1,721,010 research outputs found
Exosome-Mediated Signaling in Epithelial to Mesenchymal Transition and Tumor Progression
Growing evidence points to exosomes as key mediators of cell−cell communication, by transferring their specific cargo (e.g., proteins, lipids, DNA and RNA molecules) from producing to receiving cells. In cancer, the regulation of the exosome-mediated intercellular communication may be reshaped, inducing relevant changes in gene expression of recipient cells in addition to microenvironment alterations. Notably, exosomes may deliver signals able to induce the transdifferentiation process known as Epithelial-to-Mesenchymal Transition (EMT). In this review, we summarize recent findings on the role of exosomes in tumor progression and EMT, highlighting current knowledge on exosome-mediated intercellular communication in tumor-niche establishment, migration, invasion, and metastasis processes. This body of evidence suggests the relevance of taking into account exosome-mediated signaling and its multifaceted aspects to develop innovative anti-tumoral therapeutic approaches
A multifuctional nanoplatform for drug targeted delivery based on radiation-engineered nanogels
Under a rational design, combining biologically active molecules, ligands to specific cell receptors and fluorescent, radioactive or paramagnetic labels into a single nano-object can bridge the unique properties of the individual components and improve conventional sensing, imaging and therapeutic efficacies. The validation of these functional nano-objects requires careful testing both in terms of physico-chemical properties and biological behaviour in vitro and in vivo, prior to translation into the clinic. Ionising radiation of aqueous polymer solutions is a viable strategy to produce multifunctional nanogels from aqueous solutions of hydrophilic polymers. By proper selection of the irradiation conditions, polymer concentration and gaseous atmosphere, nanogels with the desired features in terms of dimensions, surface electric charge and chemical reactivity can be produced. In particular, radiation-engineered poly(N-vinyl pyrrolidone)-based nanogels bearing carboxyl groups and primary amines can be used as the main building block of promising theranostic nanodevices. The possibility of exploiting these functional groups to bind molecules of interest for their characterisation and biological evaluation is discussed
Molecular Mechanisms controlling EMT/MET oscillations and hepatocyte differentiation of Resident Liver Stem Cells (RLSC)
“Molecular Mechanisms Controlling EMT/MET Oscillation during Hepatic Stem Renewal and Differentiation”
Data on the effects of low iron diet on serum lipid profile in HCV transgenic mouse model
Here, we presented new original data on the effects of iron depletion on the circulating lipid profile in B6HCV mice, a murine model of HCV-related dyslipidemia. Male adult B6HCV mice were subjected to non-invasive iron depletion by low iron diet. Serum iron concentration was assessed for evaluating the effects of the dietary iron depletion. Concentrations of circulating triglycerides, total cholesterol, Low Density Lipoproteins (LDLs), High Density Lipoproteins (HDLs) were analyzed and reported by using stacked line charts. The present data indicated that low serum iron concentration is associated to i) lower serum triglycerides concentrations and ii) increased circulating LDLs. The presented original data have not been published elsewhere
Mir-675-5p supports hypoxia-induced drug resistance in colorectal cancer cells
BACKGROUND: The uncontrolled proliferation of cancer cells determines hypoxic conditions within the neoplastic mass with consequent activation of specific molecular pathways that allow cells to survive despite oxygen deprivation. The same molecular pathways are often the cause of chemoresistance. This study aims to investigate the role of the hypoxia-induced miR-675-5p in 5-Fluorouracil (5-FU) resistance on colorectal cancer (CRC) cells. METHODS: CRC cell lines were treated with 5-Fu and incubated in normoxic or hypoxic conditions; cell viability has been evaluated by MTT assay. MiR-675-5p levels were analysed by RT-PCR and loss and gain expression of the miRNA has been obtained by the transfection of miRNA antagomir or miRNA mimic. Total protein expression of different apoptotic markers was analysed through western blot assay. MirWalk 2.0 database search engine was used to investigate the putative targets of the miR-675-5p involved in the apoptotic process. Finally, the luciferase assay was done to confirm Caspase-3 as a direct target of the miR-675-5p. RESULTS: Our data demonstrated that hypoxia-induced miR-675-5p counteracts the apoptotic signal induced by 5-FU, thus taking part in the drug resistance response. We showed that the apoptotic markers, cleaved PARP and cleaved caspase-3, increased combining miR-675-5p inhibition with 5-FU treatment. Moreover, we identified pro-caspase-3 among the targets of the miR-675-5p. CONCLUSION: Our data demonstrate that the inhibition of hypoxia-induced miR-675-5p combined with 5-FU treatment can enhances drug efficacy in both prolonged hypoxia and normoxia, indicating a possible strategy to partially overcome chemoresistance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09666-2
Dynamic behaviour of hepatocyte is orchestrated by dynamic enrolment of HNF4-dependent activator and/or repressor complexes
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