Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma

Zhengbo Hu,Lugen Li,Wenxing Lan,Xiao Wei,Xiangyuan Wen,Penghuan Wu,Xianliao Zhang,Xinhua Xi,Yufa Li,Liqi Wu,Wenhu Li,Xiaohong Liao 대한암학회 2022 Cancer Research and Treatment Vol.54 No.1

Purpose Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 and nuclear factor кB (NF-κB) pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection is currently unclear. We explored it in human OS cells. Materials and Methods Multiple OS cell lines were exposed to a Wee1 inhibitor (AZD1775) and CDDP to assess the half-maximal inhibitory concentration values. Western blot, coimmunoprecipitation, confocal immunofluorescence, cell cycle, and Cell Counting Kit-8assays were performed to explore the connection between the Wee1/CDC2 and NF-κB pathways and their subsequent physiological contribution to CDDP resistance. Finally, CDDP-resistant PDX-OS xenograft models were established to confirm that AZD1775 restores the antitumor effects of CDDP. Results A sensitivity hierarchy of OS cells to CDDP and AZD1775 exists. In the highly CDDP-tolerant cell lines, Wee1 and RelA were physically crosslinked, which resulted in increased abundance of phosphorylated CDC2 (Y15) and RelA (S536) and consequent modulation of cell cycle progression, survival, and proliferation. Wee1 inhibition restored the effects of CDDP on these processes in CDDP-resistant OS cells. In addition, animal experiments with CDDP-resistant PDX-OS cells showed that AZD1775 combined with CDDP not only restored CDDP efficacy but also amplified AZD1775 in inhibiting tumor growth and prolonged the median survival of the mice. Conclusion Simultaneous enrichment of molecules in the Wee1/CDC2 and NF-κB pathways and their consequent coactivation is a new molecular mechanism of CDDP resistance in OS cells. OS with this molecular signature may respond well to Wee1 inhibition as an alternative treatment strategy. Purpose Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 and nuclear factor кB (NF-κB) pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection is currently unclear. We explored it in human OS cells.Materials and Methods Multiple OS cell lines were exposed to a Wee1 inhibitor (AZD1775) and CDDP to assess the half-maximal inhibitory concentration values. Western blot, coimmunoprecipitation, confocal immunofluorescence, cell cycle, and Cell Counting Kit-8assays were performed to explore the connection between the Wee1/CDC2 and NF-κB pathways and their subsequent physiological contribution to CDDP resistance. Finally, CDDP-resistant PDX-OS xenograft models were established to confirm that AZD1775 restores the antitumor effects of CDDP.Results A sensitivity hierarchy of OS cells to CDDP and AZD1775 exists. In the highly CDDP-tolerant cell lines, Wee1 and RelA were physically crosslinked, which resulted in increased abundance of phosphorylated CDC2 (Y15) and RelA (S536) and consequent modulation of cell cycle progression, survival, and proliferation. Wee1 inhibition restored the effects of CDDP on these processes in CDDP-resistant OS cells. In addition, animal experiments with CDDP-resistant PDX-OS cells showed that AZD1775 combined with CDDP not only restored CDDP efficacy but also amplified AZD1775 in inhibiting tumor growth and prolonged the median survival of the mice.Conclusion Simultaneous enrichment of molecules in the Wee1/CDC2 and NF-κB pathways and their consequent coactivation is a new molecular mechanism of CDDP resistance in OS cells. OS with this molecular signature may respond well to Wee1 inhibition as an alternative treatment strategy.

Impact of enhanced recovery after surgery program for hungry bone syndrome in patients on maintenance hemodialysis undergoing parathyroidectomy for secondary hyperparathyroidism

Ling Wang*,Xiaohong Zhang*,Fengqi Hu,Hai Yuan,Zhao Gao,Li He,Shuang Zou 대한외과학회 2022 Annals of Surgical Treatment and Research(ASRT) Vol.103 No.5

Purpose: Hungry bone syndrome after parathyroidectomy is an important clinical problem in patients on maintenance hemodialysis. We examined the effect of an enhanced recovery after surgery (ERAS) program on the incidence of hungry bone syndrome after parathyroidectomy in this population. Methods: This single-institution, retrospective study analyzed 108 patients on hemodialysis who underwent parathyroidectomy for secondary hyperparathyroidism. Patients were classified into the pre-ERAS (n = 52) and post-ERAS (n = 56) groups. The ERAS program identified high-risk patients and enforced aggressive measures to normalize calcium levels following parathyroidectomy. Results: There was no significant difference in age, sex, body weight, presenting symptoms, preoperative calcium and alkaline phosphatase levels, postoperative intact parathyroid levels, postoperative calcium levels at 1 and 24 hours after parathyroidectomy, and 30-day readmission rates between the groups. The post-ERAS group had significantly higher levels of postoperative calcium at 48 and 72 hours after parathyroidectomy, but a lower incidence of hungry bone syndrome and shorter postoperative length of stay. Patients with hungry bone syndrome had higher preoperative levels of alkaline phosphatase and intact parathyroid, longer postoperative length of stay, and were less likely to have been part of the ERAS program. High preoperative alkaline phosphatase levels and absence of the ERAS program were independent risk factors for hungry bone syndrome after parathyroidectomy. Conclusion: The ERAS program reduced the incidence of hungry bone syndrome and shortened the postoperative length of stay in patients on maintenance hemodialysis who underwent parathyroidectomy for secondary hyperparathyroidism.

Asymptotically Optimal Scenario-based Multi-objective Optimization for Distributed Generation Allocation and Sizing in Distribution Systems

Lizhen Wu,Xusheng Yang,Hu Zhou,Xiaohong Hao 보안공학연구지원센터 2016 International Journal of Grid and Distributed Comp Vol.9 No.4

Suitable location and optimal sizing are impact on voltage stability margin of the distributed system. It is important to accurately simulate the random output active power of Distributed Generation (DG). In order to model uncertainties of intermittent distributed generation and load, this paper proposes a multi-scenario tree model of wind-photovoltaic-load using multiple scenarios technique based on the Wasserstein distance metrics, which generates asymptotically optimal scenario. And in this paper, a multi-objective optimizes control model with scenario tree is presented, which including objectives that are the total active power losses and the voltage deviations of the bus. Moreover, a new hybrid Honey Bee Mating Optimization and Particle Swarm Optimization (HBMO-PSO) algorithm is proposed to solved the problems. In the HBMO-PSO algorithm, the mating process is corrected, which the PSO algorithm is combined with the HBMO algorithm to improve the performance of HBMO. Finally, a typical IEEE 33-bus distribution test system is used to investigate the feasibility and effectiveness of the proposed method. Simulation results illustrate the correctness and adaptability of the proposed model and the improved algorithm.

Changes in Protein Phosphorylation during Salivary Gland Degeneration in Haemaphysalis longicornis

Qi Xiao,Yuhong Hu,Xiaohong Yang,Jianna Tang,Xiaoshuang Wang,Xiaomin Xue,Mengxue Li,Minjing Wang,Yinan Zhao,Jingze Liu,Hui Wang 대한기생충학ㆍ열대의학회 2020 The Korean Journal of Parasitology Vol.58 No.2

The ticks feed large amount of blood from their hosts and transmit pathogens to the victims. The salivary gland plays an important role in the blood feeding. When the female ticks are near engorgement, the salivary gland gradually loses its functions and begins to rapidly degenerate. In this study, data-independent acquisition quantitative proteomics was used to study changes in the phosphorylation modification of proteins during salivary gland degeneration in Haemaphysalis longicornis. In this quantitative study, 400 phosphorylated proteins and 850 phosphorylation modification sites were identified. Trough RNA interference experiments, we found that among the proteins with changes in phosphorylation, apoptosis-promoting Hippo protein played a role in salivary gland degeneration.

Covalently Crosslinked Chitosan-Poly(ethylene glycol) Hybrid Hydrogels to Deliver Insulin for Adipose-Derived Stem Cells Encapsulation

Huaping Tan,Hekun Luan,Yihang Hu,Xiaohong Hu 한국고분자학회 2013 Macromolecular Research Vol.21 No.4

Biodegradable hydrogels carrying adipose-derived stem cells (ASCs) have been highlighted with promising potential regarding adipose tissue engineering. In this study, covalently crosslinked natural/synthetic hybrid hydrogels were prepared from methacrylated water soluble chitosan (N-succinyl-chitosan, SCS) and poly(ethylene glycol) (PEG) by photoinitiaing polymerization under the existence of Irgacure 2959 and the irradiation of UV light. The effect of the incorporated PEG on the in vitro morphologies, equilibrium swelling, weight loss and compressive modulus of SCS/PEG hybrid hydrogels in phosphate buffered saline (PBS) at 37 oC were studied. In order to evaluate the ability of hydrogels to effectively deliver the adipogenic factor, insulin was entrapped within hydrogels by copolymerizing methacrylated SCS/PEG. The insulin would be released from the hydrogels into the local microenvironment via the controlled weight ratio of SCS/PEG. Results demonstrated that the hybrid hydrogel with 10 wt%PEG showed a higher efficiency of insulin delivery compared to the control hydrogels. ASCs were seeded into the insulin-loaded SCS/PEG hydrogels in vitro to assess the biological performance and applicability of hydrogels as cell carriers. These characteristics provide potential opportunities for the hybrid SCS/PEG hydrogels as injectable scaffolds in soft tissue engineering applications.