A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells

IntroductionStem-like cancer cells or cancer stem cells (CSCs) may comprise a phenotypically and functionally heterogeneous subset of cells, whereas the molecular markers reflecting this CSC hierarchy remain elusive. The glycolytic enzyme alpha-enolase (ENO1) present on the surface of malignant tumor cells has been identified as a metastasis-promoting factor through its function of activating plasminogen. The expression pattern of surface ENO1 (sENO1) concerning cell-to-cell or CSC heterogeneity and its functional roles await further investigation.MethodsThe cell-to-cell expression heterogeneity of sENO1 was profiled in malignant cells from different types of cancers using flow cytometry. The subcellular localization of sENO1 and its functional roles in the invadopodia formation and cancer cell invasiveness were investigated using a series of imaging, molecular, and in vitro and in vivo functional studies.ResultsWe showed here that ENO1 is specifically localized to the invadopodial surface of a significant subset (11.1%-63.9%) of CSCs in human gastric and prostate adenocarcinomas. sENO1+ CSCs have stronger mesenchymal properties than their sENO1- counterparts. The subsequent functional studies confirmed the remarkable pro-invasive and pro-metastatic capacities of sENO1+ CSCs. Mechanistically, inhibiting the surface localization of ENO1 by downregulating caveolin-1 expression compromised invadopodia biogenesis, proteolysis, and CSC invasiveness.ConclusionsOur study identified the specific expression of ENO1 on the invadopodial surface of a subset of highly invasive and pro-metastatic CSCs. sENO1 may provide a diagnostically and/or therapeutically exploitable target to improve the outcome of patients with aggressive and metastatic cancers

Hong Kong Renal Registry Report 2012

SummaryThis report examined the characteristics and trends of dialysis and renal transplant patients among the resident population of Hong Kong who were managed by hospitals or dialysis centers of the Hospital Authority, and accounted for approximately 95% of all patients receiving renal replacement therapies (RRTs) in the territory. Patients receiving RRTs solely in the private sector were not included in this report. Data trends from 1996 to 2011 are presented. In 2011, 1115 new patients were accepted into RRT programs, and the incident rate was 157 patients per million populations (pmp). An increasing trend was noted. The incident rate was 95.1 pmp at the commencement of the annual report in 1996. The point prevalence on December 31, 2012 was 8197 with a prevalence rate of 1152.5 pmp. Overall, there were 3573 patients (43.6%) on peritoneal dialysis (PD) and 1246 patients (15.2%) on hemodialysis (HD), and 3378 patients (41.2%) were living with a functioning renal transplant. The PD/HD ratio was 74.2:25.8. The “PD First” policy was continued. The overall mortality rate among RRT patients was 9.95 patients per 100 patient-years exposed. There was a decreasing trend in mortality among PD patients. Infection and cardiovascular complications were the most common causes of death. Renal transplant was the modality with the best survival rates. The 5 years cumulative patient survival rate for patients on transplant treatment was 89.6%, whereas the corresponding patient survival rates for PD and HD patients were 50.7% and 55.7%, respectively. More than 70% of RRT patients with reports on rehabilitation were active and had normal daily activities

Modification by Influenza on Health Effects of Air Pollution in Hong Kong

Background: Both influenza viruses and air pollutants have been well documented as major hazards to human health, but few epidemiologic studies have assessed effect modification of influenza on health effects of ambient air pollutants. Objectives: We aimed to assess modifying effects of influenza on health effects of ambient air pollutants. Methods: We applied Poisson regression to daily numbers of hospitalizations and mortality to develop core models after adjustment for potential time-varying confounding variables. We assessed modification of influenza by adding variables for concentrations of single ambient air pollutants and proportions of influenza-positive specimens (influenza intensity) and their cross-product terms. Results: We found significant effect modification of influenza (p < 0.05) for effects of ozone. When influenza intensity is assumed to increase from 0% to 10%, the excess risks per 10-μg/m 3 increase in concentration of O 3 increased 0.24% and 0.40% for hospitalization of respiratory disease in the all-ages group and ≥ 65 year age group, respectively; 0.46% for hospitalization of acute respiratory disease in the all-ages group; and 0.40% for hospitalization of chronic obstructive pulmonary disease in the ≥ 65 group. The estimated increases in the excess risks for mortality of respiratory disease and chronic obstructive pulmonary disease in the all-ages group were 0.59% and 1.05%, respectively. We found no significant modification of influenza on effects of other pollutants in most disease outcomes under study. Conclusions: Influenza activity could be an effect modifier for the health effects of air pollutants particularly for O 3 and should be considered in the studies for short-term effects of air pollutants on health.published_or_final_versio

The Effects of Air Pollution on Mortality in Socially Deprived Urban Areas in Hong Kong, China

Background: Poverty is a major determinant of population health, but little is known about its role in modifying air pollution effects. Objectives: We set out to examine whether people residing in socially deprived communities are at higher mortality risk from ambient air pollution. Methods: This study included 209 tertiary planning units (TPUs), the smallest units for town planning in the Special Administrative Region of Hong Kong, China. The socioeconomic status of each TPU was measured by a social deprivation index (SDI) derived from the proportions of the population with a) unemployment, b) monthly household income < US$250, c) no schooling at all, d) one-person household, e) never-married status, and f) subtenancy, from the 2001 Population Census. TPUs were classified into three levels of SDI: low, middle, and high. We performed time-series analysis with Poisson regression to examine the association between changes in daily concentrations of ambient air pollution and daily number of deaths in each SDI group for the period from January 1996 to December 2002. We evaluated the differences in pollution effects between different SDI groups using a case-only approach with logistic regression. Results: We found significant associations of nitrogen dioxide, sulfur dioxide, particulate matter with aerodynamic diameter < 10 μm, and ozone with all nonaccidental and cardiovascular mortality in areas of middle or high SDI (p < 0.05). Health outcomes, measured as all nonaccidental, cardiovascular, and respiratory mortality, in people residing in high SDI areas were more strongly associated with SO 2 and NO 2 compared with those in middle or low SDI areas. Conclusions: Neighborhood socioeconomic deprivation increases mortality risks associated with air pollution.published_or_final_versio

A new class of pluripotent stem cell cytotoxic small molecules

10.1371/journal.pone.0085039PLoS ONE93-POLN

Complexity of the Mycoplasma fermentans M64 Genome and Metabolic Essentiality and Diversity among Mycoplasmas

Recently, the genomes of two Mycoplasma fermentans strains, namely M64 and JER, have been completely sequenced. Gross comparison indicated that the genome of M64 is significantly bigger than the other strain and the difference is mainly contributed by the repetitive sequences including seven families of simple and complex transposable elements ranging from 973 to 23,778 bps. Analysis of these repeats resulted in the identification of a new distinct family of Integrative Conjugal Elements of M. fermentans, designated as ICEF-III. Using the concept of “reaction connectivity”, the metabolic capabilities in M. fermentans manifested by the complete and partial connected biomodules were revealed. A comparison of the reported M. pulmonis, M. arthritidis, M. genitalium, B. subtilis, and E. coli essential genes and the genes predicted from the M64 genome indicated that more than 73% of the Mycoplasmas essential genes are preserved in M. fermentans. Further examination of the highly and partly connected reactions by a novel combinatorial phylogenetic tree, metabolic network, and essential gene analysis indicated that some of the pathways (e.g. purine and pyrimidine metabolisms) with partial connected reactions may be important for the conversions of intermediate metabolites. Taken together, in light of systems and network analyses, the diversity among the Mycoplasma species was manifested on the variations of their limited metabolic abilities during evolution

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school&#x2;aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

NUCLEAR MAGNETIC RESONANCE STUDIES OF PLANT-TYPE FERREDOXINS (NMR)

Plant-type 2Fe(.)2S* ferredoxins have been studied by (\u271)H and (\u2713)C NMR spectroscopy. Ferredoxins from six species (Anabaena variabilis, Anacystis nidulans, Spirulina maxima, Phytolacca americana, Spinacia oleracea, Leucaena glauca) were studied by (\u271)H NMR. The majority of the (\u2713)C NMR studies were on enriched A. variabilis ferredoxin II (ul, 20% (\u2713)C), and a few natural abundance (\u2713)C NMR studies were on S. maxima ferredoxin II. Resonances in the aromatic region of the (\u271)H spectra were assigned mainly by comparing the spectra and sequences of the six ferredoxins. The assignments were corroborated by Cr(NH(,3))(,6)(\u273+) binding experiments and chemical modifications of the proteins. Resonances in the aromatic region of the (\u2713)C spectra were assigned by cross-correlation with the assigned (\u271)H resonances: the protonated carbons were assigned by heteronuclear ((\u2713)C,(\u271)H) two-dimensional chemical shift correlated spectroscopy, and the non-protonated carbons were assigned by coherent selective decoupling experiments. The single Cr(NH(,3))(,6)(\u273+) binding site on ferredoxin discovered by Armstrong and coworkers {J. Chem. Soc. Chem. Commum. (1978) 1102-1103} was found to be near Tyr(\u2783) and Tyr(\u2725), since resonances in the (\u271)H and (\u2713)C spectra due to these residues were selectively broadened. There are several negatively-charged groups around this site, which can interact electrostatically with the positively-charged chromium(III) complex. The spin-lattice relaxation times for several non-protonated carbons near to the 2Fe(.)2S* center were found to be much shorter in oxidized ferredoxin than in reduced ferredoxin. Also there is more intensity in the aromatic region of the spectra of reduced proteins than in those of oxidized proteins. These results imply that the electron spin relaxation time (T(,e)) for the iron atoms in the reduced ferredoxin is shorter than that for those in the oxidized ferredoxin. The ferredoxin-ferredoxin NADP(\u27+) oxidoreductase complex was studied by (\u2713)C NMR. At least three glutamic acid residues on the ferredoxin molecules were found to be at or near the contact region between the proteins. The ferredoxin molecule does not undergo a major conformational change when bound to the oxidoreductase