cytometry analysis. Western blot analysis demonstrated that taxifolin treatment was associated with a reduction in the expression levels of AKT serine/threonine kinase 1 (AKT), phosphorylated (p‑Ser473) AKT, v‑myc avian myelocytomatosis viral oncogene homolog (c‑myc) and S‑phase kinase associated protein 2 (SKP‑2) in U2OS and Saos‑2 cell lines. Overexpression of AKT considerably reversed the taxifolin‑induced decrease in AKT, c‑myc and SKP‑2 protein expression and the decrease in AKT phosphorylation, suggesting that inactivation of AKT was a mediator of taxifolin‑induced inhibition of c‑myc and SKP‑2. Furthermore, overexpression of SKP‑2 in U2OS cells partially reversed the growth inhibition mediated by taxifolin. Finally, taxifolin treatment repressed cell migration and invasion in U2OS cells and this effect was markedly reversed by SKP‑2 overexpression. The results of the present study indicate that taxifolin may present a potential novel therapeutic agent for osteosarcoma treatment.

BackgroundThe optimal surgical approach for treatment of multi-level cervical disc disease is currently widely debated. Anterior cervical discectomy and fusion (ACDF) combined with cervical disc arthroplasty (CDA) has been presented as a treatment approach, but to date, there are few reports with adequate clinical and radiological data for this hybrid surgical procedure. The goal of this paper is to assess clinical and radiological outcomes in patients with cervical spondylosis in three contiguous segments after treatment with artificial disc replacement combined with fusion.Materials and methodsWe performed a retrospective review of 36 patients (mean age of 48.6 years) with contiguous three-level cervical spondylosis who were treated with ACDF coupled with CDA (hybrid surgery) between October 2008 and October 2012. Clinical evaluation was based on the Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) score, and postoperative JOA score improvement rate (IR). Radiographic parameters, angular range of motion (ROM) for C2-C7, and ROM for the superior and inferior adjacent segments were measured before the operation, at 1, 3, 6, and 12 months postoperation, and at the final follow-up evaluation. All cases were followed for at least 28 months (range 28–65 months).ResultsAll patients exhibited significant postoperative improvement in NDI and JOA scores compared to preoperative levels (P < 0.05), and these improved scores were maintained during the follow-up period. The JOA score improvement rate was 70.83 % at the final follow-up evaluation. The mean C2-C7 ROM of all cases was significantly decreased immediately after operation but recovered to preoperative levels after 12 months (P = 0.721). The ROM of the superior and inferior adjacent segments was recovered to preoperative levels after 6 months (P > 0.05). One patient required a second surgery for symptomatic adjacent segment degeneration. Neither pseudarthrosis nor other device migration was observed in any patients during the entire follow-up period.ConclusionsThese results indicate that hybrid surgery seems to be a promising, acceptable, and alternative surgical approach for the treatment of multi-level cervical disc disease.

Drug-free GLUT5-targeted Fru-MnP nanocomposites were synthesized to trigger caspases-mediated apoptosis of osteosarcoma in vitro and in vivo by producing high level of ROS under a Mn2+-driven Fenton-like reaction.

This paper adopts a method combining hybrid self-assembly, cyclic freezing-thawing and annealing treatment to prepare polyvinyl alcohol (PVA) and graphene oxide (GO) composite hydrogel. Then, the PVA-GO composite hydrogels are re-swelled in different ionic solutions (NaCl, MgCl 2 , CaCl 2 and AlCl 3) to improve mechanical strength, toughness and wear resistance by the ionic coordination bonds. The microstructure and morphology are characterized by Fourier transforms infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Scanning electron microscopy (SEM), finding that the internal structure is porous three-dimensional network. Mechanical experiments indicate that the composite hydrogel with GO content of 0.05wt% immersed in MgCl 2 solution displays the best mechanical properties overall. Its tensile strength can reach 11.10MPa and the elastic modulus reaches 1.72MPa, which is 175% and 85% higher than the pure PVA, respectively. Sliding friction experiments illustrate that the composite hydrogel immersed in AlCl 3 solution exhibits the lowest friction coefficient, and the higher the valence state of metal cation is, the better the wear reduction effect is. We expect to enrich the development of PVA-GO hydrogels in tissue engineering through synergy of hydrogen bonds and ionic coordination bonds.

The objective of the present study was to evaluate the clinical, radiological, and functional outcomes of a subscapularis transthoracic surgical approach and a posterolateral surgical approach with debridement, bone graft fusion, and internal fixation for the treatment of upper thoracic tuberculosis.There is currently debate over the best surgical approach for the treatment of upper thoracic tuberculosis. Traditionally, the subscapularis transthoracic approach has been preferred; however, the posterolateral approach has gained popularity in the past few years.A prospective, consecutive cohort of 43 upper thoracic tuberculosis patients with a mean age of 39 years (range: 20–52 years) was followed up for a minimum of 12 months (range: 12–60 months). Patients were randomly divided into 2 groups. Group A (n = 21) was treated by the subscapularis transthoracic approach and group B (n = 22) was treated by the posterolateral approach. All cases were evaluated for clinical, radiological, and functional outcomes. Intraoperative blood loss, operative duration, intraoperative and postoperative complications, hospital stay, the cure rate, fusion time, and the Frankel scale were used for clinical and functional evaluation, whereas the kyphosis angle was used for radiological evaluation.Grafted bones were fused by 10 months in all cases. There was no statistically significant difference between groups before surgery in terms of gender, age, segmental tuberculosis, erythrocyte sedimentation rate (ESR), Frankel scale, or Cobb's angle (P > 0.05). The average operative duration for Group B was lower than that of Group A. There were no significant differences in intraoperative blood loss, intraoperative and postoperative complications, hospital stay, grafted bone fusion time, or cure rate between groups (P > 0.05). The Cobb's angle correction rate for group B (68.5%) was significantly better than that of group A (30.9%). The neurological score showed significant postoperative improvement in both groups, with no significant difference between the groups.The subscapularis transthoracic approach and the posterolateral approach with debridement, bone graft fusion, and internal fixation are both sufficient and satisfactory for the surgical treatment of upper thoracic tuberculosis. However, the posterolateral approach is superior to the subscapularis transthoracic approach in terms of surgical trauma, operative time, and kyphosis correction.