Hyperhomocysteinemia and Disease-Is 10 μmol/L a Suitable New Threshold Limit?

Hyperhomocysteinemia (HHcy) is a medical condition characterized by an abnormally high level of homocysteine (Hcy) in the blood. Homocysteine is a toxic sulfur-containing amino acid that is produced during the metabolism of methionine. Under normal circumstances, Hcy is recycled back to methionine via the remethylation pathway, through the action of various enzymes and vitamins, particularly folic acid (vitamin B9) and B12 used when intracellular methionine levels are low, thus restoring the necessary levels to correctly maintain active protein synthesis.

Gut-Liver-Pancreas Axis Crosstalk in Health and Disease: From the Role of Microbial Metabolites to Innovative Microbiota Manipulating Strategies.

The functions of the gut are closely related to those of many other organs in the human body. Indeed, the gut microbiota (GM) metabolize several nutrients and compounds that, once released in the bloodstream, can reach distant organs, thus influencing the metabolic and inflammatory tone of the host. The main microbiota-derived metabolites responsible for the modulation of endocrine responses are short-chain fatty acids (SCFAs), bile acids and glucagon-like peptide 1 (GLP-1).

Effects of Reduced Extracellular Sodium Concentrations on Cisplatin Treatment in Human Tumor Cells: The Role of Autophagy.

Hyponatremia is the prevalent electrolyte imbalance in cancer patients, and it is associated with a worse outcome. Notably, emerging clinical evidence suggests that hyponatremia adversely influences the response to anticancer treatments. Therefore, this study aims to investigate how reduced extracellular [Na] affects the responsiveness of different cancer cell lines (from human colon adenocarcinoma, neuroblastoma, and small cell lung cancer) to cisplatin and the underlying potential mechanisms.

Hyponatremia Promotes Cancer Growth in a Murine Xenograft Model of Neuroblastoma.

In cancer patients, hyponatremia is detected in about 40% of cases at hospital admission and has been associated to a worse outcome. We have previously observed that cancer cells from different tissues show a significantly increased proliferation rate and invasion potential, when cultured in low extracellular [Na]. We have recently developed an animal model of hyponatremia using Foxn1nu/nu mice.

The Yin and Yang Effect of the Apelinergic System in Oxidative Stress.

Apelin is an endogenous ligand for the G protein-coupled receptor APJ and has multiple biological activities in human tissues and organs, including the heart, blood vessels, adipose tissue, central nervous system, lungs, kidneys, and liver. This article reviews the crucial role of apelin in regulating oxidative stress-related processes by promoting prooxidant or antioxidant mechanisms. Following the binding of APJ to different active apelin isoforms and the interaction with several G proteins according to cell types, the apelin/APJ system is able to modulate different intracellular signaling pathways and biological functions, such as vascular tone, platelet aggregation and leukocytes adhesion, myocardial activity, ischemia/reperfusion injury, insulin resistance, inflammation, and cell proliferation and invasion.

Hyponatremia and Cancer: From Bedside to Benchside.

Hyponatremia is the most common electrolyte disorder encountered in hospitalized patients. This applies also to cancer patients. Multiple causes can lead to hyponatremia, but most frequently this electrolyte disorder is due to the syndrome of inappropriate antidiuresis.

Isoforms of the orphan nuclear receptor COUP‑TFII differentially modulate pancreatic cancer progression.

The expression of the nuclear receptor transcription factor (TF) COUP‑TFII is broadly associated with cell differentiation and cancer development, including of pancreatic ductal adenocarcinoma (PDAC), a devastating disease with one of the poorest prognoses among cancers worldwide. Recent studies have started to investigate the pathological and physiological roles of a novel COUP‑TFII isoform (COUP‑TFII_V2) that lacks the DNA‑binding domain. As the role of the canonical COUP‑TFII in PDAC was previously demonstrated, the present study evaluated whether COUP‑TFII_V2 may have a functional role in PDAC.

Hyponatremia and Oxidative Stress.

Hyponatremia, i.e., the presence of a serum sodium concentration ([Na]) < 136 mEq/L, is the most frequent electrolyte imbalance in the elderly and in hospitalized patients.

Effects of Probiotics Administration on Human Metabolic Phenotype.

The establishment of the beneficial interactions between the host and its microbiota is essential for the correct functioning of the organism, since microflora alterations can lead to many diseases. Probiotics improve balanced microbial communities, exerting substantial health-promoting effects. Here we monitored the molecular outcomes, obtained by gut microflora modulation through probiotic treatment, on human urine and serum metabolic profiles, with a metabolomic approach.

Effects of low extracellular sodium on proliferation and invasive activity of cancer cells in vitro.

Purpose: Hyponatremia is the most common electrolyte disorder in hospitalized patients, and its etiopathogenesis is related to an underlying tumor in 14% of cases. Hyponatremia has been associated with a worse outcome in several pathologies, including cancer, in which the leading cause of this electrolyte alteration is the syndrome of inappropriate antidiuresis. The aim of this study was to analyze in vitro the effects of low extracellular [Na] in cancer progression.

Liver haploinsufficiency of RuvBL1 causes hepatic insulin resistance and enhances hepatocellular carcinoma progression.

RuvBL1 is an AAA+ ATPase whose expression in hepatocellular carcinoma (HCC) correlates with a poor prognosis. In vitro models suggest that targeting RuvBL1 could be an effective strategy against HCC. However, the role of RuvBL1 in the onset and progression of HCC remains unknown.

Peroxisome proliferator-activated receptor-γ agonist pioglitazone reduces the development of necrotizing enterocolitis in a neonatal preterm rat model.

Background: Factors affecting innate immunity and acting as inflammatory regulators, such as the nuclear peroxisome proliferator-activated receptors (PPAR) could be crucial in the pathogenesis of necrotizing enterocolitis (NEC). We hypothesized that the PPARγ agonist pioglitazone (PIO) might be effective in preventing the development of NEC and/or reducing its severity.

Methods: We studied preterm rats in which NEC was induced using the hypoxia-hypothermia model.

The orphan nuclear receptor COUP-TFII coordinates hypoxia-independent proangiogenic responses in hepatic stellate cells.

Background & Aims: Hepatic stellate cell (HSC) transdifferentiation into collagen-producing myofibroblasts is a key event in hepatic fibrogenesis, but the transcriptional network that controls the acquisition of the activated phenotype is still poorly understood. In this study, we explored whether the nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is involved in HSC activation and in the multifunctional role of these cells during the response to liver injury.

Methods: COUP-TFII expression was evaluated in normal and cirrhotic livers by immunohistochemistry and Western blot.

Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis.

Hepatitis B virus (HBV) infection is a global public health problem with approximately 2 billion people that have been exposed to the virus. HBV is a member of a family of small, enveloped DNA viruses called hepadnaviruses, and has a preferential tropism for hepatocytes of mammals and birds. Epidemiological studies have proved a strong correlation between chronic hepatitis B virus infection and the development of hepatocellular carcinoma (HCC).

Telomerase activated thymidine analogue pro-drug is a new molecule targeting hepatocellular carcinoma.

Background & Aims: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Although hepatectomy and transplantation have significantly improved survival, there is no effective chemotherapeutic treatment for HCC and its prognosis remains poor. Sustained activation of telomerase is essential for the growth and progression of HCC, suggesting that telomerase is a rational target for HCC therapy.