Group items tagged

proportionally associated with disease severity and survival

nonthyroidal illness syndrome

Patients with persistent deterioration of hormone levels (T3, T4) during the study period had higher mortality than those who normalized the function of the thyroid axis

LT3S in patients with septic shock is part of the pathophysiology of this disease and/or an associated organ (endocrine-metabolic) failure and not just an adaptive phenomenon

substitution treatment with synthetic thyroid hormones could modify the hemodynamic symptoms of septic patients, contributing in part to the decrease in their morbidity and mortality

some steroid hormone-induced nuclear events can occur in minutes

the genomic effects of steroid hormones take longer, with changes in gene expression occurring on the timescale of hours

Classical steroid hormone signaling occurs when hormone binds nuclear receptors (NR) in the cytoplasm, setting off a chain of genomic events that results in, among other changes, dimerization and translocation to the nucleus where the ligand-bound receptor forms a complex with coregulators to modulate gene transcription through direct interactions with a hormone response element (HRE)

NRs have been found at the plasma membrane of cells, where they can propagate signal transduction often through kinase pathways

Membrane-localized ER, PR and AR have been reported to modulate the activity of MAPK/ERK, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), nitric oxide (NO), PKC, calcium flux and increase inositol triphosphate (IP3) levels to promote cell processes including autophagy, proliferation, apoptosis, survival, differentiation, and vasodilation

ERα36, a 36kDa truncated form of ERα that lacks the transcriptional activation domains of the full-length protein. Membrane-localized ERα36 can activate pathways including protein kinase C (PKC) and/or mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) to promote the progression of various cancers

G protein-coupled receptor 30 (GPR30), also referred to as G protein-coupled estrogen receptor (GPER), is a membrane-localized receptor that has been observed to respond to estrogen to activate rapid signaling

hormone-responsive G protein coupled receptor is Zip9, which androgens can activate

GPRC6A is another G protein-coupled membrane receptor that is responsive to androgen

androgen-mediated non-genomic signaling through this GPCR can modulate male fertility, hormone secretion and prostate cancer progression

non-NR proteins located at the cell surface can bind to steroid hormones and respond by eliciting rapid signaling events

Estrogens have been shown to induce rapid (i.e. seconds) calcium flux via membrane-localized ER (mER)

ER-calcium dynamics lead to activation of kinase pathways such as MAPK/ERK which can result in cellular effects like migration and proliferation

17β-estradiol (E2) has been reported to promote angiogenesis through the activation of GPER

Membrane NRs may also mediate rapid signaling through crosstalk with growth factor receptors (GFR)

A similar crosstalk occurs between the receptor tyrosine kinase insulin-related growth factor-1 receptor (IGF-IR) and ERα. Not only does IGF-IR activate ERα, but inhibition of IGF-IR downregulates estrogen-mediated ERα activity, suggesting that IGF-IR is essential for maximal ERα signaling

Further, ER activates IGF-IR pathways including MAPK

GPER is involved in the transactivation of the EGFR independent of classical ER

tight interconnection between genomic and non-genomic effects of NRs.

non-genomic pathways can also lead to genomic effects

androgen-bound AR associates with the kinase Src at the plasma membrane, activating Src which then leads to a signaling cascade through MAPK/ERK

However, Src can also increase the expression of AR target genes by the ligand-independent transactivation of AR

extranuclear steroid hormone actions can potentially reprogram nuclear NR events

estrogen modulated the expression of several genes including endothelial nitric oxide synthase (eNOS) via rapid signaling pathways

epigenetic changes can then mediate genomic events in uterine tissue and breast cancer cells

Autoimmune diseases are characterized by a breakdown of mechanisms that allow the immune system to distinguish between self and nonself and maintain immunologic self-tolerance

Tregs, which are important in the maintenance of peripheral immune tolerance.

Several subtypes of Tregs exist, the most well studied being CD4+ cells that express high-level CD25 and the transcription factor forkhead box P3 (FOXP3)

Treg deficiency or dysfunction is associated with autoimmune disease

In clinical studies, decreased levels of circulating CD25+CD4+ T cells have been reported in patients with autoimmune disease

These data have led to the hypothesis that augmentation of Tregs may be a useful therapeutic strategy in autoimmune disease

Treg augmentation has resulted in clinical improvements in numerous animal models of autoimmune diseases

the administration of in vitro expanded CD4+CD25highCD127-Tregs has been found to be safe and may help to preserve β-cell function in children with T1D

ability of IL-2 to augment the numbers and function of CD4+ Tregs.

It is apparent that the original Wuhan strain and early variants of SARS-CoV-2 in 2020 were more pathogenic than later variants. This is consistent with typical viral adaptive evolution to more infectious but less pathogenic strains, a natural phenomenon

SARS-CoV-2 spike protein is pathogenic, whether from the virus or created from genetic code in mRNA and adenovectorDNA vaccines.

Evidence suggests reverse transcription of mRNA into a DNA copy is possible

further suggests the possibility of intergenerational transmission if germline cells incorporate the DNA copy into the host genome

(‘spikeopathy’) via several mechanisms that lead to inflammation, thrombogenesis, and endotheliitis-related tissue damage

Interaction of the vaccine-encoded spike protein with ACE-2, P53 and BRCA1 suggests a wide range of possible biological interference with oncological potential

Repeated COVID-19 vaccine booster doses appear to induce tolerance and may contribute to recurrent COVID-19 infection and ‘long COVID’.

spike protein is not only toxic through binding of ACE-2 receptors

interaction with cancer suppressor genes BRCA and P53

mitochondrial damage