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Nathan Goodyear

Effect of increasing glutathione with cysteine and glycine supplementation on mitochond... - 0 views

jcem.endojournals.org/...jc.2013-2376.abstract

mitochondria detoxification gluathione insulin sensitivity muscle cysteine glycine

shared by Nathan Goodyear on 01 Oct 13 - No Cached
  • Nathan Goodyear on 01 Oct 13
     
    Abstract only available due to pre-release.  Cysteine and glycine supplementation feed the glutathione pathways.  In HIV men, this improved insulin sensitivity, body composition, and muscle strength.
Nathan Goodyear

Effect of Increasing Glutathione With Cysteine and Glycine Supplementation on Mitochond... - 0 views

press.endocrine.org/...jc.2013-2376

glutathione cysteine glycine HIV insulin sensitivity metabolism muscle strenth

shared by Nathan Goodyear on 06 Jan 14 - No Cached
  • Nathan Goodyear on 06 Jan 14
     
    Supporting glutathione levels with the precursors cysteine and glycine improved insulin receptor function, body fat, and muscle strength in HIV individuals.
Nathan Goodyear

α-Lipoic Acid Induced Elevated S-adenosylhomocysteine and Depleted S-adenosyl... - 0 views

www.ncbi.nlm.nih.gov/...PMC2782850

IV alpha lipoic acid intravenous ALA cysteine SAMe liver disease cirrhosis

shared by Nathan Goodyear on 10 Feb 14 - No Cached
  • Nathan Goodyear on 10 Feb 14
     
    IV alpha lipoic acid does decrease liver cysteine and SAMe levels.
Nathan Goodyear

Effects of mercury on the isolated he... [Toxicol Appl Pharmacol. 1999] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10198276

mercury Hg heart cardiovascular disease cysteine

shared by Nathan Goodyear on 16 Sep 14 - No Cached
  • Nathan Goodyear on 16 Sep 14
     
    Hg damages the heart muscle.  In this animal study, protection of sulfhidyrl groups prevented this effect.  Examples of sulfhidryl groups is GSH, ALA, cysteine, and NAC.
Nathan Goodyear

ScienceDirect - American Heart Journal : Plasma total cysteine and total homocysteine a... - 0 views

www.sciencedirect.com/...S0002870310000815

elevated homocysteine MI risk cardiac

shared by Nathan Goodyear on 03 Aug 11 - No Cached
  • Fasting homocysteine was positively associated with MI risk
  • Fasting plasma concentration of total homocysteine, but not total cysteine, was positively associated with MI risk.
  • Nathan Goodyear on 03 Aug 11
     
    homocysteine associated with MI risk
Nathan Goodyear

PLOS ONE: N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Prelim... - 0 views

journals.plos.org/...article

Parkinsons Parkinson's disease NAC N-acetylcysteine brain

shared by Nathan Goodyear on 17 Jun 16 - No Cached
  • Nathan Goodyear on 17 Jun 16
     
    pilot study finds that NAC protects the dopaminergic neurons in the brains in cell line stud.  Clinical found increased dopamine binding in the brain compared to placebo in individuals with Parkinson's disease.
Nathan Goodyear

Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type... - 0 views

edrv.endojournals.org/...599.long

free radicals oxidative stress damage inflammation type II DM alpha lipoic acid alpha-lipoic-acid diabetes

shared by Nathan Goodyear on 02 Aug 12 - No Cached
  • In patients with diabetes, LA levels are reduced (48, 74, 103). LA has long been used for the treatment of diabetic neuropathy in Germany
  • evidence indicates that it increases insulin sensitivity in patients with type 2 diabetes
  • LA has been shown to 1) quench free radicals, 2) prevent singlet oxygen-induced DNA damage, 3) exhibit chelating activity, 4) reduce lipid peroxidation, 5) increase intracellular glutathione levels, and 6) prevent glycation of serum albumin (73, 74). LA is able to reduce oxidative stress-mediated NF-κB activation in vitro (74, 108, 109) and in patients with type 2 diabetes
  • ...2 more annotations...
  • Activation of NF-κB can also be blocked by several other thiol-containing antioxidants including N-acetyl-l-cysteine (NAC)
  • Other clinically available antioxidants reported to have antiinflammatory, antioncogenic, and/or antiatherogenic properties that have been shown to block the activation of NF-κB include resveratrol (115, 116), (-)-epicatechin-3-gallate (117), pycnogenol (118), silymarin (119), and curcumin (120)
  • Nathan Goodyear on 02 Aug 12
     
    Great read!  If you want to see how free radicals and oxidative stress contribute to inflammation and disease (DM in this case), read this article.
Nathan Goodyear

Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease - 0 views

www.medicinalnutraceutics.com/...AC%20Alzheimer's%20Disease.pdf

NAC N-acetylcysteine AD Alzheimer's disease Alzheimers inflammation AGE advanced glycation end products

shared by Nathan Goodyear on 11 Jun 12 - No Cached
  • Nathan Goodyear on 11 Jun 12
     
    NAC shown to improve secondary measures of cognitive function in small study in those with Alzheimer's disease. NAC proves to be a reliable means to reduce free radical induced advanced glycation end productions and resultant inflammation. Also was shown to be well tolerated.
Nathan Goodyear

Metabolic biomarkers of increased oxidative stress... [Am J Clin Nutr. 2004] - PubMed r... - 0 views

www.ncbi.nlm.nih.gov/...15585776

ASD autism spectrum disorder detoxification children SAMe SAH homocysteine cystathionine glutathione adenosine

shared by Nathan Goodyear on 05 Jul 11 - No Cached
  • children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione
  • This metabolic profile is consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized glutathione) in children with autism
  • increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.
  • Nathan Goodyear on 05 Jul 11
     
    detoxification impairment and the markers to assess it in children with ASD
Nathan Goodyear

Role of Oxidative Stress and the Microenvironment in Breast Cancer Development and Prog... - 0 views

www.ncbi.nlm.nih.gov/...PMC3950899

cancer oxidative stress warburg effect reverse warburg effect ROS

shared by Nathan Goodyear on 11 Nov 14 - No Cached
  • oxidative stress leads to HIF-1α accumulation
  • Oxidative stress generated by breast cancer cells activates HIF-1α and NFκB in fibroblasts, leading to autophagy and lysosomal degradation of Cav-1
  • increased levels of hydrogen peroxide in exhaled breath condensate from patients with localized breast malignancy, associated with increased clinical severity
  • ...18 more annotations...
  • Comparing mitochondrial metabolic activity revealed a difference between stroma and epithelial cells
  • Overexpression of NOX4 in normal breast epithelial cells results in cellular senescence, resistance to apoptosis, and tumorigenic transformation, as well as increased aggressiveness of breast cancer cells
  • metalloproteinases (MMP) such as MMP-2, MMP-3, and MMP-9 increase extracellular matrix turnover and are themselves activated by oxidative stress
  • Lowered expression of Cav-1 not only leads to myofibroblast conversion and inflammation but also seems to impact aerobic glycolysis, leading to secretion of high energy metabolites such as pyruvate and lactate that drive mitochondrial oxidative phosphorylation in cancer cells
  • Reverse Warburg Effect
  • secreted transforming growth factor β (TGFβ), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), fibroblast growth factor 2, and stromal-derived factor 1 (SDF1) are able to activate fibroblasts and increase cancer cell proliferation
  • oxidative stress has an important role in the initiation and preservation of breast cancer progression
  • cancer preventive role of healthy mitochondria
  • the cancer cells produce hydrogen peroxide and by driving the “Reverse Warburg Effect” initiate oxidative stress in fibroblasts. As a result of this process, fibroblasts exhibited reduced mitochondrial activity, increased glucose uptake, ROS, and metabolite production.
  • Oxidative stress results from an imbalance between unstable reactive species lacking one or more unpaired electrons (superoxide anion, hydrogen peroxide, hydroxyl radical, reactive nitrogen species) and antioxidants
  • cancer cells are able to induce drivers of oxidative stress, autophagy and mitophagy: HIF-1α and NFκB in surrounding stroma fibro-blasts
  • Studies show that loss of Cav-1 in adjacent breast cancer stroma fibroblasts can be prevented by treatment with N-acetyl cysteine, quercetin, or metformin
  • However, diets rich in antioxidants have fallen short in sufficiently preventing cancer
  • hydrogen peroxide is one of the main factors that can push fibroblasts and cancer cells into senescence
  • It is widely held that HIF-1α function is dependent upon its location within the tumor microenvironment. It acts as a tumor promoter in CAFs and as a tumor suppressor in cancer cells
  • It was reported that overexpression of recombinant (SOD2) (Trimmer et al., 2011) or injection of SOD, catalase, or their pegylated counterparts can block recurrence and metastasis in mice
  • obstructing oxidative stress in the tumor microenvironment can lead to mitophagy and promote breast cancer shutdown is a promising discovery for the development of future therapeutic interventions.
  • Recent studies show that in the breast cancer microenvironment, oxidative stress causes mitochondrial dysfunction
  • Nathan Goodyear on 11 Nov 14
     
    Really fascinating article on tumor signaling. The article points to a complex signaling between cancer cells and stromal fibroblasts that results in myofibroblast transformation that increases the microenvironment favorability of cancer. This article points to oxidative stress as the primary driving force.  
Nathan Goodyear

Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2... - 0 views

www.nature.com/...s41698-017-0044-8

cancer cancer stem cells liver cancer vitamin C IV vitamin C oncology

shared by Nathan Goodyear on 30 Jan 18 - No Cached
  • Chen et al. have revealed that ascorbate at pharmacologic concentrations (0.3–20 mM) achieved only by intravenously (i.v.) administration selectively kills a variety of cancer cell lines in vitro, but has little cytotoxic effect on normal cells.
  • Ascorbic acid (the reduced form of vitamin C) is specifically transported into cells by sodium-dependent vitamin C transporters (SVCTs)
  • SVCT-1 is predominantly expressed in epithelial tissues
  • ...41 more annotations...
  • whereas the expression of SVCT-2 is ubiquitous
  • differential sensitivity to VC may result from variations in VC flow into cells, which is dependent on SVCT-2 expression.
  • high-dose VC significantly impaired both the tumorspheres initiation (Fig. 4d, e) and the growth of established tumorspheres derived from HCC cells (Fig. 4f, g) in a time-dependent and dose-dependent manner.
  • Hepatocellular carcinoma (HCC)
  • The antioxidant, N-acetyl-L-cysteine (NAC), preventing VC-induced ROS production (a ROS scavenger), completely restored the viability and colony formation among VC-treated cells
  • DNA double-strand damage was found following VC treatment
  • DNA damage was prevented by NAC
  • Interestingly, the combination of VC and cisplatin was even more effective in reducing tumor growth and weight
  • Consistent with the in vitro results, stemness-related genes expressions in tumor xenograft were remarkably reduced after VC or VC+cisplatin treatment, whereas conventional cisplatin therapy alone led to the increase of CSCs
  • VC is one of the numerous common hepatoprotectants.
  • Interestingly, at extracellular concentrations greater than 1 mM, VC induces strong cytotoxicity to cancer cells including liver cancer cells
  • we hypothesized that intravenous VC might reduce the risk of recurrence in HCC patients after curative liver resection.
  • Intriguingly, the 5-year disease-free survival (DFS) for patients who received intravenous VC was 24%, as opposed to 15% for no intravenous VC-treated patients
  • Median DFS time for VC users was 25.2 vs. 18 months for VC non-users
  • intravenous VC use is linked to improved DFS in HCC patients.
  • In this study, based on the elevated expression of SVCT-2, which is responsible for VC uptake, in liver CSCs, we revealed that clinically achievable concentrations of VC preferentially eradicated liver CSCs in vitro and in vivo
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      the authors here made similar mistakes to the Mayo authors i.e. under doses here in this study.  They dosed at only 2 grams IVC.  A woefully low dose of IVC.
  • Additionally, we found that intravenous VC reduced the risk of post-surgical HCC progression in a retrospective cohort study.
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      positive results despite a low dose used.
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      Their comfort zone was 1mM.  They should have targeted 20-40 mM.
  • Three hundred thirty-nine participants (55.3%) received 2 g intravenous VC for 4 or more days after initial hepatectomy
  • As the key protein responsible for VC uptake in the liver, SVCT-2 played crucial roles in regulating the sensitivity to ascorbate-induced cytotoxicity
  • we also observed that SVCT-2 was highly expressed in human HCC samples and preferentially elevated in liver CSCs
  • SVCT-2 might serve as a potential CSC marker and therapeutic target in HCC
  • CSCs play critical roles in regulating tumor initiation, relapse, and chemoresistance
  • we revealed that VC treatment dramatically reduced the self-renewal ability, expression levels of CSC-associated genes, and percentages of CSCs in HCC, indicating that CSCs were more susceptible to VC-induced cell death
  • as a drug for eradicating CSCs, VC may represent a promising strategy for treatment of HCC, alone or particularly in combination with chemotherapeutic drugs
  • In HCC, we found that VC-generated ROS caused genotoxic stress (DNA damage) and metabolic stress (ATP depletion), which further activated the cyclin-dependent kinase inhibitor p21, leading to G2/M phase cell cycle arrest and caspase-dependent apoptosis in HCC cells
  • we demonstrated a synergistic effect of VC and chemotherapeutic drug cisplatin on killing HCC both in vitro and in vivo
  • Intravenous VC has also been reported to reduce chemotherapy-associated toxicity of carboplatin and paclitaxel in patients,38 but the specific mechanism needs further investigation
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      so, exclude the benefit to patients until the exact mechanism of action, which will never be fully elicited?!?!?
  • Our retrospective cohort study also showed that intravenous VC use (2 g) was related to the improved DFS in HCC patients after initial hepatectomy
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      Terribly inadequate dose.  Target is 20-40 mM which other studies have found occur with 50-75 grams of IVC.
  • several clinical trials of high-dose intravenous VC have been conducted in patients with advanced cancer and have revealed improved quality of life and prolonged OS
  • high-dose VC was not toxic to immune cells and major immune cell subpopulations in vivo
  • high recurrence rate and heterogeneity
  • tumor progression, metastasis, and chemotherapy-resistance
  • SVCT-2 was highly expressed in HCC samples in comparison to peri-tumor tissues
  • high expression (grade 2+/3+) of SVCT-2 was in agreement with poorer overall survival (OS) of HCC patients (Fig. 1c) and more aggressive tumor behavior
  • SVCT-2 is enriched in liver CSCs
  • these data suggest that SVCT-2 is preferentially expressed in liver CSCs and is required for the maintenance of liver CSCs.
  • pharmacologic concentrations of plasma VC higher than 0.3 mM are achievable only from i.v. administration
  • The viabilities of HCC cells were dramatically decreased after exposure to VC in dose-dependent manner
  • VC and cisplatin combination further caused cell apoptosis in tumor xenograft
  • These results verify that VC inhibits tumor growth in HCC PDX models and SVCT-2 expression level is associated with VC response
  • qPCR and IHC analysis demonstrated that expression levels of CSC-associated genes and percentages of CSCs in PDXs dramatically declined after VC treatment, confirming the inhibitory role of VC in liver CSCs
  • Nathan Goodyear on 30 Jan 18
     
    IV vitamin C in vitro and in vivo found to "preferentially" eradicate cancer stem cells.  In addition, IV vitamin C was found to be adjunctive to chemotherapy, found to be hepatoprotectant.  This study also looked at SVCT-2, which is the transport protein important in liver C uptake.
Nathan Goodyear

The effect of N-acetyl-l-cysteine (NAC) on liver toxicity and clinical outcome after he... - 0 views

www.ncbi.nlm.nih.gov/...PMC5974141

NAC liver toxicity

shared by Nathan Goodyear on 25 Apr 23 - No Cached
  • Nathan Goodyear on 25 Apr 23
     
    NAC lowers evidence of liver toxicity.
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