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Nathan Goodyear

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3 | EMBO Molecular Medicine - 0 views

embomolmed.embopress.org/...721.full

NAD nicotinamide riboside mitochondria vitamin B3 ATP disease

shared by Nathan Goodyear on 07 Jun 16 - No Cached
  • Nathan Goodyear on 07 Jun 16
     
    NAD in the form of nicotinamide riboside found to be effective in treating mitochondrial myopathy in animal model.
Nathan Goodyear

NAD+ and Vitamin B3: From Metabolism to Therapies - 0 views

jpet.aspetjournals.org/...883.full

NAD NADH Niacin vitamin B3

shared by Nathan Goodyear on 21 Jan 14 - No Cached
  • Nathan Goodyear on 21 Jan 14
     
    NAD+ is very important in ATP production and as a means to counter free radicals.  This is a nice discussion of NAD metabolism.  
Nathan Goodyear

Anticancer mechanisms of cannabinoids - 0 views

www.ncbi.nlm.nih.gov/...PMC4791144

THC cannabinoids cancer

shared by Nathan Goodyear on 18 Sep 18 - No Cached
  • modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival
  • cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals
  • Cannabis sativa L. (marijuana)
  • ...41 more annotations...
  • of the approximately 108 cannabinoids produced by C. sativa, Δ9-tetrahydrocannabinol (thc) is the most relevant because of its high potency and abundance in plant preparations
  • Tetrahydrocannabinol exerts a wide variety of biologic effects by mimicking endogenous substances—the endocannabinoids anandamide3 and 2-arachidonoylglycerol4,5—that engage specific cell-surface cannabinoid receptors
  • the cb2 receptor was initially described to be present in the immune system6, but was more recently shown to also be expressed in cells from other origins
  • transient receptor potential cation channel subfamily V, member 1
  • orphan G protein–coupled receptor 55
  • Most of the effects produced by cannabinoids in the nervous system and in non-neural tissues rely on cb1 receptor activation
  • two major cannabinoid-specific receptors—cb1 and cb2
  • cardiovascular tone, energy metabolism, immunity, and reproduction
  • cannabinoids are well known to exert palliative effects in cancer patients
  • best-established use is the inhibition of chemotherapy-induced nausea and vomiting
  • thc and other cannabinoids exhibit antitumour effects in a wide array of animal models of cancer
  • cannabinoid receptors and their endogenous ligands are both generally upregulated in tumour tissue compared with non-tumour tissue
  • cb2 promotes her2 (human epidermal growth factor receptor 2) pro-oncogenic signalling in breast cancer
  • pharmacologic activation of cannabinoid receptors decreases tumour growth
  • endocannabinoid signalling can also have a tumour-suppressive role
  • pharmacologic stimulation of cb receptors is, in most cases, antitumourigenic. Nonetheless, a few reports have proposed a tumour-promoting effect of cannabinoids
  • most prevalent effect is the induction of cancer cell death by apoptosis and the inhibition of cancer cell proliferation
  • impair tumour angiogenesis and block invasion and metastasis
  • thc and other cannabinoids induce the apoptotic death of glioma cells by cb1- and cb2-dependent stimulation
  • Autophagy is primarily a cytoprotective mechanism, although its activation can also lead to cell death
  • autophagy is important for cannabinoid antineoplastic activity
  • autophagy is upstream of apoptosis in the mechanism of cannabinoid-induced cell death
  • the effect of cannabinoids in hormone- dependent tumours might rely, at least in part, on the ability to interfere with the activation of growth factor receptors
  • glioma cells), pharmacologic blockade of either cb1 or cb2 prevents cannabinoid-induced cell death with similar efficacy
  • other types of cancer cells (pancreatic48, breast24, or hepatic43 carcinoma cells, for example), antagonists of cb2 but not of cb1 inhibit cannabinoid antitumour actions
  • thc promotes cancer cell death in a cb1- or cb2-dependent manner (or both) at lower concentrations
  • cannabidiol (cbd), a phytocannabinoid with a low affinity for cannabinoid receptors15, and other marijuana-derived cannabinoids57 have also been proposed to promote the apoptotic death of cancer cells acting independently of the cb1 and cb2 receptors
  • In cancer cells, cannabinoids block the activation of the vascular endothelial growth factor (vegf) pathway, an inducer of angiogenesi
  • In vascular endothelial cells, cannabinoid receptor activation inhibits proliferation and migration, and induces apoptosis
  • cb1 or cb2 receptor agonists (or both) reduce the formation of distant tumour masses in animal models of both induced and spontaneous metastasis, and inhibit adhesion, migration, and invasiveness of glioma64, breast65,66, lung67,68, and cervical68 cancer cells in culture
  • the ceramide/p8–regulated pathway plays a general role in the antitumour activity of cannabinoids targeting cb1 and cb2
  • cbd, by acting independently of the cb1 and cb2 receptors, produces a remarkable anti-tumour effect—including reduction of invasiveness and metastasis
  • cannabinoids can also enhance immune system–mediated tumour surveillance in some contexts
  • ability of thc to reduce inflammation75,76, an effect that might prevent certain types of cancer
  • recent observations suggest that the combined administration of cannabinoids with other anticancer drugs acts synergistically to reduce tumour growth
  • combined administration of gemcitabine (the benchmark agent for the treatment of pancreatic cancer) and various cannabinoid agonists synergistically reduced the viability of pancreatic cancer cells
  • Other reports indicated that anandamide and HU-210 might also enhance the anticancer activity of paclitaxel89 and 5-fluorouracil90 respectively
  • Combined administration of thc and cbd enhances the anticancer activity of thc and reduces the dose of thc needed to induce its tumour growth-inhibiting activity
  • Preclinical animal models have yielded data indicating that systemic (oral or intraperitoneal) administration of cannabinoids effectively decreases tumour growth
  • Combinations of cannabinoids with classical chemotherapeutic drugs such as the alkylating agent temozolomide (the benchmark agent for the management of glioblastoma80,84) have been shown to produce a strong anticancer action in animal models
  • pharmacologic inhibition of egfr, erk83, or akt enhances the cell-death-promoting action of thc in glioma cultures (unpublished observations by the authors), which suggests that targeting egfr and the akt and erk pathways could enhance the antitumour effect of cannabinoids
  • Nathan Goodyear on 18 Sep 18
     
    Good review of the anticancer effects of cananbinoids.
Nathan Goodyear

PPARs, Obesity, and Inflammation - 0 views

www.ncbi.nlm.nih.gov/...PMC1783744

obesity inflammation PPARs perioxisome proliferator-activated receptor

shared by Nathan Goodyear on 16 Jan 12 - No Cached
  • increase of 61% within 10 years
  • Many of the inflammatory markers found in plasma of obese individuals appear to originate from adipose tissue
  • obesity is a state of chronic low-grade inflammation that is initiated by morphological changes in the adipose tissue.
  • ...19 more annotations...
  • secretion of MCP-1, resistin, and other proinflammatory cytokines is increased by obesity, the adipose secretion of the anti-inflammatory protein adiponectin is decreased
  • the peroxisome proliferators- activated receptor (PPAR) family are involved in the regulation of inflammation and energy homestasis
  • natural agonists, including unsaturated fatty acids and eicosanoids
  • PPARα also regulates inflammatory processes, mainly by inhibiting inflammatory gene expression
  • upregulation of COX-2 is seen in alcoholic steatohepatitis and nonalcoholic steatohepatitis and has been directly linked to the progression of steatosis to steatohepatitis, the inhibitory effect of PPARα on COX-2 may reduce steatohepatitis
  • PPARα agonists have a clear anorexic effect resulting in decreased food intake, evidence is accumulating that PPARα may also directly influence adipose tissue function, including its inflammatory status.
  • PPARα may govern adipose tissue inflammation in three different ways: (1) by decreasing adipocyte hypertrophy, which is known to be connected with a higher inflammatory status of the tissue [3, 11, 59], (2) by direct regulation of inflammatory gene expression via locally expressed PPARα, or (3) by systemic events likely originating from liver
  • PPARγ is considered the master regulator of adipogenesis
  • PPARγ2, which is adipose-tissue specific
  • Unsaturated fatty acids and several eicosanoids serve as endogenous agonists of PPARγ
  • two different molecular mechanisms have been proposed by which anti-inflammatory actions of PPARγ are effectuated: (1) via interference with proinflammatory transcription factors including STAT, NF-κB, and AP-1
  • and (2) by preventing removal of corepressor complexes from gene promoter regions resulting in suppression of inflammatory gene transcription
  • diet-induced obesity is associated with increased inflammatory gene expression in adipose tissue via adipocyte hypertrophy and macrophage infiltration
  • PPARγ is able to reverse macrophage infiltration, and subsequently reduces inflammatory gene expression
  • Inflammatory adipokines mainly originate from macrophages which are part of the stromal vascular fraction of adipose tissue [18, 19], and accordingly, the downregulation of inflammatory adipokines in WAT by PPARγ probably occurs via effects on macrophages
  • By interfering with NF-κB signaling pathways, PPARγ is known to decrease inflammation in activated macrophages
  • Recent data suggest that activation of PPARγ in fatty liver may protect against inflammation
  • PPARs may influence the inflammatory response either by direct transcriptional downregulation of proinflammatory genes
  • anti-inflammatory properties of PPARs in human obesity
  • Nathan Goodyear on 16 Jan 12
     
    PPARs play pivotal in obesity.  PPARs appear to reduce the inflammatory cascade associated with obesity.  Downregulation of PPARs are associated with increased inflammation.  Natural PPARs include unsaturated fats and eicosanoids.
almotamaiz1973

أسرار ثورة 23 يوليو، خفايا ثورة 23 جويلية، خبايا ثورة 23 يوليو - موقع الأمنيات - 0 views

alumniyat.net/...%d9%8a%d9%88%d9%84%d9%8a%d9%88

تاريخ

shared by almotamaiz1973 on 27 Jul 22 - No Cached
  • almotamaiz1973 on 27 Jul 22
     
    تعتبر ثورة 23 يوليو المصرية من أهم الأحداث في التاريخ الحديث. حيث كانت انتفاضة شعبية نجحت في الإطاحة بالرئيس حسني مبارك من السلطة، وكانت إيذانا ببداية عهد جديد لمصر ، وظل الحدث محاطًا بالسرية بسبب المصالح السياسية على جانبي المحيط الأطلسي، ولكن هناك بعض أسرار ثورة 23 يوليو، مثيرة للاهتمام. قد لا تعرفونها. وعليه إليكم بعض خبايا انتفاضة 23 يوليو الهامة والتي تعتبر منعرج هام في التاريخ المصري.
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