11 research outputs found

    Reducing the Side-Effects of Cisplatin to Improve the Social Acceptance of Chemotherapy as CAM Adjunct in Cancer Treatment

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    Background:In sociology, the prevalence of cancer is interpreted as a broken social contract that requires behaviour change. Complementary and alternative medicine (CAM) is a vital social phenomenon, whose usage is socially patterned out. Perceptions of the limitations of chemotherapy and radiotherapy among cancer patients have contributed to the preference for CAM use, particularly plant-derived polysaccharides like HemoHIM, which contain cisplatin. This research was undertaken to show whether co-administration of vitamin C with cisplatin in chemotherapy can prevent or reduce the side-effects of cisplatin nephrotoxicity. Objectives:The objective of this study was to overturn social perceptions of conventional therapy as associated with nephrotoxicity. It investigates the renoprotective effects of high-dose vitamin C by performing an animal experiment to determine body weight, organ weight, and biochemical blood parameters; as well as to measure inflammatory cytokines. Design:Mice were randomly divided into five groups (control; and 500, 1000, and 2000 mg/kg of vitamin C with cisplatin). All groups except for the control group were intraperitoneally injected with 5- mg/kg cisplatin for 10 days, and the mice in the respective groups were orally administered each 500-, 1000-, 2000- mg/kg vitamin C 2 h prior to cisplatin treatment. After 10 days, the mice were sacrificed, and their blood samples and kidney tissues were obtainedfor further analysis. Setting and location:Republic of Korea Methods:Blood samples from animal experiments and tissue preparation were analyzed using real-time quantitative polymerase chain reaction. Results:The intraperitoneal injection of cisplatinreduced body weight, and elevated levels of blood urea nitrogen, serum creatinine, and uric acid. It also triggered an inflammatory response in the mouse kidney by inducing the pro-inflammatory cytokines TNFα, IL-6, and IL-1β and increasing in the expression of iNOS, and IL-4. Renal injury was decreased by the administration of vitamin C; the oral administration of vitamin C (500, 1000, 2000 mg/kg) decreased or normalized the renal function through the attenuation of cisplatin-induced inflammatory cytokines and the modulation of biochemical parameters (ALT, AST, cholesterol, TG, HDL, LDL, blood urea nitrogen, creatinine, and Uric acid) following the intraperitoneal injection of cisplatin. Conclusion:The results of our present study suggest that the co-administration of vitamin C with cisplatin chemotherapy is a promising method to prevent or reduce the side effects of cisplatin nephrotoxicity. These findings can remodel how the Korean society thinks, approaches and fights cancer by showing how nephrotoxicity can be counteracted to ensure social acceptance of CAM as an adjunctive to cisplatin therapy. Keywords:Complementary and alternative medicine, CAM, Vitamin C, Renoprotective therapy, Cisplatin, Nephrotoxicity, High-dose vitamin C DOI: 10.7176/JHMN/81-11 Publication date:October 31st 2020

    Pyruvate Dehydrogenase Kinase Is a Metabolic Checkpoint for Polarization of Macrophages to the M1 Phenotype

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    Metabolic reprogramming during macrophage polarization supports the effector functions of these cells in health and disease. Here, we demonstrate that pyruvate dehydrogenase kinase (PDK), which inhibits the pyruvate dehydrogenase-mediated conversion of cytosolic pyruvate to mitochondrial acetyl-CoA, functions as a metabolic checkpoint in M1 macrophages. Polarization was not prevented by PDK2 or PDK4 deletion but was fully prevented by the combined deletion of PDK2 and PDK4; this lack of polarization was correlated with improved mitochondrial respiration and rewiring of metabolic breaks that are characterized by increased glycolytic intermediates and reduced metabolites in the TCA cycle. Genetic deletion or pharmacological inhibition of PDK2/4 prevents polarization of macrophages to the M1 phenotype in response to inflammatory stimuli (lipopolysaccharide plus IFN-γ). Transplantation of PDK2/4-deficient bone marrow into irradiated wild-type mice to produce mice with PDK2/4-deficient myeloid cells prevented M1 polarization, reduced obesity-associated insulin resistance, and ameliorated adipose tissue inflammation. A novel, pharmacological PDK inhibitor, KPLH1130, improved high-fat diet-induced insulin resistance; this was correlated with a reduction in the levels of pro-inflammatory markers and improved mitochondrial function. These studies identify PDK2/4 as a metabolic checkpoint for M1 phenotype polarization of macrophages, which could potentially be exploited as a novel therapeutic target for obesity-associated metabolic disorders and other inflammatory conditions

    Porous silicon nanowires for lithium rechargeable batteries

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    Porous silicon nanowire is fabricated by a simple electrospinning process combined with a magnesium reduction; this material is investigated for use as an anode material for lithium rechargeable batteries. We find that the porous silicon nanowire electrode from the simple and scalable method can deliver a high reversible capacity with an excellent cycle stability. The enhanced performance in terms of cycling stability is attributed to the facile accommodation of the volume change by the pores in the interconnect and the increased electronic conductivity due to a multi-level carbon coating during the fabrication process.

    One-dimensional nanostructured vanadium oxides with single-crystalline structure synthesized by cellulose nanocrystal-template-assisted hydrothermal method for Li-ion battery cathodes

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    Cellulose nanocrystals (CNCs) have emerged as a promising templating material due to unique features, such as high surface area, surface hydroxyl groups and rod-like shape, which allow for sustainable nanoscale control of advanced functional materials. Especially, such high surface functionality and specific morphology can be imparted on the resultant nanomaterials with beneficial properties during templating. Here, we present synthesis of one-dimensional (1D) nanostructured vanadium oxides, such as VO2(B) and V2O5·nH2O nanobelts, with single- crystalline structure by hydrothermal treatment using CNCs as a sacrificial template. Importantly, the single-crystal vanadium oxide nanobelts exhibit the enhanced electrochemical performance of Li ion batteries with high specific capacity (> 300mAh/g) and long lifespan (> 244mAh/g at 50 cycles) compared to the polycrystalline nanoflakes counterpart. Furthermore, we suggest that during hydrothermal treatment the sacrificial CNC template-derived carbon is beneficial for electron transfer in cathode materials. Thus, we demonstrate that the utilization of CNC templating to develop novel single-crystalline oxide cathode nanomaterials can provide a fruitful pathway for extraordinary electrochemical performance of next-generation alkaline batteries. © 2023, The Author(s), under exclusive licence to Springer Nature B.V.FALS

    Extremely high yield conversion from low-cost sand to high-capacity Si electrodes for Li-ion batteries

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    Although magnesiothermic reduction has attracted immense attention as a facile route for the fabrication of mass-scale Si nanostructures for high-capacity lithium-ion battery applications, its low conversion yield (98%) of magnesiothermic reduction based on control of reaction pressure is reported. The successful use of sand as a nearly infinite and extremely low-cost source for the high-yield fabrication of nanostructured Si electrodes for Li-ion batteries is demonstrated. On the basis of a step-by-step analysis of the material's structural, morphological, and compositional changes, a two-step conversion reaction mechanism is proposed that can clearly explain the phase behavior and the high conversion yield. The excellent charge-discharge performance (specific capacities over 1500 mAh g(-1) for 100 cycles) of the hierarchical Si nanostructure suggests that this facile, fast, and high-efficiency synthesis strategy from ultralow-cost sand particles provides outstanding cost-effectiveness and possible scalability for the commercialization of Si electrodes for energy-storage applications.

    Image_2_Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance.TIF

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    <p>Obesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to investigate whether the nuclear lamina regulates obesity-mediated chronic inflammation. In this study, we show that lamin A/C mediates inflammation in macrophages. The gene and protein expression levels of lamin A/C are significantly increased in epididymal adipose tissues from obese rodent models and omental fat from obese human subjects compared to their lean controls. Flow cytometry and gene expression analyses reveal that the protein and gene expression levels of lamin A/C are increased in adipose tissue macrophages (ATMs) by obesity. We further show that ectopic overexpression of lamin A/C in macrophages spontaneously activates NF-κB, and increases the gene expression levels of proinflammatory genes, such as Il6, Tnf, Ccl2, and Nos2. Conversely, deletion of lamin A/C in macrophages reduces LPS-induced expression of these proinflammatory genes. Importantly, we find that myeloid cell-specific lamin A/C deficiency ameliorates obesity-induced insulin resistance and adipose tissue inflammation. Thus, our data suggest that lamin A/C mediates the activation of ATM inflammation by regulating NF-κB, thereby contributing to the development of obesity-induced insulin resistance.</p

    Table_2_Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance.PDF

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    <p>Obesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to investigate whether the nuclear lamina regulates obesity-mediated chronic inflammation. In this study, we show that lamin A/C mediates inflammation in macrophages. The gene and protein expression levels of lamin A/C are significantly increased in epididymal adipose tissues from obese rodent models and omental fat from obese human subjects compared to their lean controls. Flow cytometry and gene expression analyses reveal that the protein and gene expression levels of lamin A/C are increased in adipose tissue macrophages (ATMs) by obesity. We further show that ectopic overexpression of lamin A/C in macrophages spontaneously activates NF-κB, and increases the gene expression levels of proinflammatory genes, such as Il6, Tnf, Ccl2, and Nos2. Conversely, deletion of lamin A/C in macrophages reduces LPS-induced expression of these proinflammatory genes. Importantly, we find that myeloid cell-specific lamin A/C deficiency ameliorates obesity-induced insulin resistance and adipose tissue inflammation. Thus, our data suggest that lamin A/C mediates the activation of ATM inflammation by regulating NF-κB, thereby contributing to the development of obesity-induced insulin resistance.</p

    Image_1_Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance.TIF

    No full text
    <p>Obesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to investigate whether the nuclear lamina regulates obesity-mediated chronic inflammation. In this study, we show that lamin A/C mediates inflammation in macrophages. The gene and protein expression levels of lamin A/C are significantly increased in epididymal adipose tissues from obese rodent models and omental fat from obese human subjects compared to their lean controls. Flow cytometry and gene expression analyses reveal that the protein and gene expression levels of lamin A/C are increased in adipose tissue macrophages (ATMs) by obesity. We further show that ectopic overexpression of lamin A/C in macrophages spontaneously activates NF-κB, and increases the gene expression levels of proinflammatory genes, such as Il6, Tnf, Ccl2, and Nos2. Conversely, deletion of lamin A/C in macrophages reduces LPS-induced expression of these proinflammatory genes. Importantly, we find that myeloid cell-specific lamin A/C deficiency ameliorates obesity-induced insulin resistance and adipose tissue inflammation. Thus, our data suggest that lamin A/C mediates the activation of ATM inflammation by regulating NF-κB, thereby contributing to the development of obesity-induced insulin resistance.</p
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