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star yu

Presión arterial alta para personas con PKD:causa y tratamiento - 0 views

www.enfermedad-renal.com/...2069.html

enfermedad renal poliquística tratamiento

shared by star yu on 08 Mar 15 - No Cached
  • star yu on 08 Mar 15
     
    Por lo general, PKD menudo se acompaña con la presión arterial alta. Debido a la hipertensión, los pacientes con PKD sufrirían síntomas como dolor de cabeza, mareos, náuseas y vómitos, etc., aún más grave, presión arterial alta puede acumular el proceso de fibrosis renal.Entonces, cómo y por qué la presión arterial alta aparecería en las personas con enfermedad renal poliquística?
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

Renin-angiotensin system and cancer: A review - 0 views

www.oatext.com/system-and-cancer-A-review.php

renin angiotensin system cancer

shared by Nathan Goodyear on 10 Sep 18 - No Cached
  • crucial role of the RAS in the development and maintenance of cancer
  • kidneys, which produce renin in response to decreased arterial pressure, reduced sodium in the distal tubule, or sympathetic nervous system activity via the β-adrenergic receptors
  • Renin is secreted from the juxtaglomerular cells into the bloodstream where it encounters angiotensinogen (AGN), normally produced by the liver
  • ...22 more annotations...
  • Renin catalyses the conversion of AGN to angiotensin I (ATI), which is quickly cleaved by angiotensin converting enzyme (ACE) to form angiotensin II (ATII)
  • ATII triggers the release of aldosterone from the adrenal glands, which stimulates reabsorption of sodium and water and thereby increases blood volume and blood pressure
  • ATII also acts on smooth muscle to cause vasoconstriction of the arterioles
  • ATII promotes the release of antidiuretic hormone from the posterior pituitary gland, which results in water retention and triggers the thirst reflex
  • ability of non-CSCs to ‘de-differentiate’ into CSCs due to epigenetic or environmental factors, which further increases the complexity of tumour biology and treatment
  • efficacy of RAS modulators on cancer in both cancer models and cancer patients
  • A localised (‘paracrine’) RAS mechanism has been identified in many types of cancers, and interruption of the control of the RAS is thought to be the basis for its role in cancer
  • Components of the RAS are expressed by these CSCs, supporting the hypothesis of the presence of a ‘paracrine RAS’ in regulating these CSCs
  • Renin is an enzyme normally released by the kidneys in response to falling arterial pressure
  • a study of GBM demonstrating overexpression of PRR coupled with the observation that inhibition of renin reduces cellular proliferation and promotes apoptosis
  • PRR has been found to be vital for normal Wnt signalling
  • A major focus of PRR research is its relationship with Wnt signalling
  • suggest a crucial role for PRR activation on the proliferation of CSCs, possibly via Wnt/β-catenin signalling, leading to carcinogenesis.
  • Angiotensin converting enzyme (ACE), also known as CD143, is the endothelial-bound peptidase which physiologically converts ATI to ATII
  • ACE is crucial in the regulation of blood pressure, angiogenesis and inflammation
  • results suggest that an overactive ACE promotes cancer growth and progression, and an inhibited or low-activity ACE may have cancer-protective effects
  • When bound to ATII or ATIII it causes vasoconstriction by stimulating the release of vasopressin, reabsorption of water and sodium by promoting secretion of aldosterone and insulin, fibrosis, cellular growth and migration, pro-inflammation, glucose release from the liver, increased plasma triglyceride concentration, and reduced gluconeogenesis
  • ATIIR1 is a G-protein-coupled receptor, with downstream signalling involved in vasodilation, hypertrophy and NF-κB activation leading to TNF-α and PAI-1 expression
  • ATIIR1 has well-documented links with cancer, with one study demonstrating its overexpression in ~20% of breast cancer patients
  • the effect of RAS dysregulation has been associated with increased VEGF expression and angiogenesis in cancers
  • In ovarian and cervical cancer, ATIIR1 overexpression has been shown to be an indicator of tumour invasiveness
  • administration of ATIIR1 blockers (ARBs) have been associated with reduced tumour size, reduction in tumour vascularisation, lower occurrence of metastases, and lower VEGF levels
  • Nathan Goodyear on 10 Sep 18
     
    Great review on RAS in cancer.
trungtamnamkhoa

Learn About Male Foreskin Disease - Men's Health Clinic - 1 views

menhealth.vn/...bao-quy-dau

hormone Testosterone Men Disease Male cancer health healthy

shared by trungtamnamkhoa on 25 Jun 19 - No Cached
  • trungtamnamkhoa on 25 Jun 19
     
    Long foreskin It was a situation in which he was always so shy when he opened his eyes even though he could easily go out easily, without pain, without tightening. Even when "greeting the flag" he kept hiding the ball under the glans or just poking out. Must have to wait for the hand of "big brother" to slide down to bear the road to see the world around. When you have a clear understanding of the above concepts, the men of the race race to wonder, "Why is the foreskin of my friend not narrowed but why are my and my brother's bad luck?". The doctor asked for the correct answer, partly because of his bad luck, from birth to growing up, the foreskin was like that, "keep loving and protecting the foreskin." But it is not uncommon for other reasons to make men suffer because of foreskin: First, we have to recall the untimely and improper foreskin effects of parents when children are young. It is these overly "anxious" actions of parents that have counterproductive and narrowed down the latter. There are some autoimmune diseases, making the foreskin a fibrous day, loss of elasticity, gradually worsening, called BXO (balanitisxerotica obliterans) - a narrowed glans. This can also be interpreted as a form of glans, which can even cause narrowing of the urinary tract to lead to urinary retention. Some cases of glans and foreskin have been repeatedly infected by microbiological agents (bacteria, viruses, fungi, etc.), which can be re-infected and non-stop treatment is also available. can lead to complications of fibrosis and secondary stenosis
Nathan Goodyear

Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic... - 0 views

pubmed.ncbi.nlm.nih.gov/24239723

metabolic endotoxemia NF-kappaB vitamin C inflammation NFKB

shared by Nathan Goodyear on 09 Oct 21 - No Cached
  • Nathan Goodyear on 09 Oct 21
     
    Vitamin C inhibits metabolic endotoxemia NFKB inflammatory signaling.
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

Vitamin C alleviates hyperuricemia nephropathy by reducing inflammation and fibrosis - ... - 0 views

pubmed.ncbi.nlm.nih.gov/34160066

hyperuricemia vitamin C xanthine oxidase IL-6 uric acid

shared by Nathan Goodyear on 07 Jun 22 - No Cached
  • Nathan Goodyear on 07 Jun 22
     
    Vitamin C reduces xanthine oxidase and uric acid levels by at least 20%. Again, another study shows a reduction in IL-6.
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