Bisphenol A shown to disrupt ovarian estrogen production from exposure in adults. The point of this that is important is that BPA, a xenoestrogen, can infact disrupt physiologic hormone production in adults, and contribute to ovarian failure. BPA, itself, is 1,000 fold weaker than E2, yet it disrupts ovarian function.
Polychlorinated biphenyl (PCBs) shown to disrupt thyroid hormone function through disruption of the transthyretin binding sites. Not only is it a xenoestrogen, but it disrupts thyroid function too.
Inflammation disrupts HPA axis. This is no surprise as we Know that inflammation can disrupt Testosterone in men and progesterone production in women. This study suggests that this HPA axis disruption contributes to CAD.
Glyphosate, component of Roundup is well known to be an endocrine disruptor. This rat study describes the mechanism of disruption of the Sertoli cells resulting in male infertility. In addition to the disruption of spermatogenesis, Glyphosate was shown to deplete glutathione levels compromising detoxification. If that is not enough, oxidative damage marker TBARS was elevated.
Ovarian cancer is the most lethal gynecologic malignancy and the fifth-most cause of overall cancer death of women in developed countries
An increasingly accepted cancer stem cell hypothesis regards tumors as caricatures of normal organs, possessing a hierarchy of cell types, at various stages of aberrant differentiation, descended from precursor tumor-initiating cells (TIC) cells that are highly resistant to conventional cytotoxics
Significant changes of gene expression in 2,928 genes were identified after niclosamide treatment for different time periods
uncoupling of mitochondrial oxidative phosphorylation is believed to be its anti-helminthic mechanism of action
we hypothesized that niclosamides antagonistic effects on OTICs could, in part, be due to its disruption of metabolism
Our results showed that genes participating in protein complexes of oxidative phosphorylation were downregulated
niclosamide treatment resulted in a more than 20% increase in reactive oxygen species (ROS) in cultured OTICs
niclosamide, which has proved to be safe and effective for the past 2 decades against numerous parasites, inhibited OTIC growth both in vitro and in vivo
niclosamide represses metabolic enzymes responsible for bioenergetics, biosynthesis, and redox regulation specifically in OTICs, presumably leading to mitochondrial intrinsic apoptosis pathways, loss of tumor stemness, and growth inhibition
Niclosamide is believed to inhibit mitochondrial oxidative phosphorylation
Niclosamide was reported to inactivate NF-κB, causing mitochondrial damage and the generation of ROS, leading to apoptosis of leukemic stem cells
niclosamide were identified in a screen for mTOR-signaling inhibitors
mTOR was reported to maintain stemness properties of HSCs by inhibiting mitochondrial biogenesis and ROS levels (39), implying that mTOR inhibitors (such as niclosamide) may interfere with mitochondria and various metabolic pathways in TICs via disruption of antioxidant responses
We observed Wnt hyperactivity in OTICs, in agreement with previous hypotheses of Wnt inhibitor effectiveness as an ovarian cancer therapy
niclosamide has now been independently identified in screens for Wnt inhibitors
downregulation of the Wnt/β-catenin target oncogenes survivin and c-Myc
ovarian carcinogenesis, the cell-to-cell signaling pathway Notch (8), were also suppressed by niclosamide (data not shown). These results agree with another recent niclosamide study in leukemia (49), and it has been widely hypothesized that disruption of Notch signaling may represent a highly effective therapy for ovarian and other solid tumors, via its essentiality to maintaining TIC stemness
Niclosamide, common anti-parasitic medication, inhibits cellular metabolism and increases ROS; both of which provide powerful anti-proliferative, anti-cancer treatment mechanism in TICs. Powerful target therapy for cancer stem cells. Also shown to inhibit Wnt stimulated oncogenes survivin and c-Myc, disrupts Notch signaling, inactivates NF-kappaBeta, and inhibits mTOR-signaling. This has been found in in vitro and in vivo studies.
Endocrine Disrupting Chemicals from 1970 still disrupting hormones today. Three fold increase in DHEA in 3 year old children via saliva and androstenedione in mothers compared to controls.
an association between disrupted nocturnal sleep and flattened diurnal cortisol rhythm in women with metastatic breast cancer
They suggest that the stress-buffering effects of sleep may be associated with improved parasympathetic tone and normalized cortisol patterns during the day.
this study from 2009 showed how disrupted/imbalanced gut flora leads to leaky gut. This case, high bacteroides relative to bifidobacterium and lactobacillus resulted in disruption of the zonulin pathway and thus lncreased intestinal permeability.
Low Testosterone found to disrupt restful sleep in men. However, in contrast, Testosterone doping leads to sleep disruption as well. I love how the authors describe it: ...in supra therapeutic doses, or in the context abuse."
Endocrine Disrupting chemicals, xenoestrogens, alter the hormone receptors very early. Increased estrogenic load with the change in ER increase prostate cancer.
High protein intake can lead to insulin resistance. Glucose regulation by insulin and skeletal muscle removal of glucose is disrupted by high amino acid intake through disruption of secondary insulin signaling.