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Vivian Juang,1 Hsin-Pin Lee,2 Anya Maan-Yuh Lin,1,3 Yu-Li Lo1 1Department and Institute of Pharmacology, National Yang-Ming University, 2Department of Biological Sciences and Technology, National University of Tainan, 3Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China Abstract: Antimicrobial peptides (AMPs) have been recently evaluated as a new generation of adjuvants in cancer chemotherapy. In this study, we designed PEGylated liposomes encapsulating epirubicin as an antineoplastic agent and tilapia hepcidin 2–3, an AMP, as a multidrug resistance (MDR) transporter suppressor and an apoptosis/autophagy modulator in human cervical cancer HeLa cells. Cotreatment of HeLa cells with PEGylated liposomal formulation of epirubicin and hepcidin 2–3 significantly increased the cytotoxicity of epirubicin. The liposomal formulations of epirubicin and/or hepcidin 2–3 were found to noticeably escalate the intracellular H2O2 and O2- levels of cancer cells. Furthermore, these treatments considerably reduced the mRNA expressions of MDR protein 1, MDR-associated protein (MRP) 1, and MRP2. The addition of hepcidin 2–3 in liposomes was shown to markedly enhance the intracellular epirubicin uptake and mainly localized into the nucleus. Moreover, this formulation was also found to trigger apoptosis and autophagy in HeLa cells, as validated by significant increases in the expressions of cleaved poly ADP ribose polymerase, caspase-3, caspase-9, and light chain 3 (LC3)-II, as well as a decrease in mitochondrial membrane potential. The apoptosis induction was also confirmed by the rise in sub-G1 phase of cell cycle assay and apoptosis percentage of annexin V/propidium iodide assay. We found that liposomal epirubicin and hepcidin 2–3 augmented the accumulation of GFP-LC3 puncta as amplified by chloroquine, implying the involvement of autophagy. Interestingly, the partial inhibition of necroptosis and the epithelial–mesenchymal transition by this combination was also verified. Altogether, our results provide evidence that coincubation with PEGylated liposomes of hepcidin 2–3 and epirubicin caused programmed cell death in cervical cancer cells through modulation of multiple signaling pathways, including MDR transporters, apoptosis, autophagy, and/or necroptosis. Thus, this formulation may provide a new platform for the combined treatment of traditional chemotherapy and hepcidin 2–3 as a new adjuvant for effective MDR reversal. Keywords: multidrug resistance, liposomes, antimicrobial peptide, epirubicin, apoptosis, autophagy

Abstract Nanometric cutting involves materials removal and deformation evolution in the surface at nanometer scale. At this length scale, atomistic simulation is a very useful tool to study the cutting process. In this study, large-scale molecular dynamics (MD) simulations with the model size up to 10 millions atoms have been performed to study three-dimensional nanometric cutting of copper. The EAM potential and Morse potential are used, respectively, to compute the interaction between workpiece atoms and the interactions between workpiece atoms and tool atoms. The material behavior, surface and subsurface deformation, dislocation movement, and cutting forces during the cutting processes are studied. We show that the MD simulation model of nanometric cutting has to be large enough to eliminate the boundary effect. Moreover, the cutting speed and the cutting depth have to be considered in determining a suitable model size for the MD simulations. We have observed that the nanometric cutting process is accompanied with complex material deformation, dislocation formation, and movement. We find that as the cutting depth decreases, the tangential cutting force decreases faster than the normal cutting force. The simulation results reveal that as the cutting depth decreases, the specific cutting force increases, i.e., “size effect” exists in nanometric cutting.

This work investigates the effects of interlayer hybrid fiber dispersion on the impact response of carbon-flax epoxy hybrid laminates at low carbon volume fractions, and benchmarks the mechanical performance enhancement against the non-hybrid flax epoxy. Five hybrid laminate stacking sequences with similar carbon-to-flax weight ratio were fabricated and subjected to low-velocity impact at three different energy values, generating non-perforated and perforated damage states. A virtual drop-weight impact test that models intralaminar failure based on continuum damage mechanics approach, and delamination using cohesive elements, was also implemented to evaluate the material behavior and damage development in the composites. Simulation results were then verified against experimental data. Results suggested that positioning stiffer carbon plies at the impact face does not necessarily lead to enhancement of the hybrid's impact properties. On the contrary, flax plies at the impacted side lead to significant improvement in impact resistance compared to the non-hybrid flax composite with similar thickness. Results of finite element analysis showed that carbon plies play a significant role in the hybrid laminate's energy absorption characteristics due to lower failure strain. [ABSTRACT FROM AUTHOR]

Objectives:The aim of this study was to evaluate the costs and effectiveness associated with no screening, Helicobacter pyloriserology screening, and the 13C-urea breath test (UBT) for gastric cancer in the Chinese population.Methods:A Markov model simulation was carried out in Singaporean Chinese at 40 years of age (n= 478,500) from the perspective of public healthcare providers. The main outcome measures were costs, number of gastric cancer cases prevented, life-years saved, quality-adjusted life-years (QALYs) gained from the screening age to death, and incremental cost-effectiveness ratios (ICERs), which were compared among the three strategies. The uncertainty surrounding ICERs was addressed by scenario analyses and probabilistic sensitivity analysis using Monte Carlo simulation.Results: The ICER of serology screening versus no screening was $25,881 per QALY gained (95 percent confidence interval (95 percent CI), $5,700 to $120,000). The ICER of UBT versus no screening was $53,602 per QALY gained (95 percent CI, $16,000 to $230,000). ICER of UBT versus serology screening was $470,000 per QALY gained, for which almost all random samples of the ICERs distributed above $50,000 per QALY.Conclusions: It cannot be confidently concluded that either H pyloriscreening was a cost-effective strategy compared with no screening in all Chinese at the age of 40 years. Nevertheless, serology screening has demonstrated much more potential to be a cost-effective strategy, especially in the population with higher gastric cancer prevalence. [ABSTRACT FROM AUTHOR]

Cancer is primarily a disease of older adults. However, little data is available on the clinical features of cervical cancer in elderly patients. We investigated the trends in incidence and clinical features associated with cervical cancer among the elderly in Korea during the period of 1993-2002. We obtained data from the National Cervical Cancer Incidence Database, which was constructed in collaboration with the Korea Central Cancer Registry (KCCR) and Korea Gynecologic Cancer Registry (KGCR). A total of 44 191 women with cervical cancer were diagnosed between 1993 and 2002. Patients were divided into three groups based on age: /=70 years (Group 3). During this period, upward incidence trends were noted in Group 3 while constant and downward incidence trends were noted in Groups 1 and 2, respectively. Pooled analysis across years revealed that squamous cell carcinoma and advanced stage (IIB, III, and IV) were more common in Group 3 than in Groups 1 and 2. With regard to primary treatments in the elderly patients, surgery appeared to be performed increasingly despite the fact that advanced stage (IIB, III, and IV) was more common in Group 3 than in Groups 1 and 2. Our findings suggest that the incidence of cervical cancer in the elderly is increasing in Korea, while it is decreasing overall. The current health service must emphasize education for the elderly about cervical cancer prevention while concentrating on screening. [ABSTRACT FROM AUTHOR]

Background: Studies have found that reproductive factors might have a variable effect on the occurrence of breast cancer (BC) according to the existence or not of a family history of BC. The effect of a family history of BC on the risk of BC may also vary according to the age at diagnosis and the degree of kinship. This may confound the relation between familial risk and reproductive factors. A combined analysis was performed to study the interaction between familial risk and reproductive factors according to degree of familiality, age at interview and menopausal status.Methods: The present analysis included 2948 cases and 4170 controls in seven case-control studies from four countries. The combined relative risks were estimated using a Bayesian random-effects logistic regression model.Results: The main effects of reproductive life factors on the risk of BC are in agreement with previous studies. Two-way interactions between subject's age or menopausal status and a family history of BC were not significant. Although the three-way interaction between age, familial risk and parity was not significant, familial risk seemed to be increased slightly for women with high parity compared with women with low parity in the older age group, and seemed to be slightly decreased for women with high parity compared with women with low parity in younger women. The subject's age also appeared to have an effect on the interaction between familial risk and the age at first childbirth (P = 0.1).Conclusions: A possible influence of reproductive and menstrual factors on familial risk of BC has been suggested previously and was also evident in the present study. Three-way interactions between age, family history and parity or age at first childbirth might exist and they merit further investigation. [ABSTRACT FROM AUTHOR]

Background: Chinese females are distinguished internationally as having relatively high lung cancer incidence rates despite a low prevalence of cigarette smoking. In Singapore, this population comprises several dialect groups which have origins in different regions in China, each with its own traditional cultural practices.Methods: An analysis of 4029 incident cases of the disease notified to the Singapore Cancer Registry for 1968-1992 was undertaken to provide some insight into important aetiologic factors among these women.Results: The age-standardized incidence rate of lung cancer rose from 17.3 per 100,000 woman-years in 1968-1972 to 23.0 in 1978-1982 before falling off in more recent years. Age-period-cohort analysis indicated significant period and birth cohort effects, with the risk being highest for women born around 1908. Between the major dialect groups, Cantonese women had a significantly high rate compared with Hokkiens (relative risk [RR] = 2.6, 95% CI: 2.4-2.8). Histologically, there appears to be an increase in the proportion of adenocarcinomas diagnosed over this period (25.8% in 1968-1972 to 51.3% in 1988-1992).Conclusion: Our results suggest that traditional practices which have decreased over the years, and are more prominent among Southern Chinese, may play a part in the aetiology of lung cancer locally. [ABSTRACT FROM AUTHOR]

Objectives: To quantify the improvement in health outcomes in patients after total knee replacement (TKR).Methods: This was a two-year non-randomized prospective observational study in knee osteoarthritis (OA) patients undergone TKR. Patients were interviewed one week before, six months after, and two years after surgery using a standardized questionnaire including the SF-36, the Oxford Knee Score (OKS), and the Knee Society Clinical Rating Scale (KSS). A generalized estimating equation (GEE) model was used to estimate the magnitudes of the changes with and without the adjustment of age, ethnicity, BMI, and years with OA.Results: A total of 298 (at baseline), 176 (at six-months), and 111 (at two-years) eligible patients were included in the analyses. All the scores changed significantly over time, with the exception of SF-36 social functioning, vitality, and mental health. With the adjustment of covariates, the magnitude of changes in these scores was similar to those without the adjustment.Conclusions: Both general and knee-specific physical functioning had been significantly improved after TKR, while other health domains have not been substantially improved after the surgery. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Asian Indian men are reported to have a higher incidence of coronary heart disease than men of other ethnic groups worldwide. Among the many hypotheses, one possible risk factor may be related to their dietary habits. This study estimated the plasma concentrations of fatty acids, antioxidant vitamins, and selenium in Indians and Chinese of Singapore. METHODS: The study population consisted of 145 Indian men and 147 Chinese men ages 26 to 79 y from a cross-sectional survey, the National University of Singapore Heart Study. RESULTS: Our findings indicated that Indians had lower plasma concentrations of docosahexanoic acid (3.07% versus 3.54%, P < 0.001), alpha-linolenic acid (0.48% versus 0.57%, P < 0.001), and total omega-3 fatty acids (4.71% versus 5.27%, P < 0.001) than did the Chinese. Arachidonic acid was higher in Indians (4.83%) than in the Chinese (4.51%, P = 0.007). The ratio of omega-3 acid to omega-6 fatty acid was also lower in Indians (0.15) than in the Chinese (0.16, P = 0.007). There were no significant differences in the concentrations of monounsaturated fatty acids, but saturated fatty acids were higher in Indians (39.17%) than in the Chinese (38.28%, P < 0.001). Analysis of vitamins A, C, and E showed no significant differences between Indians (0.67, 5.72, and 13.04 mg/L, respectively) and Chinese (0.68, 6.48, and 12.71 mg/L, respectively); however, serum concentration of selenium in Indians (117.49 microg/L) was significantly lower than in the Chinese (126.72 microg/L, P < 0.001). CONCLUSION: The results suggest that lower plasma concentrations of omega-3 fatty acids and selenium and higher concentrations of arachidonic acid and saturated fatty acids in Indians may reflect lower intakes of marine foods and, as a consequence, higher susceptibility to coronary heart disease. [ABSTRACT FROM AUTHOR]