Scope
Endothelial dysfunction is an important mechanism in the development of atherosclerosis and is thought to be critical for predicting cardiovascular diseases. Previous reports suggested that ...chlorogenic acid (CGA) is a potent antioxidant and anti‐inflammatory compound. The molecular mechanisms underlying the inhibitory effects of CGA on oxLDL‐induced oxidative injuries in human endothelial cells are still largely unknown. This study is aimed to test the hypothesis that CGA protects against oxLDL‐facilitated oxidative stress by upregulating SIRT1 and to explore the role of AMPK/PGC‐1 pathway and mitochondrial biogenesis.
Methods and results
HUVECs were treated with oxLDL in the presence or absence of CGA pretreatment. Our data indicated that CGA pretreatment increased SIRT1 deacetylase activity levels. In addition, CGA reversed oxLDL‐impaired SIRT1 and AMPK/PGC‐1 activity and mitigated oxLDL‐induced oxidative stress and dysfunction of mitochondrial biogenesis. However, silencing SIRT1, AMPK, and PGC‐1 abated the ability of CGA to protect against oxidative stress. Results from the present study also suggested that CGA inhibits oxLDL‐induced endothelial apoptosis through modulating SIRT1 and AMPK/PGC‐1 function.
Conclusion
These findings provide new insights into possible molecular mechanisms by which CGA mitigates oxLDL‐induced endothelial oxidative stress and mitochondrial dysfunction by activating SIRT1 and modulating the AMPK/PGC‐1 signaling pathway.
Chlorogenic acid (CGA) is a potent antioxidant and anti‐inflammatory compound. This study found that CGA reduces oxLDL‐induced oxidative damage in human endothelial cells. The signaling transduction pathways of SIRT1‐mediated anti‐atherosclerotic effects involve maintaining mitochondrial biogenesis, thereby inhibiting ROS generation and oxidative stress and apoptosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Scope
Atherosclerotic cardiovascular disease is the most prevalent cause of mortality and morbidity. Fucoxanthin (FX) possesses anti‐hypertensive and anti‐obesity properties. However, the molecular ...mechanisms underlying the inhibitory effects of FX on oxidized low‐density lipoprotein (oxLDL)‐induced oxidative injuries in human endothelial cells are still largely unknown. This study aims to test the hypothesis that FX protects against oxLDL‐induced oxidative stress by upregulating AMP‐activated protein kinase (AMPK) and to explore the roles of cAMP response element binding protein (CREB) and peroxisome proliferator‐activated receptor gamma coactivator‐1α (PGC‐1α).
Methods and Results
Human umbilical vein endothelial cells are treated with oxLDL in the presence or absence of FX. FX significantly increases AMPK phosphorylation. In addition, FX diminishes oxLDL‐mediated nicotinamide adenine dinucleotide phosphate oxidase activation by inhibiting protein kinase C and subsequently inducing reactive oxygen species generation and impairing the activity of the endogenous antioxidant enzyme superoxidase dismutase. Furthermore, FX restores oxLDL‐mediated dephosphorylation of phosphoinositide‐3‐kinase/Akt and decreases CREB and PGC‐1α expression to nearly normal levels. Moreover, FX ameliorates the oxLDL‐mediated suppression of mitochondrial function and apoptosis.
Conclusion
These findings provide new insights into the possible molecular mechanisms by which FX mitigates oxLDL‐induced endothelial oxidative stress and mitochondrial dysfunction.
Fucoxanthin (FX) is a natural marine carotenoid derived from edible seaweeds such as brown seaweeds. In the present study, FX ameliorated oxidized low‐density lipoprotein‐induced oxidative damage to endothelial cells, as confirmed by the inhibition of nicotinamide adenine dinucleotide phosphate oxidase and subsequent reactive oxygen species generation and mitochondrial dysfunction.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Lamin B receptor (LBR) is a polytopic membrane protein residing in the inner nuclear membrane in association with the nuclear lamina. We demonstrate that human LBR is essential for cholesterol ...synthesis. LBR mutant derivatives implicated in Greenberg skeletal dysplasia or Pelger-Huët anomaly fail to rescue the cholesterol auxotrophy of a LBR-deficient human cell line, consistent with a loss-of-function mechanism for these congenital disorders. These disease-causing variants fall into two classes: point mutations in the sterol reductase domain perturb enzymatic activity by reducing the affinity for the essential cofactor NADPH, while LBR truncations render the mutant protein metabolically unstable, leading to its rapid degradation at the inner nuclear membrane. Thus, metabolically unstable LBR variants may serve as long-sought-after model substrates enabling previously impossible investigations of poorly understood protein turnover mechanisms at the inner nuclear membrane of higher eukaryotes.
Utilizing CO2 as one of the monomer resources, poly(vinylcyclohexene carbonates) (PVCHCs) are used as the precursor for preparing cationic PVCHCs (CPVCHCs) via thiol‐ene click functionalization. ...Through the functionalization, CPVCHC‐43 with a tertiary amine density of 43% relative to the backbone is able to display a significantly antibacterial ability against Staphylococcus aureus (S. aureus). Blending CPVCHC‐43 with polyacrylonitrile (PAN), CPVCHC/PAN nanofiber meshes (NFMs) have been successfully prepared by electrospinning. More importantly, two crucial fibrous structural factors including CPVCHC/PAN weight ratio and fiber diameter have been systematically investigated for the effects on the antibacterial performance of the NFMs. Sequentially, a quaternization treatment has been employed on the NFMs with an optimal fibrous structure to enhance the antibacterial ability. The resulting quaternized NFMs have demonstrated the great biocidal effects against Gram‐positive and Gram‐negative bacteria. Moreover, the excellent biocompatibility of the quaternized NFMs have also been thoroughly evaluated and verified.
Cationic poly(vinylcyclohexene carbonates) (CPVCHCs), a CO2‐based functional polycarbonate polymer, has been synthesized through ring‐opening copolymerization and thiol‐ene functionalization. CPVCHC/polyacrynolitrile nanofiber meshes (NFMs) with an optimal fibrous structure regarding the antibacterial ability have been prepared via electrospinning. The NFMs have been quaternized, and demonstrated their great biocidal effects against Gram‐positive and Gram‐negative bacteria. The quaternized NFMs have also exhibited excellent biocompatibility.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Galectin‐3, a biomarker linking oxidative stress and inflammation, participates in different mechanisms related to atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. ...Accumulating evidence indicates that galectin‐3 may also promote atherogenesis through inducing endothelial dysfunction. Lectin‐like oxidized low‐density lipoprotein (oxLDL) receptor‐1 (LOX‐1), a receptor for oxLDL uptake, contributes to oxLDL‐induced endothelial dysfunction. Whether galectin‐3 induces endothelial dysfunction through modulation of LOX‐1‐mediated signaling remains unclear. In the present study, we explored the mechanisms underlying galectin‐3 enhanced cytotoxicity of oxLDL in human umbilical vein endothelial cells (HUVECs) and the role of LOX‐1. Incubation of HUVECs with galectin‐3 increased the expression of LOX‐1 in RNA and protein levels. In addition, the expression of LOX‐1 induced by oxLDL was promoted by galectin‐3. However, pretreatment of LOX‐1 antibody reduced LOX‐1 mRNA expression level in cells with oxLDL plus galectin‐3 incubation. Compared to cells treated with oxLDL alone, reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and subsequent activation of p38 mitogen‐activated protein kinases followed by nuclear factor kappa B (NF‐κB) activation and related inflammatory responses including adhesion molecule expression, adhesiveness of monocytic cells, and IL‐8 release were also aggravated in cells treated with galectin‐3 combined with oxLDL. Compared to cells treated with galectin‐3 plus oxLDL group. We found that LOX‐1 antibody mitigated NADPH oxidase activity, p‐38 up‐regulation, NF‐κB activation, and proinflammatory responses in cells treated with galectin‐3 combined with oxLDL. We conclude that galectin‐3 enhances endothelial LOX‐1 expression and propose a new mechanism by which galectin‐3 may promote endothelial dysfunction by inducing inflammation via LOX‐1/ROS/p38/NF‐κB‐mediated signaling pathway.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Oxygen is essentially required by most eukaryotic organisms as a scavenger to remove harmful electron and hydrogen ions or as a critical substrate to ensure the proper execution of enzymatic ...reactions. All nucleated cells can sense oxygen concentration and respond to reduced oxygen availability (hypoxia). When oxygen delivery is disrupted or reduced, the organisms will develop numerous adaptive mechanisms to facilitate cells survived in the hypoxic condition. Normally, such hypoxic response will cease when oxygen level is restored. However, the situation becomes complicated if hypoxic stress persists (chronic hypoxia) or cyclic normoxia-hypoxia phenomenon occurs (intermittent hypoxia). A series of chain reaction-like gene expression cascade, termed hypoxia-mediated gene regulatory network, will be initiated under such prolonged or intermittent hypoxic conditions and subsequently leads to alteration of cellular function and/or behaviors. As a result, irreversible processes occur that may cause physiological disorder or even pathological consequences. A growing body of evidence implicates that hypoxia plays critical roles in the pathogenesis of major causes of mortality including cancer, myocardial ischemia, metabolic diseases, and chronic heart and kidney diseases, and in reproductive diseases such as preeclampsia and endometriosis. This review article will summarize current understandings regarding the molecular mechanism of hypoxia in these common and important diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Major Facilitator Superfamily (MFS) transporters play an important role in multidrug resistance in fungi. We report an AaMFS19 gene encoding a MFS transporter required for cellular resistance to ...oxidative stress and fungicides in the phytopathogenic fungus Alternaria alternata. AaMFS19, containing 12 transmembrane domains, displays activity toward a broad range of substrates. Fungal mutants lacking AaMFS19 display profound hypersensitivities to cumyl hydroperoxide, potassium superoxide, many singlet oxygen-generating compounds (eosin Y, rose Bengal, hematoporphyrin, methylene blue, and cercosporin), and the cell wall biosynthesis inhibitor, Congo red. AaMFS19 mutants also increase sensitivity to copper ions, clotrimazole, fludioxonil, and kocide fungicides, 2-chloro-5-hydroxypyridine (CHP), and 2,3,5-triiodobenzoic acid (TIBA). AaMFS19 mutants induce smaller necrotic lesions on leaves of a susceptible citrus cultivar. All observed phenotypes in the mutant are restored by introducing and expressing a wild-type copy of AaMFS19. The wild-type strain of A. alternata treated with either CHP or TIBA reduces radial growth and formation and germination of conidia, increases hyphal branching, and results in decreased expression of the AaMFS19 gene. The expression of AaMFS19 is regulated by the Yap1 transcription activator, the Hog1 and Fus3 mitogen-activated protein (MAP) kinases, the 'two component' histidine kinase, and the Skn7 response regulator. Our results demonstrate that A. alternata confers resistance to different chemicals via a membrane-bound MFS transporter.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nanofiber meshes (NFMs) loaded with therapeutic agents are very often employed to treat hard-to-heal wounds such as diabetic wounds. However, most of the NFMs have limited capability to load multiple ...or hydrophilicity distinctive-therapeutic agents. The therapy strategy is therefore significantly hampered. To tackle the innate drawback associated with the drug loading versatility, a chitosan-based nanocapsule-in-nanofiber (NC-in-NF) structural NFM system is developed for simultaneous loading of hydrophobic and hydrophilic drugs. Oleic acid-modified chitosan is first converted into NCs by the developed mini-emulsion interfacial cross-linking procedure, followed by loading a hydrophobic anti-inflammatory agent Curcumin (Cur) into the NCs. Sequentially, the Cur-loaded NCs are successfully introduced into reductant-responsive maleoyl functional chitosan/polyvinyl alcohol NFMs containing a hydrophilic antibiotic Tetracycline hydrochloride. Having a co-loading capability for hydrophilicity distinctive agents, biocompatibility, and a controlled release property, the resulting NFMs have demonstrated the efficacy on promoting wound healing either in normal or diabetic rats.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Existing literature has reported inequities in access to Canadian health care services among immigrants. The aim of this scoping review was (a) to explore research regarding Canadian immigrants’ ...unique experiences in accessing healthcare, and (b) to provide suggestions for future research and programming considering the identified immigrant-specific service gaps in health care. We searched MEDLINE, CINAHL, EMBASE, and Google Scholar, following the Arksey and O’Malley (2005) framework. The review’s findings suggest unmet health care access needs specific to immigrants in Canada, with the most common access barriers including communication, socioeconomic, and cultural barriers. The scoping review expands on the immigrant health care experiences and accessibility factors through a thematic analysis. Findings suggest that developing community-based programming, improving training for health care providers in culturally competent care, and policies that address the social determinants of health can improve health care accessibility among immigrants.
Cranberry, a polyphenol-rich functional food, is commonly used for the prophylaxis of urinary tract infections. Gefitinib, an anticancer agent clinically prescribed to treat non-small-cell lung ...cancer, is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and metabolized mainly by cytochrome P450 (CYP) 3A4 and CYP2D6. This study used gefitinib as a probe substrate to investigate the modulation of cranberry on P-gp, BCRP, CYP3A4 and CYP2D6. Rats were administered gefitinib with and without 5.0 g/kg of cranberry as juice (CJ). The concentration of gefitinib in serum was determined by LC-MS/MS. The results showed that CJ significantly increased the Cmax and AUC0-t of gefitinib by 28% and 55%, respectively. Mechanism studies indicated that CJ activated P-gp, and cranberry metabolites (CM) inhibited CYP2D6. Moreover, the protein level of P-gp in rat enterocytes was decreased, whereas that in hepatocytes was increased. In addition, the protein levels of BCRP, CYP3A4 and CYP2D6 in enterocytes and hepatocytes were decreased. In conclusion, CJ ingestion affected the activities and protein levels of P-gp, BCRP, CYP3A4 and CYP2D6.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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