200 research outputs found
Hypoxia mediates cancer development and progression through HIF-1a and microRNA regulation
No full textBackground: MicroRNAs (miRNAs) are small non coding RNAs which play a role in several cellular
processes such as apoptosis, cell differentiation, proliferation and stress response. Thus, changes in
miRNA expression are associated with the development and progression of human disease like
cancer and many other systemic diseases. MiRNAs expression could be influenced by different
stimuli such as oxidative stress, inflammatory response and hypoxia. Lately, some hypoxia-inducible
miRNAs (HRMs, hypoxia-regulated miRNAs) have been identified. These HRMs are often activated
in different types of cancers, suggesting their role in tumorigenesis.
Obstructive sleep apnea (OSA) is a breathing disorder characterized by recurrent obstructions of the
upper airway associated with increased inspiratory efforts, intermittent hypoxemia and sleep
fragmentation. Recent experiments suggest that cancer could be a disease associated with this sleep
breathing disorder. The mechanisms that regulate gene expression during hypoxia are not fully
understood but miRNAs expression seems to have an important role in various processes.
On these basis, the main aims of this experimental thesis are: i) to evaluate the roles of continuous
hypoxia (CH) and miRNAs in cancer; ii) to evaluate how hypoxia could influence the expression of
specific miRNAs in cells; iii) to assess the differences in the expression profile of specific miRNAs
induced by continuous and intermittent hypoxia; iv) to evaluate changes in miRNAs expression in
controls or patients affected by OSA and/or cancer and in colorectal cancer cells exposed to
intermittent hypoxia (IH), and to evaluate their impact on tumor progression in vitro.
Materials and Methods: For this purpose, I used qRT-PCR to detect miRNAs expression both CaCo2
cells exposed to CH or IH, to 2 to 24/32h, with or without acriflavine (ACF), a HIF-1 inhibitor and in
patients’ sera. MTT and transwell invasion test were applied to investigate the proliferation and
migration of CaCo2 exposed to IH and treated with miRNA inhibitors or ACF. HIF-1 activity was
evaluated in CaCo2 cells after IH.
Results: The levels of almost all analyzed miRNAs (miR-21, miR-23b, miR-26a, miR-27b, and miR-
145) were greater in continuous hypoxia versus normoxia. Furthermore, the expression of nearly all
miRNAs was higher in IH than in CH.
In addition, the levels of miR-21, miR-26a and miR-210 increased in OSA and ONCO-OSA patients
compared to controls. MiR-23b increased in ONCO-OSA patients, and miR-27b and miR-145
increased in OSA but not ONCO-OSA patients.
MiR-21, miR-26a, miR-23b and miR-210 increased in cells after IH. Proliferation and migration were
increased by IH and reduced after either miRNA inhibition or ACF treatment. MiRNA inhibition
reduces HIF-1α gene expression. Conversely, the expression of these miRNAs was significantly
decreased after ACF treatment.
Conclusions: We identified a series of miRNAs, induced by the hypoxic environment, in malignancies
associated with hypoxia, especially OSA-associated intermittent hypoxia.
These data would demonstrate that there is a different response between the condition of
intermittent versus chronic hypoxia, and the former appears to be much more harmful in terms of
stimulation of the expression of some miRNAs. These miRNAs could be implicated in cancer
development and progression through a regulatory loop involving HIF-1
EVs-miRNA: The New Molecular Markers for Chronic Respiratory Diseases
No full textIdiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and sleep disorders are chronic respiratory diseases that affect the airways, compromising lung function over time. These diseases affect hundreds of millions of people around the world and their frequency seems to be increasing every year. Extracellular vesicles (EVs) are small-sized vesicles released by every cell in the body. They are present in most body fluids and contain various biomolecules including proteins, lipids, mRNA and non-coding RNA (micro-RNA). The EVs can release their cargo, specifically micro-RNAs (miRNAs), to both neighboring and/or distal cells, playing a fundamental role in cell–cell communication. Recent studies have shown their possible role in the pathogenesis of various chronic respiratory diseases. The expression of miRNAs and, in particular, of miRNAs contained within the extracellular vesicles seems to be a good starting point in order to identify new potential biomarkers of disease, allowing a non-invasive clinical diagnosis. In this review we summarize some studies, present in the literature, about the functions of extracellular vesicles and miRNAs contained in extracellular vesicles in chronic respiratory diseases and we discuss the potential clinical applications of EVs and EVs-miRNAs for their possible use such as future biomarkers
Obstructive Sleep Apnea: A Look towards Micro-RNAs as Biomarkers of the Future
No full textSleep-disordered breathing (SDB) includes a broad spectrum of diseases, of which obstructive sleep apnea syndrome (OSA) is the most clinically significant manifestation. OSA is a respiratory disorder characterized by episodes of complete or partial obstruction of the upper airways that disturb ventilation and sleep architecture. In recent years, interest in the clinical implications of OSA seems to have increased, probably due to the numerous studies that have shown the existence of an important correlation between OSA and cardiovascular, dysmetabolic, and neoplastic changes. The guidelines currently available highlight the importance of diagnosis and effective treatment for OSA, underlining the need for new biomarkers that are useful in clinical practice, feasible, and reproducible to guide medical decision making. In this review, we intend to provide an overview of the potential role of microRNAs as new indicators for OSA management. MicroRNAs (miRNAs) are small non-coding RNA molecules that play an important role in RNA silencing and regulation of gene expression at the post-transcriptional level. These can bind specifically to their target genes by forming silencing complexes, thus inducing degradation or altered gene expression. A wide range of miRNAs have been extensively studied in a variety of diseases including cancer, and recently, miRNAs have been shown to have enormous potential to function as diagnostic and clinical biomarkers of disease. This review includes recent studies that establish the inevitable role of miRNAs in the pathogenesis of OSA
Effect of Hypoxia-Induced Micro-RNAs Expression on Oncogenesis
No full textMicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. An aberrant regulation of gene expression by miRNAs is associated with numerous diseases, including cancer. MiRNAs expression can be influenced by various stimuli, among which hypoxia; however, the effects of different types of continuous hypoxia (moderate or marked) on miRNAs are still poorly studied. Lately, some hypoxia-inducible miRNAs (HRMs, hypoxia-regulated miRNAs) have been identified. These HRMs are often activated in different types of cancers, suggesting their role in tumorigenesis. The aim of this study was to evaluate changes in miRNAs expression both in moderate continuous hypoxia and marked continuous hypoxia to better understand the possible relationship between hypoxia, miRNAs, and colorectal cancer. We used RT-PCR to detect the miRNAs expression in colorectal cancer cell lines in conditions of moderate and marked continuous hypoxia. The expression of miRNAs was analyzed using a two-way ANOVA test to compare the differential expression of miRNAs among groups. The levels of almost all analyzed miRNAs (miR-21, miR-23b, miR-26a, miR-27b, and miR-145) were greater in moderate hypoxia versus marked hypoxia, except for miR-23b and miR-21. This study identified a series of miRNAs involved in the response to different types of continuous hypoxia (moderate and marked), highlighting that they play a role in the development of cancer. To date, there are no other studies that demonstrate how these two types of continuous hypoxia could be able to activate different molecular pathways that lead to a different expression of specific miRNAs involved in tumorigenesis
Chronic hepatitis B in children after e antigen seroclearance: Final report of a 29-year longitudinal study
No full textChronic hepatitis B is usually a benign disease in Caucasian children; however, the long-term prognosis remains unsettled. This report describes the results of a 29-year longitudinal study including 99 white children with chronic hepatitis B, mainly acquired horizontally: 91 were hepatitis B e antigen (HBeAg) positive (4 had cirrhosis), and 8 were HBeAg negative at presentation. Of the 91 HBeAg-positive children, 89 underwent HBeAg seroconversion after a mean period of 5.2 +/- 4.0 years and were included in the study. Of the 85 children without cirrhosis, one had HBeAg-negative hepatitis and the other 84 became inactive carriers. During a mean follow-up of 14.5 +/- 6.1 years after HBeAg seroclearance, 4 carriers experienced reactivation, and 3 of them had HBeAg-negative hepatitis at the last follow-up. Of the 8 initially HBeAg-negative children, 2 had HBeAg-negative hepatitis, and 6 were inactive carriers. Of the 4 children with cirrhosis, 2 had hepatocellular carcinoma (HCC) and remained alive and 2 lost the histological features of cirrhosis in adulthood. Two patients with HBeAg-negative hepatitis and 1 with cirrhosis had experienced drug abuse. At the end of follow-up, 15 of the 89 initially HBeAg-positive patients and 2 of 8 initially HBeAg-negative children had cleared hepatitis B surface antigen. In conclusion, the overall prognosis for chronic hepatitis B in horizontally infected Caucasian children is favorable; however, some patients progress to HCC and HBeAg-negative hepatitis. Long-term monitoring is important, as is counseling on cofactors of liver damage, such as alcohol and drug abuse
The role of DNA amplification and cultural growth in complicated acute appendicitis
No full textBacterial growth of peritoneal fluid specimens obtained during surgical procedures for acute appendicitis may be useful to optimize further antibiotic therapy in complicated cases. DNA amplification represents a fast technique to detect microbial sequences. We aimed to compare the potential of DNA amplification versus traditional bacterial growth culture highlighting advantages and drawbacks in a surgical setting. Peritoneal fluid specimens were collected during surgery from 36 children who underwent appendectomy between May and December 2012. Real-time polymerase chain reaction (RT-PCR) and cultures were performed on each sample. RT-PCR showed an amplification of 16S in 18/36 samples, Escherichia coli (in 7 cases), Pseudomonas aeruginosa (3), Fusobacterium necrophorum (3), Adenovirus (2), E.coli (1), Klebsiella pneumoniae (1), Serratia marcescens/Enterobacter cloacae (1). Bacterial growth was instead observed only in four patients (3 E.coli and 1 P.aeruginosa and Bacteroides ovatus). Preoperative C-reactive protein and inflammation degree, the most reliable indicators of bacterial translocation, were elevated as expected. DNA amplification was a quick and useful method to detect pathogens and it was even more valuable in detecting aggressive pathogens such as anaerobes, difficult to preserve in biological cultures; its drawbacks were the lack of biological growths and of antibiograms. In our pilot study RT-PCR and cultures did not influence the way patients were treated
Searching for airways biomarkers useful to identify progressive pulmonary fibrosis
No full textAbstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with unknown etiology. To date, the identification of new diagnostic, prognostic and progression biomarkers of IPF turns out to be necessary. MicroRNA (miRNA) are small non-coding RNAs which negatively regulate gene expression at the post-transcriptional level in several biological and pathological processes. An aberrant regulation of gene expression by miRNA is often associated with various diseases, including IPF. As result, miRNAs have emerged as potential biomarkers with relevance to pulmonary fibrosis. Several reports suggested that miRNAs are secreted as microvesicles or exosome, and hance they are stable and can be readily detected in the circulation. In the contest of miRNAs as circulating biomarkers, different studies show their role in various types of interstitial lung diseases and suggest that these small molecules could be used as prognostic markers of the disease. Exosomes are small, lipid-bound vesicles able to carry various elements of the naïve cells such as proteins, lipids, mRNAs and miRNA to facilitate cell communication under normal and diseases condition. Exosomal miRNAs (exo-miRNA) have been studied in relation to many diseases. However, there is little or no knowledge regarding exo-miRNA in bronchoalveolar lavage (BAL) in IPF. Our study's aim is to evaluate the changes in the expression of two exo-miRNAs in BAL, respectively miR-21 and miR-92a, through highlighting the differences between IPF, progressive pulmonary fibrosis (PPF) and not-progressive pulmonary fibrosis (nPPF). Methods Exosomes were characterized by Western Blot and Multiplex Surface Marker Analysis. Exosomal miRNA expression was performed by qRT-PCR. ANOVA or Kruskal–Wallis test, based on data normality, was used to compare the differential expression between groups. Results MiR-21 expression was significantly higher in the nPPF group than in both IPF and PPF. A result that could point above a possible role of miR-21, as a biomarker in the differential diagnosis between PPF and nPPF. MiR-92a, indeed, was down regulated in PPF compared to IPF and down regulated in PPF compared to nPPF. Conclusions This study demonstrated the putative role of both miR-21 and miR-92a as possible biomarkers of pulmonary fibrosis progression. Moreover, the role of exo-miRNAs is examined as a possible future direction that could lead to new therapeutic strategies for the treatment of progressive and non-progressive pulmonary fibrosis
Serotypes and antibiotic susceptibility of Streptococcus pneumoniae isolated from hospitalized patients with community-acquired pneumonia in Italy
No full textPneumonia remain an important public health problem. The primary objective was to determine the proportion of community-acquired pneumonia that is attributable to Streptococcus pneumoniae infection; secondary objectives were the description of community-acquired pneumonia attributable to Streptococcus pneumoniae according to socio-demographic and clinical variables, the clinical evolution of community-acquired pneumonia and the description of the serotype distribution of vaccine-preventable disease and antibiotic resistance rate of pneumococcal infections
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