Mutant p53-Associated Molecular Mechanisms of ROS Regulation in Cancer Cells

The TP53 tumor suppressor gene is the most frequently altered gene in tumors and an increasing number of studies highlight that mutant p53 proteins can acquire oncogenic properties, referred to as gain-of-function (GOF). Reactive oxygen species (ROS) play critical roles as intracellular messengers, regulating numerous signaling pathways linked to metabolism and cell growth. Tumor cells frequently display higher ROS levels compared to healthy cells as a result of their increased metabolism as well as serving as an oncogenic agent because of its damaging and mutational properties. Several studies reported that in contrast with the wild type protein, mutant p53 isoforms fail to exert antioxidant activities and rather increase intracellular ROS, driving a pro-tumorigenic survival. These pro-oxidant oncogenic abilities of GOF mutant p53 include signaling and metabolic rewiring, as well as the modulation of critical ROS-related transcription factors and antioxidant systems, which lead ROS unbalance linked to tumor progression. The studies summarized here highlight that GOF mutant p53 isoforms might constitute major targets for selective therapeutic intervention against several types of tumors and that ROS enhancement driven by mutant p53 might represent an "Achilles heel" of cancer cells, suggesting pro-oxidant drugs as a therapeutic approach for cancer patients bearing the mutant TP53 gene

Echocardiographic Assessment after Surgical Repair of Tetralogy of Fallot

Surgical correction of Tetralogy of Fallot is still one of the most frequently performed intervention in pediatric cardiac surgery, and in many cases it is far from being a complete and definitive correction. It is rather an excellent palliation that solves the problem of cyanosis but predisposes the patients to medical and surgical complications during follow-up. The decision-making process regarding the treatment of late sequel are among the most discussed topics in adult congenital cardiology. In postoperative Fallot patients, echocardiography is used as the first method of diagnostic imaging and currently allows both a qualitative observation of the anatomical alterations and a detailed quantification of right ventricular volumes and function, of the right ventricular outflow tract, and of the pulmonary valve and pulmonary arteries. The literature introduced many quantitative echocardiographic criteria useful for the understanding of the pathophysiological mechanisms involving the right ventricle and those have made much more objective any decision-making processes

Detection of influenza A(H1N1)pdm09 virus in a patient travelling from Shanghai to Italy in July 2018: an uncommon clinical presentation in a non-seasonal period

Influenza is one of the most common infectious diseases in travellers, especially in those returning from subtropical and tropical regions.In late June 2018 an influenza A(H1N1)pdm09 virus infection was diagnosed in a 36-years-old man, returned from a travel in Shanghai and hospitalized at the Ospedale Policlinico San Martino, Genoa, Italy, with a diagnosis of fever and an uncommon clinical presentation characterised by a persistent leukopenia. Phylogenetic analysis revealed a closeness with influenza A(H1N1)pdm09 strains circulating in the US in May-June 2018.Prompt recognition of influenza infection led to a proper case management, demonstrating the crucial role of the continuous influenza surveillance programme

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Correlation between Low Folate Levels and Hyperhomocysteinemia, but not with Vitamin B12 in Hypertensive Patients.

INTRODUCTION: Hypertension is considered to be among the most important risk factors for cardiovascular and cerebrovascular diseases. In recent years, several investigators have reported that high plasma levels of total homocysteine (t-hcy) has a key role in the development of hypertension, and the deficiency of B complex vitamins could increase the risk of hypertension. The purpose of this study was to investigate the relationship between plasma homocysteine, folate and vitamin B12 in hypertensive patients. MATERIALS AND METHODS: In 116 patients with hypertension and 81 healthy subjects, total plasma homocysteine, vitamin B12 and folate levels were measured. RESULTS AND DISCUSSION: Homocysteine was significantly higher in patients than in control subjects (22.9±3.5 versus 9.0±2.3 μmol/L respectively, p0.05). Our results confirmed that, as previously observed, elevated t-hcy levels and low folate levels, but not vitamin B12 levels, are significantly associated with hypertension

Regulation of Autophagy by Nuclear GAPDH and Its Aggregates in Cancer and Neurodegenerative Disorders

Several studies indicate that the cytosolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has pleiotropic functions independent of its canonical role in glycolysis. The GAPDH functional diversity is mainly due to post-translational modifications in different amino acid residues or due to protein−protein interactions altering its localization from cytosol to nucleus, mitochondria or extracellular microenvironment. Non-glycolytic functions of GAPDH include the regulation of cell death, autophagy, DNA repair and RNA export, and they are observed in physiological and pathological conditions as cancer and neurodegenerative disorders. In disease, the knowledge of the mechanisms regarding GAPDH-mediated cell death is becoming fundamental for the identification of novel therapies. Here, we elucidate the correlation between autophagy and GAPDH in cancer, describing the molecular mechanisms involved and its impact in cancer development. Since autophagy is a degradative pathway associated with the regulation of cell death, we discuss recent evidence supporting GAPDH as a therapeutic target for autophagy regulation in cancer therapy. Furthermore, we summarize the molecular mechanisms and the cellular effects of GAPDH aggregates, which are correlated with mitochondrial malfunctions and can be considered a potential therapeutic target for various diseases, including cancer and neurodegenerative disorders