Skip to main content

Home/ Dr. Goodyear/ Group items tagged ROS

Rss Feed Group items tagged

Filter: All | Bookmarks | Topics Simple Middle
Nathan Goodyear

http://www.jgld.ro/2009/2/15.pdf - 0 views

www.jgld.ro/15.pdf

Lead lead toxicity liver enzymes

shared by Nathan Goodyear on 09 Mar 15 - No Cached
  • Nathan Goodyear on 09 Mar 15
     
    Lead toxicity associated with liver damage and elevated liver enzymes in case study.
Nathan Goodyear

Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk - 0 views

jme.endocrinology-journals.org/...R51.full

metabolic endotoxemia obesity insulin resistance cardiovascular disease LPS inflammation

shared by Nathan Goodyear on 04 Aug 14 - No Cached
  • Weight gain has been associated with a higher gut permeability
  • a high-fat diet promotes LPS absorption
  • higher concentrations of fatty acids impair intestinal barrier integrity
  • ...37 more annotations...
  • The starting point for innate immunity activation is the recognition of conserved structures of bacteria, viruses, and fungal components through pattern-recognition receptors
  • TLRs are PRRs that recognize microbe-associated molecular patterns
  • TLRs are transmembrane proteins containing extracellular domains rich in leucine repeat sequences and a cytosolic domain homologous to the IL1 receptor intracellular domain
  • The major proinflammatory mediators produced by the TLR4 activation in response to endotoxin (LPS) are TNFα, IL1β and IL6, which are also elevated in obese and insulin-resistant patients
  • Obesity, high-fat diet, diabetes, and NAFLD are associated with higher gut permeability leading to metabolic endotoxemia.
  • Probiotics, prebiotics, and antibiotic treatment can reduce LPS absorption
  • LPS promotes hepatic insulin resistance, hypertriglyceridemia, hepatic triglyceride accumulation, and secretion of pro-inflammatory cytokines promoting the progression of fatty liver disease.
  • In the endothelium, LPS induces the expression of pro-inflammatory, chemotactic, and adhesion molecules, which promotes atherosclerosis development and progression.
  • In the adipose tissue, LPS induces adipogenesis, insulin resistance, macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines and chemokines.
  • the gut microbiota has been recently proposed to be an environmental factor involved in the control of body weight and energy homeostasis by modulating plasma LPS levels
  • dietary fats alone might not be sufficient to cause overweight and obesity, suggesting that a bacterially related factor might be responsible for high-fat diet-induced obesity.
  • This was accompanied in high-fat-fed mice by a change in gut microbiota composition, with reduction in Bifidobacterium and Eubacterium spp.
  • n humans, it was also shown that meals with high-fat and high-carbohydrate content (fast-food style western diet) were able to decrease bifidobacteria levels and increase intestinal permeability and LPS concentrations
  • it was demonstrated that, more than the fat amount, its composition was a critical modulator of ME (Laugerette et al. 2012). Very recently, Mani et al. (2013) demonstrated that LPS concentration was increased by a meal rich in saturated fatty acids (SFA), while decreased after a meal rich in n-3 polyunsaturated fatty acids (n-3 PUFA).
  • this effect seems to be due to the fact that some SFA (e.g., lauric and mystiric acids) are part of the lipid-A component of LPS and also to n-3 PUFA's role on reducing LPS potency when substituting SFA in lipid-A
  • these experimental results suggest a pivotal role of CD14-mediated TLR4 activation in the development of LPS-mediated nutritional changes.
  • This suggests a link between gut microbiota, western diet, and obesity and indicates that gut microbiota manipulation can beneficially affect the host's weight and adiposity.
  • endotoxemia was independently associated with energy intake but not fat intake in a multivariate analysis
  • in vitro that endotoxemia activates pro-inflammatory cytokine/chemokine production via NFκB and MAPK signaling in preadipocytes and decreased peroxisome proliferator-activated receptor γ activity and insulin responsiveness in adipocytes.
  • T2DM patients have mean values of LPS that are 76% higher than healthy controls
  • LPS-induced release of glucagon, GH and cortisol, which inhibit glucose uptake, both peripheral and hepatic
  • LPSs also seem to induce ROS-mediated apoptosis in pancreatic cells
  • Recent evidence has been linking ME with dyslipidemia, increased intrahepatic triglycerides, development, and progression of alcoholic and nonalcoholic fatty liver disease
  • The hepatocytes, rather than hepatic macrophages, are the cells responsible for its clearance, being ultimately excreted in bile
  • All the subclasses of plasma lipoproteins can bind and neutralize the toxic effects of LPS, both in vitro (Eichbaum et al. 1991) and in vivo (Harris et al. 1990), and this phenomenon seems to be dependent on the number of phospholipids in the lipoprotein surface (Levels et al. 2001). LDL seems to be involved in LPS clearance, but this antiatherogenic effect is outweighed by its proatherogenic features
  • LPS produces hypertriglyceridemia by several mechanisms, depending on LPS concentration. In animal models, low-dose LPS increases hepatic lipoprotein (such as VLDL) synthesis, whereas high-dose LPS decreases lipoprotein catabolism
  • When a dose of LPS similar to that observed in ME was infused in humans, a 2.5-fold increase in endothelial lipase was observed, with consequent reduction in total and HDL. This mechanism may explain low HDL levels in ‘ME’ and other inflammatory conditions such as obesity and metabolic syndrome
  • It is known that the high-fat diet and the ‘ME’ increase intrahepatic triglyceride accumulation, thus synergistically contributing to the development and progression of alcoholic and NAFLD, from the initial stages characterized by intrahepatic triglyceride accumulation up to chronic inflammation (nonalcoholic steatohepatitis), fibrosis, and cirrhosis
  • On the other hand, LPS activates Kupffer cells leading to an increased production of ROS and pro-inflammatory cytokines like TNFα
  • high-fat diet mice presented with ME, which positively and significantly correlated with plasminogen activator inhibitor (PAI-1), IL1, TNFα, STAMP2, NADPHox, MCP-1, and F4/80 (a specific marker of mature macrophages) mRNAs
  • prebiotic administration reduces intestinal permeability to LPS in obese mice and is associated with decreased systemic inflammation when compared with controls
  • Cani et al. also found that high-fat diet mice presented with not only ME but also higher levels of inflammatory markers, oxidative stress, and macrophage infiltration markers
  • This suggests that important links between gut microbiota, ME, inflammation, and oxidative stress are implicated in a high-fat diet situation
  • high-fat feeding is associated with adipose tissue macrophage infiltration (F4/80-positive cells) and increased levels of chemokine MCP-1, suggesting a strong link between ME, proinflammatory status, oxidative stress, and, lately, increased CV risk
  • LPS has been shown to promote atherosclerosis
  • markers of systemic inflammation such as circulating bacterial endotoxin were elevated in patients with chronic infections and were strong predictors of increased atherosclerotic risk
  • As a TLR4 ligand, LPS has been suggested to induce atherosclerosis development and progression, via a TLR4-mediated inflammatory state.
  • Nathan Goodyear on 04 Aug 14
     
    Very nice updated review on Metabolic endotoxemia
Nathan Goodyear

British Journal of Cancer - Dichloroacetate inhibits aerobic glycolysis in multiple mye... - 0 views

www.nature.com/...bjc2013120a.html

DCA dichloroacetate cancer

shared by Nathan Goodyear on 19 Nov 14 - No Cached
  • Nathan Goodyear on 19 Nov 14
     
    Dichloroacetate (DCA) inhibits aerobic glycolysis via inhibition of Pyruvate Dehydrogenase kinase (PDK), which allows for the phosphorylation of Pyruvate Dehydrogenase and the formation of acetylCo-A.  This then feeds the krebs cycle.  Increased mitochondrial activity increases ROS and resultant apoptosis of cancer cells.
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
  • increased levels of hydrogen peroxide in exhaled breath condensate from patients with localized breast malignancy, associated with increased clinical severity
  • Oxidative stress generated by breast cancer cells activates HIF-1α and NFκB in fibroblasts, leading to autophagy and lysosomal degradation of Cav-1
  • ...18 more annotations...
  • Comparing mitochondrial metabolic activity revealed a difference between stroma and epithelial cells
  • metalloproteinases (MMP) such as MMP-2, MMP-3, and MMP-9 increase extracellular matrix turnover and are themselves activated by oxidative stress
  • 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
  • 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
  • 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.
  • 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
  • hydrogen peroxide is one of the main factors that can push fibroblasts and cancer cells into senescence
  • 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

Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation - 0 views

www.ncbi.nlm.nih.gov/...PMC3601023

cancer DCA

shared by Nathan Goodyear on 12 Nov 14 - No Cached
  • the oral bioavailability of DCA is nearly 100%
  • the oral bioavailability of DCA is almost 100%.
  • DCA can penetrate into the traditional chemotherapy sanctuary sites. Interestingly, it was reported that DCA could penetrate across the BBB,30 exhibiting the potential activity for brain therapy.
  • ...23 more annotations...
  • Clinical studies of DCA have shown reduced lactate levels
  • It has been reported that DCA activates the PDH by inhibition of PDK in a dose-dependent manner, and results in increased delivery of pyruvate into the mitochondria
  • The antitumor activity of DCA on nonsmall cell lung cancer, breast cancer, glioblastomas, and endometrial and prostate cancer cells has been demonstrated
  • It is well known that many chemotherapeutic agents have a low therapeutic index in brain tumors.
  • The most common metabolic hallmark of cancer cells is their propensity to metabolize glucose to lactic acid at a high rate even in the presence of oxygen
  • Pyruvate dehydrogenase kinase (PDK) is a gate-keeping enzyme that regulates the flux of carbohydrates (pyruvate) into the mitochondria
  • In the presence of activated PDK, pyruvate dehydrogenase (PDH), a critical enzyme that converts pyruvate to acetyl-CoA instead of lactate in glycolysis, is inhibited, limiting the entry of pyruvate into the mitochondria.
  • the level of Hsp70 was significantly decreased
  • DCA can penetrate the BBB
  • It has been reported that DCA treatment resulted in an increase in the proportion of tumor cells in the S phase, showing a decrease in proliferation as well as the induction of apoptosis
  • Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport, and/or stabilization by acting as a molecular chaperone, leading to the inhibition of apoptosis by both caspase-dependent and/or independent pathways
  • HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion, and metastasis
  • Considering the fact that high expression of HSPs is essential for cancer survival, the inhibition of HSPs is an important strategy of anticancer therapy.
  • In addition, after 5 years of continued treatment with oral DCA at a dose of 25 mg/kg, the serum DCA levels are only slightly increased compared with the levels after the first several doses, also showing its safety for oral administration at this dose.
  • DCA can enter the circulation rapidly after oral administration and then generate the stimulation of PDH activity generally within minutes.
  • Our in vivo results in tumor tissues indicated that DCA significantly induced ROS production and decreased MMP in tumor tissues
  • The numbers of microvessels in the DCA treatment groups were significantly decreased, suggesting the potential antiangiogenic effect of DCA
  • Under hypoxic conditions, hypoxia-inducible factor (HIF-1α) is activated and induces angiogenesis
  • In addition, HIF-1α can also induce the expression of PDK,48 which can inhibit the activity of PDH
  • The inhibition effect of DCA on HIF-1α would decrease vascular endothelial growth factor and inhibit angiogenesis
  • the antiangiogenic effect in the 25 mg/kg treatment group was lower than that in 75 mg/kg or 125 mg/kg treatment groups
  • In conclusion, DCA induces the apoptosis of C6 cells through the activation of the mitochondrial pathway, arresting the cell cycle of C6 cells in S phase and down-regulating Hsp70 expression.
  • DCA significantly induced the ROS production and decreased the MMP in tumor tissues. Our in vivo antitumor activity results also indicated that DCA has an antiangiogenic effect
  • Nathan Goodyear on 12 Nov 14
     
    DCA as proposed therapy in cancer.
Nathan Goodyear

Induction of Heme Oxygenase-1 and Ferritin in the Kidney in Warm Antibody Hemolytic Anemia - 0 views

www.ncbi.nlm.nih.gov/...PMC2709285

ferritin HO-1 acute kidney injury heme-oxygenate-1 AKI

shared by Nathan Goodyear on 24 May 20 - No Cached
  • Nathan Goodyear on 24 May 20
     
    induction of HO-1 induces ferritin increase to counter ROS to prolong survival. This is not a bad thing, but a survival mechanism in the short term.
Nathan Goodyear

Evaluation of artemisinins for the treatment of acute myeloid leukemia - 0 views

www.ncbi.nlm.nih.gov/...PMC4918815

DHA AML acute myeloid leukemia artesunate artemisinins

shared by Nathan Goodyear on 29 May 20 - No Cached
  • Nathan Goodyear on 29 May 20
     
    cell study finds artesuante and DHA augment Ara-c in AML via increase in ROS.
Nathan Goodyear

NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond - PMC - 0 views

www.ncbi.nlm.nih.gov/...PMC8924116

cancer NETosis SARS-CoV-2 COVID COVID-19 COVID19 platelets

shared by Nathan Goodyear on 18 Apr 23 - No Cached
  • Pneumonia is a typical symptom of COVID-19 infection, while acute respiratory distress syndrome (ARDS) and multiple organ failure are common in severe COVID-19 patients
  • NETs are important for preventing pathogen invasion, their excessive formation can result in a slew of negative consequences, such as autoimmune inflammation and tissue damage
  • SARS-CoV-2 infection has also been linked to increased neutrophil-to-lymphocyte ratios, which is associated with disease severity and clinical prognosis
  • ...40 more annotations...
  • NETosis is a special form of programmed cell death in neutrophils, which is characterized by the extrusion of DNA, histones, and antimicrobial proteins in a web-like structure known as neutrophil extracellular traps (NETs)
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Definition
  • increased generation of reactive oxygen species (ROS) is a crucial intracellular process that causes NETosis
  • Another indirect route of SARS-CoV-2-induced NET production is platelet activation
  • When NETs are activated in the circulation, they can also induce hypercoagulability and thrombosis
  • In COVID-19, major NET protein cargos of NETs (i.e., NE, MPO, and histones) are significantly elevated.
  • SARS-CoV-2 can also infect host cells through noncanonical receptors such as C-type lectin receptors
  • Immunopathological manifestations, including cytokine storms and impaired adaptive immunity, are the primary drivers behind COVID-19, with neutrophil infiltration being suggested as a significant cause
  • NETosis and NETs are increasingly recognized as causes of vascular injury
  • SARS-CoV-2 and its components (e.g., spike proteins and viral RNA) attach to platelets and increase their activation and aggregation in COVID-19, resulting in vascular injury and thrombosis, both of which are linked to NET formation
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Connects SARS-CoV-2 to TLR on Platelets to NETosis to metastasis.
  • NET formation may be caused by activated platelets rather than SARS-CoV-2 itself
  • NETosis, leading to aberrant immunity such as cytokine storms, autoimmune disorders, and immunosuppression.
  • early bacterial coinfections were more prevalent in COVID-19 patients than those infected with other viruses
  • NETosis and NETs may also have a role in the development of post COVID-19 syndromes, including lung fibrosis, neurological disorders, tumor growth, and worsening of concomitant disease
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      NETosis-> tumor growth
  • NETs and other by-products of NETosis have been shown to act as direct inflammation amplifiers. Hyperinflammation
  • “cytokine storm”
  • SARS-CoV-2 drives NETosis and NET formation to allow for the release of free DNA and by-products (e.g., elastases and histones). This may trigger surrounding macrophages and endothelial cells to secrete excessive proinflammatory cytokines and chemokines, which, in turn, enhance NET formation and form a positive feedback of cytokine storms in COVID-19
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Cycle of hyperinflammation
  • NET release enables self-antigen exposure and autoantibody production, thereby increasing the autoinflammatory response
  • patients with COVID-19 who have higher anti-NET antibodies are more likely to be detected with positive autoantibodies [e.g., antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA)]
  • COVID-19 NETs may act as potential inducers for autoimmune responses
  • have weakened adaptive immunity as well as a high level of inflammation
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Immunomodulation
  • tumor-associated NETosis and NETs promote an immunosuppressive environment in which anti-tumor immunity is compromised
  • NETs have also been shown to enhance macrophage pyroptosis in sepsis
  • facilitating an immunosuppressive microenvironment
  • persistent immunosuppression may result in bacterial co-infection or secondary infection
  • can enhance this process by interacting with neutrophils through toll-like receptor 4 (TLR4), platelet factor 4 (PF4), and extracellular vesicle-dependent processes
  • NET-induced immunosuppression in COVID-19 in the context of co-existing bacterial infection
  • Following initial onset of COVID-19, an estimated 50% or more of COVID-19 survivors may develop multi-organ problems (e.g., pulmonary dysfunction and neurologic impairment) or have worsening concomitant chronic illness
  • NETs in the bronchoalveolar lavage fluid of severe COVID-19 patients cause EMT in lung epithelial cells
  • decreased E-cadherin (an epithelial marker) expression
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Leads to emt
  • COVID-19 also has a long-term influence on tumor progression
  • Patients with tumors have been shown to be more vulnerable to SARS-CoV-2 infection and subsequent development of severe COVID-19
  • patients who have recovered from COVID-19 may have an increased risk of developing cancer or of cancer progression and metastasis
  • awaken cancer cells
  • NETs have been shown to change the tumor microenvironment
  • enhance tumor progression and metastasis
  • vitamin C has been tested in phase 2 clinical trials aimed at reducing COVID-19-associated mortality by reducing excessive activation of the inflammatory response
  • vitamin C is an antioxidant that significantly attenuates PMA-induced NETosis in healthy neutrophils by scavenging ROS
  • vitamin C may also inhibit NETosis and NET production in COVID-19
  • Metformin
  • Vitamin C
  • Nathan Goodyear on 18 Apr 23
     
    NETosis intimately involved in progressive COVID, long COVID, autoimmunity, and cancer
Nathan Goodyear

Tumor regionalization after surgery: Roles of the tumor microenvironment and neutrophil... - 0 views

www.nature.com/...s12276-022-00784-2

TME NETosis metastasis surgery cancer tumor microenvironment

shared by Nathan Goodyear on 20 Apr 23 - No Cached
  • tumor surgery must be carefully considered because the risk of metastasis could be increased by the surgical procedure.
  • NETosis, which is the process of forming neutrophil extracellular traps (NETs)
  • surgery-induced metastasis
  • ...61 more annotations...
  • surgery per se can promote cancer metastasis through a series of local and systemic events
  • surgery results in a serious wound that disrupts the structural barrier preventing the outspreading of cancer cells, change the properties of the cancer cells and stromal cells remaining in the tumor microenvironment, or impairs the host defense systems against cancers
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Key point; add to presentation on surgery and metastasis
  • After the primary tumor is surgically removed, the metastases can start to grow vigorously via neoangiogenesis because the circulating inhibitors disappear
  • infection and inflammation during the postoperative period have been reported to increase the risk of cancer recurrence in patients
  • Surgeons have long suspected that surgery, even if it is a necessary step in cancer treatment, facilitates cancer metastasis
  • Surgery-induced cancer metastasis has been well established in animal models
  • tumor cell dissemination, tumor-favoring immune responses, and neoangiogenesis
  • the surgical resection of primary tumors is beneficial is controversial
  • CTCs abruptly increase just after surgery
  • Even externally palpitating tumors for diagnosis could increase the numbers of CTCs in skin cancer and breast cancer
  • excessive glucocorticoids negatively modulate immune functions
  • immune surveillance against tumors is considered to be impaired by surgical stress
  • In addition to glucocorticoids, during stimulation of the HPA axis, the catecholamine hormones epinephrine and norepinephrine are released from the adrenal medulla
  • NK cell suppression may be attributed to increased levels of catecholamines as well as glucocorticoids
  • In mice bearing a primary tumor, it was observed that the removal of the primary tumor facilitated the growth of highly vascularized metastases
  • primary tumors may secrete angiogenic inhibitors as well as angiogenic activators
  • second phase of tumor recurrence and metastasis, which are newly acquired events, rather than just outcomes of incomplete treatment.
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Another key point
  • double-edged sword
  • HIF-1 in neutrophils plays a critical role in NETosis and bacteria-killing activity
  • neutrophils play various roles in the initiation and progression of cancer
  • NETosis
  • many inflammatory and neoplastic diseases
  • formation of neutrophil extracellular traps (NETs), which are large extracellular complexes composed of chromatin and cytoplasmic/granular proteins1
  • NETosis has been highlighted as an inflammatory event that promotes cancer metastasis
  • Once activated, neutrophils produce intracellular precursors by using DNA, histones, and granular and cytoplasmic proteins and then spread the mature form of NETs out around themselves
  • A series of these events is called NETosis.
  • neutrophil elastase, myeloperoxidase, cathepsin G, proteinase 3, lactoferrin, gelatinase, lysozyme C, calprotectin, neutrophil defensins, and cathelicidins
  • innate immune response against infection
  • Neutrophils are the most abundant type of granulocytes, comprising 40–70% of all white blood cells
  • two types of NEToses, suicidal (or lytic) NETosis and vital NETosis
  • Suicidal NETosis mainly depends on the production of reactive oxygen species (ROS)
  • Since neutrophils die during this process, it is called suicidal NETosis.
  • vital NETosis
  • vital NETosis occurs independently of ROS production
  • Vital NETosis can be induced by Gram-negative bacteria. LPS
  • NETs are present in a variety of cancers, such as lung cancer, colon cancer, ovarian cancer, and leukemia
  • neutrophils actively undergo NETosis in the tumor microenvironment
  • Hypoxia
  • NETosis plays a pivotal role in noninfectious autoimmune diseases,
  • cytokines
  • tumor-derived proteases
  • tumor exosomes
  • NETosis generally actively progresses in the tumor microenvironment.
  • the proliferative cytokines TGFβ and IL-10 and the angiogenic factor VEGF are representative of neutrophil-derived tissue repair proteins.
  • NETosis is a defense system to protect the body from invading pathogens
  • when neutrophils are excessively stimulated, they produce excess NETs, thereby leading to pathological consequences
  • plasma levels of NETosis markers are elevated after major surgeries
  • local invasion, intravasation into the blood or lymphatic vessels, escape from the immune system, anchoring to capillaries in target organs, extravasation into the organs, transformation from dormant cells to proliferating cells, colonization to micrometastases, and growth to macrometastases
  • NETs promote metastasis at multiple steps
  • NETs loosen the ECM and capillary wall to promote the intravasation of cancer cells
  • NETs and platelets wrap CTCs, which protects them from attack by immune cells and shearing force by blood flow
  • NETs promote the local invasion of cancer cells by degrading the extracellular matrix (ECM)
  • neutrophil elastase, matrix metalloproteinase 9, and cathepsin G
  • NETs also promote the intravasation of cancer cells
  • millions of tumor cells are released into the circulation every day,
  • NETs can wrap up CTCs with platelets
  • β1-integrin plays an important role in the interaction between CTCs and NETs
  • NET-platelet-CTC aggregates.
  • After metastasizing to distant tissues, tumor cells are often found to remain dormant for a period of time and unexpectedly regrow late
  • NETs are believed to participate in the reactivation of dormant cancer cells in metastatic regions
  • NET-associated proteases NE and MMP-9 were found to be responsible for the reactivation of dormant cancer cells
  • Nathan Goodyear on 20 Apr 23
     
    Surgery induced metastasis: it is real and steered by NETosis.
pharmacybiz

Reverse Decision Declining Romosozumab Use For Osteoporosis - 0 views

www.pharmacy.biz/mosozumab-use-for-osteoporosis

Romosozumab-Use-For-Osteoporosis Pharmacy-Business news-UK New-treatment-for-osteoporosis-2021 Romosozumab-osteoporosis Romosozumab-NICE

shared by pharmacybiz on 07 Jan 22 - No Cached
  • pharmacybiz on 07 Jan 22
     
    More than 100 NHS clinicians have urged the National Institute for Health and Care Excellence (NICE) to change its decision - declining recommendation of romosozumab, the first new osteoporosis medication for over a decade. In a joint letter published on January 2, the clinicians warned of the consequences of barring access to the drug to those who suffer the bone-weakening disease. The joint letter, led by the Royal Osteoporosis Society (ROS), raised concern over the scarcity of the drug pipeline for osteoporosis and lack of public funding for new research. It quoted recent government research that showed the National Institute for Health Research (NIHR) invested less than £1 million in osteoporosis research in 2020-21, against the £4.6 billion per year cost to the NHS of fractures. Craig Jones, chief executive of the Royal Osteoporosis Society said: "We're calling on NICE and the applicant company to get back round the table and work with us to ensure equal access to this important new treatment.
Nathan Goodyear

α-Lipoic Acid and Cardiovascular Disease - 0 views

jn.nutrition.org/...3327.full

cardiovascular disease CVD alpha alpha lipoic acid ALA antioxidant antioxidants ROS reactive oxygen species

shared by Nathan Goodyear on 20 Feb 13 - No Cached
  • Nathan Goodyear on 20 Feb 13
     
    Great read for anyone interested in the antioxidant properties of ALA.  
Nathan Goodyear

Redox imbalance in Parkinson's disease. [Biochim Biophys Acta. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18358848

Parkinson's disease ROS oxidative stress dopamine

shared by Nathan Goodyear on 14 Dec 11 - No Cached
  • Nathan Goodyear on 14 Dec 11
     
    oxidative stress and Parkinson's disease
Nathan Goodyear

Diabetes mellitus and the risk of dementia: The Ro... [Neurology. 1999] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10599761

insulin resistance dementia brain neurology diabetes

shared by Nathan Goodyear on 11 Jun 12 - No Cached
  • Nathan Goodyear on 11 Jun 12
     
    the use of insulin in diabetes is associated with a 430% increase risk of developing dementia.  Wow!!  Just the present of Diabetes, almost doubled the risk.  Add in extra insulin and it is like throwing fuel to the fire that exists in the brain.
Nathan Goodyear

Curcumin-induced Apoptosis of Human Colon Cancer Colo 205 Cells through the Production ... - 0 views

ar.iiarjournals.org/...4379.short

colon colon cancer cancer curcumin tumeric

shared by Nathan Goodyear on 22 Jan 14 - No Cached
  • Nathan Goodyear on 22 Jan 14
     
    Curcumin found to induce apoptosis, cell death, of colon cancer cells.
Nathan Goodyear

Methylmercury induces oxidative injury, alterations in permeability and glutamine trans... - 0 views

www.ncbi.nlm.nih.gov/...PMC1847599

methylmercury mercury astrocytes glutamate mitochondria brain inflammation oxidative ROS

shared by Nathan Goodyear on 26 Nov 13 - No Cached
  • Nathan Goodyear on 26 Nov 13
     
    methylmercury mediates neurotoxicity via mitochondrial damage, inflammation, and oxidative stress.  Astrocytes accumulated the methyl mercury.  The destruction of the astrocytes will result in an increase in glutamate.  Methylmercury is synergistic with other toxins in the development of immunoexcitotoxicity.
Nathan Goodyear

Chronic Testosterone Replacement Exerts Cardioprotection against Cardiac Ischemia-Reper... - 0 views

www.ncbi.nlm.nih.gov/...PMC4379072

cardiovascular disease cardiovascular disease heart health Testosterone low T low Testosterone hormone hormones

shared by Nathan Goodyear on 04 Jun 15 - No Cached
  • In this study, the cardioprotective effects of testosterone in testosterone-deprived rats heart with I/R injury were demonstrated
  • Prior to I/R injury, testosterone replacement provided cardioprotective effects in testosterone-deprived rats as indicated by (1) improved cardiac functions by markedly preserved %EF and %FS, and (2) attenuated cardiac sympathovagal imbalance by a markedly decreased LF/HF ratio
  • Testosterone replacement exerts cardioprotective effects by improving left ventricular function and cardiac sympathovagal balance impaired by testosterone deprivation in ORX rats
  • ...3 more annotations...
  • During the I/R period, testosterone replacement in ORX rats exerted the beneficial effects as indicated by (1) improved left ventricular pressure; (2) markedly decreased infarct size; (3) reduced fatal cardiac arrhythmias by increased time to 1st VT/VF onset and reduced arrhythmia scores; and (4) attenuated cardiac mitochondrial dysfunction caused by I/R injury by reducing ROS production, cardiac mitochondrial swelling and mitochondria membrane depolarization.
  • Chronic testosterone replacement also ameliorates left ventricular dysfunction, and reduces the infarct size and cardiac arrhythmias impaired by I/R injury under testosterone-deprived conditions
  • The mechanisms responsible for these beneficial effects of testosterone could be due to its ability to attenuate cardiac mitochondrial dysfunction and cardiomyocyte apoptosis
  • Nathan Goodyear on 04 Jun 15
     
    animal study finds that Testosterone therapy is cardioprotective in a preventative mode and with myocardial injury.  Normalization of Testosterone in these animals with low T reduced infant injury size and improved heart function.  
Nathan Goodyear

Oxidative stress, mitochondrial dysfunction and ce... [J Neurol Sci. 2005] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...15896810

CoQ10 mitochondria neurodegenerative disease Alzheimer's Parkinsons MS ALS oxidative stress

shared by Nathan Goodyear on 07 Feb 11 - No Cached
  • There is significant evidence that the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Friedreich's ataxia (FRDA), multiple sclerosis and amyotrophic lateral sclerosis, may involve the generation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) associated with mitochondrial dysfunction
  • Nathan Goodyear on 07 Feb 11
     
    Mitochondrial dysfunction at heart of diseases such as Parkinson's, Alzheimers, MS, ALS..
Nathan Goodyear

Journal of Clinical Investigation -- Oxidation of tetrahydrobiopterin leads to uncoupli... - 0 views

www.jci.org/14172

tetrahydrobiopterin cardiovascular disease hypertension

shared by Nathan Goodyear on 29 Apr 11 - No Cached
  • Tetrahydrobiopterin is a critical cofactor for the NO synthases
  • at hypertension produces a cascade involving production of ROSs from the NADPH oxidase leading to oxidation of tetrahydrobiopterin and uncoupling of endothelial NO synthase (eNOS). This decreases NO production and increases ROS production from eNOS
  • Tetrahydrobiopterin oxidation may represent an important abnormality in hypertension
  • ...1 more annotation...
  • Treatment strategies that increase tetrahydrobiopterin or prevent its oxidation may prove useful in preventing vascular complications of this common disease.
  • Nathan Goodyear on 29 Apr 11
     
    tetrahydrobiopterin deficiency plays role in cardiovasular disease
Nathan Goodyear

Association of testosterone with estrogen abolishes the beneficial effects of estrogen ... - 0 views

ajpheart.physiology.org/...ajpheart.00681.2014

Testosterone Estrogen CVD cardiovascular health disease heart hormone hormones women female

shared by Nathan Goodyear on 02 Feb 15 - No Cached
  • Nathan Goodyear on 02 Feb 15
     
    Testosterone reduced the vascular benefits of Estrogen (conjugated equine Estrogen) in female rat model.  Testosterone is seeing widespread use in women with very little positive data.  In fact, the majority of data points to poor metabolic effects and poor outcomes.
« First ‹ Previous 41 - 60 of 85 Next › Last »
Showing 20▼ items per page