• The Korean Journal of Food And Nutrition
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• v.33 no.3
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• pp.347-355
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• 2020

Cognitive impairment is considered to be key research topics in the field of neurodegenerative diseases and in understanding of learning and memory. In the present study, we investigated neuroprotective effects of Schisandra chinensis (SC) and Ribes fasciculatum (RF) extracts in hydrogen peroxide-induced neuronal cell death in vitro and scopolamine-induced cognitive impairment in Sprague Dawley^® (SD) rat in vivo. Apoptotic cell death in neuroblastic PC12 cell line was induced by hydrogen peroxide for 1 hour at 100 μM. However, mixture of SC and RF treatment prevented peroxide induced PC12 cell death with no neurotoxic effects. For in vivo experiment, the effect of SC and RF extracts on scopolamine-induced cognitive impairment in SD rat was evaluated by spontaneous alternation behavior in Y-Maze test. After 30 min scopolamine injection, the scopolamine-induced rats presented significantly decreased % spontaneous alteration and acetylcholine level, compared to non-induced group. However, treatment of SC+RF extracts rescued the reduced % spontaneous alteration with acetylcholine concentration from hippocampus in scopolamine-induced rats. These results suggested that mixture of SC and RF extract may be a potential natural therapeutic agent for the prevention of cognitive impairment.

• BMB Reports
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• v.42 no.8
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• pp.475-481
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• 2009

Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer's disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second major mechanism of cognitive impairment has been linked to obesity and Type 2 diabetes (T2DM). Human and experimental animal studies revealed that neurodegeneration associated with peripheral insulin resistance is likely effectuated via a liver-brain axis whereby toxic lipids, including ceramides, cross the blood brain barrier and cause brain insulin resistance, oxidative stress, neuro-inflammation, and cell death. In essence, there are dual mechanisms of brain insulin resistance leading to AD-type neurodegeneration: one mediated by endogenous, CNS factors; and the other, peripheral insulin resistance with excess cytotoxic ceramide production.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.381-388
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• 2020

Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to drug addiction and causes serious health complications, including attention deficit, memory loss and cognitive decline. These neurological complications are strongly associated with METH-induced neurotoxicity and neuroinflammation, which leads to neuronal cell death. The current review investigates the molecular mechanisms underlying METH-mediated neuronal damages. Our analysis demonstrates that the process of neuronal impairment by METH is closely related to oxidative stress, transcription factor activation, DNA damage, excitatory toxicity and various apoptosis pathways. Thus, we reach the conclusion here that METH-induced neuronal damages are attributed to the neurotoxic and neuroinflammatory effect of the drug. This review provides an insight into the mechanisms of METH addiction and contributes to the discovery of therapeutic targets on neurological impairment by METH abuse.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.108-111
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• 2003

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra. While its precise etiology is unknown, such factors as oxidative stress, impairment of mitochondrial respiration, excitotoxicity and inflammation may play roles in its pathogenesis. Although the role of apoptosis in the process of dopaminergic neuronal death has been highlighted in studies using postmortem brains and experimental models of PD, other evidence implicates both apoptosis and non-apoptotic death in PD. (omitted)

• International Journal of Oral Biology
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• v.49 no.2
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• pp.27-33
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• 2024

Diabetes, a chronic hyperglycemic condition, is caused by insufficient insulin secretion or functional impairment. Long-term inadequate regulation of blood glucose levels or hyperglycemia can lead to various complications, such as retinopathy, nephropathy, and cardiovascular disease. Recent studies have explored the molecular mechanisms linking diabetes to bone loss and an increased susceptibility to fractures. This study reviews the characteristics and molecular mechanisms of diabetes-induced bone disease. Depending on the type of diabetes, changes in bone tissue vary. The molecular mechanisms responsible for bone loss in diabetes include the accumulation of advanced glycation end products (AGEs), upregulation of inflammatory cytokines, induction of oxidative stress, and deficiencies in insulin/IGF-1. In diabetes, alveolar bone loss results from complex interactions involving oral bacterial infections, host responses, and hyperglycemic stress in periodontal tissues. Therapeutic strategies for diabetes-induced bone loss may include blocking the AGEs signaling pathway, decreasing inflammatory cytokine activity, inhibiting reactive oxygen species generation and activity, and controlling glucose levels; however, further research is warranted.

• YAKHAK HOEJI
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• v.8 no.1
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• pp.12-29
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• 1964

The oral administration of deer horn extract was proved to cause a considerable amelioration to the impairment of hepatic oxidative phosphorylation and to the decrease of ATP content in liver tissue induced by cholesterol ingestion. Deer horn extract was shown to accelerate considerably incorporation of acetate-1-C$^{14}$ into cholesterol in liver tissue and it tends to restore a decrease of GOT activity of liver tissue, caused by cholesterol administration. Histological examination showed that deer horn extract had a remarkable preventive effect against fatty infiltration of organs such as liver, heart, spleen, and adrenal gland of cholesterol given rabbits.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5031-5035
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• 2013

Zizyphus spina-christi (ZSC) fruit is a rich source of bioactive compounds but any medicinal properties in chemoprevention of colon cancer have hitherto not been studied. The aim of the present study was to examine in vivo protective effects of ZSC water extract on colon carcinogenesis in azoxymethane (AOM)-treated rats. Our results showed that ZSC significantly reduced AOM-induced colonic aberrant crypt foci development and AOM-induced oxidative stress as indicated by restoration of endogenous glutathione depletion and abrogating the impairment of total antioxidant capacity. Caspase-3 cleavage, which has been considered as an apoptotic index, was almost undetectable in AOM-treated rats and ZSC exhibited pro-apoptotic effects evidenced by increased levels of cleaved caspase-3. In the studied model, our findings provide the first in vivo evidence that ZSC extract could inhibit the early stage of colon carcinogenesis by preventing oxidative stress and inducing apoptosis.

• Biomolecules & Therapeutics
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• v.20 no.4
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• pp.357-370
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• 2012

Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major significance in tumor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large field or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional deficits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a significant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cellular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the identification of novel therapeutic targets. Specifically, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-inflammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defining a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy.

• Nutrition Research and Practice
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• v.16 no.2
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• pp.147-160
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• 2022

BACKGROUND/OBJECTIVES: Patients with chronic kidney disease (CKD) have a high concentration of uremic toxins in their blood and often experience muscle atrophy. Indoxyl sulfate (IS) is a uremic toxin produced by tryptophan metabolism. Although an elevated IS level may induce muscle dysfunction, the effect of IS on physiological concentration has not been elucidated. Additionally, the effects of ursolic acid (UA) on muscle hypertrophy have been reported in healthy models; however, it is unclear whether UA ameliorates muscle dysfunction associated with chronic diseases, such as CKD. Thus, this study aimed to investigate whether UA can improve the IS-induced impairment of mitochondrial biogenesis. MATERIALS/METHODS: C2C12 cells were incubated with or without IS (0.1 mM) and UA (1 or 2 μM) to elucidate the physiological effect of UA on CKD-related mitochondrial dysfunction and its related mechanisms using real-time reverse transcription-polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. RESULTS: IS suppressed the expression of differentiation marker genes without decreasing cell viability. IS decreased the mitochondrial DNA copy number and ATP levels by downregulating the genes pertaining to mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam, Sirt1, and Mef2c), fusion (Mfn1 and Mfn2), oxidative phosphorylation (Cycs and Atp5b), and fatty acid oxidation (Pdk4, Acadm, Cpt1b, and Cd36). Furthermore, IS increased the intracellular mRNA and secretory protein levels of interleukin (IL)-6. Finally, UA ameliorated the IS-induced impairment in C2C12 cells. CONCLUSIONS: Our results indicated that UA improves the IS-induced impairment of mitochondrial biogenesis by affecting differentiation, ATP levels, and IL-6 secretion in C2C12 cells. Therefore, UA could be a novel therapeutic agent for CKD-induced muscle dysfunction.

• Preventive Nutrition and Food Science
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• v.20 no.3
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• pp.198-203
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• 2015

The present study was conducted to assess the status of vitamin C among healthy young adults in relation to serum antioxidant parameters [glutathione (GSH), thiols, and total antioxidant capacity, (TAC)], and oxidative stress markers [malondialdehyde (MDA), and nitrites plus nitrates (NN)]. A prospective study included 200 young adults, and their dietary intake was assessed by using food diaries. Fasting plasma vitamin C, serum levels of GSH, thiols, TAC, MDA, and NN were measured using biochemical assays. It was observed that 38% of the enrolled subjects, n=76, had an adequate dietary intake of vitamin C (ADI group). Meanwhile, 62%, n=124, had a low dietary intake of vitamin C (LDI group) as compared to the recommended dietary allowances. The fasting plasma level of vitamin C was significantly higher in the ADI group as compared to the LDI group. Oxidative stress in the sera of the LDI group was evidenced by depletion of GSH, low thiols levels, impairment of TAC, an elevation of MDA, and increased NN. In the ADI group, positive correlations were found between plasma vitamin C and serum antioxidant parameters (GSH, thiols, and TAC). Meanwhile, the plasma vitamin C was negatively correlated with serum MDA and NN levels. This study reveals a significant increase of oxidative stress status and reduced antioxidant capacity in sera from healthy young adults with low intake of the dietary antioxidant, vitamin C.