Elemene Injection Overcomes Paclitaxel Resistance in Breast Cancer through AR/RUNX1 Signal: Network Pharmacology and Experimental Validation.

Background: Paclitaxel (PTX) is a cornerstone chemotherapy for Breast Cancer (BC), yet its impact is limited by emerging resistance. Elemene Injection (EI) has shown potential in overcoming chemotherapy resistance. However, the efficacy by which EI restores PTX sensitivity in BC and the implicated molecular mechanism remain uncharted.

Quantitative Autoradiographic Method for Determination of Regional Rates of Cerebral Protein Synthesis In Vivo.

Protein synthesis is required for development and maintenance of neuronal function and is involved in adaptive changes in the nervous system. Moreover, it is thought that dysregulation of protein synthesis in the nervous system may be a core phenotype in some developmental disorders. Accurate measurement of rates of cerebral protein synthesis in animal models is important for understanding these disorders.

Decreased rates of cerebral protein synthesis measured in vivo in a mouse model of Tuberous Sclerosis Complex: unexpected consequences of reduced tuberin.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder affecting about 1 in 6000 people and is caused by mutations in either TSC1 or TSC2. This disorder is characterized by increased activity of mammalian target of rapamycin complex 1 (mTORC1), which is involved in regulating ribosomal biogenesis and translation initiation. We measured the effects of Tsc2 haploinsufficiency (Tsc2 ) in 3-month-old male mice on regional rates of cerebral protein synthesis (rCPS) by means of the in vivo L-[1- C]leucine method.

R-Baclofen Reverses a Social Behavior Deficit and Elevated Protein Synthesis in a Mouse Model of Fragile X Syndrome.

Background: Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability and the single genomic cause of autism spectrum disorders. It is caused by the absence of a fragile X mental retardation gene (Fmr1) product, FMRP, an RNA-binding translation suppressor. Elevated rates of protein synthesis in the brain and an imbalance between synaptic signaling via glutamate and γ-aminobutyric acid (GABA) are both considered important in the pathogenesis of FXS.

Cerebral protein synthesis in a knockin mouse model of the fragile X premutation.

The (CGG)n-repeat in the 5'-untranslated region of the fragile X mental retardation gene (FMR1) gene is polymorphic and may become unstable on transmission to the next generation. In fragile X syndrome, CGG repeat lengths exceed 200, resulting in silencing of FMR1 and absence of its protein product, fragile X mental retardation protein (FMRP). CGG repeat lengths between 55 and 200 occur in fragile X premutation (FXPM) carriers and have a high risk of expansion to a full mutation on maternal transmission.

Voluntary exercise regionally augments rates of cerebral protein synthesis.

Exercise is a natural form of neurophysiologic stimulation that has known benefits for mental health, maintenance of cerebral function, and stress reduction. Exercise is known to induce an upregulation of brain-derived neurotrophic factor and this is thought to be involved in associated increases in neural plasticity. Protein synthesis is also an essential component of adaptive plasticity.

Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome.

Individuals with fragile X syndrome (FXS), an inherited form of cognitive disability, have a wide range of symptoms including hyperactivity, autistic behavior, seizures and learning deficits. FXS is caused by silencing of FMR1 and the consequent absence of fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that associates with polyribosomes and negatively regulates translation.

A mouse model of the fragile X premutation: effects on behavior, dendrite morphology, and regional rates of cerebral protein synthesis.

Carriers of FMR1 premutation alleles have 55-200 CGG repeats in the 5' untranslated region of the gene. These individuals are at risk for fragile X associated primary ovarian insufficiency (females) and, in late life, fragile X associated tremor and ataxia syndrome (males, and to a lesser extent, females). Premutation carrier status can also be associated with autism spectrum disorder, attention deficit hyperactivity disorder, and some cognitive deficits.

Effect of high-salt diet on vascular relaxation and oxidative stress in mesenteric resistance arteries.

This study tested the hypothesis that superoxide levels are elevated in isolated mesenteric resistance arteries (100-300 microm) from rats fed a short-term high-salt (HS) diet (4% NaCl for 3 days) compared to controls fed a low-salt (LS) diet (0.4% NaCl). Vascular relaxation induced by the superoxide dismutase mimetic tempol (4-hydroxytetramethylpiperidine-1-oxyl), the NADPH oxidase inhibitor apocynin and the xanthine/xanthine oxidase inhibitor oxypurinol was significantly larger in mesenteric arteries from animals fed HS diet compared to arteries from animals fed LS diet.

Salt-induced ANG II suppression impairs the response of cerebral artery smooth muscle cells to prostacyclin.

Recent studies have demonstrated that cerebral arteries from rats fed a high-salt (HS) diet exhibit impaired vasodilation and altered electrophysiological response to reduction in PO2. The present study examined whether an increase in salt intake alters the response of vascular smooth muscle cells (VSMC) to prostacyclin, a crucial mediator of hypoxic dilation in cerebral arteries. VSMC were isolated from cerebral arteries of male Sprague-Dawley rats maintained on an HS (4% NaCl) or a low-salt diet (0.

Effect of high-salt diet on NO release and superoxide production in rat aorta.

Sprague-Dawley rats were fed either a high-salt (HS) diet (4.0% NaCl) or a low-salt (LS) diet (0.4% NaCl) for 3 days.