Ndufc2, a subunit of the NADH: ubiquinone oxidoreductase, plays a key role in the assembly and activity of complex I within the mitochondrial OXPHOS chain. Its deficiency has been shown to be involved in diabetes, cancer and stroke. To improve our knowledge on the mechanisms underlying the increased disease risk due to Ndufc2 reduction, we performed the present in vitro study aimed at the fine characterization of the derangements in mitochondrial structure and function consequent to Ndufc2 deficiency. We found that both fibroblasts obtained from skin of heterozygous Ndufc2 knock-out rat model showed marked mitochondrial dysfunction and PBMC obtained from subjects homozygous for the TT genotype of the rs11237379/NDUFC2 variant, previously shown to associate with reduced gene expression, demonstrated increased generation of reactive oxygen species and mitochondrial damage. The latter was associated with increased oxidative stress and significant ultrastructural impairment of mitochondrial morphology with a loss of internal cristae. In both models the exposure to stress stimuli, such as high-NaCl concentration or LPS, exacerbated the mitochondrial damage and dysfunction. Resveratrol significantly counteracted the ROS generation. These findings provide additional insights on the role of an altered pattern of mitochondrial structure–function as a cause of human diseases. In particular, they contribute to underscore a potential genetic risk factor for cardiovascular diseases, including stroke.

Background Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related mortality; nevertheless, there are few data regarding detection of circulating tumor cells (CTCs) in NSCLC, compared to other kinds of cancers in which their prognostic roles have already been defined. This difference is likely due to detection methods based on the epithelial marker expression which ignore CTCs undergoing epithelial-mesenchymal transition (CTCsEMT). Methods After optimization of the test with spiking experiments of A549 cells undergoing TGF-β1-induced EMT (A549EMT), the CTCsEMT were enriched by immunomagnetic depletion of leukocytes and then characterized by a RT-PCR assay based on the retrieval of epithelial and EMT-related genes. Blood samples from ten metastatic NSCLC patients before starting treatment and during chemotherapy were used to test this approach by longitudinal monitoring. Ten age- and sex-matched healthy subjects were also enrolled as controls. Results Recovery experiments of spiked A549EMT cells showed that the RT-PCR assay is a reliable method for detection of CTCsEMT. CTCsEMT were detected in three patients at baseline and in six patients after four cycles of cysplatin-based chemotherapy. Longitudinal monitoring of three patients showed that the CTCsEMT detection is related to poor therapeutic response. Conclusions The RT-PCR-based approach for the evaluation of CTCsEMT phenotype could be a promising and inexpensive tool to predict the prognosis and the therapeutic response in NSCLC patients.

Oxidative stress is currently viewed as a key factor in the genesis and progression of Heart Failure (HF). The aim of this study was to characterize the mitochondrial changes linked to oxidative stress generation in circulating peripheral blood mononuclear cells isolated from chronic HF patients (HF_PBMCs) in order to highlight the involvement of mitochondrial dysfunction in the pathophysiology of HF.To assess the production of reactive oxygen species (ROS), mitochondrial function and ultrastructure and the mitophagic flux in circulating PBMCs we enrolled 15 patients with HF and a control group of ten healthy subjects. The HF_PBMCs showed a mitochondrial population consisting of damaged and less functional organelles responsible of higher superoxide anion production both at baseline and under in vitro stress conditions, with evidence of cellular apoptosis. Although the mitophagic flux at baseline was enhanced in HF_PBMCs at level similar to those that could be achieved in control PBMCs only under inflammatory stress conditions, the activation of mitophagy was unable to preserve a proper mitochondrial dynamics upon stress stimuli in HF.In summary, circulating HF_PBMCs show structural and functional derangements of mitochondria with overproduction of reactive oxidant species. This mitochondrial failure sustains a leucocyte dysfunctional status in the blood that may contribute to development and persistence of stress conditions within the cardiovascular system in HF.

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells.

In all four cases, it was put in evidence a prolonged use of a nasal decongestant containing mineral oils. In literature, the most cases described are characterized by a subclinical evolution and were presented as ground glass opacities which evolve, in the later phases, in an interstitial involvement or in a peripheral mass, simulating a lung tumour.