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Nathan Goodyear

https://academic.oup.com/DocumentLibrary/humupd/PR/dmx022_final.pdf - 0 views

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    The problem of male infertility continues to grow. New study finds that from 1973 to 2011, sperm count among men in North America, Europe, Australia, and New Zealand drop by 50-60%.
Nathan Goodyear

Oncotarget | Vitamin C and Doxycycline: A synthetic lethal combination therapy targeting metabolic flexibility in cancer stem cells (CSCs) - 0 views

  • These eight distinct cancer types included: DCIS, breast (ER(+) and ER(-)), ovarian, prostate, lung, and pancreatic carcinomas, as well as melanoma and glioblastoma. Doxycycline was also effective in halting the propagation of primary cultures of CSCs from breast cancer patients, with advanced metastatic disease (isolated from ascites fluid and/or pleural effusions)
  • Doxycycline behaves as a strong radio-sensitizer, successfully overcoming radio-resistance in breast CSCs
  • cancer cells can indeed escape the effects of Doxycycline, by reverting to a purely glycolytic phenotype. Fortunately, the metabolic inflexibility conferred by this escape mechanism allows Doxycycline-resistant (DoxyR) CSCs to be more effectively targeted with many other metabolic inhibitors, including Vitamin C, which functionally blocks aerobic glycolysis
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  • Vitamin C inhibits GAPDH (a glycolytic enzyme) and depletes the cellular pool of glutathione, resulting in high ROS production and oxidative stress
  • DoxyR CSCs are between 4- to 10-fold more susceptible to the effects of Vitamin C
  • Doxycycline and Vitamin C may represent a new synthetic lethal drug combination for eradicating CSCs, by ultimately targeting both mitochondrial and glycolytic metabolism
  • inhibiting their propagation in the range of 100 to 250 µM
  • metabolic flexibility in cancer cells allows them to escape therapeutic eradication, leading to chemo- and radio-resistance
  • used doxycycline to pharmacologically induce metabolic inflexibility in CSCs, by chronically inhibiting mitochondrial biogenesis
  • This treatment resulted in a purely glycolytic population of surviving cancer cells
  • DoxyR cells are mainly glycolytic
  • MCF7 cells survive and develop Doxycycline-resistance, by adopting a purely glycolytic phenotype
  • Cancer stem cells (CSCs) are thought to be the “root cause” of tumor recurrence, distant metastasis and therapy-resistance
  • the conserved evolutionary similarities between aerobic bacteria and mitochondria, certain classes of antibiotics inhibit mitochondrial protein translation, as an off-target side-effect
  • Vitamin C was more potent than 2-DG; it inhibited DoxyR CSC propagation by > 90% at 250 µM and 100% at 500 µM
  • IC-50
  • DoxyR CSCs are between 4- to 10-fold more sensitive to Vitamin C than control MCF7 CSCs
  • Berberine, which is a naturally occurring antibiotic that also behaves as an OXPHOS inhibitor
  • treatment with Berberine effectively inhibited the propagation of the DoxyR CSCs by > 50% at 1 µM and > 80% at 10 µM.
  • Doxycycline, a clinically approved antibiotic, induces metabolic stress in cancer cells. This allows the remaining cancer cells to be synchronized towards a purely glycolytic phenotype, driving a form of metabolic inflexibility
  • Doxycycline-driven aerobic glycolysis
  • new synthetic lethal strategy for eradicating CSCs, by employing i) Doxycycline (to target mitochondria) and ii) Vitamin C (to target glycolysis)
  • Doxycycline inhibits mitochondrial biogenesis and OXPHOS,
  • hibits glycolytic metabolism by targeting and inhibiting the enzyme GAPDH
  • CSCs act as the main promoter of tumor recurrence and patient relapse
  • a metabolic shift from oxidative to glycolytic metabolism represents an escape mechanism for breast cancer cells chronically-treated with a mitochondrial stressor like Doxycycline, as mitochondrial dys-function leads to a stronger dependence on glucose
  • Vitamin C has been demonstrated to selectively kill cancer cells in vitro and to inhibit tumor growth in experimental mouse models
  • many of these actions have been attributed to the ability of Vitamin C to act as a glycolysis inhibitor, by targeting GAPDH and depleting the NAD pool
  • here we show that DoxyR CSCs are more vulnerable to the inhibitory effects of Vitamin C, at 4- to 10-fold lower concentrations, between 100 to 250 μM
  • concurrent use of Vitamin C, with standard chemotherapy, reduces tumor recurrence and patient mortality
  • after oral administration, Vitamin C plasma levels reach concentrations of ~70-220 μM
  • intravenous administration results in 30- to 70- fold higher plasma concentrations of Vitamin C
  • pro-oxidant activity results from Vitamin C’s action on metal ions, which generates free radicals and hydrogen peroxide, and is associated with cell toxicity
  • it has been shown that high-dose Vitamin C is more cytotoxic to cancer cells than to normal cells
  • This selectivity appears to be due to the higher catalase content observed in normal cells (~10-100 fold greater), as compared to tumor cells. Hence, Vitamin C may be regarded as a safe agent that selectively targets cancer cells
  • the concurrent use of Doxycycline and Vitamin C, in the context of this infectious disease, appeared to be highly synergistic in patients
  • Goc et al., 2016, showed that Doxycycline is synergistic in vitro with certain phytochemicals and micronutrients, including Vitamin C, in the in vitro killing of the vegetative spirochete form of Borrelia spp., the causative agent underlying Lyme disease
  • Doxycycline, an FDA-approved antibiotic, behaves as an inhibitor of mitochondrial protein translation
  • CSCs successfully escape from the anti-mitochondrial effects of Doxycycline, by assuming a purely glycolytic phenotype. Therefore, DoxyR CSCs are then more susceptible to other metabolic perturbations, because of their metabolic inflexibility
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    Not especially new, but IV vitamin C + daily doxycycline found to kill cancer stem cells.
spineneuro

Top Spinal Fusion Doctors India to Perform Innovative New Spinal Fusion Surgery in India - 0 views

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    The new spinal fusion surgery in India method accomplished by top spinal fusion doctors in India uses a small device referred to as the minuteman® fusion plate. Spine and Neuro Surgery Hospital India International Helpline Number : +91-9325887033 Email id: enquiry@spineandneurosurgeryhospitalindia.com
pharmacybiz

Walgreens Starts Strategic Review For Boots UK - 0 views

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    Walgreens Boots Alliance, the parent company of Boots UK, has begun a strategic review of its business in the United Kingdom, chief executive officer Rosalind Brewer said on Tuesday (January 11) - as the pharmacy chain tries to renew its focus on US healthcare. Boots has over 2,200 stores across the UK, which include pharmacies, health and beauty stores, among others, according to the chain's website. "This review is very much in line with our renewed priorities and strategic direction. In particular, our increased focus on US healthcare. While the process is at an exploratory stage, we do expect to move quickly," Brewer said at the JP Morgan Healthcare Conference. The review comes at a time when the company, which was formed in 2014 after the acquisition of stake in Alliance Boots by Walgreens, moves beyond its drugstores with its investments in two smaller healthcare providers, CareCentrix and VillageMD.
pharmacybiz

NHS New Campaign To Promote Better Care For Mental Health - 0 views

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    The NHS is going to launch a new campaign using the iconic Beatles song 'Help!" to encourage people to take better care of their mental health. The campaign, being launched today (January 17), is backed by some of the UK's biggest artists, urging people to seek support for their mental wellbeing. Since the beginning of the pandemic around 2.3 million people have come forward for NHS talking therapies, with over 50 per cent being concerned about their mental health last year. The NHS is encouraging anybody experiencing anxiety, depression, or other common mental health concerns to experience how talking therapies can help them. NHS mental health talking therapies are a confidential service run by fully trainedexperts that can be accessed through self-referral or GP practice.
fitspresso

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

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    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
indian-health

Les meilleures cliniques dentaires de New Delhi sont sûres, professionnelles, conviviales et rentables - 0 views

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    Chaque année, des milliers de patients du monde entier se rendent à Delhi pour se faire soigner dans les meilleures cliniques dentaires de New Delhi.
indian-health

Get Your Old Smile Back With Dental Surgery India - 0 views

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    Around 15,000 foreigners travel every year for dental surgery India has come to be one of the hotspots due to its affordability. Getting dental works at best dental clinics of New Delhi are actually extra lower priced than western international countries.
spineneuro

Dr. Sandeep Vaishya Fortis Gurgaon Bringing New Gamma Knife Icon Technology - 101 Press Release - 0 views

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    Dr. Sandeep Vaishya Fortis Gurgaon is announcing today it will be the first in India to offer the new leksell gamma knife® icon™ stereotactic radiosurgery device. Gamma knife icon radiosurgery typically requires only a one-time treatment but may be used more than once for patients with brain metastases.
George Thomas

China to lift ban on disposable foamed plastic tableware - 0 views

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    Plastics News Portal, Plastics Jobs, Plastics Directory And Trade Website for World and India - Plasticsinfomart.com
George Thomas

TPE kills pathogens without toxins - 0 views

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    Plastics News Portal, Plastics Jobs, Plastics Directory And Trade Website for World and India - Plasticsinfomart.com
vrocky

Apple iPhone 7, 7 Plus launch in India | Technology News in vie2day - 0 views

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    Apple iPhone 7, 7 Plus will launch in India on 7th October 2016 starting price is Rs 60000 with minimum 32 GB memory. latest Technology News updates
Pot Valet

THC and CBD - What's the Difference? | Pot Valet News - 0 views

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    If you're new to the world of marijuana, you might wonder what THC and CBD are and how are they different. It's important to understand the effects of these two substances before you choose what type of marijuana you want.
arunaraayala

Ola Play In-Car Entertainment Platform Now Available to All Customers - Locality News - 0 views

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    Ola Play was so far totally available for Ola Select customers and the policy to spread to more than 50,000 Ola Prime vehicles by March 2017. Cab aggregator Ola on Friday drawn-out Ola Play, its in-car entertainment podium for ride-sharing, to all of its clients through Ola Prime Play classification. Launched in the month of ...
Nathan Goodyear

US lowers cutoff for lead poisoning in young kids | Fox News - 0 views

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    new CDC guidelines lower lead toxicity levels in children.  CDC: " there is no safe level of blood lead in children".  If no level is safe in children, what about other age groups?
Nathan Goodyear

Researchers establish benefits of high-dose vitamin C for ovarian cancer patients - 0 views

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    statement from KU on their new study on IV vitamin C in stage III and IV ovarian cancer.
Nathan Goodyear

New Study Links Aluminum Adjuvants in Vaccines with Neurological Disorders | Health Impact News - 0 views

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    good review of the biochemistry of neuroinflammation and aluminum from Macrophagic myofasciitis.
mdcurebyaerotel

New Science To Relieve Your Pain - 0 views

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    Need a permanent solution for your lower back pain? There is new science to relieve your pain. Give a try to MDcure. It comes with 30 days money back guarantee and a 1 year of limited warranty. You can directly place an order through our website.
Nathan Goodyear

Testosterone therapy not associated with myocardial infarction, stroke | Endocrinology - 0 views

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    Retrospective study finds no increase in new MI and/or stroke in men with Testosterone therapy.  There are some men that Testosterone therapy is cardioprotective and some that are not.
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