Swainsonine Activates Mitochondria-mediated Apoptotic Pathway in Human Lung Cancer A549 Cells and Retards the Growth of Lung Cancer Xenografts

Swainsonine (1, 2, 8-trihyroxyindolizidine, SW), a natural alkaloid, has been reported to exhibit anti-cancer activity on several mouse models of human cancer and human cancers in vivo. However, the mechanisms of SW-mediated tumor regression are not clear. In this study, we investigated the effects of SW on several human lung cancer cell lines in vitro. The results showed that SW significantly inhibited these cells growth through induction of apoptosis in different extent in vitro. Further studies showed that SW treatment up-regulated Bax, down-regulated Bcl-2 expression, promoted Bax translocation to mitochondria, activated mitochondria-mediated apoptotic pathway, which in turn caused the release of cytochrome c, the activation of caspase-9 and caspase-3, and the cleavage of poly (ADP-ribose) polymerase (PARP), resulting in A549 cell apoptosis. However, the expression of Fas, Fas ligand (FasL) or caspase-8 activity did not appear significant changes in the process of SW-induced apoptosis. Moreover, SW treatment inhibited Bcl-2 expression, promoted Bax translocation, cytochrome c release and caspase-3 activity in xenograft tumor cells, resulting in a significant decrease of tumor volume and tumor weight in the SW-treated xenograft mice groups in comparison to the control group. Taken together, this study demonstrated for the first time that SW inhibited A549 cancer cells growth through a mitochondria-mediated, caspase-dependent apoptotic pathway in vitro and in vivo

Application of carbon nanoparticles combined with refined extracapsular anatomy in endoscopic thyroidectomy

ObjectiveTo evaluate the value of refined extracapsular anatomy combined with carbon nanoparticle suspension tracing technology for protecting parathyroid function and the thoroughness of lymph node dissection in the central region during endoscopic thyroid cancer surgery.Patients and methodsRetrospective clinical data analysis was performed on 108 patients who underwent endoscopic thyroid cancer surgery at the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from November 2019 to November 2022. Before surgery, thyroid function tests, color Doppler ultrasounds and neck-enhanced CT scans were performed on all patients. Cytopathological diagnosis obtained via ultrasound-guided fine-needle aspiration served as confirmation for the primary diagnosis. It was determined whether to perform a total thyroidectomy or a hemithyroidectomy (HT) together with preventive unilateral (ipsilateral) central neck dissection. Follow-up times were 1 to 34 months.ResultsTransient neuromuscular symptoms were present in 3.70% (4/108) cases, with no permanent neuromuscular symptoms or permanent hypoparathyroidism. Regarding transient hypoparathyroidism, the patients recovered after three months and did not need long-term calcium supplementation. The number of harvested LNs (mean± SD) was 5.54 ± 3.84, with ≤5 in 57.41% (62/108) and >5 in 42.59% (46/108) cases. The number of patients with metastatic LNs was 37.96% (41/108), with ≤2 in 65.85% (27/41) and >2 in 34.15% (14/41) cases.ConclusionsFine extracapsular anatomy combined with carbon nanoparticle suspension tracing is effective in endoscopic thyroid cancer surgery. It can improve the thoroughness of prophylactic central neck dissection and recognition of the parathyroid gland and avoid parathyroid injury and other complications to effectively protect parathyroid function

MEIS2C and MEIS2D promote tumor progression via Wnt/β-catenin and hippo/YAP signaling in hepatocellular carcinoma

Abstract Background MEIS2 has been identified as one of the key transcription factors in the gene regulatory network in the development and pathogenesis of human cancers. Our study aims to identify the regulatory mechanisms of MEIS2 in hepatocellular carcinoma (HCC), which could be targeted to develop new therapeutic strategies. Methods The variation of MEIS2 levels were assayed in a cohort of HCC patients. The proliferation, clone-formation, migration, and invasion abilities of HCC cells were measured to analyze the effects of MEIS2C and MEIS2D (MEIS2C/D) knockdown with small hairpin RNAs in vitro and in vivo. Chromatin immunoprecipitation (ChIP) was performed to identify MEIS2 binding site. Immunoprecipitation and immunofluorescence assays were employed to detect proteins regulated by MEIS2. Results The expression of MEIS2C/D was increased in the HCC specimens when compared with the adjacent noncancerous liver (ANL) tissues. Moreover, MEIS2C/D expression negatively correlated with the prognosis of HCC patients. On the other hand, knockdown of MEIS2C/D could inhibit proliferation and diminish migration and invasion of hepatoma cells in vitro and in vivo. Mechanistically, MESI2C activated Wnt/β-catenin pathway in cooperation with Parafibromin (CDC73), while MEIS2D suppressed Hippo pathway by promoting YAP nuclear translocation via miR-1307-3p/LATS1 axis. Notably, CDC73 could directly either interact with MEIS2C/β-catenin or MEIS2D/YAP complex, depending on its tyrosine-phosphorylation status. Conclusions Our studies indicate that MEISC/D promote HCC development via Wnt/β-catenin and Hippo/YAP signaling pathways, highlighting the complex molecular network of MEIS2C/D in HCC pathogenesis. These results suggest that MEISC/D may serve as a potential novel therapeutic target for HCC.https://deepblue.lib.umich.edu/bitstream/2027.42/152244/1/13046_2019_Article_1417.pd

Dynamic Modeling and Inverse Dynamic Analysis of Flexible Parallel Robots

This paper presents a method for the dynamic modeling of parallel robots with flexible links and rigid moving platform based on finite element theory. The relation between elastic displacements of links is investigated, taking into consideration the coupling effects of elastic motion and rigid motion. The kinematic and dynamic constraint conditions of elastic displacements of flexible parallel robots are presented. The Kineto-Elastodynamics theory and Timoshenko beam theory are employed to derive the equations of motion, considering the effects of distributed mass, lumped mass, rotary inertia, shearing deformation, bending deformation, lateral deformations and all the dynamic coupling terms. The dynamic behavior due to flexibility of links is well illustrated through numerical simulation. Compared with the results of SAMCEF software simulation, the numerical simulation results show good coherence and the advantages of the method. The flexibility of links is demonstrated to have significant impact on system performance and stability. A method for the inverse dynamic analysis of flexible parallel robots is presented

A Hybrid Spectrum Combinational Auction Mechanism Based on a Weighted Bipartite Graph for Energy Internet in Smart Cities

Energy Internet (EI) is aimed at sustainable computing by integrating various energy forms into a highly flexible grid similar to the Internet. The network subsystems of EI connect different components to enable real-time monitoring, controlling, and management. In this paper, the spectrum allocation problem of the cognitive radio network for EI in a smart city is investigated. The network spectrum allocation with both heterogeneous primary operators and secondary users is formulated as the combinatorial auction problem and then is converted to a subset selection problem on a weighted bipartite graph. We propose a hybrid algorithm to solve the problem. Firstly, the proposed algorithm uses a constructive procedure based on the Kuhn-Munkres algorithm to obtain an initial solution. Then, a local search is used to improve the solution quality. In addition, the truthfulness of the auction is guaranteed by adopting a “Vickrey-like” mechanism. Simulation results show that the performance of the proposed algorithm is better than existing greedy algorithms in terms of the social welfare, seller revenue, buyer satisfaction ratio, and winning buyer ratio

A hydrodynamic model coupled multiple scenarios for plain river network and its application

The plain river network is not only complex in shape but also contains many complex scenarios, such as interval inflow and outflow, hydraulic structures and water storage area, etc., which increases the difficulty of runoff simulation in plain river network. To address this problem, a hydrodynamic (HD) model coupled multiple scenarios that may occur in plain river network was proposed, which was used to simulate the runoff process of the plain river network. To illustrate the proposed model, Xi River was chosen as a study area. We designed some experiments for each scenario, and the experimental results show that simulation results have good consistency with the observation. It is worth noting that the simulation accuracy of the water level is always higher than the simulation accuracy of the flow. Moreover, the runoff simulation accuracy of runoff events with large runoff is relatively high. It turns out that HD model is suitable for runoff simulation of plain river network. In addition, we compared the flood diversion effects of water storage area and sluice, and the results show that the effect of water storage area is more obvious than sluice, and the flood diversion method combined with sluice and water storage area has better flood diversion effect. In conclusion, HD model is good at simulating floodplain storage effects, backwater and the change of water level and flow under the condition of engineering dispatching, which has important guiding significance for flood control in plain river network

A hydrodynamic model coupled multiple scenarios for plain river network and its application

The plain river network is not only complex in shape but also contains many complex scenarios, such as interval inflow and outflow, hydraulic structures and water storage area, etc., which increases the difficulty of runoff simulation in plain river network. To address this problem, a hydrodynamic (HD) model coupled multiple scenarios that may occur in plain river network was proposed, which was used to simulate the runoff process of the plain river network. To illustrate the proposed model, Xi River was chosen as a study area. We designed some experiments for each scenario, and the experimental results show that simulation results have good consistency with the observation. It is worth noting that the simulation accuracy of the water level is always higher than the simulation accuracy of the flow. Moreover, the runoff simulation accuracy of runoff events with large runoff is relatively high. It turns out that HD model is suitable for runoff simulation of plain river network. In addition, we compared the flood diversion effects of water storage area and sluice, and the results show that the effect of water storage area is more obvious than sluice, and the flood diversion method combined with sluice and water storage area has better flood diversion effect. In conclusion, HD model is good at simulating floodplain storage effects, backwater and the change of water level and flow under the condition of engineering dispatching, which has important guiding significance for flood control in plain river network

Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells