Synthesis of Multifunctional Eu(III) Complex Doped Fe3O4/Au Nanocomposite for Dual Photo-Magnetic Hyperthermia and Fluorescence Bioimaging.

In this paper, the luminescent complex Eu(3-thenoyltrifluoroacetonate)3 was integrated with Fe3O4 and gold (Au) nanoparticles to form a multifunctional nanocomposite, Fe3O4/Au/Eu(TTA)3 (FOASET NC), for dual magnetic-photothermal therapy and biomedical imaging. Upon functionalization with amine-NH2, the FOASET NC exhibits a small size of 60-70 nm and strong, sharp emission at λmax = 614 nm, enhanced by surface plasmon resonance (SPR) of Au nanoparticles that provided an effective label for HT29 colorectal cancer cells by fluorescence microscopy imaging. In addition, a hyperthermia temperature (42-46 °C) was completely achieved by using these FOASET NCs in an aqueous solution with three heating modes for (i) Magnetic therapy (MT), (ii) Photothermal therapy (PT), and (iii) Dual magnetic-photothermal therapy (MPT). The heating efficiency was improved in the dual magnetic-photothermal heating mode.

The Effects of 2',4'-Dihydroxy-6'-methoxy-3',5'- dimethylchalcone from Cleistocalyx operculatus Buds on Human Pancreatic Cancer Cell Lines.

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a principal natural chalcone of Cleistocalyx operculatus buds, suppresses the growth of many types of cancer cells. However, the effects of this compound on pancreatic cancer cells have not been evaluated. In our experiments, we explored the effects of this chalcone on two human pancreatic cancer cell lines. A cell proliferation assay revealed that DMC exhibited concentration-dependent cytotoxicity against PANC-1 and MIA PACA2 cells, with IC50 values of 10.5 ± 0.8 and 12.2 ± 0.9 µM, respectively. Treatment of DMC led to the apoptosis of PANC-1 by caspase-3 activation as revealed by annexin-V/propidium iodide double-staining. Western blotting indicated that DMC induced proteolytic activation of caspase-3 and -9, degradation of caspase-3 substrate proteins (including poly[ADP-ribose] polymerase [PARP]), augmented bak protein level, while attenuating the expression of bcl-2 in PANC-1 cells. Taken together, our results provide experimental evidence to support that DMC may serve as a useful chemotherapeutic agent for control of human pancreatic cancer cells.

A facilitated social innovation: stakeholder groups using Plan-Do-Study-Act cycles for perinatal health across levels of the health system in Cao Bang province, Vietnam.

BACKGROUND: Universal coverage of evidence-based interventions for perinatal health, often part of evidence-based guidelines, could prevent most perinatal deaths, particularly if entire communities were engaged in the implementation. Social innovations may provide creative solutions to the implementation of evidence-based guidelines, but successful use of social innovations relies on the engagement of communities and health system actors. This proof-of-concept study aimed to assess whether an earlier successful social innovation for improved neonatal survival that employed regular facilitated Plan-Do-Study-Act meetings on the commune level was feasible and acceptable when implemented on multiple levels of the health system (52 health units) and resulted in actions with plausibly favourable effects on perinatal health and survival in Cao Bang province, northern Vietnam. METHODS: The Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework guided the implementation and evaluation of the Perinatal Knowledge-Into-Practice (PeriKIP) project. Data collection included facilitators' diaries, health workers' knowledge on perinatal care, structured observations of antenatal care, focus group discussions with facilitators, their mentors and representatives of different actors of the initiated stakeholder groups and an individual interview with the Reproductive Health Centre director. Clinical experts assessed the relevance of the identified problems and actions taken based on facilitators' diaries. Descriptive statistics included proportions, means, and t-tests for the knowledge assessment and observations. Qualitative data were analysed by content analysis. RESULTS: The social innovation resulted in the identification of about 500 relevant problems. Also, 75% of planned actions to overcome prioritised problems were undertaken, results presented and a plan for new actions to achieve the group's goals to enhance perinatal health. The facilitators had significant roles, ensuring that the stakeholder groups were established based on principles of mutual respect. Overall, the knowledge of perinatal health and performance of antenatal care improved over the intervention period. CONCLUSIONS: The establishment of facilitated local stakeholder groups can remedy the need for tailored interventions and grassroots involvement in perinatal health and provide a scalable structure for focused efforts to reduce preventable deaths and promote health and well-being.

Pop2 phosphorylation at S39 contributes to the glucose repression of stress response genes, HSP12 and HSP26.

The S. cerevisiae Pop2 protein is an exonuclease in the Ccr4-Not complex that is a conserved regulator of gene expression. Pop2 regulates gene expression post-transcriptionally by shortening the poly(A) tail of mRNA. A previous study has shown that Pop2 is phosphorylated at threonine 97 (T97) by Yak1 protein kinase in response to glucose limitation. However, the physiological importance of Pop2 phosphorylation remains unknown. In this study, we found that Pop2 is phosphorylated at serine 39 (S39) under unstressed conditions. The dephosphorylation of S39 was occurred rapidly after glucose depletion, and the addition of glucose to the glucose-deprived culture recovered this phosphorylation, suggesting that Pop2 phosphorylation at S39 is regulated by glucose. This glucose-regulated phosphorylation of Pop2 at S39 is dependent on Pho85 kinase. We previously reported that Pop2 takes a part in the cell wall integrity pathway by regulating LRG1 mRNA; however, S39 phosphorylation of Pop2 is not involved in LRG1 expression. On the other hand, Pop2 phosphorylation at S39 is involved in the expression of HSP12 and HSP26, which encode a small heat shock protein. In the medium supplemented with glucose, Pop2 might be phosphorylated at S39 by Pho85 kinase, and this phosphorylation contributes to repress the expression of HSP12 and HSP26. Glucose starvation inactivated Pho85, which resulted in the derepression of HSP12 and HSP26, together with other glucose sensing mechanisms. Our results suggest that Pho85-dependent phosphorylation of Pop2 is a part of the glucose sensing system in yeast.

Polygonum multiflorum root extract as a potential candidate for treatment of early graying hair.

Despite Polygonum multiflorum (PM) has been experiencely used as a drug to treat early graying hair phenomenon in Asian countries for a long time, there is limited study examined the real biological effects of PM on hair graying in vitro and in vivo. In this study, we investigated the effects of PM root extract (PM-RE) on melanin synthesis in human melanoma SKMEL-28 cells and embryos/larvae of wild-type strain AB zebrafish. We also preliminary revealed the molecular mechanism of early hair graying phenomenon in both in vitro and in vivo models. Our results showed that PM-RE significantly induced melanin synthesis in melanin-producing SKMEL-28 melanoma cells and also in zebrafish embryos/larvae at 4-day postfertilization through activation of MC1R/MITF/tyrosinase-signaling pathway. We also investigated the differences in genotype between graying hair follicle and black hair follicle of young peoples and found that early hair graying phenomenon may be related to downregulation of MC1R/MITF/tyrosinase pathway. Taken together, we suggested that PM-RE at safe doses could be used as a potential agent for the treatment of early hair graying and other loss pigmentation-related diseases.

Analysis of the Physiological Activities of Scd6 through Its Interaction with Hmt1.

Scd6, a yeast homologue of human RAP55, is a component of messenger ribonucleoproteins (mRNPs) that repress translation by binding to translation initiation factors, and also is a decapping activator along with the binding partners Edc3 and Dhh1. Herein, we report that Scd6 is a substrate of the intrinsic protein arginine methyltransferase, Hmt1, in budding yeast Saccharomyces cerevisiae. Mass spectrometric analysis revealed that several arginine residues within the Scd6 RGG motif, which is important for mRNA binding, were methylated in Hmt1 dependent manner. Under stress conditions such as glucose starvation, Scd6 localized to cytoplasmic processing bodies (P-bodies) wherein translationally repressed mRNPs and untranslated mRNAs accumulate. Localization of Scd6 to P-bodies was impaired in hmt1 deletion mutant and in the presence of methylation-deficient substitution of Scd6. In addition, deletion of scd6 and dhh1 led to severe synthetic growth defect at high temperature. Methylation-deficient mutation of Scd6 suppressed the phenotypic defects of scd6 dhh1 double mutant, whereas methylation-mimic mutation did not, suggesting that the arginine methylation might negatively regulate Scd6 function relating to Dhh1. Therefore, the present data suggest that Hmt1-based arginine methylation is required for Scd6 localization and function.

Surveillance of dengue and chikungunya infection in Dong Thap, Vietnam: A 13-month study.

OBJECTIVE: To establish a surveillance in Dong Thap, at the border with Cambodia by assessing the presence of DENV serotypes and CHIKV among patients hospitalized at Dong Thap general hospital. METHODS: Cross-sectional descriptive analysis was conducted on a cohort of 131 patients hospitalized with acute fever and symptoms compatible with dengue or chikungunya. The study was conducted from January 2012 to February 2013. The full clinical picture was established as well as serological and molecular detection. Serological analysis was sequentially performed on blood samples collected on admission and an average of seven days after admission. The detection of IgM antibody to DENV was performed by IgM capture ELISA and the detection of DENV and CHIKV RNA was done by reverse-transcription multiplex PCR. RESULTS: 101 patients out of 131 (77%) were confirmed with dengue. All four dengue serotypes were detected with a predominance of DENV2 and DENV4. No chikungunya infection was detected although reported in neighboring Cambodia. A differential efficiency of serological dengue detection was observed. Efficiency was 29% upon admission and 53% after seven days on the same patients. 30 patients out of 131 (23%) were negative with both DENV and CHIKV. CONCLUSIONS: Dengue is at risk of being underestimated and chikungunya is not systematically detected. Changes in detection and surveillance procedures are therefore discussed to increase efficiency of dengue detection and continue the monitoring the emergence of CHIKV in Dong Thap province and in Vietnam.

Role of Aedes aegypti and Aedes albopictus during the 2011 dengue fever epidemics in Hanoi, Vietnam.

OBJECTIVE: To record the human cases of dengue fever (DF) and investigate the Aedes mosquito species circulating during the Hanoi 2011 DF epidemics. METHODS: 24 different outbreak points were recorded in 8 districts between August and December 2011. RESULTS: 140 patients were hospitalized following dengue diagnostic with a predominance of males (59.3%) and the 15-34 age class. Only DENV-1 (11.27%) and DENV-2 (88.73%) serotypes were detected in human samples. Mosquito sampling performed in and around patients households revealed the predominance of Aedes aegypti (A. aegypti) (95.15%) versus Aedes albopictus (4.85%). CONCLUSIONS: There is a positive correlation between the population density of A. aegypti and the number of human cases and duration of outbreaks. This was not observed for Aedes albopictus. Three pools of A. aegypti were positive with dengue virus, two with DENV-1 and one with DENV-2.

Evaluation of an Epitypified Ophiocordyceps formosana (Cordyceps s.l.) for Its Pharmacological Potential.

The substantial merit of Cordyceps s.l. spp. in terms of medicinal benefits is largely appreciated. Nevertheless, only few studies have characterized and examined the clinical complications of the use of health tonics containing these species. Here, we epitypified C. formosana isolates that were collected and characterized as Ophiocordyceps formosana based on morphological characteristics, molecular phylogenetic analyses, and metabolite profiling. Thus, we renamed and transferred C. formosana to the new protologue Ophiocordyceps formosana (Kobayasi & Shimizu) Wang, Tsai, Tzean & Shen comb. nov. Additionally, the pharmacological potential of O. formosana was evaluated based on the hot-water extract from its mycelium. The relative amounts of the known bioactive ingredients that are unique to Cordyceps s.l. species in O. formosana were found to be similar to the amounts in O. sinensis and C. militaris, indicating the potential applicability of O. formosana for pharmacological uses. Additionally, we found that O. formosana exhibited antioxidation activities in vitro and in vivo that were similar to those of O. sinensis and C. militaris. Furthermore, O. formosana also displayed conspicuously effective antitumor activity compared with the tested Cordyceps s.l. species. Intrinsically, O. formosana exhibited less toxicity than the other Cordyceps species. Together, our data suggest that the metabolites of O. formosana may play active roles in complementary medicine.