Lipids and Alzheimer's Disease Kao, Yu-Chia; Ho, Pei-Chuan; Tu, Yuan-Kun ...
International journal of molecular sciences,
02/2020, Letnik:
21, Številka:
4
Journal Article
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Lipids, as the basic component of cell membranes, play an important role in human health as well as brain function. The brain is highly enriched in lipids, and disruption of lipid homeostasis is ...related to neurologic disorders as well as neurodegenerative diseases such as Alzheimer's disease (AD). Aging is associated with changes in lipid composition. Alterations of fatty acids at the level of lipid rafts and cerebral lipid peroxidation were found in the early stage of AD. Genetic and environmental factors such as apolipoprotein and lipid transporter carrying status and dietary lipid content are associated with AD. Insight into the connection between lipids and AD is crucial to unraveling the metabolic aspects of this puzzling disease. Recent advances in lipid analytical methodology have led us to gain an in-depth understanding on lipids. As a result, lipidomics have becoming a hot topic of investigation in AD, in order to find biomarkers for disease prediction, diagnosis, and prevention, with the ultimate goal of discovering novel therapeutics.
Estrogen deficiency is one of the main causes of postmenopausal osteoporosis in elderly women. Hormone replacement therapy has been employed to manage postmenopausal osteoporosis; however, it has ...raised concerns related to heart attacks and breast cancer. Sesame oil has been reported to affect sex hormone status. The aim of the present study is to evaluate the effect of sesame oil supplement on postmenopausal osteoporosis in rats. We used female Sprague Dawley rats that underwent bilaterally ovariectomy (OVX) as an experimental postmenopausal osteoporosis animal model. These rats were orally administrated sesame oil (0.25 or 0.5 mL/kg/day) for four months as the therapeutic group. We assessed bone mineral density (BMD) and the levels of osteocalcin, procollagen-I C-terminal propeptide (PICP), collagen cross-linked N-telopeptide (NTx), estradiol, and aromatase in the sera. The daily supplementation of sesame oil significantly increased BMD, serum osteocalcin levels, and trabecular areas in the OVX-treated rats. Sesame oil also elevated serum PICP levels and decreased NTx levels in these rats. Furthermore, sesame oil effectively maintained serum estradiol and aromatase levels in the OVX-induced osteoporosis rats. In conclusion, daily supplementation of sesame oil prevents postmenopausal osteoporosis by maintaining serum estrogen and aromatase levels, while also modulating the imbalance between bone formation and resorption in osteoporosis rats.
Emerging evidence has indicated that the perturbed expression of homocysteine (Hcy) may induce mitochondrial dysfunction and disturb bone metabolism. Sirtuin 1 (SIRT1) and AMP-activated protein ...kinase (AMPK) are two critical sensors that regulate mitochondrial biogenesis and have been recognized as therapeutic targets in osteoarthritis (OA). This study was designed to test whether Hcy caused pro-osteoarthritic changes through modulation of SIRT1 and AMPK. Our results showed that administration of Hcy reduced the SIRT1/AMPK/PGC-1α signaling in chondrocytes, leading to mitochondrial dysfunction as a result of increased oxidative stress and apoptosis. Moreover, we demonstrated that the expression of NF-κB, COX-2, IL-8, and MMP-13 were elevated subsequent to inhibition of SIRT1/AMPK/PGC-1α/PPAR-γ pathway by homocysteine, thereby causing detrimental effects on chondrocytes. In the animal model of diet-induced hyperhomocysteinemia (HHcy), we observed the similar findings that SIRT1/PGC-1α/PPAR-γ cascades were downregulated with elevated MMP-13 and COX-2. Taken together, data from the current study revealed that the reduced SIRT1 by Hcy may contribute to degradative cartilage process, which provided insight into the etiology of OA.
•Homocysteine-reduced SIRT1 leads to downregulation of phosphorylated AMPK and PGC-1α.•Homocysteine-inhibited SIRT1 results in mitochondrial dysfunction.•Homocysteine-induced oxidative stress is reversed by activation of SIRT1/AMPK/PGC-1α signaling.•Homocysteine-induced pro-apoptosis effect is rescued by overexpression of SIRT1/AMPK/PGC-1α cascades.•Expression levels of pro-inflammatory mediators and MMP13 are elevated subsequent to suppression of PPAR-γ by homocysteine.
Rheumatoid arthritis (RA) is a chronic inflammatory condition known for its irreversible destructive impact on the joints. Chondrocytes play a pivotal role in the production and maintenance of the ...cartilage matrix. However, the presence of inflammatory cytokines can hinder chondrocyte proliferation and promote apoptosis. Isoliquiritigenin (ISL), a flavonoid, potentially exerts protective effects against various inflammatory diseases. However, its specific role in regulating the nuclear factor E2-associated factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in chondrocytes in RA remains unclear. To investigate this, this study used human chondrocytes and Sprague-Dawley rats to construct in vitro and in vivo RA models, respectively. The study findings reveal that cytokines markedly induced oxidative stress, the activation of matrix metalloproteinases, and apoptosis both in vitro and in vivo. Notably, ISL treatment significantly mitigated these effects. Moreover, Nrf2 or HO-1 inhibitors reversed the protective effects of ISL, attenuated the expression of Nrf2/HO-1 and peroxisome proliferator-activated receptor gamma-coactivator-1α, and promoted chondrocyte apoptosis. This finding indicates that ISL primarily targets the Nrf2/HO-1 pathway in RA chondrocytes. Moreover, ISL treatment led to improved behavior scores, reduced paw thickness, and mitigated joint damage as well as ameliorated oxidative stress in skeletal muscles in an RA rat model. In conclusion, this study highlights the pivotal role of the Nrf2/HO-1 pathway in the protective effects of ISL and demonstrates the potential of ISL as a treatment option for RA.
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●Isoliquiritigenin ameliorates rheumatoid arthritis via suppressing apoptosis in vitro and in vivo.●Isoliquiritigenin alleviates oxidative stress in rheumatoid arthritis chondrocytes and skeletal muscles.●Isoliquiritigenin treatment led to improved behavior scores, and mitigated joint damage in rat rheumatoid arthritis model.●Isoliquiritigenin protects against rheumatoid arthritis-induced oxidative stress via regulating Nrf2/HO-1 pathway.
Inhibiting osteoclasts and osteoclast precursors to reduce bone resorption is an important strategy to treat osteoclast-related diseases, such as osteoporosis, inflammatory bone loss, and malignant ...bone metastasis. However, the mechanism by which apoptosis is induced in the osteoclasts and their precursors are not completely understood. Here, we used nitrogen-containing bisphosphonate zoledronic acid (ZA) to induce cell apoptosis in human and murine osteoclast precursors and mature osteoclast-like cells. Caspase-3-mediated cell apoptosis occurred following the ZA (100 μM) treatment. Reactive oxygen species (ROS) were also generated in a time-dependent manner. Following knock-down of the p47
expression, which is required for ROS activation, or co-treatment with the ROS inhibitor, N-acetyl-L-cysteine, ZA-induced apoptosis was significantly suppressed in both osteoclast precursors and mature osteoclast-like cells. The ROS-activated mitogen-activated protein kinases pathways did not trigger cell apoptosis. However, a ROS-regulated Mcl-1 decrease simultaneously with glycogen synthase kinase (GSK)-3β promoted cell apoptosis. These findings show that ZA induces apoptosis in osteoclast precursors and mature osteoclast-like cells by triggering ROS- and GSK-3β-mediated Mcl-1 down-regulation.
Osteoarthritis (OA) is a degenerative joint disease affecting a large population of people. Although the elevated expression of PKR (double stranded RNA-dependent protein kinase) and MMP-13 ...(collagenase-3) have been indicated to play pivotal roles in the pathogenesis of OA, the exact mechanism underlying the regulation of MMP-13 by PKR following inflammatory stimulation was relatively unknown. The purpose of this study was to determine the signaling pathway involved in the PKR-mediated induction of MMP-13 after TNF-α-stimulation. In this study, cartilages of knee joint were obtained from OA subjects who underwent arthroplastic knee surgery. Cartilages were used for tissue analysis or for chondrocytes isolation. In results, the upregulated expression of PKR was observed in damaged OA cartilages as well as in TNF-α-stimulated chondrocytes. Phosphorylation of PKC (protein kinase C) was found after TNF-α administration or PKR activation using poly(I:C), indicating PKC was regulated by PKR. The subsequent increased activity of NADPH oxidase led to oxidative stress accumulation and antioxidant capacity downregulation followed by an exaggerated inflammatory response with elevated levels of COX-2 and IL-8 via ERK/NF-κB pathway. Activated ERK pathway also impeded the inhibition of MMP-13 by PPAR-γ. These findings demonstrated that TNF-α-induced PKR activation triggered oxidative stress-mediated inflammation and MMP-13 in human chondrocytes. Unraveling these deregulated signaling cascades will deepen our knowledge of OA pathophysiology and provide aid in the development of novel therapies.
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Studies investigating the performance of self‐care and visual perception in young children with autism spectrum disorder (ASD) are limited. The relationship between self‐care performance and visual ...perception ability in young children with ASD is not yet clearly understood. Here, self‐care performance was evaluated by the caregivers and therapists of children with ASD. The differences in self‐care performance and visual perception ability were investigated in 66 children with ASD and 66 typically developing (TD) children between the ages of 48–83 months. The relationships between self‐care and visual perception were tested in both two groups. The Assessment of Motor and Process Skills (AMPS) and the Chinese version of the Pediatric Evaluation of Disability Inventory (PEDI‐C) were used to assess the children's self‐care performance. The Test of Visual Perceptual Skills‐Third Edition (TVPS‐3) and the Developmental Test of Visual Perception‐Third Edition (DTVP‐3) were used to evaluate visual perception ability. Young children with ASD obtained significantly lower scores for self‐care performance (AMPS and PEDI‐C) and visual perception ability (TVPS‐3 and DTVP) compared with TD children. Additionally, positive correlations were found between self‐care performance and visual perception ability in young children with ASD. The results provide a valuable contribution to our understanding about self‐care and visual perception performance of young children with ASD. The findings of this research highlight the need for pediatric practitioners to include self‐care and visual‐motor integration evaluations for young children with ASD.
Lay Summary
Young children with ASD obtained significantly lower scores for self‐care performance and visual perception ability compared with TD children. Positive correlations were found between self‐care performance and visual perception ability in young children with ASD. The results provide a valuable contribution to our understanding about self‐care and visual perception performance of young children with ASD.
This book offers a homogeneous presentation of the many faces of non-equilibrium thermodynamics. The first part is devoted to a description of the nowadays thermodynamic formalism recognized as the ...classical theory of non-equilibrium processes. This part of the book may serve as a basis to an introductory course dedicated to first-year graduate students in sciences and engineering. The classical description can however not be complete, as it rests on the hypothesis of local equilibrium. This has fostered the development of many theories going beyond local equilibrium and which cannot be put aside. The second part of the book is concerned with these different approaches, and will be of special interest for PhD students and researchers. For the sake of homogeneity, the authors have used the general structure and methods presented in the first part. Indeed, besides their differences, all these formalisms are not closed boxes but present some overlappings and parallelisms which are emphasized in this book. For pedagogical reasons, some problems have been analysed within the different formalisms to underline their differences and their convergences.
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