Insulin Resistance Increases TNBC Aggressiveness and Brain Metastasis via Adipocyte-derived Exosomes.

Unlabelled: Patients with triple negative breast cancer (TNBC) and comorbid Type 2 Diabetes (T2D), characterized by insulin resistance of adipose tissue, have higher risk of metastasis and shorter survival. Adipocytes are the main non-malignant cells of the breast tumor microenvironment (TME). However, adipocyte metabolism is usually ignored in oncology and mechanisms that couple T2D to TNBC outcomes are poorly understood.

Novel plasma exosome biomarkers for prostate cancer progression in co-morbid metabolic disease.

Comorbid Type 2 diabetes (T2D), a metabolic complication of obesity, associates with worse cancer outcomes for prostate, breast, head and neck, colorectal and several other solid tumors. However, the molecular mechanisms remain poorly understood. Emerging evidence shows that exosomes carry miRNAs in blood that encode the metabolic status of originating tissues and deliver their cargo to target tissues to modulate expression of critical genes.

The crosstalk within the breast tumor microenvironment in type II diabetes: Implications for cancer disparities.

Obesity-driven (type 2) diabetes (T2D), the most common metabolic disorder, both increases the incidence of all molecular subtypes of breast cancer and decreases survival in postmenopausal women. Despite this clear link, T2D and the associated dysfunction of diverse tissues is often not considered during the standard of care practices in oncology and, moreover, is treated as exclusion criteria for many emerging clinical trials. These guidelines have caused the biological mechanisms that associate T2D and breast cancer to be understudied.

Exosomes as novel biomarkers in metabolic disease and obesity-related cancers.

Exosomes include plasma-transported vesicles that are secreted by human tissues and reflect metabolic status. The profile of exosomes (particularly microRNA content) is altered in metabolic disease. In type 2 diabetes mellitus, exosomes circulating in plasma induce transcriptional changes related to tumour progression and pro-metastatic phenotypes in target cancer cells, potentially linking obesity to cancer progression and metastasis.

A Blunted Sympathetic Function and an Enhanced Nitrergic Activity Contribute to Reduce Mesenteric Resistance in Hyperthyroidism.

We aimed to determine whether an experimental model of hyperthyroidism could alter the function of sympathetic and nitrergic components of mesenteric innervation. For this purpose, male Wistar rats were divided into (1) control rats (CT) and (2) rats infused with L-Thyroxine (HT). Body weight gain and adipose tissue accumulation were lower in HT rats, while systolic blood pressure and citrate synthase activity in the soleus muscle were increased by HT.

Beneficial Effect of a Multistrain Synbiotic on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats: The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase A.

A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available .

Acute-on-chronic liver disease enhances phenylephrine-induced endothelial nitric oxide release in rat mesenteric resistance arteries through enhanced PKA, PI3K/AKT and cGMP signalling pathways.

Acute-on-chronic liver disease is a clinical syndrome characterized by decompensated liver fibrosis, portal hypertension and splanchnic hyperdynamic circulation. We aimed to determine whether the alpha-1 agonist phenylephrine (Phe) facilitates endothelial nitric oxide (NO) release by mesenteric resistance arteries (MRA) in rats subjected to an experimental microsurgical obstructive liver cholestasis model (LC). Sham-operated (SO) and LC rats were maintained for eight postoperative weeks.

Thyroid hormones affect nitrergic innervation function in rat mesenteric artery: Role of the PI3K/AKT pathway.

We aimed to determine the influence of nitrergic innervation function on the decreased mesenteric arterial tone induced by high levels of triiodothyronine (T3), as a model of acute thyroiditis, as well as the mechanism/s implicated. We analysed in mesenteric segments from male Wistar rats the effect of 10 nmol/L T3 (2 h) on the vasomotor response to electrical field stimulation (EFS) in the presence/absence of specific neuronal NOS (nNOS) inhibitor L-NPA, or superoxide anion scavenger tempol. Nitric oxide (NO) release was measured in the presence/absence of tempol or PI3K inhibitor LY294002.

Decompensated liver cirrhosis and neural regulation of mesenteric vascular tone in rats: role of sympathetic, nitrergic and sensory innervations.

We evaluated the possible alterations produced by liver cholestasis (LC), a model of decompensated liver cirrhosis in sympathetic, sensory and nitrergic nerve function in rat superior mesenteric arteries (SMA). The vasoconstrictor response to electrical field stimulation (EFS) was greater in LC animals. Alpha-adrenoceptor antagonist phentolamine and P2 purinoceptor antagonist suramin decreased this response in LC animals more than in control animals.