1,721,177 research outputs found
Exosomes as "translational" cancer promoter organelles
No full textThe term Exosome has come into use to define nanovesicles contained in multivesicular endosomes (MVE), secreted by fusion of MVE with the plasma membrane. Exosomes are secreted in vivo by almost any cell type and
can be isolated from body fluids. Indeed, circulating vesicles account for both exosomes and microvesicles (MVs), which can be purified by various purification methods and fully discriminated according to their shape, size and CD markers. Due to their protein and RNA content,once internalized, exosomes have the potential to act as “translational” organelles, altering the expression pattern of recipient cells, their growth, and fate. In fact, exosomes are involved in many of physio-pathological processes, thereby including cancer
Beneficial effect of antioxidants in retinopathies: a new hypothesis.
No full textThe retina is the most oxygen consuming tissue of the body. Rod and cone photoreceptors efficiently carry out visual cascades, which are energetically costly processes. Data has recently been published that suggests that the metabolic support to phototransduction in the rod outer segment (OS) may originate directly in the OS, which is able to conduct aerobic metabolism. This oxygen-handling activity of the rod OS, which was never suspected before, appears to be a primary cause of the generation of reactive oxygen species directly inside the OS. Oxidative stress has been hypothesised to contribute to most of the neurodegenerative retinal pathologies, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa and photoreceptor cell death after retinal detachment. Many natural antioxidant compounds are routinely used in experimental or human therapies for preventing or delaying photoreceptor degeneration in those pathologies. Here it is proposed that the ultimate reason for the beneficial actions of antioxidants in preventing or retarding the effect on the retinal degenerative pathologies can be found in their action on reactive oxygen species generated by the ectopic mitochondrial electron transport chain (ETC) coupled to FoF1-ATP synthase in rod OS disks. In fact, if not adequately coupled, the ETC generates reactive oxygen species that, in turn, can act on the polyunsaturated fatty acids which the rod OS is rich in. If correct, the mechanism put forward here would provide a potential for the molecular basis of therapies with antioxidants for retinal degenerative diseases
Potential role of endothelial cell surface ectopic redox complexes in COVID-19 disease pathogenesis
No full textThe novel coronavirus infectious disease (COVID-19) has rapidly spread and poses a great challenge to researchers, both in elucidating its pathogenic mechanism and developing effective treatments. It has been recently proposed that COVID-19 is an endothelial disease. Indeed, the COVID-19 virus binds to angiotensin-converting enzyme type 2 (ACE2), which is expressed in endothelial cells. ACE2 could be implicated in the production of reactive oxygen species (ROS) caused by endothelial dysfunction due to viral damage. Consequently, oxidative stress could prime these cells to acquire a pro-thrombotic and pro-inflammatory phenotype, predisposing patients to thromboembolic and vasculitic events and to disseminated intravascular coagulopathy (DIC). This implies a pivotal role played by oxygen in the pathogenetic mechanism of COVID-19 disease, in that its availability would tune the oxidant state and consequent damage
Cancer exosomes in urine: a promising biomarker source
No full textIn face of innovative therapeutic strategies for cancer diagnosis and treatment, and of the elusiveness of renal and urinary tract tumors, the identification of novel biomarkers for diagnosis, prognosis, selection and monitoring of therapies is a primary target of research. The concept of "precision medicine" for tailoring the oncologic management in a minimally invasive fashion is considered a new epoch in cancer management. Extracellular vesicles, and exosomes in particular, carry lipids, mRNAs, non-coding RNAs, DNA, and active proteins, are present in a variety of bodily fluids including urine. In fact, urinary exosomes contain most of the urinoma proteins. Exosomes are nanovesicles originating from an endocytic pathway of the endocellular membranes and upon release are actors of intercellular communication, able to induce phenotypic changes including tumorigenesis and metastasis, in recipient cells. Tumor-derived exosomes play critical roles in all stages of tumor development and metastasis of almost all cancer types. Exosomal proteins may serve as biomarkers for clinical applications, still to be validated. Please reword the next sentence. Not clear. Exosomes extracellular gather in urine, thus becoming a great resource for recovery of biomarkers and a promising non-invasive diagnostic instrument for renal disease. Liquid biopsies (body fluids) may be preferable to tumor tissue biopsies since they are less invasive. Urinary exosomes in particular are available in great quantity in a noninvasive way and are representative of each of the cells of the urinary tract. In the present review, we summarize our knowledge of the urine exosomes with a new vision as liquid biopsy and high-throughput techniques. The emerging metabolic signature of urinary exosomes is also discussed in terms of its potential clinical application
The good and bad sides of exosomes: pre-metastatic niche formation, cancer biomarker and therapy carriers
No full textExosomes, nanovesicles of endocytic origin, are secreted by most cell types; cancer cells representing no exception. Exosomes facilitate intercellular communication as they deliver diverse proteins, mRNA, miRNA and lipids. In this review, we discuss how exosomes represent one of the main risks associated with cancer but also one of the most promising new tools to fight it. Exosomes appear to function as signalling molecules between the tumour microenvironment, i.e., the complex of both cancer and stromal cells, and the rest of the body. Cancer-derived exosomes have been shown to drive the initiation and progression of metastasis, by transporting their cargoes to target tissues. In this respect, exosomes are implicated in cancer progression, dissemination and therapy resistance. However, exosomes are also emerging as a key tool in precision medicine, pivotal for cancer liquid biopsy in early diagnosis and for assessing when there is a recurrence. Profiling exosomal cancer-derived nucleic acids by ultrasensitive next-generation sequencing along with mapping the protein profile utilizing high-throughput proteomics will allow earlier cancer detection, therapeutic stratification and monitoring of response to therapy. Exosomes are also a promising new tool for cancer immunotherapy. Clinically utilizing exosomes for these applications in cancer diagnosis and therapeutics will be the next challenge
A viewpoint about Lenadogene nolparvovec failing to meet its primary endpoint even though it permanently corrects the m.11778G>A mutation causative of LHON
No full textMelatonin and abeta, macular degeneration and alzheimers disease: same disease, different outcomes?
No full textAging is the common denominator and the highest risk factor for macular degeneration and Alzheimers Disease (AD). Important pathological hallmarks common to both diseases are the presence of amyloid β (Aβ) in the senile plaques of the AD brain and in the drusen of age-related macular degeneration (AMD) patients, oxidative stress, and apoptotic cell death. Data suggest that a common pathogenic mechanism might exist between AMD and AD. Brain and eye depend on redox electrons from pyridinic and flavinic nucleotides to produce ATP, and reactive oxygen intermediates (ROI). Disorganization of mitochondrial structure and decline in mitochondrial oxidative phosphorylation (OXPHOS) functioning, as well as hypometabolism and alterations in mitochondrial DNA are aging features. Because ROI damage and mitochondrial dysregulation are prominent in AMD and AD and their relationship to the redox state is unclear we addressed a new hypothesis according to which the interaction of melatonin vs Aβ are intertwined to balance of the intra- and extra-mitochondrial energy production. This balance would be impaired by the ageing process and environmental/genetic factors, ultimately leading to AD and /or AMD
Tamponi Laminari Chemiosmotici: ipotesi di un loro contributo alla sintesi nanomeccanica dell'ATP
No full textNeurocognitive functioning impairment after anti-cancer drug treatment:which is the link with demyelination? (RE: Neurocognitive functioning in adult survivors of childhood non-central nervous system cancer
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