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1.
PLoS One ; 19(7): e0301319, 2024.
Article in English | MEDLINE | ID: mdl-39042640

ABSTRACT

BACKGROUND: Heart failure (HF) is becoming a growing public health concern. Diagnostic tests for determining the severity of HF often come with high costs and require specialized expertise, which makes it difficult to assess HF severity, especially in low-income countries or at primary healthcare facilities. Recently, red blood cell distribution width (RDW) has emerged as a promising, easily accessible marker associated with HF severity. The study aimed to assess changes in RDW levels in HF patients and the diagnostic value of RDW in detecting acute heart failure (AHF) among HF patients. METHODS: We conducted a cross-sectional examination involving 351 participants divided into HF and non-HF cohorts. HF was defined and categorized according to the diagnostic and treatment guidelines for AHF and chronic heart failure (CHF) set forth by the European Society of Cardiology (2021). Univariate and multivariate analysis of factors associated with AHF was performed. RESULTS: The study revealed that HF patients displayed higher median RDW levels (14.90% [13.70-17.00]) compared to non-HF individuals (13.00% [12.23-13.78]). RDW was notably elevated in HF patients with left ventricular ejection fraction < 50% compared to those with left ventricular ejection fraction ≥ 50%. ROC curve analysis of RDW for AHF detection identified a cutoff value of 13.85%, with a sensitivity of 86.05% and specificity of 47.18%, statistically significant at p < 0.001. RDW > 13.85% was identified as an independent risk factor for AHF in patients with HF, with odds ratios of 2.644 (95% CI, 1.190-5.875; p = 0.017). CONCLUSION: The study revealed significant RDW variations in patients with CHF and AHF compared to the control group. These findings suggest that RDW could be a biomarker for detecting HF severity.


Subject(s)
Erythrocyte Indices , Heart Failure , Humans , Heart Failure/blood , Heart Failure/diagnosis , Female , Cross-Sectional Studies , Male , Middle Aged , Aged , Vietnam/epidemiology , Erythrocytes/pathology , ROC Curve , Biomarkers/blood , Stroke Volume , Southeast Asian People
2.
J Med Chem ; 67(7): 5216-5232, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38527911

ABSTRACT

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) protein. This epithelial anion channel regulates the active transport of chloride and bicarbonate ions across membranes. Mutations result in reduced surface expression of CFTR channels with impaired functionality. Correctors are small molecules that support the trafficking of CFTR to increase its membrane expression. Such correctors can have different mechanisms of action. Combinations may result in a further improved therapeutic benefit. We describe the identification and optimization of a new pyrazolol3,4-bl pyridine-6-carboxylic acid series with high potency and efficacy in rescuing CFTR from the cell surface. Investigations showed that carboxylic acid group replacement with acylsulfonamides and acylsulfonylureas improved ADMET and PK properties, leading to the discovery of the structurally novel co-corrector GLPG2737. The addition of GLPG2737 to the combination of the potentiator GLPG1837 and C1 corrector 4 led to an 8-fold increase in the F508del CFTR activity.


Subject(s)
Cystic Fibrosis , Humans , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Mutation , Cell Membrane/metabolism , Carboxylic Acids/therapeutic use , Benzodioxoles/pharmacology , Aminopyridines/therapeutic use
3.
RSC Adv ; 12(55): 35730-35743, 2022 Dec 12.
Article in English | MEDLINE | ID: mdl-36545079

ABSTRACT

Although medicinal herbs contain many biologically active ingredients that can act as antibiotic agents, most of them are difficult to dissolve in lipids and absorb through biofilms in the gastrointestinal tract. Besides, silver nanoparticles (AgNPs) have been widely used as a potential antibacterial agent, however, to achieve a bactericidal effect, high concentrations are required. In this work, AgNPs were combined into plant-based antibiotic nanoemulsions using biocompatible alginate/carboxyl methylcellulose scaffolds. The silver nanoparticles were prepared by a green method with an aqueous extract of Allium sativum or Phyllanthus urinaria extract. The botanical antibiotic components in the alcoholic extract of these plants were encapsulated with emulsifier poloxamer 407 to reduce the particle size, and make the active ingredients both water-soluble and lipid-soluble. Field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray (EDX) analysis showed that the prepared nanosystems were spherical with a size of about 20 nm. Fourier transform infrared spectroscopy (FTIR) confirmed the interaction of the extracts and the alginate/carboxyl methylcellulose carrier. In vitro drug release kinetics of allicin and phyllanthin from the nanosystems exhibited a retarded release under different biological pH conditions. The antimicrobial activity of the synthesized nanoformulations were tested against Escherichia coli. The results showed that the nanosystem based on Allium sativum possesses a significantly higher antimicrobial activity against the tested organisms. Therefore, the combination of AgNPs with active compounds from Allium sativum extract is a good candidate for in vivo infection treatment application.

4.
Oxid Med Cell Longev ; 2022: 5262677, 2022.
Article in English | MEDLINE | ID: mdl-35633880

ABSTRACT

Parkinson's disease (PD) is characterized by progressive locomotive defects and loss of dopaminergic neurons. Polyscias fruticosa leaves are used by Vietnamese as herbal medicines to support the treatment of some diseases related to neurodegeneration such as Parkinson's and Alzheimer's diseases. However, recent scientific data have not provided sufficient evidence for the use of P. fruticosa leaves to treat PD or decelerate PD progression. In the present study, the capacity of P. fruticosa leaf extract for PD treatment on the dietary supplementation was investigated using dUCH-knockdown Drosophila model. The results indicated that P. fruticosa leaf extract decelerated dopaminergic neuron degeneration induced by dUCH knockdown in not only the larval stage but also the adult stage, which might result in the amelioration in locomotor ability of dUCH-knockdown larvae and flies. Furthermore, antioxidant activities and some key phytochemicals such as saponins, polyphenols, and flavonoids that might contribute to the effects of the P. fruticosa leaf extract were identified.


Subject(s)
Araliaceae , Parkinson Disease , Animals , Dopaminergic Neurons , Drosophila , Drosophila melanogaster , Parkinson Disease/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use
5.
J Biosci Bioeng ; 134(1): 41-47, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35589487

ABSTRACT

In aquaculture systems, the treatment of nitrogen pollution has always been a center of attention due to its impact on productiveness. The bioremediation method based on simultaneous nitrification and denitrification was often used to effectively remove ammonium, nitrite, and nitrate compounds. In addition, the attachment and biofilm formation of the nitrogen-converting bacteria on carriers had superior removal efficiency over the suspended bacteria. Thus, this study focused on the fabrication of a porosity floatable expanded clay (EC) carrier that provided the basic structure for the immobilization of the nitrifiers Nitrosomonas sp., Nitrobacter sp., and the denitrifier Bacillus sp. The EC was also coated with alginate and essential nutrient to support the cohesion and growth of bacteria. Especially, the selected Bacillus sp. previously proved was able to reduce nitrite/nitrate in aerobic conditions. The co-immobilization of these three aerobic bacteria on the prepared carrier would simply the treatment process in practical use. Initial results showed that the integration of essential nutrients (N, P, K) on alginate coated EC (EC_Alg_N) increased bacterial density to (57 ± 3) × 107 - (430 ± 30) × 108 CFU/g, which then led to the enhancement of removal efficiency up to 91.62 ± 0.67% in the medium containing initial nitrogen content of 60 mg-N/L. The nitrogen removal efficacy of bacterial immobilized EC_Alg_N remained at 83.95 ± 0.15% after being reused for 6 cycles. In conclusion, the bacterial immobilized EC_Alg_N could be a potential material for nitrogen polluted wastewater treatment in aquaculture systems.


Subject(s)
Bacillus , Nitrogen , Aerobiosis , Alginates , Aquaculture , Bacteria/genetics , Clay , Denitrification , Nitrates , Nitrification , Nitrites/chemistry , Nitrogen/chemistry , Wastewater/microbiology
6.
Materials (Basel) ; 15(6)2022 Mar 10.
Article in English | MEDLINE | ID: mdl-35329508

ABSTRACT

The high electron mobility transistor (HEMT) structures on Si (111) substrates were fabricated with heavily Fe-doped GaN buffer layers by metalorganic chemical vapor deposition (MOCVD). The heavy Fe concentrations employed for the purpose of highly insulating buffer resulted in Fe segregation and 3D island growth, which played the role of a nano-mask. The in situ reflectance measurements revealed a transition from 2D to 3D growth mode during the growth of a heavily Fe-doped GaN:Fe layer. The 3D growth mode of Fe nano-mask can effectively annihilate edge-type threading dislocations and improve transfer properties in the channel layer, and consequently decrease the vertical leakage current by one order of magnitude for the applied voltage of 1000 V. Moreover, the employment of GaN:C film on GaN:Fe buffer can further reduce the buffer leakage-current and effectively suppress Fe diffusion.

7.
Nanomaterials (Basel) ; 11(7)2021 Jul 07.
Article in English | MEDLINE | ID: mdl-34361152

ABSTRACT

The effect of Mg doping on the electrical and optical properties of the p-GaN/AlGaN structures on a Si substrate grown by metal organic chemical vapor deposition was investigated. The Hall measurement showed that the activation efficiency of the sample with a 450 sccm Cp2Mg flow rate reached a maximum value of 2.22%. No reversion of the hole concentration was observed due to the existence of stress in the designed sample structures. This is attributed to the higher Mg-to-Ga incorporation rate resulting from the restriction of self-compensation under compressive strain. In addition, by using an AlN interlayer (IL) at the interface of p-GaN/AlGaN, the activation rate can be further improved after the doping concentration reaches saturation, and the diffusion of Mg atoms can also be effectively suppressed. A high hole concentration of about 1.3 × 1018 cm-3 can be achieved in the p-GaN/AlN-IL/AlGaN structure.

8.
J Med Chem ; 63(22): 13526-13545, 2020 11 25.
Article in English | MEDLINE | ID: mdl-32902984

ABSTRACT

GPR84 is a medium chain free fatty acid-binding G-protein-coupled receptor associated with inflammatory and fibrotic diseases. As the only reported antagonist of GPR84 (PBI-4050) that displays relatively low potency and selectivity, a clear need exists for an improved modulator. Structural optimization of GPR84 antagonist hit 1, identified through high-throughput screening, led to the identification of potent and selective GPR84 inhibitor GLPG1205 (36). Compared with the initial hit, 36 showed improved potency in a guanosine 5'-O-[γ-thio]triphosphate assay, exhibited metabolic stability, and lacked activity against phosphodiesterase-4. This novel pharmacological tool allowed investigation of the therapeutic potential of GPR84 inhibition. At once-daily doses of 3 and 10 mg/kg, GLPG1205 reduced disease activity index score and neutrophil infiltration in a mouse dextran sodium sulfate-induced chronic inflammatory bowel disease model, with efficacy similar to positive-control compound sulfasalazine. The drug discovery steps leading to GLPG1205 identification, currently under phase II clinical investigation, are described herein.


Subject(s)
Drug Discovery/methods , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/metabolism , Acetates/chemistry , Acetates/pharmacology , Allosteric Regulation/drug effects , Allosteric Regulation/physiology , Animals , Caco-2 Cells , Cells, Cultured , Dogs , Drug Evaluation, Preclinical/methods , Female , HEK293 Cells , Humans , Male , Mice , Mice, Inbred BALB C , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Rats , Rats, Sprague-Dawley
9.
Sci Rep ; 10(1): 12972, 2020 Jul 31.
Article in English | MEDLINE | ID: mdl-32737426

ABSTRACT

Two-dimensional (2D) layered GaSe films were grown on GaAs (001), GaN/Sapphire, and Mica substrates by molecular beam epitaxy (MBE). The in situ reflective high-energy electron diffraction monitoring reveals randomly in-plane orientations of nucleated GaSe layers grown on hexagonal GaN/Sapphire and Mica substrates, whereas single-orientation GaSe domain is predominant in the GaSe/GaAs (001) sample. Strong red-shifts in the frequency of in-plane [Formula: see text] vibration modes and bound exciton emissions observed from Raman scattering and photoluminescence spectra in all samples are attributed to the unintentionally biaxial in-plane tensile strains, induced by the dissimilarity of symmetrical surface structure between the 2D-GaSe layers and the substrates during the epitaxial growth. The results in this study provide an important understanding of the MBE-growth process of 2D-GaSe on 2D/3D hybrid-heterostructures and pave the way in strain engineering and optical manipulation of 2D layered GaSe materials for novel optoelectronic integrated technologies.

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