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Nathan Goodyear

Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxid... - 0 views

www.ncbi.nlm.nih.gov/...PMC3180189

cancer reverse warburg effect warburg effect NF-kapppB HIF-1alpha Cav-1 H2O2

shared by Nathan Goodyear on 12 Nov 14 - No Cached
  • reducing oxidative stress with powerful antioxidants, is an important strategy for cancer prevention, as it would suppress one of the key early initiating steps where DNA damage and tumor-stroma metabolic-coupling begins. This would prevent cancer cells from acting as metabolic “parasites
  • Oxidative stress in cancer-associated fibroblasts triggers autophagy and mitophagy, resulting in compartmentalized cellular catabolism, loss of mitochondrial function, and the onset of aerobic glycolysis, in the tumor stroma. As such, cancer-associated fibroblasts produce high-energy nutrients (such as lactate and ketones) that fuel mitochondrial biogenesis and oxidative metabolism in cancer cells. We have termed this new energy-transfer mechanism the “reverse Warburg effect.
  • Then, oxidative stress, in cancer-associated fibroblasts, triggers the activation of two main transcription factors, NFκB and HIF-1α, leading to the onset of inflammation, autophagy, mitophagy and aerobic glycolysis in the tumor microenvironment
  • ...38 more annotations...
  • oxidative stress and ROS, produced in cancer-associated fibroblasts, has a “bystander effect” on adjacent cancer cells, leading to DNA damage, genomic instability and aneuploidy, which appears to be driving tumor-stroma co-evolution
  • tumor cells produce and secrete hydrogen peroxide, thereby “fertilizing” the tumor microenvironment and driving the “reverse Warburg effect.”
  • This type of stromal metabolism then produces high-energy nutrients (lactate, ketones and glutamine), as well as recycled chemical building blocks (nucleotides, amino acids, fatty acids), to literally “feed” cancer cells
  • loss of stromal caveolin (Cav-1) is sufficient to drive mitochondrial dysfunction with increased glucose uptake in fibroblasts, mimicking the glycolytic phenotype of cancer-associated fibroblasts.
  • oxidative stress initiated in tumor cells is transferred to cancer-associated fibroblasts.
  • Then, cancer-associated fibroblasts show quantitative reductions in mitochondrial activity and compensatory increases in glucose uptake, as well as high ROS production
  • These findings may explain the prognostic value of a loss of stromal Cav-1 as a marker of a “lethal” tumor microenvironment
  • aerobic glycolysis takes place in cancer-associated fibroblasts, rather than in tumor cells, as previously suspected.
  • our results may also explain the “field effect” in cancer biology,5 as hydrogen peroxide secreted by cancer cells, and the propagation of ROS production, from cancer cells to fibroblasts, would create an increasing “mutagenic field” of ROS production, due to the resulting DNA damage
  • Interruption of this process, by addition of catalase (an enzyme that detoxifies hydrogen peroxide) to the tissue culture media, blocks ROS activity in cancer cells and leads to apoptotic cell death in cancer cells
  • In this new paradigm, cancer cells induce oxidative stress in neighboring cancer-associated fibroblasts
  • cancer-associated fibroblasts have the largest increases in glucose uptake
  • cancer cells secrete hydrogen peroxide, which induces ROS production in cancer-associated fibroblasts
  • Then, oxidative stress in cancer-associated fibroblast leads to decreases in functional mitochondrial activity, and a corresponding increase in glucose uptake, to fuel aerobic glycolysis
  • cancer cells show significant increases in mitochondrial activity, and decreases in glucose uptake
  • fibroblasts and cancer cells in co-culture become metabolically coupled, resulting in the development of a “symbiotic” or “parasitic” relationship.
  • cancer-associated fibroblasts undergo aerobic glycolysis (producing lactate), while cancer cells use oxidative mitochondrial metabolism.
  • We have previously shown that oxidative stress in cancer-associated fibroblasts drives a loss of stromal Cav-1, due to its destruction via autophagy/lysosomal degradation
  • a loss of stromal Cav-1 is sufficient to induce further oxidative stress, DNA damage and autophagy, essentially mimicking pseudo-hypoxia and driving mitochondrial dysfunction
  • loss of stromal Cav-1 is a powerful biomarker for identifying breast cancer patients with early tumor recurrence, lymph-node metastasis, drug-resistance and poor clinical outcome
  • this type of metabolism (aerobic glycolysis and autophagy in the tumor stroma) is characteristic of a lethal tumor micro-environment, as it fuels anabolic growth in cancer cells, via the production of high-energy nutrients (such as lactate, ketones and glutamine) and other chemical building blocks
  • the upstream tumor-initiating event appears to be the secretion of hydrogen peroxide
  • one such enzymatically-active protein anti-oxidant that may be of therapeutic use is catalase, as it detoxifies hydrogen peroxide to water
  • numerous studies show that “catalase therapy” in pre-clinical animal models is indeed sufficient to almost completely block tumor recurrence and metastasis
  • by eliminating oxidative stress in cancer cells and the tumor microenvironment,55 we may be able to effectively cut off the tumor's fuel supply, by blocking stromal autophagy and aerobic glycolysis
  • breast cancer patients show systemic evidence of increased oxidative stress and a decreased anti-oxidant defense, which increases with aging and tumor progression.68–70 Chemotherapy and radiation therapy then promote further oxidative stress.69 Unfortunately, “sub-lethal” doses of oxidative stress during cancer therapy may contribute to tumor recurrence and metastasis, via the activation of myofibroblasts.
  • a loss of stromal Cav-1 is associated with the increased expression of gene profiles associated with normal aging, oxidative stress, DNA damage, HIF1/hypoxia, NFκB/inflammation, glycolysis and mitochondrial dysfunction
  • cancer-associated fibroblasts show the largest increases in glucose uptake, while cancer cells show corresponding decreases in glucose uptake, under identical co-culture conditions
  • Thus, increased PET glucose avidity may actually be a surrogate marker for a loss of stromal Cav-1 in human tumors, allowing the rapid detection of a lethal tumor microenvironment.
  • it appears that astrocytes are actually the cell type responsible for the glucose avidity.
  • In the brain, astrocytes are glycolytic and undergo aerobic glycolysis. Thus, astrocytes take up and metabolically process glucose to lactate.7
  • Then, lactate is secreted via a mono-carboxylate transporter, namely MCT4. As a consequence, neurons use lactate as their preferred energy substrate
  • both astrocytes and cancer-associated fibroblasts express MCT4 (which extrudes lactate) and MCT4 is upregulated by oxidative stress in stromal fibroblasts.34
  • In accordance with the idea that cancer-associated fibroblasts take up the bulk of glucose, PET glucose avidity is also now routinely used to measure the extent of fibrosis in a number of human diseases, including interstitial pulmonary fibrosis, postsurgical scars, keloids, arthritis and a variety of collagen-vascular diseases.
  • PET glucose avidity and elevated serum inflammatory markers both correlate with poor prognosis in breast cancers.
  • PET signal over-estimates the actual anatomical size of the tumor, consistent with the idea that PET glucose avidity is really measuring fibrosis and inflammation in the tumor microenvironment.
  • human breast and lung cancer patients can be positively identified by examining their exhaled breath for the presence of hydrogen peroxide.
  • tumor cell production of hydrogen peroxide drives NFκB-activation in adjacent normal cells in culture6 and during metastasis,103 directly implicating the use of antioxidants, NFκB-inhibitors and anti-inflammatory agents, in the treatment of aggressive human cancers.
  • Nathan Goodyear on 12 Nov 14
     
    Good description of the communication between cancer cells and fibroblasts.  This theory is termed the "reverse Warburg effect".
Nathan Goodyear

The use of serum deoxythymidine kinase as a prognostic marker, and in the monitoring of... - 0 views

www.ncbi.nlm.nih.gov/...PMC2011337

thymidine kinase 1 TK-1cancer

shared by Nathan Goodyear on 11 Feb 15 - No Cached
  • Nathan Goodyear on 11 Feb 15
     
    Thymidine kinase 1 useful as a prognostic biomarker and to monitor therapy efficacy. TK-1 levels were very low in those without cancer. Higher TK-1 levels pretreatment were associated with poor prognosis and poor survival. TK-1 "increases with progress of the disease, decreases during successful therapy, and finally increases during relapse.
Nathan Goodyear

Thymidine kinase in breast cancer. - 0 views

www.ncbi.nlm.nih.gov/...PMC1971480

thymidine kinase 1 TK-1cancer

shared by Nathan Goodyear on 11 Feb 15 - No Cached
  • Nathan Goodyear on 11 Feb 15
     
    Thymidine kinase is a good marker for DNA synthesis and proliferative activity in cancer. Healthy controls had low TK-1 levels. In contrast, advancing stage of disease was associated with increasing TK-1 levels. TK-1 also was useful in following treatment efficacy. Inflammatory GI disease was found have TK-1 levels comparable to "healthy" controls. This is important to be able to differentiate between inflammation and a useful cancer biomarker
Nathan Goodyear

Testosterone level in men with type 2 diabetes mellitus and related metabolic... - 0 views

www.ncbi.nlm.nih.gov/...PMC4364844

low T low Testosterone Diabetes Testosterone men male hormones metabolic syndrome

shared by Nathan Goodyear on 30 Mar 15 - No Cached
  • defined by consistent symptoms and signs of androgen deficiency, and an unequivocally low serum testosterone level
  • the threshold serum testosterone level below which adverse clinical outcomes occur in the general population is not known
  • most population-based studies use the serum testosterone level corresponding to the lower limit, quoted from 8.7 to 12.7 nmol/L, of the normal range for young Caucasian men as the threshold
    • Nathan Goodyear
      Nathan Goodyear on 31 Mar 15
       
      this equals 251 to 366 in serum Total Testosterone
  • ...57 more annotations...
  • Researchers tried to examine whether serum total or free testosterone would be a better/more reliable choice when studying the effect of testosterone. The results were mixed. Some reported significant associations of both serum total and free testosterone level with clinical parameters25, whereas others reported that only serum free testosterone26 or only serum total testosterone6 showed significant associations.
  • −0.124 nmol/L/year in serum total testosterone
    • Nathan Goodyear
      Nathan Goodyear on 31 Mar 15
       
      this equates to a 4 ng/dl decline annually in total Testosterone.
  • In experimental studies, androgen receptor knockout mice developed significant insulin resistance rapidly
  • In mouse models, testosterone promoted differentiation of pluripotent stem cells to the myogenic lineage
  • testosterone decreased insulin resistance by enhancing catecholamine induced lipolysis in vitro, and reducing lipoprotein lipase activity and triglyceride uptake in human abdominal tissue in vivo
  • by promoting lipolysis and myogenesis, testosterone might lead to improved insulin resistance
  • testosterone regulated skeletal muscle genes involved in glucose metabolism that led to decreased systemic insulin resistance
  • In the liver, hepatic androgen receptor signaling inhibited development of insulin resistance in mice
  • independent and inverse association of testosterone with hepatic steatosis shown in a cross-sectional study carried out in humans
  • In short, androgen improves insulin resistance by changing body composition and reducing body fat.
  • Although a low serum testosterone level could contribute to the development of obesity and type 2 diabetes through changes in body composition, obesity might also alter the metabolism of testosterone
  • In obese men, the peripheral conversion from testosterone to estrogen could attenuate the amplitude of luteinizing hormone pulses and centrally inhibit testosterone production
  • leptin, an adipokine, has been shown to be inversely correlated with serum testosterone level in men
  • Leydig cells expressed leptin receptors and leptin has been shown to inhibit testosterone secretion, suggesting a role of obesity and leptin in the pathogenesis of low testosterone
    • Nathan Goodyear
      Nathan Goodyear on 31 Mar 15
       
      So what is "unequivocal"?
  • Baltimore Longitudinal Study of Aging (BLSA) cohort made up of 3,565 middle-class, mostly Caucasian men from the USA, the incidence of low serum total testosterone increased from approximately 20% of men aged over 60 years, 30% over 70 years, to 50% over 80 years-of-age
  • 30–44% sex hormone binding globulin (SHBG)-bound testosterone and 54–68% albumin-bound testosterone
  • As the binding of testosterone to albumin is non-specific and therefore not tight, the sum of free and albumin-bound testosterone is named bioavailable testosterone, which reflects the hormone available at the cellular level
  • Serum total testosterone is composed of 0.5–3.0% of free testosterone unbound to plasma proteins
  • alterations in SHBG concentration might affect total serum testosterone level without altering free or bioavailable testosterone
  • listed in Table​T
  • A significant, independent and longitudinal effect of age on testosterone has been observed with an average change of −0.124 nmol/L/year in serum total testosterone28. The same trend has been shown in Europe and Australia
  • Asian men residing in HK and Japan, but not those living in the USA, had 20% higher serum total testosterone than in Caucasians living in the USA, as shown in a large multinational observational prospective cohort of the Osteoporotic Fractures in Men Study
  • subjects with chronic diseases consistently had a 10–15% lower level compared with age-matched healthy subjects
  • In Caucasians, the mean serum total testosterone level for men in large epidemiological studies has been reported to range from 15.1 to 16.6 nmol/L
  • Asians, higher values, ranging from 18.1 to 19.1 nmol/L, were seen in Korea and Japan
  • Chinese middle-aged men reported a similar mean serum testosterone level of 17.1 nmol/L in 179 men who had a family history of type 2 diabetes and 17.8 nmol/L in 128 men who had no family history of type 2 diabetes
  • The reduction of total testosterone was 0.4% per year in both groups
  • HK involving a cohort of 1,489 community-dwelling men with a mean age of 72 years, a mean serum total testosterone of 19.0 nmol/L was reported
  • pro-inflammatory factors, such as tumor necrosis factor-α in the testes, could locally inhibit testosterone biosynthesis in Leydig cells47, and testosterone treatment in men was shown to reduce the level of tumor necrosis factor-α
  • In Asians, a genetic deletion polymorphism of uridine diphosphate-glucuronosyltransferase UGT2B17 was associated with reduced androgen glucuronidation. This resulted in higher level of active androgen in Asians as compared to Caucasians, as Caucasians' androgen would be glucuronidated into inactive forms faster.
  • Compared with Caucasians, the frequency of this deletion polymorphism of UGT2B17 was 22-fold higher in Asian subjects
  • Other researchers have suggested that environmental, but not genetic, factors influenced serum total testosterone
  • The basal and ligand-induced activity of the AR is inversely associated with the length of the CAG repeat chain
  • In the European Male Aging Study, increased estrogen/androgen ratio in association with longer AR CAG repeat was observed
  • a smaller number of AR CAG repeat had been shown to be associated with benign prostate hypertrophy and faster prostate growth during testosterone treatment
  • In India, men with CAG ≤19 had increased risk of prostate cancer
  • the odds of having a short CAG repeat (≤17) were substantially higher in patients with lymph node-positive prostate cancer than in those with lymph node-negative disease or in the general population
  • assessing the polymorphism at the AR level could be a potential tool towards individualized assessment and treatment of hypogonadism.
  • In elderly men, there was reduced testicular response to gonadotropins with suppressed and altered pulsatility of the hypothalamic pulse generator
  • a significant, independent and longitudinal effect of age on serum total testosterone level had been observed
  • A significant graded inverse association between serum testosterone level and insulin levels independent of age has also been reported in Caucasian men
  • Low testosterone is commonly associated with a high prevalence of MES
  • most studies showed that changes in serum testosterone level led to changes in body composition, insulin resistance and the presence of MES, the reverse might also be possible
  • MES predicted a 2.6-fold increased risk of development of low serum testosterone level independent of age, smoking and other potential confounders
  • Other prospective studies have shown that development of MES accelerated the age-related decline in serum testosterone level
  • In men with type 2 diabetes, changes in serum testosterone level over time correlated inversely with changes in insulin resistance
  • weight loss by either diet control or bariatric surgery led to a substantial increase in total testosterone, especially in morbidly obese men, and the rise in serum testosterone level was proportional to the amount of weight lost
  • To date, published clinical trials are small, of short duration and often used pharmacological, not physiological, doses of testosterone
  • In the population-based Osteoporotic Fractures in Men Study cohort from Sweden, men in the highest quartile of serum testosterone level had the lowest risk of cardiovascular events compared with men in the other three quartiles (hazard ratio [HR] 0.70
  • low serum total testosterone was associated with a significant fourfold higher risk of cardiovascular events when comparing men from the lowest testosterone tertile with those in the highest tertile
  • Shores et al. were the first to report that low serum testosterone level, including both serum total and free testosterone, was associated with increased mortality
  • low serum total testosterone predicted increased risk of cardiovascular mortality with a HR of 1.38
  • low serum total testosterone increased all-cause (HR 1.35, 95% CI 1.13–1.62, P < 0.001) and cardiovascular mortality (HR 1.25
  • European Association for the Study of Diabetes 2013 suggested there was an inverse relationship between serum testosterone level and acute myocardial infarction
  • Diabetic men in the highest quartile of serum total testosterone had a significantly reduced risk of acute MI when compared with those in the lower quartiles
  • serum total testosterone level in the middle two quartiles at baseline predicted reduced incidence of death compared with having the highest and lowest levels
  • Nathan Goodyear on 30 Mar 15
     
    Nice review of Testosterone levels and some of the evidence linking Diabetes with low T.  However, the conclusion by the authors regarding what is causing the low T in men with Diabetes is baffling.  The literature does not point to one cause, it is clearly multifactorial--obesity, inflammation, high aromatase activity...I would suggest the authors continue their readings in the manner.
Nathan Goodyear

Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine | PNAS - 0 views

www.pnas.org/10238

AML leukemia acute myeloid leukemia MDS vitamin C cancer

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Vitamin C alone at concentrations up to 57 μM had little effect on cell growth but was toxic at 228 μM (SI Appendix, Fig. S1B), in line with recent studies of high vitamin C concentrations (125–2,000 μM)
  • In our combination approach, vitamin C increased the effects of low doses of 5-aza-CdR, with 57 μM vitamin C almost doubling the growth inhibition
  • Using the Chou–Talalay method (28), we found that the two compounds indeed acted synergistically, rather than additively, to inhibit cancer cell growth over the physiological ranges of vitamin C in healthy individuals (26–84 μM)
  • ...12 more annotations...
  • These results show that targeting the cancer DNA methylome by combining low-dose 5-aza-CdR and vitamin C stimulates the expression of ERVs, the induction of a cell-autonomous immune activation response, and increased apoptosis of cancer cells
  • The addition of vitamin C to treatment protocols therefore may be a straightforward way to increase the clinical efficacy of such drugs in MDS and leukemia patients
  • Vitamin C deficiency has been seen previously in patients with multiple types of cancer, including hematological malignancies (35⇓–37). We predict that these patients might receive the most benefits from the combination treatment.
  • induction of an innate immune response
  • We therefore measured plasma concentrations of vitamin C in a small number of patients with miscellaneous hematologic malignancies. Strikingly, 58% of patients with hematological neoplasia who were not taking vitamin C supplements had severe vitamin C deficiency (serum concentration <11.4 μM, at which clinical features of scurvy may be manifested) (34), and 33% had vitamin C levels below the normal range
  • it is possible that vitamin C was oxidized to DHA before it was transported into the cells
  • Oral administration of vitamin C should be sufficient for the therapeutic strategy, because the concentrations reported in this study would not require i.v. administration.
    • Nathan Goodyear
      Nathan Goodyear on 12 May 18
       
      This statement lacks a basic understanding of vitamin C pharmacokinetics.
  • Vitamin C is an essential nutrient for humans and has been reported to increase IFN levels in human cells upon virus infection
  • daily treatment with vitamin C alone at physiological concentrations enhanced the expression of viral-defense genes relative to untreated cells
  • When combined with low-dose 5-aza-CdR, physiological concentrations of vitamin C synergistically inhibited cancer-cell growth and induced apoptosis. Such synergy was associated with increased ERV expression and dsRNA in treated cells. The mechanism of action differs from that of vitamin C at higher doses, which involves its pro-oxidant activity, including GSH inhibition, to generate reactive oxygen species
  • This activity has been shown to induce DNA damage and to enhance the sensitivities of myeloid malignancies, multiple myeloma, and cutaneous T-cell lymphoma to arsenic trioxide (41⇓⇓–44). It also can increase chemosensitivity of ovarian cancer cells (27) and selectively kill KRAS or BRAF mutant colorectal cancer cells by inhibiting GAPDH
  • reactive oxygen species
  • Nathan Goodyear on 12 May 18
     
    91% of patients with hematologic malignancies have vitamin C levels that are either low or severly deficient. This study found that vitamin C plus low dose DNA methyltransferase inhibitors have synergistic inhibition of cancer cell proliferation and increased apoptosis.  Unfortunately, the authors claimed that oral vitamin C would be sufficient which indicates an incredible lack of understanding of vitamin C pharmacokinetics.
Nathan Goodyear

Ibuprofen alters human testicular physiology to produce a state of compensated hypogona... - 0 views

www.pnas.org/...1715035115.full

ibuprofen Testosterone epigenetics hormones low Testosterone low T

shared by Nathan Goodyear on 09 Jan 18 - No Cached
  • The levels of LH in the ibuprofen group had increased by 23% after 14 d of administration
  • This increase was even more pronounced at 44 d, at 33%
  • We found an 18% decrease (P = 0.056) in the ibuprofen group compared with the placebo group after 14 d (Fig. 1A) and a 23% decrease (P = 0.02) after 44 d (Fig. 1C). Taken together, these in vivo data suggest that ibuprofen induced a state of compensated hypogonadism during the trial, which occurred as early as 14 d and was maintained until the end of the trial at 44 d
  • ...27 more annotations...
  • We first investigated testosterone production after 24 and 48 h of ibuprofen exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent (β = −0.405, P = 0.01 at 24 h and β = −0.664, P < 0.0001 at 48 h) (Fig. 2A) and was augmented over time
  • The AMH data show that the hypogonadism affected not only Leydig cells but also Sertoli cells and also occurred as early as 14 d of administration
  • Sertoli cell activity showed that AMH levels decreased significantly with ibuprofen administration, by 9% (P = 0.02) after 14 d (Fig. 1B) and by 7% (P = 0.05) after 44 d compared with the placebo group
  • Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection except in one experiment with DHEA
  • Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory effect on the expression of these genes (Fig. 3 B–D), consistent with that seen above in our ex vivo organ model. Taken together, these data examining effects on the endocrine cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of steroidogenesis.
  • Suppression of gene expression concerned the initial conversion of cholesterol to the final testosterone synthesis. Hence, expression of genes involved in cholesterol transport to the Leydig cell mitochondria was impaired
  • A previous study reported androsterone levels decreased by 63% among men receiving 400 mg of ibuprofen every 6 h for 4 wk
  • We next examined the gene expression involved in testicular steroidogenesis ex vivo and found that levels of expression of every gene that we studied except CYP19A1 decreased after exposure for 48 h compared with controls
  • the changes in gene expression indicate that the transcriptional machinery behind the endocrine action of Leydig cells was most likely impaired by ibuprofen exposure.
  • Together, these data show that ibuprofen also directly impairs Sertoli cell function ex vivo by inhibiting transcription
  • ibuprofen use in men led to (i) elevation of LH; (ii) a decreased testosterone/LH ratio and, to a lesser degree, a decreased inhibin B/FSH ratio; and (iii) a reduction in the levels of the Sertoli cell hormone AMH
  • The decrease in the free testosterone/LH ratio resulted primarily from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen exposure. Our data from the ex vivo experiments support this notion, indicating that the observed elevation in LH resulted from ibuprofen’s direct antiandrogenic action
  • AMH levels were consistently suppressed by ibuprofen both in vivo and ex vivo, indicating that this hormone is uncoupled from gonadotropins in adult men. The ibuprofen suppression of AMH further demonstrated that the analgesic targeted not only the Leydig cells but also the Sertoli cells, a feature encountered not only in the human adult testis but also in the fetal testis
  • ibuprofen displayed broad transcription-repression abilities involving steroidogenesis, peptide hormones, and prostaglandin synthesis
  • a chemical compound, through its effects on the signaling compounds, can result in changes in the testis at gene level, resulting in perturbations at higher physiological levels in the adult human
  • The analgesics acetaminophen/paracetamol and ibuprofen have previously been shown to inhibit the postexercise response in muscles by repressing transcription
  • Previous ex vivo studies on adult testis have indeed pointed to an antiandrogenicity, only on Leydig cells, of phthalates (41), aspirin, indomethacin (42), and bisphenol A (BPA) and its analogs
  • ibuprofen’s effects were not restricted to Leydig and Sertoli cells, as data showed that the expression of genes in peritubular cells was also affected
  • short-term exposure
  • In the clinical setting, compromised Leydig cell function resulting in increased insensitivity to LH is defined as compensated hypogonadism (4), an entity associated with all-cause mortality
  • compensated hypogonadic men present with an increased likelihood of reproductive, cognitive, and physical symptoms
  • an inverse relationship was recently reported between endurance exercise training and male sexual libido
  • AMH concentrations are lower in seminal plasma from patients with azoospermia than from men with normal sperm levels
  • inhibin B is a key clinical marker of reproductive health (32). The function of AMH, also secreted by Sertoli cells, and its regulation through FSH remain unclear in men
  • the striking dual effect of ibuprofen observed here on both Leydig and Sertoli cells makes this NSAID the chemical compound, of all the chemical classes considered, with the broadest endocrine-disturbing properties identified so far in men.
  • after administration of 600 mg of ibuprofen to healthy volunteers
  • 14 d or at the last day of administration at 44 d
  • Nathan Goodyear on 09 Jan 18
     
    ibuprofen alters genetic expression that results in decreased Testosterone production.
Nathan Goodyear

A cross-sectional study of different patterns of oral contraceptive use among premenopa... - 0 views

www.ncbi.nlm.nih.gov/...PMC3123282

birth control pills OCP contraception IGF-1 HGH pre-menopausal women human growth hormone

shared by Nathan Goodyear on 20 Feb 13 - No Cached
  • Nathan Goodyear on 20 Feb 13
     
    Birth control pills were found to reduce IGF-1 levels in the short term and long term.  Those that had used birth control pills had lower IGF-1 levels compared to those that had never used birth control pills.  This fits with the current knowledge that oral estrogen reduces HGH and IGF-1.  Those were in post-menopausal women, but this is in pre-menopaus women.  This has implications on health, weight, disease...
Nathan Goodyear

Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effe... - 0 views

www.jbc.org/...23111.long

HIF-1alpha cancer Hypoxia-inducible Factor 1

shared by Nathan Goodyear on 17 Oct 13 - No Cached
  • HIF-1 activation is highly associated with cancer cell growth and survival, tumor development, tumor angiogenesis, and poor clinical prognosis
  • The adaptation of cancer cells to hypoxia is mediated via hypoxia-inducible Factor 1 (HIF-1),1 a key transcription factor that up-regulates a series of genes involved in glycolytic energy metabolism, angiogenesis, cell survival, and erythropoiesis. Included among these genes are vascular endothelial growth factor (VEGF), erythropoietin (EPO), glucose transporters (GLUT), and several glycolytic enzymes (12, 13).
  • Nathan Goodyear on 17 Oct 13
     
    good discussion of HIF-1alpha and cancer
wheelchairindia9

A Friendly Tricycle For Disabled People - 0 views

www.blogroll.net/article.php

A Friendly Tricycle For Disabled People more stability lower centre of gravity durability and safety dynamic lateral stability better handling and control

shared by wheelchairindia9 on 21 Apr 15 - No Cached
  • wheelchairindia9 on 21 Apr 15
     
    A tricycle for special needs is made so can go along for the ride in wheelchair or sitting in a special seat, both of which are attached right in front of another adult's trike. Tricycles to accommodate a vast array of special needs. Hand-pedaled recumbent tricycles are available for those without the use of their legs. Children, teens and adults with cerebral palsy and similar disorders can select tricycles specially designed to increase strength and coordination. Caregivers to autistic children can ride with their child on tandem special needs tricycles built to accommodate one adult and one child rider. Accessories are also available to convert standard trikes to suit specific needs. The objective of tricycle design is to produce wheelchairs that perform well and can provide appropriate seating and postural support without compromising strength, durability and safety. A Hand Driven Tricycle, abbreviated to trike is a three-wheeled passenger vehicle, usually carrying a single rider. The tricycle consists of a motorbike and an attached passenger sidecar and should not be confused with the tricycle. The trike is a motorized three-wheeled pedicab. Human-powered trikes are powered by pedals or hand cranks. Motorized trikes use motorcycle or scooter,or electric motors. Tricycles tend to be used for commercial purposes: such as "pedicabs" for transport passengers, and freight trikes for making deliveries. In the adult-sized tricycles are used primarily for recreation, shopping, and exercise. Tricycles are favoured by children and senior adults alike for their apparent stability versus a bicycle; but a conventional trike has poor dynamic lateral stability, and the rider must take care when cornering to avoid tipping the trike over. Standard Single Hand Driven Tricycle: Frame : Made by E.R.W. Tubes 22.22 mm- 18 G. Seat & Back : MS, CRC Sheet Seat Size 18"x 16" Wheel Size : Wheel Diameter 28"x 1 1/2" Tyre and Tube Standard Company. Parts : Standard Quality
wheelchairindia9

A Friendly Tricycle For Disabled People - 0 views

www.articlesbase.com/...r-disabled-people-7248754.html

A Friendly Tricycle For Disabled People more stability lower centre of gravity durability and safety dynamic lateral stability better handling and control

shared by wheelchairindia9 on 17 Apr 15 - No Cached
  • wheelchairindia9 on 17 Apr 15
     
    A tricycle for special needs is made so can go along for the ride in wheelchair or sitting in a special seat, both of which are attached right in front of another adult's trike. Tricycles to accommodate a vast array of special needs. Hand-pedaled recumbent tricycles are available for those without the use of their legs. Children, teens and adults with cerebral palsy and similar disorders can select tricycles specially designed to increase strength and coordination. Caregivers to autistic children can ride with their child on tandem special needs tricycles built to accommodate one adult and one child rider. Accessories are also available to convert standard trikes to suit specific needs. The objective of tricycle design is to produce wheelchairs that perform well and can provide appropriate seating and postural support without compromising strength, durability and safety. A Hand Driven Tricycle, abbreviated to trike is a three-wheeled passenger vehicle, usually carrying a single rider. The tricycle consists of a motorbike and an attached passenger sidecar and should not be confused with the tricycle. The trike is a motorized three-wheeled pedicab. Human-powered trikes are powered by pedals or hand cranks. Motorized trikes use motorcycle or scooter,or electric motors. Tricycles tend to be used for commercial purposes: such as "pedicabs" for transport passengers, and freight trikes for making deliveries. In the adult-sized tricycles are used primarily for recreation, shopping, and exercise. Tricycles are favoured by children and senior adults alike for their apparent stability versus a bicycle; but a conventional trike has poor dynamic lateral stability, and the rider must take care when cornering to avoid tipping the trike over. Standard Single Hand Driven Tricycle: Frame : Made by E.R.W. Tubes 22.22 mm- 18 G. Seat & Back : MS, CRC Sheet Seat Size 18"x 16" Wheel Size : Wheel Diameter 28"x 1 1/2" Tyre and Tube Standard Company. Parts : Standard Quality
wheelchairindia9

A Friendly Tricycle For Disabled People - 0 views

www.apsense.com/...cycle-for-disabled-people.html

A Friendly Tricycle For Disabled People more stability lower centre of gravity durability and safety dynamic lateral stability better handling and control

shared by wheelchairindia9 on 17 Apr 15 - No Cached
  • wheelchairindia9 on 17 Apr 15
     
    A tricycle for special needs is made so can go along for the ride in wheelchair or sitting in a special seat, both of which are attached right in front of another adult's trike. Tricycles to accommodate a vast array of special needs. Hand-pedaled recumbent tricycles are available for those without the use of their legs. Children, teens and adults with cerebral palsy and similar disorders can select tricycles specially designed to increase strength and coordination. Caregivers to autistic children can ride with their child on tandem special needs tricycles built to accommodate one adult and one child rider. Accessories are also available to convert standard trikes to suit specific needs. The objective of tricycle design is to produce wheelchairs that perform well and can provide appropriate seating and postural support without compromising strength, durability and safety. A Hand Driven Tricycle, abbreviated to trike is a three-wheeled passenger vehicle, usually carrying a single rider. The tricycle consists of a motorbike and an attached passenger sidecar and should not be confused with the tricycle. The trike is a motorized three-wheeled pedicab. Human-powered trikes are powered by pedals or hand cranks. Motorized trikes use motorcycle or scooter,or electric motors. Tricycles tend to be used for commercial purposes: such as "pedicabs" for transport passengers, and freight trikes for making deliveries. In the adult-sized tricycles are used primarily for recreation, shopping, and exercise. Tricycles are favoured by children and senior adults alike for their apparent stability versus a bicycle; but a conventional trike has poor dynamic lateral stability, and the rider must take care when cornering to avoid tipping the trike over. Standard Single Hand Driven Tricycle: Frame : Made by E.R.W. Tubes 22.22 mm- 18 G. Seat & Back : MS, CRC Sheet Seat Size 18"x 16" Wheel Size : Wheel Diameter 28"x 1 1/2" Tyre and Tube Standard Company. Parts : Standard Quality
Nathan Goodyear

Thymidine Kinase 1 Upregulation Is an Early Event in Breast Tumor Formation - 0 views

www.hindawi.com/...575647

thymidine kinase 1 TK-1 cancer breast cancer

shared by Nathan Goodyear on 19 Feb 15 - No Cached
  • Thymidine kinase 1 (TK1), a proliferation marker involved in DNA repair
  • prognostic potential
  • TK1 upregulation is an early event in tumor tissue formation
  • Nathan Goodyear on 19 Feb 15
     
    Upregulation of TK-1 found to be an early event in breast tumor development. This has implications in precancerous tissue and elevations correlate to stage of cancer. TK-1 has also been found to correlate with Cancer recurrence.
wheelchairindia9

A Friendly Tricycle For Disabled People - 0 views

www.articlepoint.org/...cycle-for-disabled-people.aspx

A Friendly Tricycle For Disabled People more stability lower centre of gravity durability and safety dynamic lateral stability better handling and control

shared by wheelchairindia9 on 20 Apr 15 - No Cached
  • wheelchairindia9 on 20 Apr 15
     
    A tricycle for special needs is made so can go along for the ride in wheelchair or sitting in a special seat, both of which are attached right in front of another adult's trike. Tricycles to accommodate a vast array of special needs. Hand-pedaled recumbent tricycles are available for those without the use of their legs. Children, teens and adults with cerebral palsy and similar disorders can select tricycles specially designed to increase strength and coordination. Caregivers to autistic children can ride with their child on tandem special needs tricycles built to accommodate one adult and one child rider. Accessories are also available to convert standard trikes to suit specific needs. The objective of tricycle design is to produce wheelchairs that perform well and can provide appropriate seating and postural support without compromising strength, durability and safety. A Hand Driven Tricycle, abbreviated to trike is a three-wheeled passenger vehicle, usually carrying a single rider. The tricycle consists of a motorbike and an attached passenger sidecar and should not be confused with the tricycle. The trike is a motorized three-wheeled pedicab. Human-powered trikes are powered by pedals or hand cranks. Motorized trikes use motorcycle or scooter,or electric motors. Tricycles tend to be used for commercial purposes: such as "pedicabs" for transport passengers, and freight trikes for making deliveries. In the adult-sized tricycles are used primarily for recreation, shopping, and exercise. Tricycles are favoured by children and senior adults alike for their apparent stability versus a bicycle; but a conventional trike has poor dynamic lateral stability, and the rider must take care when cornering to avoid tipping the trike over. Standard Single Hand Driven Tricycle: Frame : Made by E.R.W. Tubes 22.22 mm- 18 G. Seat & Back : MS, CRC Sheet Seat Size 18"x 16" Wheel Size : Wheel Diameter 28"x 1 1/2" Tyre and Tube Standard Company. Parts : Standard Quality
wheelchairindia9

Pristine Flex Ostrich Mobility Wheelchair - 0 views

www.wheelchairindia.com/...ex-Ostrich-Mobility-Wheelchair

Pristine Flex Ostrich Mobility Wheelchair Ostrich Mobility Wheelchair pristine flex electric wheelchair Ostrich Wheel Chair Pristine FLEX Ostrich Pristine FLEX

shared by wheelchairindia9 on 04 Mar 16 - No Cached
  • wheelchairindia9 on 04 Mar 16
     
    Pristine Flex Ostrich Mobility Wheelchair Pristine is the most stylish powered wheelchair with revolutionary Split Frame Chassis (SFC). This indoor outdoor mobility equipment gives great comfort, stability and safety even in the toughest outdoor conditions. The body panels and the shopping basket make this equipment best suited for your kind of lifestyle. Pristine Flex Ostrich Mobility Wheelchair Features Split Frame Chassis (SFC). Call alarm, fault alarm, reverse alarm (on request). Low voltage alarm. Key pad locking. Mobility cut-off while charging. Auto shut-off after 3 minutes. Five speed selector. Length adjustable joystick control unit (can be changed from left to right and vice versa). Foldable, height adjustable and angle adjustable foot rest. Wide arm rest with height and width adjustment. Bucket seat with headrest and lap belt. Seat can be folded for transportation. Seat reclines 25 degrees in 6 steps. Removable and width adjustable calf support. Reflectors as per standards. Head lamp. Tail lamp. Pristine Flex Ostrich Mobility Wheelchair Specifications Load capacity: 110 Kg Speed: 9.5 Kmph max Speed selection: 5 speeds, Speed 1- 1.5Kmph, Speed 2-2.5 Kmph, speed 3- 4.8 Kmph, Speed 4- 7.2 Kmph, Speed 5- 9.5 Kmph Power: 320W Motor speed: 5300 rpm Gear ratio: 32:1 Brake: Electromagnetic Permissible Gradeability: 12 Degrees Drive range: 32-35 Km Ground clearance:2.5 inches Turn circle radius: 620mm Tire: Puncture free foam filled rubber tires Front- Tire diameter: 220X55 mm, Rear- Tire diameter: 320X72mm, Anti tippers-1 inch solid Battery: 24 Volt 48 Ah Sealed Maintenance Free VRLA Charger Input-230/240 Volts AC Single phase, Output-24 Volts-4 Amps DC Overall length with footrest (at 90 degree):1180mm, Overall width:640mm, Overall height: 1250mm, Overall height after folding the seat: 690mm, Overall weight: 102 Kg Seat depth: 500mm, Seat width:480mm, Backrest height: 540mm (without head rest), Backrest width: 440mm, Se
Nathan Goodyear

Revised estimates for the number of human and bacteria cells in the body | bioRxiv - 0 views

biorxiv.org/...036103

gut flora gut gut microbiome gut microbiota

shared by Nathan Goodyear on 12 Jan 16 - No Cached
  • Nathan Goodyear on 12 Jan 16
     
    Good science always challenges established dogma.  Only abstract available here.  Study calls into question the 10:1 claim: bacteria out number human cells by 10:1.  New study finds ratio more near 1:1.  
Nathan Goodyear

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical respo... - 0 views

www.ncbi.nlm.nih.gov/...PMC6114970

cancer metabolism breast cancer glutamine glutamate aspartate oncogenes

shared by Nathan Goodyear on 24 Sep 18 - No Cached
  • We now recognize that human cancers evolve in an environment of metabolic stress. Rapidly proliferating tumor cells deprived of adequate oxygen, nutrients, hormones and growth factors up-regulate pathways that address these deficiencies to overcome hypoxia (HIF), vascular insufficiency (VEGF), growth factor deprivation (EGFR, HER2) and the loss of hormonal support (ER, PR, AR) all to enhance survival and proliferation
  • RAS, PI3K, TP53 and MYC
  • The results suggest that breast cancer could be preceded by systemic subclinical disturbances in glucose-insulin homeostasis characterized by mild, likely asymptomatic, IEM-like biochemical changes
  • ...16 more annotations...
  • The process would include variable periods of hyperinsulinemia with the consequent systemic MYC activation of glycolysis, glutaminolysis, structural lipidogenesis and further exacerbation of hypoglycemia, the result of MYC's known role as an inhibitor of liver gluconeogenesis
  • The metabolic changes we describe in breast cancer arise in concert with IEM-like changes in oxidative phosphorylation as detected by increased values of the ratio lactate/pyruvate (Supplementary Table 2A, 2B) characteristic of Ox/Phos deficiency [25]. In our study, 76% (70/92) of the European breast cancer patients had lactate/pyruvate ratios values higher than the normal value of 25.8
  • four-fold higher frequency of cancer (including breast) in patients with energy metabolism disorders
  • growing recognition that cancer cells differ from their normal counterparts in their use of nutrients, synthesis of biomolecules and generation of energy
  • glutamine concentrations in the cancer patients were reduced to nearly 1/8 of the levels observed in the normal population
  • blood concentrations of aspartate (p = 1.7e-67, FDR = 8.3e-67) (Figure ​(Figure1E)1E) and glutamate (p = 6.4e-96, FDR = 6.2e-95) (Figure ​(Figure1F)1F) were nearly 10 fold higher than the normal ranges of 0–5 μM/L and 40 μM/L, respectively
  • glutamine consumption associated with parallel increases in glutamate and aspartate (Figure ​(Figure1A1A red arrows) is considered a hallmark of MYC-driven “glutaminolysis”
  • Gln/Glu ratio inversely correlates with i- late stage metabolic syndrome and with ii- increased chance of death
  • changes in glutamine consumption, reflected by the Gln/Glu ratio could provide a metabolic link between breast cancer initiation and diabetes, reflective of a systemic metabolic reprogramming from glucose to glutamine as the preferred source of precursors for biosynthetic reactions and cellular energy
  • lower Gln/Glu ratios inversely correlated with insulin resistance and the risk of diabetes
  • the metabolic dependencies of cancer characterized by excessive glycolysis, glutaminolysis and malignant lipidogenesis, previously considered a consequence of local tumor DNA aberration [23] could, instead, represent a systemic biochemical aberration that predates and very likely promotes tumorigenesis
  • these metabolic disturbances would be expected to remain extant after therapeutic interventions
  • accumulation of very long chain acylcarnitines such as C14:1-OH (p = 0.0, FDR = 0.0), C16 (p = 0.0, FDR = 0.0), C18 (p = 0.0, FDR = 0.0) and C18:1 (p = 1.73e-322, FDR = 1.16-321) and lipids containing VLCFA (lysoPC a C28:0) (p = 1.14-e95, FDR = 1.65e-95) in the blood of breast and colon cancer patients
  • Among the most powerful metabolic equations for MYC-activation is that which links the widely used MYC-driven desaturation marker ratio of SFA/MUFA to the MYC glutaminolysis-associated ratio of (Asp/Gln)
  • liver dysfunction shares many features with both IEM and cancer suggesting a role for hepatic dysfunction in carcinogenesis
  • cancer “conscripts” the human genome to meet its needs under conditions of systemic metabolic stress
  • Nathan Goodyear on 24 Sep 18
     
    Breast cancer is a metabolic disease.  Now, where have I heard that cancer is a metabolic disease?
Nathan Goodyear

Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde... - 0 views

www.hindawi.com/...360438

MDA malondialdehyde peroxidation oxidative stress free radicals

shared by Nathan Goodyear on 05 Dec 17 - No Cached
  • Hydroxyl radicals cause oxidative damage to cells because they unspecifically attack biomolecules [22] located less than a few nanometres from its site of generation and are involved in cellular disorders such as neurodegeneration [23, 24], cardiovascular disease [25], and cancer [26, 27].
  • It is generally assumed that in biological systems is formed through redox cycling by Fenton reaction, where free iron (Fe2+) reacts with hydrogen peroxide (H2O2) and the Haber-Weiss reaction that results in the production of Fe2+ when superoxide reacts with ferric iron (Fe3+)
  • other transition-metal including Cu, Ni, Co, and V can be responsible for formation in living cells
  • ...20 more annotations...
  • The hydroperoxyl radical () plays an important role in the chemistry of lipid peroxidation
  • The is a much stronger oxidant than superoxide anion-radical
  • Lipid peroxidation can be described generally as a process under which oxidants such as free radicals or nonradical species attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs) that involve hydrogen abstraction from a carbon, with oxygen insertion resulting in lipid peroxyl radicals and hydroperoxides as described previously
  • under medium or high lipid peroxidation rates (toxic conditions) the extent of oxidative damage overwhelms repair capacity, and the cells induce apoptosis or necrosis programmed cell death
  • The overall process of lipid peroxidation consists of three steps: initiation, propagation, and termination
  • Once lipid peroxidation is initiated, a propagation of chain reactions will take place until termination products are produced.
  • The main primary products of lipid peroxidation are lipid hydroperoxides (LOOH)
  • Among the many different aldehydes which can be formed as secondary products during lipid peroxidation, malondialdehyde (MDA), propanal, hexanal, and 4-hydroxynonenal (4-HNE) have been extensively studied
  • MDA has been widely used for many years as a convenient biomarker for lipid peroxidation of omega-3 and omega-6 fatty acids because of its facile reaction with thiobarbituric acid (TBA)
  • MDA is one of the most popular and reliable markers that determine oxidative stress in clinical situations [53], and due to MDA’s high reactivity and toxicity underlying the fact that this molecule is very relevant to biomedical research community
  • 4-HNE is considered as “second toxic messengers of free radicals,” and also as “one of the most physiologically active lipid peroxides,” “one of major generators of oxidative stress,” “a chemotactic aldehydic end-product of lipid peroxidation,” and a “major lipid peroxidation product”
  • MDA is an end-product generated by decomposition of arachidonic acid and larger PUFAs
  • Identifying in vivo MDA production and its role in biology is important as indicated by the extensive literature on the compound (over 15 800 articles in the PubMed database using the keyword “malondialdehyde lipid peroxidation” in December 2013)
  • MDA reactivity is pH-dependent
  • When pH decreases MDA exists as beta-hydroxyacrolein and its reactivity increases
  • MAA adducts are shown to be highly immunogenic [177–181]. MDA adducts are biologically important because they can participate in secondary deleterious reactions (e.g., crosslinking) by promoting intramolecular or intermolecular protein/DNA crosslinking that may induce profound alteration in the biochemical properties of biomolecules and accumulate during aging and in chronic diseases
  • MDA is an important contributor to DNA damage and mutation
  • This MDA-induced DNA alteration may contribute significantly to cancer and other genetic diseases.
  • Dietary intake of certain antioxidants such as vitamins was associated with reduced levels of markers of DNA oxidation (M1dG and 8-oxodG) measured in peripheral white blood cells of healthy subjects, which could contribute to the protective role of vitamins on cancer risk
  • 4-HNE is an extraordinarily reactive compound
  • Nathan Goodyear on 05 Dec 17
     
    Great review of lipid peroxidation
fitspresso

https://www.fitspresso-co.com/ - 0 views

www.fitspresso-co.com

fitspresso fit spresso us uk buy usa 2023 pros 2022 2024 pills order price weight loss espresso fitespresso review amazon tablet reviews customer supplement does it work

shared by fitspresso on 27 Sep 23 - No Cached
  • fitspresso on 27 Sep 23
     
    FitSpresso™ | Official Site fitspresso-co.com FitSpresso Only $39/Bottle Limited Time Offer! FitSpresso Special Deal + Special 51% Discount Save $660 + 180 Days Money Back Guarantee FitSpresso Herpesyl Five Star A dietary product formulated to assist users in reducing weight can increase other advantages that can support overall health. This product can assist users in getting closer to the desirable body weight. Regular Price: 149/per bottle Only for: $39/per bottle Buy Now What IsFitSpresso? FitSpresso is promoted as a natural supplement that comes in the form of diet pills, and it can aid in rapid and efficient weight loss, similar to many other supplements. The term "natural supplements refers to a nutritional supplement that is made entirely of natural, chemical-free materials. You can utilize these organic ingredients to aid in natural weight loss. It can speed up your body's metabolism and assist with other crucial processes. All parts of our bodies are impacted by weight increase, and not only do we need to deal with the increased weight, but we also need to deal with the numerous problems and illnesses that come along with it. This refers to the risk of developing chronic cardiac conditions, low blood pressure, and, in some circumstances, problems with blood sugar. However, FitSpresso even with its bright and bold claims, can help you efficiently manage your weight and completely avoid these extra uncomfortable problems. FitSpresso is a supplement that comes in the form of a pill, which makes it tasty, simple to swallow, and handy. According to the manufacturer, these diet tablets are GMO-free and toxic-free, making them edible. This is why we have things such as weight loss supplements. Thanks to modern advancements, we can just take a dietary supplement pill to bring about significant weight loss in a completely healthy and natural manner. Not only this, but dietary supplements can also support healthy blood sugar levels and help with
Nathan Goodyear

Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth ho... - 0 views

erc.endocrinology-journals.org/...583.long

HGH GH IGF-1 IGFBP-1 IGFBP-3 breast cancer premenopause premenopausal women Nurses Health Study Nurses Health Study II

shared by Nathan Goodyear on 06 Jul 12 - No Cached
  • Nathan Goodyear on 06 Jul 12
     
    GH, IGF-1, IGFBP-1, and IGFBP-3 were not found to be associated with increased risk of breast cancer in premenopuasal women.
Nathan Goodyear

High Glucose-Induced Expression of Proinflammatory Cytokine and Chemokine Genes in Mono... - 0 views

diabetes.diabetesjournals.org/...1256.abstract

glucose diabetes IR insulin resistance inflammation TNF-alpha MCP-1 IL-1B

shared by Nathan Goodyear on 11 Jun 12 - No Cached
  • HG significantly increased the expression of monocyte chemoattractant protein-1 (MCP-1), TNF-α, β2-integrin, interleukin-1β, and others. HG treatment increased transcription of the MCP-1 gene, MCP-1 protein levels, and adhesion of THP-1 cells to endothelial cells. HG-induced MCP-1 mRNA expression and monocyte adhesion were blocked by specific inhibitors of oxidant stress, protein kinase C, ERK1/2, and p38 mitogen-activated protein kinases
  • Nathan Goodyear on 11 Jun 12
     
    High glucose associated with significant increase in inflammatory signaling.
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