| 1. |
- Stanaway, Jeffrey D., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 2. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 3. |
- Khoa, Nguyen Manh, et al.
(författare)
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Compounds from aerial parts of Isodon lophanthoides and their effects of cytotoxicity and LPS-induced IL-1β and IL-10 production in RAW 264.7 macrophages
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Ingår i: Vietnam Journal of Chemistry. - 2572-8288.
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Tidskriftsartikel (refereegranskat)abstract
- The bioassay-guided isolation of compounds from the aerial parts of Isodon lophanthoides (IL) resulted in the identification of five compounds (1–5). The chemical structures of 1–5 were determined through spectral analyses and compared to those identified in the literature to be 4-hydroxybenzoic acid (1), protocatechuic acid (2), rosmarinic acid (3), coetsoidin B (4), and coetsoidin A (5). Compounds 1, 4, and 5 were found for the first time in the aerial parts of IL. Compounds 1 and 2 displayed potent cytotoxic activity against A549, MCF-7, HepG2, and HL60 cancer cell lines, with IC50 values ranging from 13.93 to 18.69 µm and from 11.97 to 18.30 µm, respectively. Compounds 1‒5 significantly inhibited LPS-induced IL-1β production in RAW 264.7 macrophages compared to the LPS 5 ng/mL control group, resulting in IL-1β concentrations ranging from 34.92 to 46.91 pg/mL. Additionally, compounds 1‒5 exhibited notable stimulation of IL-10 production, with IL-10 levels ranging from 358.77 to 478.23 pg/mL, compared to the LPS 5 ng/mL control group. These findings highlight the potential of compounds 1‒5 and the IL extracts for the cytotoxic effects on cancer cell lines and on LPS-induced IL-1β and IL-10 production in RAW 264.7 macrophages.
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| 4. |
- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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| 5. |
- Diep Vu, Thi, et al.
(författare)
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Identification and Cytotoxic Evaluation of Pregnane Saponins from the Twigs and Leaves of Dregea volubilis
- 2023
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Ingår i: Chemistry and Biodiversity. - 1612-1872.
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Tidskriftsartikel (refereegranskat)abstract
- Four new polyhydroxy pregnane glycosides, named volubilosides G−K (3, 5–7), along with three known secondary metabolites, dregeoside Da1 (1), dregeoside Ka1 (2), and volubiloside E (4) were isolated from the twigs and leaves of Dregea volubilis (DV). The chemical structures of these compounds (1–7) were elucidated using spectroscopic techniques (1D and 2D NMR and HR-ESI-MS analyses) and compared with those in the published literature. Compounds (1–7) were evaluated for cytotoxicity against eight cancer cell lines (MB49, K562, MKN-7, HT29, A549, MCF-7, MDA-MB-231, and HepG2), revealing varying levels of cytotoxic effects with IC50 values ranging from 4.29 to 21.05 μM. The results indicated that compounds 1–7 may serve as potential lead compounds for the discovery and development of novel anti-cancer drugs.
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| 6. |
- Le, Ha V., et al.
(författare)
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A sulfonate ligand-defected Zr-based metal-organic framework for the enhanced selective removal of anionic dyes
- 2024
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Ingår i: RSC Advances. - 2046-2069. ; 14:23, s. 16389-16399
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we introduce a novel defective analogue of the representative 6-connected zirconium-based metal-organic framework (MOF-808), by employing 5-sulfoisophthalic acid monosodium salt (H2BTC-SO3Na) as a defect inducer via a mixed-linker approach. The structural integrity and different physicochemical properties were investigated by various characterization techniques, including powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and nitrogen physisorption at 77 K. Additionally, proton nuclear magnetic resonance (1H-NMR), energy-dispersive X-ray (EDX), and inductively coupled plasma optical emission spectroscopy (ICP-OES) were employed to confirm the presence of 6.9 mol% of the 5-sulfoisophthalate ligand within the highly crystalline MOF-808 structure. The defective material exhibited significant enhancements in the removal efficiency of various organic dyes, including approximately 64% and 77% for quinoline yellow and sunset yellow, and 56% and 13% for rhodamine B and malachite green, compared to its pristine counterpart. Importantly, the defective MOF-808 showed a remarkable selectivity toward anionic species in binary-component dyes comprising both anionic and cationic dyes.
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| 7. |
- Nguyen, Tra My, et al.
(författare)
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Effects of Coumarins from Roots of Paramignya scandens (Griff.) Craib on LPS-induced IL-1β and IL-10 Cytokine Production in RAW 264.7 Macrophages
- 2024
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Ingår i: Natural Product Sciences. - 1226-3907. ; 30:1, s. 30-38
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Tidskriftsartikel (refereegranskat)abstract
- Based on our previous study, we evaluated the modulatory effects on LPS-induced IL-1β and IL-10 cytokine production in RAW 264.7 macrophages of several medicinal herbs, including P. scandens. The results showed that P. scandens extract showed significant effects on LPS-induced IL-1β and IL-10 cytokine production in RAW 264.7 macrophages. Therefore, in the current research, we focused on the P. scandens sample. Cytokine production effects bioassay-guided isolation of ethyl acetate fraction of 70% ethanol extract from roots of Paramignya scandens (XL) obtained seven coumarins (1–7). Their chemical structures were identified using spectroscopic methods (NMR and MS) and compared with those previously published data to be xanthyletin (1), luvangetin (2), clausenidin (3), nordentatin (4), dentatin (5), clausarin (6), and anisocoumarin E (7). This study represents the first report on the presence of compounds 3, 6, and 7 in the Paramignya genus and compounds 1 and 2 in XL. All isolates (1–7) exhibited significant inhibition of LPS-induced interleukin (IL)-1β production compared to the LPS 5 ng/mL control group, with IL-1β concentrations ranging from 42.77 to 69.76 pg/mL. Additionally, the IL-10 production induced by compounds 1‒7 in LPS-stimulated RAW 264.7 macrophages ranged from 175.98 to 321.56 pg/mL, demonstrating a marked increase as compared to the LPS 5 ng/mL control group. The stimulatory effect on IL-10 production and inhibitory effect on IL-1β production of compounds 1, 2, and 6 gradually increased with the test concentration in both RAW 264.7 macrophages and LPS-induced RAW 264.7 macrophages. Compounds 1, 2, and 6 inhibited IL-1β production in LPS-induced RAW 264.7 macrophages with IC50 values of 10.70 ± 1.18 µM, 8.57 ± 1.05 µM, and 17.43 ± 1.05 µM, respectively. These findings highlight the potential of all the compounds derived from P. scandens roots in inducing IL-1β and IL-10 cytokines activity in LPS-stimulated RAW 264.7 macrophages. The results contributed to expanding the knowledge of the chemistry and bioactivities of P. scandens and provided valuable data for future investigations on this species.
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| 8. |
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| 9. |
- Bui, Ha Thi Thu, et al.
(författare)
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The Association Between Gender Inequalities and Women's Utilization of Maternal Health Services : A Cross-Sectional Survey in Eight South Central Coast Provinces, Vietnam
- 2018
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Ingår i: Journal of Public Health Management and Practice. - 1078-4659 .- 1550-5022. ; 24:2, s. S19-S27
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gender inequalities influence the utilization of maternal health services in Vietnam, but little research has been published. This study, therefore, aimed to explore the association between gender inequalities and women's utilization of maternal health services in Vietnam.Methods: The study was conducted in 8 provinces in the South Central Coast region of Vietnam during August 2013 to May 2014. A total of 907 women who delivered a year prior to the date of interview participated in the study. A multiple logistic regression model was used to examine the association between gender inequalities (including sociodemographic determinants of health) and utilization of 4 or more antenatal care (ANC4+) services, institutional delivery, and ever used contraceptive methods.Results: The utilization rate of maternal health services was varied, from 53.9% for ANC4+ to 87.7% for ever used a contraceptive method and 97% for institutional delivery. Ethnicity was identified as the most influential variable out of all sociodemographic determinants of health. Regarding gender inequalities, couple communication was the only variable having significant association with women's utilization of maternal health services.Conclusion: Women's equal role within context of their daily life and relations with their husbands (discussing maternal care with husband and having equal income to husband) supported their use of maternal health services. Therefore, there should be concerted efforts from all relevant stakeholders including the health system to focus on disadvantaged women in planning and delivery of maternal health services, especially to ethnic minority women. Male involvement strategy should be implemented to promote maternal health care, especially during the prenatal and postpartum period. To provide more culturally sensitive and right-based approaches in delivery of maternal health services to disadvantaged women in Vietnam, interventions are recommended that promote male involvement, that is, to engage men in service delivery to adapt and ensure the most appropriate and effective maternal health care.
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| 10. |
- Chuong, Nguyen Canh, et al.
(författare)
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Amniocentesis test uptake for congenital defects : Decision of pregnant women in Vietnam
- 2018
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Ingår i: Health Care for Women International. - : TAYLOR & FRANCIS INC. - 0739-9332 .- 1096-4665. ; 39:4, s. 493-504
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Tidskriftsartikel (refereegranskat)abstract
- Our study aimed to identify the knowledge, attitude, and factors associated with uptake of amniocentesis test amongst pregnant women of advanced maternal age (35+ years old). A cross-sectional survey was performed on 481 participants in 2016. Women with higher educational attainment, higher income level, having a baby with congenital defects, and women with better knowledge and/or attitude about amniocentesis test were more likely to accept the test. Our study suggested the importance of counseling for women and more time should be given for them to absorb information before they make their decision to uptake the amniocentesis test.
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| 11. |
- Dao, Trong Tuan, et al.
(författare)
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Resveratrol suppressed lps-induced cox-2 VIA miR-146a-5p inhibition in raw246.7 cells
- 2017
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Ingår i: Farmacia. - 0014-8237. ; 65:2, s. 214-218
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Tidskriftsartikel (refereegranskat)abstract
- Trans-resveratrol (Res) is a well-known natural stilbene frequently found in grapes which have been reported to possess antioxidant, anti-cancer activities and inhibited COX-2 expression. MicroRNAs (miRNAs) are short endogenous non-coding RNAs involved in the regulation of mRNA stability and protein synthesis. In our research, resveratrol isolated from Vitis heyneana Roem. & Schult Vitis heyneana was observed to suppress lipopolysaccharides (LPS)-induced COX-2 expression in Raw264.7 cells in a dose dependent manner. Using qPCR it was revealed that LPS induced the expression of miR-25, miR- 125a, miR-125b, miR-146a-5p, miR-146a-3p and miR-455. However, we only observed miR-146a-5p expression significantly decreased in resveratrol compared to untreated-control group. In addition, resveratrol abrogated the effect of miR-146a-5p mimic induced-COX-2 expression in Raw264.7 cells. Taken together, this study demonstrated for the first time the involvement of miR-146a-5p in resveratrol inhibited LPS-induced COX-2 expression in Raw264.7 cells.
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| 12. |
- Duc, Duong M., 1984-, et al.
(författare)
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A Secular Trend in Birth Weight and Delivery Practices in Periurban Vietnam During 2005-2012
- 2017
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Ingår i: Asia-Pacific journal of public health. - : SAGE PUBLICATIONS INC. - 1010-5395 .- 1941-2479. ; 29:5 Suppl., s. 18S-24S
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Tidskriftsartikel (refereegranskat)abstract
- The remarkable increase in Vietnamese economic conditions can increase the birth weight in neonates and better delivery practices among women. The Chi Linh Health and Demographic Surveillance System started in 2004. An open cohort of data consisting of about 57561 people from 17993 households has been followed primarily with respect to demography, economy, and education. The aim of this research is to study secular trends in delivery practice and birth weight in the past decade (2005-2012) in Chi Linh. We found a significant change in delivery rates at hospitals and cesarean section rates, but the birth weights over a decade of drastic economic development were stable. Furthermore, the findings show significant associations of birth weight and delivery practices with the child's sex, mother's age, and household income. Our results might be considered as representative for other similar periurban settings in Vietnam. We suggest that appropriate policies should be developed given the reduction in the use of delivery services in commune health centers in urban areas.
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| 13. |
- Hoa, Hoang Thai, et al.
(författare)
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Effects of compounds from physalis angulata on fatty acid synthesis and glucose metabolism in HEPG2 cells via the AMP-activated protein kinase pathway
- 2020
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Ingår i: Natural Product Sciences. - 1226-3907. ; 26:3, s. 200-206
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Tidskriftsartikel (refereegranskat)abstract
- The ability of the total extract from Physalis angulata; three fractions after partitioning with n-hexane, ethyl acetate (TBE), and water; and four withanolides (compounds 1 – 4) to phosphorylate 5'-adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells was evaluated. The TBE fraction (50 μg/mL) activated p-ACC and p-AMPK expression most strongly. Compounds 1 – 4 (10 μM) upregulated p-ACC expression at different levels. Compound 4 induced the most significant changes in p-AMPK expression, followed by 1 and 2. Sterol regulatory element-binding proteins (SREBPs) play a functional role in the transcriptional regulation of the lipogenic pathway, including fatty acid synthase (FAS) and ACC. The effects of compounds 2 and 4 (10 μM) on FAS and SREBP-1c expression under high glucose conditions (30 mM) in HepG2 cells were evaluated further. Both dose-dependently inhibited FAS and SREBP-1c expression as well as lipid accumulation (1 – 10 μM) were compared to high-concentration glucose control, which upregulated FAS and SREBP-1c. These results suggest that compounds 2 and 4 upregulate AMPK, suppress FAS and SREBP-1c, and have potential effects on glucose and lipid metabolism.
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| 14. |
- Le, Vui Thi, et al.
(författare)
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Sex Ratio at Birth in Vietnam : Results From Data in CHILILAB HDSS, 2004 to 2013
- 2017
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Ingår i: Asia-Pacific journal of public health. - : SAGE PUBLICATIONS INC. - 1010-5395 .- 1941-2479. ; 29:5 Suppl., s. 25S-34S
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to explore the association of demographic and socioeconomic characteristics and imbalanced sex ratio at birth (SRB) in Chi Linh district, Hai Duong. The data were collected from a longitudinal study using a community-based periodic, referred as Chi Linh Health and Demographic Surveillance System (CHILILAB HDSS) during 2004 to 2013. A total of 7568 children were analyzed. Results showed that SRB in Chi Linh dramatically increased to the imbalanced sex ratio (114.6 boys to 100 girls) by 2013. SRB was associated with birth order and sex of preceding siblings. SRB was extremely high among families without any sons (136/100). SRB was highest among families having third or more children (175/100). Imbalanced SRB was more likely to occur among women working in small business/homemakers and others, women who attained high education level, and women in wealthy households. We suggested further efforts to tackle imbalanced SRB in periurban areas in Vietnam.
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| 15. |
- Nguyen, Thi Thu, et al.
(författare)
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Cytotoxic sesquiterpenes and diterpenes from the rhizomes of Curcuma zedoaroides Chaveer. & Tanee
- 2024
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Ingår i: Biochemical Systematics and Ecology. - 0305-1978. ; 112
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Tidskriftsartikel (refereegranskat)abstract
- A phytochemical investigation of Curcuma zedoaroides rhizomes resulted in the isolation of ten sesquiterpenes (1–10) and two diterpenes (11−12). The structure of compounds 1–12 was identified as phaeocaulisin E (1), zedoarondiol (2), isozedoarondiol (3), isoprocurcumenol (4), neoprocurcumenol (5), procurcumenol (6), 1-epi-procurcumenol (7), aerugidiol (8), curcumenol (9), curcumenone (10), curcuminol E (11), and zerumin A (12) using MS and NMR methods. Remarkably, all these compounds were found in C. zedoaroides for the first time and their chemotaxonomic significance was also discussed. Moreover, the fractionated extracts of C. zedoaroides (n-hexane, ethyl acetate, and water) were demonstrated to have effects on eight cancer cell lines (A549, MCF-7, HT-29, MB49, HepG2, MDA-MB231, JB6-C141, and K562), exhibiting IC50 values ranging from 5.43 to 11.96 μg/mL. Compounds 1–9 and 11−12 displayed significant activity against five cancer cell lines (A549, MCF-7, MDA-MB231, HL-60, and HepG2), with IC50 values ranging from 3.13 μM to 30.10 μM. The most potent effect was observed in the A549 cell line (IC50: 3.13–13.54 μM).
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| 16. |
- Duc, Duong M., 1984-, et al.
(författare)
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Measuring local healthcare context for knowledge translation in primary and secondary levels of care in northern Vietnam: A cross-sectional study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe influence of context in shaping the effectiveness of knowledge translation (KT) is widely recognized. The Context Assessment for Community Health (COACH) tool aims to assess contextual aspects that are of importance for KT in healthcare in low- and middle-income settings. This study used the COACH tool to describe healthcare context as perceived by health workers in primary and secondary levels of care in a northern province in Vietnam and to further evaluate the internal structure of the COACH tool.MethodsThis cross-sectional study administered the COACH tool to 677 eligible health workers in primary and secondary levels of care. The relationships between individual background variables and COACH dimensions were analysed using binary logistic regression. Further, internal construct validity was calculated by a first-order independent cluster model confirmatory factor analysis (CFA).ResultsOverall, the healthcare context was perceived as supportive for KT. Gender, age, and geographic location showed significant relationships to one of the COACH dimensions. Male health workers rated their Commitment to work as lower than female health workers (OR=0.39, 95% CI: 0.20–0.78). There were, however, only minor differences in scores for the dimensions of context, at each health facility as well as between health facilities. The CFA asserted an acceptable internal structure of the COACH tool.ConclusionsThe survey enhanced the understanding of how aspects of the healthcare context for KT are perceived by health workers at primary and secondary levels of care in a province in Vietnam. There was an overall positive perception of the work context with only minor variability, reflecting a ‘receptive to change’ context for KT. This should, however, be interpreted with caution due to the risk of social desirability response bias. The findings on the acceptable internal structure of the COACH tool supports its further use as a valid instrument.
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| 17. |
- Hassan, Noor, et al.
(författare)
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Biochemical and structural characterization of a thermostable beta-glucosidase from Halothermothrix orenii for galacto-oligosaccharide synthesis
- 2015
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Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 99:4, s. 1731-1744
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Tidskriftsartikel (refereegranskat)abstract
- Lactose is a major disaccharide by-product from the dairy industries, and production of whey alone amounts to about 200 million tons globally each year. Thus, it is of particular interest to identify improved enzymatic processes for lactose utilization. Microbial beta-glucosidases (BGL) with significant beta-galactosidase (BGAL) activity can be used to convert lactose to glucose (Glc) and galactose (Gal), and most retaining BGLs also synthesizemore complex sugars from the monosaccharides by transglycosylation, such as galacto-oligosaccharides (GOS), which are prebiotic compounds that stimulate growth of beneficial gut bacteria. In this work, a BGL from the thermophilic and halophilic bacterium Halothermothrix orenii, HoBGLA, was characterized biochemically and structurally. It is an unspecific beta-glucosidase with mixed activities for different substrates and prominent activity with various galactosidases such as lactose. We show that HoBGLA is an attractive candidate for industrial lactose conversion based on its high activity and stability within a broad pH range (4.5-7.5), with maximal beta-galactosidase activity at pH 6.0. The temperature optimum is in the range of 65-70 degrees C, and HoBGLA also shows excellent thermostability at this temperature range. The main GOS products from HoBGLA transgalactosylation are beta-D-Galp-(1 -> 6)-D-Lac (6GALA) and beta-D-Galp-(1 -> 3)-D-Lac (3GALA), indicating that D-lactose is a better galactosyl acceptor than either of the monosaccharides. To evaluate ligand binding and guide GOS modeling, crystal structures of HoBGLA were determined in complex with thiocellobiose, 2-deoxy-2-fluoro-D-glucose and glucose. The two major GOS products, 3GALA and 6GALA, were modeled in the substrate-binding cleft of wild-type HoBGLA and shown to be favorably accommodated.
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| 18. |
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| 19. |
- Hassan, Noor, et al.
(författare)
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Engineering a thermostable Halothermothrix orenii beta-glucosidase for improved galacto-oligosaccharide synthesis
- 2016
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Ingår i: Applied Microbiology and Biotechnology. - : Springer. - 0175-7598 .- 1432-0614. ; 100:8, s. 3533-3543
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Tidskriftsartikel (refereegranskat)abstract
- Lactose is produced in large amounts as a by-product from the dairy industry. This inexpensive disaccharide can be converted to more useful value-added products such as galacto-oligosaccharides (GOSs) by transgalactosylation reactions with retaining beta-galactosidases (BGALs) being normally used for this purpose. Hydrolysis is always competing with the transglycosylation reaction, and hence, the yields of GOSs can be too low for industrial use. We have reported that a beta-glucosidase from Halothermothrix orenii (HoBGLA) shows promising characteristics for lactose conversion and GOS synthesis. Here, we engineered HoBGLA to investigate the possibility to further improve lactose conversion and GOS production. Five variants that targeted the glycone (-1) and aglycone (+1) subsites (N222F, N294T, F417S, F417Y, and Y296F) were designed and expressed. All variants show significantly impaired catalytic activity with cellobiose and lactose as substrates. Particularly, F417S is hydrolytically crippled with cellobiose as substrate with a 1000-fold decrease in apparent k(cat), but to a lesser extent affected when catalyzing hydrolysis of lactose (47-fold lower k(cat)). This large selective effect on cellobiose hydrolysis is manifested as a change in substrate selectivity from cellobiose to lactose. The least affected variant is F417Y, which retains the capacity to hydrolyze both cellobiose and lactose with the same relative substrate selectivity as the wild type, but with similar to 10-fold lower turnover numbers. Thin-layer chromatography results show that this effect is accompanied by synthesis of a particular GOS product in higher yields by Y296F and F417S compared with the other variants, whereas the variant F417Y produces a higher yield of total GOSs.
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| 20. |
- Nguyen, Ha Thu, et al.
(författare)
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CDN1163, an activator of sarco/endoplasmic reticulum Ca2+ ATPase, up-regulates mitochondrial functions and protects against lipotoxicity in pancreatic β-cells
- 2023
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Ingår i: British Journal of Pharmacology. - 0007-1188. ; 180:21, s. 2762-2776
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: High levels of Ca2+ in the endoplasmic reticulum (ER), established by the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), are required for protein folding and cell signalling. Excessive ER Ca2+ release or decreased SERCA activity induces unfolded protein accumulation and ER stress in pancreatic β-cells, leading to defective insulin secretion and diabetes. Here we have investigated the consequences of enhancing ER Ca2+ uptake on β-cell survival and function. Experimental Approach: The effects of SERCA activator, CDN1163, on Ca2+ homeostasis, protein expression, mitochondrial activities, insulin secretion, and lipotoxicity have been studied in mouse pancreatic β-cells and MIN6 cells. Key Results: CDN1163, increased insulin synthesis and exocytosis from islets. CDN1163 also increased the sensitivity of the cytosolic Ca2+ oscillation response to glucose and potentiated it in dispersed and sorted β-cells. CDN1163 augmented the ER and mitochondrial Ca2+ content, the mitochondrial membrane potential, respiration, and ATP synthesis. CDN1163 up-regulated expression of inositol 1,4,5-trisphosphate receptors and antioxidant enzymes, and mitochondrial biogenesis, including peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α). Overexpression of SERCA2a or 2b replicated the effects of CDN1163, while knockdown of SERCA2 abolished the stimulatory actions of CDN1163. In palmitate-treated β-cells, CDN1163 prevented ER Ca2+ depletion, mitochondrial dysfunction, cytosolic and mitochondrial oxidative stress, defective insulin secretion, and apoptotic cell death. Conclusions and Implications: Activation of SERCA enhanced mitochondrial bioenergetics and antioxidant capability, suppressing the cytotoxic effects of palmitate. Our results suggest that targeting SERCA could be a novel therapeutic strategy to protect β-cells from lipotoxicity and the development of Type 2 diabetes.
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| 21. |
- Nguyen, Ha Thu, et al.
(författare)
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Regulation of autophagy by perilysosomal calcium : a new player in β-cell lipotoxicity
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Ingår i: Experimental and Molecular Medicine. - 1226-3613.
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Forskningsöversikt (refereegranskat)abstract
- Autophagy is an essential quality control mechanism for maintaining organellar functions in eukaryotic cells. Defective autophagy in pancreatic beta cells has been shown to be involved in the progression of diabetes through impaired insulin secretion under glucolipotoxic stress. The underlying mechanism reveals the pathologic role of the hyperactivation of mechanistic target of rapamycin (mTOR), which inhibits lysosomal biogenesis and autophagic processes. Moreover, accumulating evidence suggests that oxidative stress induces Ca2+ depletion in the endoplasmic reticulum (ER) and cytosolic Ca2+ overload, which may contribute to mTOR activation in perilysosomal microdomains, leading to autophagic defects and β-cell failure due to lipotoxicity. This review delineates the antagonistic regulation of autophagic flux by mTOR and AMP-dependent protein kinase (AMPK) at the lysosomal membrane, and both of these molecules could be activated by perilysosomal calcium signaling. However, aberrant and persistent Ca2+ elevation upon lipotoxic stress increases mTOR activity and suppresses autophagy. Therefore, normalization of autophagy is an attractive therapeutic strategy for patients with β-cell failure and diabetes.
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| 22. |
- Nguyen, Thu-Ha, et al.
(författare)
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Characterization and molecular cloning of a heterodimeric beta-galactosidase from the probiotic strain Lactobacillus acidophilus R22
- 2007
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Ingår i: FEMS Microbiology Letters. - : Oxford University Press. - 0378-1097 .- 1574-6968. ; 269:1, s. 136-144
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Tidskriftsartikel (refereegranskat)abstract
- beta-Galactosidase from the probiotic strain Lactobacillus acidophilus R22 was purified to apparent homogeneity by ammonium sulphate fractionation, hydrophobic interaction, and affinity chromatography. The enzyme is a heterodimer consisting of two subunits of 35 and 72 kDa, as determined by gel electrophoresis. The optimum temperature of beta-galactosidase activity was 55 degrees C (10-min assay) and the range of pH 6.5-8, respectively, for both o-nitrophenyl-beta-D-galactopyranoside (oNPG) and lactose hydrolysis. The K-m and V-max values for lactose and oNPG were 4.04 +/- 0.26 mM, 28.8 +/- 0.2 mu mol D-glucose released per min per mg protein, and 0.73 +/- 0.07 mM, 361 +/- 12 mu mol o-nitrophenol released per min per mg protein, respectively. The enzyme was inhibited by high concentrations of oNPG with K-i,K-s=31.7 +/- 3.5 mM. The enzyme showed no specific requirements for metal ions, with the exception of Mg2+, which enhanced both activity and stability. The genes encoding this heterodimeric enzyme, lacL and lacM, were cloned, and compared with other beta-galactosidases from lactobacilli. beta-Galactosidase from L. acidophilus was used for the synthesis of prebiotic galacto-oligosaccharides (GOS) from lactose, with the maximum GOS yield of 38.5% of total sugars at about 75% lactose conversion.
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