| 1. |
- Dahan, Diana, et al.
(författare)
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MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction
- 2017
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Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 54:4, s. 246-256
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Methods: Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. Results: No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor mRNAs were unchanged. Contraction by the 5-HT2A agonist TCB-2 was increased in Dicer KO as was the response to the 5-HT2B agonist BW723C86. Effects of Src and protein kinase C inhibition were similar in control and KO arteries, but the effect of inhibition of Rho kinase was reduced. We identified miR-30c as a potential candidate for 5-HT2A receptor regulation as it repressed 5-HT2A mRNA and protein. Conclusion: Our findings show that 5-HT receptor signaling in the arterial wall is subject to regulation by microRNAs and that this entails altered 5-HT2A receptor expression and signaling.
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| 2. |
- 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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| 3. |
- Brisuda, Antonín, et al.
(författare)
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Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.
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| 4. |
- Ha, Do Thi, et al.
(författare)
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Anti-inflammatory effect of oligostilbenoids from Vitis heyneana in LPS-stimulated RAW 264.7 macrophages via suppressing the NF-ΚB activation
- 2018
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Ingår i: Chemistry Central Journal. - : Springer Science and Business Media LLC. - 1752-153X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vitis heyneana is widely distributed in the north of Vietnam, it has been used in Vietnamese traditional medicine as an agent for treatment of arthritis, bronchitis, carbuncles and inflammatory conditions, and menstrual irregularities. However, this plant has not been investigated in phytochemical constituents and biological effects, especially in the anti-inflammatory property. Results: Bioassay-guided fractionation of the EtOAc soluble fraction from the aerial part of Vitis heyneana resulted in the isolation of a series of oligostilbenoids as piceid (1), 2-r-viniferin (2), betulifol A (3), vitisinol C (4), (-)-trans-ε-viniferin (5), α-viniferin (6), shoreaketon (7), amurensin B (8), vitisinol B (9), and cis-vitisin B (10). Compound 5 showed the most potent inhibitory activities by suppressing LPS-induced COX-2 expression and PGE2 production. This compound exhibited significantly reduced LPS-induced nitric oxide (NO) release in a dose-dependent manner. These effects are accompanied with the inhibition of transcription factor NF-ΚB activation. Conclusion: The results suggested that trans-ε-viniferin exerts anti-inflammatory effects via suppression the NF-ΚB activation in RAW 264.7 cells. [Figure not available: see fulltext.]
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| 5. |
- Hien, Tran Thi, et al.
(författare)
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Bladder cancer therapy without toxicity—A dose-escalation study of alpha1-oleate
- 2020
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 147:9, s. 2479-2492
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Tidskriftsartikel (refereegranskat)abstract
- Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. Our study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intravesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17 mM) on days 3 to 11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group, compared to sham-treated mice. Tumor markers Ki-67, Cyclin D1 and VEGF were inhibited in a dose-dependent manner, as was the expression of cancer-related genes. Remarkably, toxicity for healthy tissue was not detected in alpha1-oleate-treated, tumor-bearing mice or healthy mice or rabbits, challenged with increasing doses of the active complex. The results define a dose-dependent therapeutic effect of alpha1-oleate in a murine bladder cancer model.
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| 6. |
- Ho, James C.S., et al.
(författare)
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Lipid bilayer composition as a determinant of cancer cell sensitivity to tumoricidal protein-lipid complexes
- 2022
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Ingår i: BioFactors. - : Wiley. - 0951-6433 .- 1872-8081. ; 48:5, s. 1145-1159
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Tidskriftsartikel (refereegranskat)abstract
- Complexes formed by the alpha1 N-terminal peptide of alpha-lactalbumin and oleic acid (alpha1-oleate) interact with lipid bilayers. Plasma membrane perturbations trigger tumor cell death but normal differentiated cells are more resistant, and their plasma membranes are less strongly affected. This study examined membrane lipid composition as a determinant of tumor cell reactivity. Bladder cancer tissue showed a higher abundance of unsaturated lipids enriched in phosphatidylcholine, PC (36:4) and PC (38:4), and sphingomyelin, SM (36:1) than healthy bladder tissue, where saturated lipids predominated and the lipid extracts from bladder cancer tissue inhibited the tumoricidal effect of the complex more effectively than healthy tissue extracts. Furthermore, unsaturated PC in solution inhibited tumor cell death, and the complex interacted with giant unilamellar vesicles formed by PC, confirming the affinity of alpha1-oleate for fluid membranes enriched in PC. Quartz Crystal Microbalance with dissipation monitoring (QCM-D) detected a preference of the complex for the liquid-disordered phase, suggesting that the insertion into PC-based membranes and the resulting membrane perturbations are influenced by membrane lipid saturation. The results suggest that the membrane lipid composition is functionally important and that specific unsaturated membrane lipids may serve as “recognition motifs” for broad-spectrum tumoricidal molecules such as alpha1-oleate.
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| 7. |
- 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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| 8. |
- Nguyen, Viet-Tien, et al.
(författare)
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GIS Based Novel Hybrid Computational Intelligence Models for Mapping Landslide Susceptibility : A Case Study at Da Lat City, Vietnam
- 2019
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Ingår i: Sustainability. - Switzerland : MDPI. - 2071-1050. ; 11:24
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Tidskriftsartikel (refereegranskat)abstract
- Landslides affect properties and the lives of a large number of people in many hilly parts of Vietnam and in the world. Damages caused by landslides can be reduced by understanding distribution, nature, mechanisms and causes of landslides with the help of model studies for better planning and risk management of the area. Development of landslide susceptibility maps is one of the main steps in landslide management. In this study, the main objective is to develop GIS based hybrid computational intelligence models to generate landslide susceptibility maps of the Da Lat province, which is one of the landslide prone regions of Vietnam. Novel hybrid models of alternating decision trees (ADT) with various ensemble methods, namely bagging, dagging, MultiBoostAB, and RealAdaBoost, were developed namely B-ADT, D-ADT, MBAB-ADT, RAB-ADT, respectively. Data of 72 past landslide events was used in conjunction with 11 landslide conditioning factors (curvature, distance from geological boundaries, elevation, land use, Normalized Difference Vegetation Index (NDVI), relief amplitude, stream density, slope, lithology, weathering crust and soil) in the development and validation of the models. Area under the receiver operating characteristic (ROC) curve (AUC), and several statistical measures were applied to validate these models. Results indicated that performance of all the models was good (AUC value greater than 0.8) but B-ADT model performed the best (AUC= 0.856). Landslide susceptibility maps generated using the proposed models would be helpful to decision makers in the risk management for land use planning and infrastructure development.
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| 9. |
- Yacoub, Sophie, et al.
(författare)
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Cardiac function in Vietnamese patients with different dengue severity grades
- 2012
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Ingår i: Critical Care Medicine. - : Wolters Kluwer. - 0090-3493 .- 1530-0293. ; 40:2, s. 477-483
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dengue continues to cause significant global morbidity and mortality. Severe disease is characterized by cardiovascular compromise from capillary leakage. Cardiac involvement in dengue has also been reported but has not been adequately studied. Setting: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Subjects and Design: Seventy-nine patients aged 8–6 yrs with different dengue severity grades were studied using echocardiography including tissue Doppler imaging. The patients were split into severity grades: dengue, dengue with warning signs, and severe dengue. Changes in cardiac functional parameters and hemodynamic indices were monitored over the hospital stay. Intervention: None. Measurements and Main Results: Patients with severe dengue had worse cardiac function compared with dengue in the form of left ventricular systolic dysfunction with increased left myocardial performance index (0.58 [0.26–0.80] vs. 0.38 [0.22–0.70], p = .006). Septal myocardial systolic velocities were reduced (6.4 [4.8–10] vs. 8.1 [6–13] cm/s, p = .01) as well as right ventricular systolic (11.4 [7.5–17] vs. 13.5 [10–17] cm/s, p = .016) and diastolic velocities (13 [8–23] vs. 17 [12–25] cm/s, p = .0026). In the severe group, these parameters improved from hospital admission to discharge; septal myocardial systolic velocities to 8.8 (7–11) cm/s (p = .002), right ventricular myocardial systolic velocities to 15.0 (11.8–23) cm/s, (p = .003), and diastolic velocity to 21 (11–25) cm/s (p = .002). Patients with cardiac impairment were more likely to have significant pleural effusions. Conclusions: Patients with severe dengue have evidence of systolic and diastolic cardiac impairment with septal and right ventricular wall being predominantly affected.
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| 10. |
- Abdulla, Salim, et al.
(författare)
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Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative : an individual patient data meta-analysis
- 2015
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Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance, and to assess the relationships between parasite clearance and risk of recrudescence during follow-up. Methods: Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC1/2 and risk of recrudescence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive. Results: PC1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28-63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC1/2 > 5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC1/2 by 8.1 % (95 % CI 3.2-12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC1/2 (HR = 2.91, 95 % CI 1.95-4.34 for twofold increase, p < 0.001) and high initial parasitaemia (HR = 2.23, 95 % CI 1.44-3.45 for tenfold increase, p < 0.001) were associated independently with an increased risk of recrudescence. In western Cambodia, the region with the highest prevalence of artemisinin resistance, there was no evidence for increasing PC1/2 since 2007. Conclusions: Several factors affect PC1/2. As substantial heterogeneity in parasite clearance exists between locations, early detection of artemisinin resistance requires reference PC1/2 data. Studies with frequent parasite count measurements to characterize PC1/2 should be encouraged. In western Cambodia, where PC1/2 values are longest, there is no evidence for recent emergence of higher levels of artemisinin resistance.
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