Steroidal Saponins from Paris polyphylla Induce Apoptotic Cell Death and Autophagy in A549 Human Lung Cancer Cells

He, Hao,Sun, Yan-Ping,Zheng, Lei,Yue, Zheng-Gang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Background: Paris polyphylla (Chinese name: Chonglou) had been traditionally used for a long time and shown anti-cancer action. Based on the previous study that paris polyphylla steroidal saponins (PPSS) induced cytotoxic effect in human lung cancer A549 cells, this study was designed to further illustrate the mechanisms underlying. Materials and Methods: The mechanisms involved in PPSS-induced A549 cell death were investigated by phase contrast microscopy and fluorescence microscopy, flow cytometry and western blot analysis, respectively. Results: PPSS decreased the proportion of viable A549 cells, and exposure of A549 cells to PPSS led to both apoptosis and autophagy. Apoptosis was due to activations of caspase-8, caspase-3, as well as cleavage of PARP, and autophagy was confirmed by up-regulation of Beclin 1 and the conversion from LC3 I to LC3 II. Conclusions: PPSS was able to induce lung cancer A549 cell apoptosis and autophagy in vitro, the results underlining the possibility that PPSS would be a potential candidate for intervention against lung cancer.

Growth of Human Colon Cancer Cells in Nude Mice is Delayed by Ketogenic Diet With or Without Omega-3 Fatty Acids and Medium-chain Triglycerides

Hao, Guang-Wei,Chen, Yu-Sheng,He, De-Ming,Wang, Hai-Yu,Wu, Guo-Hao,Zhang, Bo Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Background: Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Materials and Methods: Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of $600mm^3$ to $700mm^3$. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). Results: The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Conclusions: Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.

Steroidal Saponins from Paris polyphylla Suppress Adhesion, Migration and Invasion of Human Lung Cancer A549 Cells Via Down-Regulating MMP-2 and MMP-9

He, Hao,Zheng, Lei,Sun, Yan-Ping,Zhang, Guang-Wei,Yue, Zheng-Gang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: Tumor metastases are the main reasons for oncotherapy failure. Paris polyphylla (Chinese name: Chonglou) has traditionally been used for its anti-cancer actions. In this article, we focus on the regulation of human lung cancer A549 cell metastases and invasion by Paris polyphylla steroidal saponins (PPSS). Materials and Methods: Cell viability was evaluated in A549 cells by MTT assay. Effects of PPSS on invasion and migration were investigated by wound-healing and matrigel invasion chamber assays. Adhesion to type IV collagen and laminin was evaluated by MTT assay. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. Results: PPSS exerted growth inhibitory effects on A549 cells, and effectively inhibited A549 cell adhesion, migration and invasion in a concentration-dependent manner. Western blotting and gelatin zymography analysis revealed that PPSS inhibited the expression and secretion of MMP-2 and MMP-9 in A549 cells. Conclusions: PPSS has the potential to suppress the migration, adhesion and invasion of A549 cells. PPSS could be a potential candidate for interventions against lung cancer metastases.

Multi-winding Boost Multi-input DC-DC Converter Type Distributed Generation System

Hao He,Daolian Chen,Yanhui Qiu 전력전자학회 2019 ICPE(ISPE)논문집 Vol.2019 No.5

The multi-winding Boost multi-input DC-DC converter type distributed generation system is proposed in the paper, the circuit topology, the maximum power and the master-slave power phase-shift PWM energy management control strategy are studied. Through the magnetic flux superposition of the high-frequency transformer, multiple input sources could supply power to the load simultaneously in a high-frequency switching period. Designed and developed 1kVA dual-input grid-connected and grid-off inverter prototypes have the advantages such as highfrequency isolation, wide regulating range of duty cycle, high conversion efficiency, smooth transition among different operating modes, etc.

Association of CYP2C19 Polymorphisms with Survival of Breast Cancer Patients Using Tamoxifen: Results of a Meta-analysis

Bai, Lan,He, Juan,He, Gong-Hao,He, Jian-Chang,Xu, Fan,Xu, Gui-Li Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Background: Previous studies accessing the association of CYP2C19 with outcomes of patients using tamoxifen for breast cancer have yielded conflicting results. The aim of this meta-analysis is to obtain a more precise estimate of effects of CYP2C19 polymorphisms and to clarify their effects on survival of the breast cancer patients using tamoxifen. Materials and Methods: A systematic search of PubMed and Embase was performed, comparing patients with or without $CYP2C19^*2$ and $CYP2C19^*17$, relevant articles searched for. The following outcomes were included from the eligible studies: disease-free survival (DFS) and overall survival (OS), expressed by hazard ratios (HR) with corresponding 95% confidence interval (CI). Subgroup analysis by genotypes was also performed. Pooled estimates were calculated using random-effect model in accordance to the heterogeneity. Results: Six studies met the inclusion criteria. The integrated OR on the association between CYP2C19 and DFS, calculated by the random-effect model, was 0.54 (95%CI=0.34-0.84, p=0.013). Subgroup analysis showed that both $CYP2C19^*2$ and $CYP2C19^*17$ were associated with increased survival. The pooled results of two studies for OS were OR=0.46 (95%CI=0.21-1.01, p=0.233). Conclusions: This meta-analysis suggests that the $CYP2C19^*2$ and $CYP2C19^*17$ genotypes are associated with increased survival in breast cancer patients using tamoxifen.

Development and Validation of Nomograms to Provide Individualized Predictions of Sur-vival Benefits from Surgery in Patients with Intermediate/Advanced Hepatocel-lular Carcinoma

( Wen-tao Yan ),( Jia-he Wang ),( Ming-da Wang ),( Zheng Wang ),( Bing Quan ),( Ya-hao Zhou ),( Wei-min Gu ),( Hong Wang ),( Ting-hao Chen ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: According to the BCLC treatment guidelines, surgery does not be recommended for intermediate/advanced hepatocellular carcinoma (HCC). In real world, however, liver resections are often performed in patients with intermediate/ advanced but resectable HCC, especially in the East. Methods: We retrospectively evaluated multicentric data of 1,325 patients newly diagnosed with intermediate/advanced HCC who underwent curative resection. We randomly divided the subjects into development (n = 875) and validation (n = 450) samples. Multivariate Cox proportional hazards models were developed and separately validated on the basis of patients’ clinicopathological variables assessed for associations with 1-year recurrence and 3-year mortality. The discriminatory accuracy of these models was compared with conventional tools by analyzing receiver operating characteristic (ROC) curves. Results: He statistical nomograms built based on performance status, Child-Pugh grade, portal hypertension, preoperative alpha-fetoprotein level, tumor rupture, largest tumor diameter, tumor number, macrovascular and microvascular invasion, and satellites had good calibration and discriminatory abilities, with c-indices of 0.70 (1-year recurrence) and 0.68 (3-year survival), respectively. These models showed satisfactory goodness-of-fit and discrimination abilities in the validation cohort (c-index, 0.68 for 1-year recurrence and 0.69 for 3-year survival). The areas under the ROC curve using these nomograms exceeded those of traditional staging systems, indicating superior discriminatory capability (c-indices, 0.60-0.63 and 0.56-0.62, respectively). Conclusions: Our proposed online nomograms, which present graphically postoperative prognostic models for recurrence and survival in patients with intermediate/advanced but resectable HCC, offer valuable guidance to surgeons and hepatologists for individually predicting survival benefits from surgery and planning recurrence surveillance and adjuvant therapy.

Partition-based 3 + 2-axis tool path generation for freeform surface machining using a non-spherical tool

Hao Jiancheng,Li Zhaoyu,Li Xiangyu,Xie Fubao,He Dong,Tang Kai 한국CDE학회 2022 Journal of computational design and engineering Vol.9 No.5

When machining a complex freeform part, using a non-spherical tool could significantly improve the machining efficiency, as one can adaptively adjust the tool posture to maximize its contact area with the part surface. However, since adjusting the tool posture requires changing the tool orientation, a five-axis machine tool is needed, which is extremely expensive as compared to a conventional three-axis machine tool. Moreover, for a complex freeform surface with high curvature variation, to match its curvature change, the tool axis has to drastically change accordingly, thus inducing high velocity and acceleration on the machine tool’s rotary axes. To address these issues, in this paper we propose a partition-based 3 + 2-axis strategy for machining a general complex freeform surface with a non-spherical tool. As only a finite small number of distinct tool orientations are needed for 3 + 2-axis machining, an indexed three-axis machine tool suffices, thus relieving the need of an expensive five-axis machine tool. In addition, the much-increased rigidity of the three linear axes of the machine tool will greatly improve the kinematics and dynamics of the machine tool and thus enhance the machining accuracy. Experiments in both computer simulation and physical machining are carried out, whose results confirm that, when compared to using a conventional spherical cutter, by using a non-spherical cutter and adaptively adjusting the contacting tool posture and the feed direction, significant improvement in machining efficiency could be achieved, e.g., more than 50% achieved in our experiments.

Chloroplast genomic comparison of two sister species Allium macranthum and A. fasciculatum provides valuable insights into adaptive evolution

Hao Li,Deng‑Feng Xie,Jun‑Pei Chen,Song‑Dong Zhou,Xing‑Jin He 한국유전학회 2020 Genes & Genomics Vol.42 No.5

Background Allium macranthum and Allium fasciculatum are two sister species and their natural populations are separated by high mountains and deep valleys with exact opposite habitat. The chloroplast genome in angiosperms has showed useful for investigating plant evolution and systematic studies. Objective Comparative analysis of these genomes revealed potential markers and phylogenetic analysis, and discuss the influence of positive selected sites on adaptive evolution. Methods Here, we sequenced the complete chloroplast genomes of these two species and analyzed the repeat sequences components, nucleotide diversity, selection pressure and the phylogeny relationships with related species. Results A typical quadripartite structure was detected with a genome size changed from 152,148 to 152,931 bp. We identified 67 and 79 simple sequence repeats in A. macranthum and A. fasciculatum, in which the mono-nucleotide repeats A/T possess the highest percentage. Three mutational hotspots (rpl32, rps16 and matK) at the SSC and LSC regions were observed, which showed remarkably higher Pi value (> 0.03). Additionally, eight genes (rpoA, atpF, cemA, rps4, ccsA, rpoC2, rpl14 and clpP) exhibited elevated pairwise Ka/Ks ratios in alpine species. Phylogenetic analyses based on the CDS sequences and the whole complete genomes showed same topologies with high support, and A. macranthum was closely clustered with A. fasciculatum within the fourteen Amaryllidaceae species. Conclusion Their coding proteins of these genes often functioned in chloroplast protein synthesis, gene transcription, energy transformation and regulation and photosynthesis. These results provide valuable insights into the alpine species adaptation and evolution.

MiR-371 promotes proliferation and metastasis in hepatocellular carcinoma by targeting PTEN

( Hao Wang ),( Yi Zhao ),( Tingsong Chen ),( Guofang Liu ),( Nan He ),( Heping Hu ) 생화학분자생물학회 2019 BMB Reports Vol.52 No.5

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. MiR-371 has recently emerged as an important regulator in tumorigenesis, and may serve as a biomarker for malignant tumors. We transfected miR-371 or its inhibitor in two human HCC cell lines, then used 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, soft agar colony formation, and transwell migration assays to evaluate the effects on cell proliferation, migration, and invasion. We found that miR-371 was positively correlated with HCC metastasis and poor prognosis in the inflicted patients, and the high expression of miR-371 was promoted, whereas a low level of miR-371 depressed cell proliferation and invasion. We found PTEN to be a direct target of miR-371. The overexpression or knockdown of PTEN exhibited the opposite effects from those of miR-371 on cell proliferation and migration. Our study demonstrates that miR-371 promotes proliferation and metastasis in HCC by targeting PTEN. [BMB Reports 2019; 52(5): 312-317]

Review of the Molecular Pathogenesis of Osteosarcoma

He, Jin-Peng,Hao, Yun,Wang, Xiao-Lin,Yang, Xiao-Jin,Shao, Jing-Fan,Guo, Feng-Jin,Feng, Jie-Xiong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on the primary tumor and have limited efficacy for metastatic OSA. A better understanding of the OSA pathogenesis may provide a rational basis for innovative treatment strategies especially for metastases. The aim of this review is to give an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell proliferation, apoptosis, migration, and chemotherapy resistance, and how improved understanding might contribute to designing a better treatment target for OSA.