metainflammation
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Vitamin C increases DNA breaks and suppresses DNA damage-independent activation of ATM ... - 0 views
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JCI - Inflammatory links between obesity and metabolic disease - 0 views
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The chronic nature of obesity produces a tonic low-grade activation of the innate immune system that affects steady-state measures of metabolic homeostasis over time
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Multiple inflammatory inputs contribute to metabolic dysfunction, including increases in circulating cytokines (10), decreases in protective factors (e.g., adiponectin; ref. 11), and communication between inflammatory and metabolic cells
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Physiologic enhancement of the M2 pathways (e.g., eosinophil recruitment in parasitic infection) also appears to be capable of reducing metainflammation and improving insulin sensitivity (27).
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increasing adiposity results in a shift in the inflammatory profile of ATMs as a whole from an M2 state to one in which classical M1 proinflammatory signals predominate (21–23).
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Independent of obesity, hypothalamic inflammation can impair insulin release from β cells, impair peripheral insulin action, and potentiate hypertension (63–65).
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inflammation in pancreatic islets can reduce insulin secretion and trigger β cell apoptosis leading to decreased islet mass, critical events in the progression to diabetes (33, 34)
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Since an estimated excess of 20–30 million macrophages accumulate with each kilogram of excess fat in humans, one could argue that increased adipose tissue mass is de facto a state of increased inflammatory mass
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Upon stimulation by LPS and IFN-γ, macrophages assume a classical proinflammatory activation state (M1) that generates bactericidal or Th1 responses typically associated with obesity
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DIO, metabolites such as diacylglycerols and ceramides accumulate in the hypothalamus and induce leptin and insulin resistance in the CNS (58, 59)
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saturated FAs, which activate neuronal JNK and NF-κB signaling pathways with direct effects on leptin and insulin signaling (60)
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Lipid infusion and a high-fat diet (HFD) activate hypothalamic inflammatory signaling pathways, resulting in increased food intake and nutrient storage (57)
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Maternal obesity is associated with endotoxemia and ATM accumulation that may affect the developing fetus (73)
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a risk factor for obesity in offspring, and involves inflammatory macrophage infiltration that can alter the maternal-fetal circulation (74
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Of these PRRs, TLR4 has received the most attention, as this receptor can be activated by free FAs to generate proinflammatory signals and activate NF-κB
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The adipokine adiponectin has long been recognized to have positive benefits on multiple cell types to promote insulin sensitivity and deactivate proinflammatory pathways.
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adiponectin stimulates ceramidase activity and modulates the balance between ceramides and sphingosine-1-phosphate
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Inhibition of ceramide production blocks the ability of saturated FAs to induce insulin resistance (101)
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shared by Nathan Goodyear on 10 Jan 12
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Macrophage-secreted factors induce adipocyte inflammation and insulin resistance 10.101... - 0 views
www.sciencedirect.com/...S0006291X06000714
inflammation insulin resistance ATM macrophages obesity overweight weight-loss
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shared by Nathan Goodyear on 10 Jan 12
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ingentaconnect Adipose Tissue Macrophages, Low Grade Inflammation and Insulin Re... - 0 views
www.ingentaconnect.com/...art00009
ATMs obesity inflammation inflammatory reaction insulin resistance IR diabetes DM type II macrophages
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Acute Transverse Myelitis (ATM):Clinical Review of 43 Patients With COVID-19-Associated... - 0 views
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shared by Nathan Goodyear on 04 Jan 13
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Adipose tissue macrophages: p... [Curr Opin Clin Nutr Metab Care. 2011] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...21587064
adipose tissue macrophages ATMs adipose tissue obesity M2 M1 macrophages
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shared by Nathan Goodyear on 03 Jan 12
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Regulatory Mechanisms for Adipose Tissue M1 and M2 Macrophages in Diet-Induced Obese Mice - 0 views
diabetes.diabetesjournals.org/...2574.full
obesity overweight weight-loss M1 macrophage M2 ATM inflammation TNF-alpha IL-6
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M1 macrophages (and a high M1/M2 ratio) promote inflammation and insulin resistance in obese individuals; This is in contrast to M2 macrophages. Obese individuals will see a shift in M2 to M1. The exact mechanism is yet unknown. But M2 macrophages have been shown to resolve insulin resistance in this obese mice model
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Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic... - 0 views
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Recent reports indicate that a certain ROS concentration is required for high-dose vitamin C to induce cytotoxicity in cancer cells.
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In this study, we report that PAA is efficacious in killing MM cells in vitro and in vivo models, which generated levels of 20–40 mM ascorbate and 500 nM ascorbyl radicals after intraperitoneal administration of 4 g ascorbate per kilogram of body weight (Chen et al., 2008Chen et al., 2008), in xenograft MM mice
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These data suggest that PAA may show a therapeutic advantage to blood cancers vs solid tumors because of the communication between tumor cells and blood plasma
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These results strongly suggest that the mechanism of PAA killing of MM cells is indeed iron-dependent
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These results suggest that PAA administration in SMM may be able to prevent progression to symtomatic MM
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A recent study by Yun and colleagues demonstrated that vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH, but spares normal cells
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RAS family genes show the most frequent mutations in MM. KRAS, NRAS and BRAF are mutated in 22%, 20% and 7% of MM samples
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the disease stage rather than the mutation of RAS and/or BRAF is the major predictive factor for PAA sensitivity in MM treatment
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Other molecular mechanisms including ATP depletion and ATM-AMPK signaling have been reported to explain PAA-induced cell death
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Our findings complement reported studies and further address the mechanism of action using clinical samples in which we observed that PAA killed tumor cells with high iron content, suggesting that iron might be the initiator of PAA cytotoxicity
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combination of PAA with standard therapeutic drugs, such as melphalan, may significantly reduce the dose of melphalan needed
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Combined treatment of reduced dose melphalan with PAA achieved a significantly longer progression-free survival than the same dose of melphalan alone.
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These data also suggest that the bone marrow suppression induced by high-dose melphalan can be ameliorated by the combination of PAA with lower dose of melphalan because of the lack of toxicity of PAA on normal cells with low iron content.
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In MM preclinical and clinical studies, ascorbate was used as an adjunct drug and showed controversial results (Harvey et al., 2009, Perrone et al., 2009, Held et al., 2013, Sharma et al., 2012, Nakano et al., 2011, Takahashi, 2010, Sharma et al., 2009, Qazilbash et al., 2008). However, none of these tests used pharmacological doses of ascorbate and intravenous administration
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Cameron and Pauling reported that high doses of vitamin C increased survival of patients with cancer
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pharmacologically dosed ascorbic acid (PAA) 50–100 g (Chen et al., 2008, Padayatty et al., 2004, Hoffer et al., 2008, Padayatty et al., 2006, Welsh et al., 2013), administered intravenously, has potent anti-cancer activity and its role as anti-cancer therapy is being studied at the University of Iowa and in other centers
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In the presence of catalytic metal ions like iron, PAA administered intravenously exerts pro-oxidant effects leading to the formation of highly reactive oxygen species (ROS), resulting in cell death
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The survival of CD138+ cells in vitro was significantly decreased following PAA treatment in all 9 MM
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In contrast, no significant change of cell viability was observed in CD138− BM cells from the same patients
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the combination of melphalan plus PAA showed greater tumor burden reduction than each drug alone, suggesting a synergistic activity between these two drugs
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adding deferoxamine (DFO), an iron chelator, to OCI-MY5 cells before PAA treatment was also sufficient to prevent PAA-induced cellular death
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PAA by reacting with LIP and generating ROS induces mitochondria-mediated apoptosis in which AIF1 cleavage is important for cell death.
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shared by Nathan Goodyear on 18 May 17
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Hyperbaric oxygen therapy promotes neurogenesis: where do we stand? - 0 views
www.ncbi.nlm.nih.gov/...PMC3231808
hbot hyperbaric therapy hyperbaric brain TBI stroke neurogenesis neuorplasticity
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activated by hypoxia, HIF-1α causes the transcription of its regulated downstream genes, including erythropoietin (EPO) and VEGF which are known to promote neurogenesis
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The safety of HBOT was also evaluated and it was pointed out that, if given at proper paradigms, like 1.5 ATA for 60 minutes, HBOT will not cause oxygen toxicity
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Rockswold et al., on the other hand, found that HBOT might be potentially beneficial for severe TBI patients
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McDonagh et al., concluded that there was insufficient evidence to establish the effectiveness of HBOT in the treatment of TBI
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The first multicenter, randomized, double-blind, controlled trial in 2009 found that 40-hour HBOT of 24% oxygen at 1.3 ATM produced significant improvement in children's overall functioning, receptive language, social interaction, eye contact, and sensory/cognitive awareness compared to those received slightly pressurized room air
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Another study in 2010 on 16 autism patients, adopting a similar treatment paradigm, showed no effect on a wide array of behavioral evaluations
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To date, there is little evidence that HBOT causes malignant growth or metastasis. A history of malignancy should therefore not be considered as a contraindication for HBOT
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HBOT enhances the production of reactive oxygen species (ROS) and causes oxidative stress in body tissues
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Excessive accumulation of oxidative stress may contribute to neurodegenerative processes and cell death in the brain, as seen in diseases like Alzheimer's disease (AD) and Parkinson's disease (PD)
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process that results in a functional improvement of cellular stress resistance, survival, and longevity in response to sub-lethal levels of stress
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