Search

Colorectal cancer (CRC) develops by genetic and epigenetic alterations. However, the molecular mechanisms underlying metastatic dissemination remain unclear and could benefit from multi-omics investigations of specific protein families. Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in ECM remodeling and the processing of bioactive molecules. Increased MMP expression promotes the hallmarks of tumor progression, including angiogenesis, invasion, and metastasis, and is correlated with a shortened survival. Nevertheless, the collective role and the possible coordination of MMP members in CRC are poorly investigated. Here, we performed a multi-omics analysis of MMP expression in CRC using data mining and experimental investigations. Several databases were used to deeply mine different expressions between tumor and normal tissues, the genetic and epigenetic alterations, the prognostic value as well as the interrelationships with tumor immune-infiltrating cells (TIICs). A special focus was placed on to MMP2 and MMP9: their expression was correlated with immune markers and the interaction network of co-expressed genes disclosed their implication in epithelial to mesenchymal transition (EMT) and immune response. Finally, the activity levels of MMP2 and MMP9 in a cohort of colon cancer samples, including tissues and the corresponding sera, was also investigated by zymography. Our findings suggested that MMPs could have a high potency, as they are targeted in colon cancer, and might serve as novel biomarkers, especially for their involvement in the immune response. However, further studies are needed to explore the detailed biological functions and molecular mechanisms of MMPs in CRC, also in consideration of their expression and different regulation in several tissues.

Colon cancer is an aggressive tumor form with a poor prognosis. This study reports a comparative proteomic analysis performed by using two-dimensional differential in-gel electrophoresis (2D-DIGE) between 26 pooled colon cancer surgical tissues and adjacent non-tumoral tissues, to identify potential target proteins correlated with carcinogenesis. The DAVID functional classification tool revealed that most of the differentially regulated proteins, acting both intracellularly and extracellularly, concur across multiple cancer steps. The identified protein classes include proteins involved in cell proliferation, apoptosis, metabolic pathways, oxidative stress, cell motility, Ras signal transduction, and cytoskeleton. Interestingly, networks and pathways analysis showed that the identified proteins could be biologically inter-connected to the tumor-host microenvironment, including innate immune response, platelet and neutrophil degranulation, and hemostasis. Finally, transgelin (TAGL), here identified for the first time with four different protein species, collectively down-regulated in colon cancer tissues, emerged as a top-ranked biomarker for colorectal cancer (CRC). In conclusion, our findings revealed a different proteomic profiling in colon cancer tissues characterized by the deregulation of specific pathways involved in hallmarks of cancer. All of these proteins may represent promising novel colon cancer biomarkers and potential therapeutic targets, if validated in larger cohorts of patients.

An array of diimidazolium salts has been synthesized and used to investigate their anti-microbial and anti-proliferative activities. In particular, salts based on the 3,30-di-n-alkyl-1,10-(1,n-phenylenedimethylene)- diimidazolium cation and differing in the alkyl chain length on the imidazolium ion, the isomeric substitution on the aromatic spacer and in the anion nature were used. The anti-proliferative activity was evaluated against cervical (HeLa), colon adenocarcinoma (HT-29) and breast (SKBR3) cancer cell lines. In the latter case, also a morphological assessment after treatment with salts was performed. All salts were tested for their hemolytic activity against human erythrocytes. On the other hand, the anti-microbial activity was investigated using both Gram-negative (Escherichia coli) and Gram-positive (Kokuria rhizophila, Staphilococcus aureus and Bacillus subtilis) strains. On the whole, the data collected demonstrate that biological activity is the result of the combined action of both cation and anion structures. In general, the cation hydrophobicity plays the most significant role with structural features of the anion becoming more relevant in the presence of a shorter alkyl chain on the cationic head.

In cases of morbid obesity, obstructive sleep apnea (OSA) was associated with biopsy-proven liver damage. The role of non-invasive techniques to monitor liver changes during OSA treatment with continuous positive airway pressure (CPAP) is unknown. We used non-invasive ultrasound techniques to assess liver steatosis and fibrosis in severe OSA patients at diagnosis and during long-term CPAP treatment. Fifteen consecutive patients with severe OSA (apnea hypopnea index 52.5 ± 19.1/h) were studied by liver ultrasound and elastography (Fibroscan) at 6-mo (n = 3) or 1-y (n = 12) follow-up. Mean age was 49.3 ± 11.9 y, body mass index (BMI) was 35.4 ± 6.4 kg/m(2). Adherence to CPAP was ≥5 h/night. At baseline, most patients had severe liver steatosis independent of BMI; at follow-up, liver steatosis was not statistically different, but a relationship between severity of steatosis and BMI became apparent (Spearman's rho: 0.53, p = 0.03). Significant fibrosis as assessed by Fibroscan was absent at diagnosis or follow-up (failure or unreliable measurements in four markedly obese patients). Therefore, ultrasound liver assessment is feasible in most OSA patients, and CPAP treatment may positively affect liver steatosis.

We describe the case of an adolescent who was admitted to the hospital because of sudden occurrence of chest pain, dyspnea and subcutaneous emphysema. On admission, physical examination revealed subcutaneous crepitations in the superior part of the rib cage, and auscultation of the chest showed widespread wheezing. The radiological assessment confirmed the diagnosis of pneumomediastinum and pneumothorax. A follow-up CT scan performed one week after the admission showed almost complete resolution of the radiological alterations. At the following visits, the patient was asymptomatic, but reported to have suffered from frequent episodes of rhinorrea, sneezing, nasal blockage, and sometimes, chest tightness, especially during exposure to pets and/or windy weather. Skin prick testing showed sensitivities to dermatophagoides pteronyssinus and farinae, grass pollen and dog dander. Spirometry documented significant improvement in lung function after short-acting bronchodilator, allowing for the diagnosis of asthma to be made. Although pneumomediastinum may be a complication of various respiratory diseases, including asthma, it has never been reported as the first presentation of underlying bronchial asthma. Herein, the physiopathological mechanisms, the diagnostic procedures and treatment of pneumomediastinum in asthma are discussed. We suggest that the diagnosis of asthma should be considered in the differential diagnosis of pneumomediastinum in adolescence.

To the Editors: Obstructive sleep apnoea (OSA) is often associated with metabolic disturbances, including altered glucose metabolism and dyslipidaemia, which probably contribute to the increased cardiovascular risk in these patients 1. The concept of the metabolic syndrome (MetS) as a cluster of cardiometabolic risk factors has gained popularity in recent years, and a much higher prevalence of the MetS has been found in OSA patients compared with the general population in several studies 1. While the MetS largely reflects the effects of visceral obesity, environmental factors, i.e. the type of diet, could also play some role. The Mediterranean diet, rich in olive oil and fish, is protective against the MetS 2–4, but no study has examined the association of MetS and OSA in Mediterranean countries. We hypothesised that prevalence of the MetS might be lower in OSA patients living in the Mediterranean area compared with the prevalence values found in non-Mediterranean countries. Therefore, we retrospectively assessed the prevalence of the MetS according to the modified National Health and Nutrition Examination Survey Adult Treatment Panel (ATP) III criteria 5 in consecutive patients referred to sleep laboratories in Italy (n = 107), Spain (n = 138) and Greece (n = 218). Patients diagnosed with OSA in the period July 2007–September 2008 in Palermo, Italy (Respiratory Section, DIBIMIS, University of Palermo, and CNR Institute of Biomedicine and Molecular Immunology), Palma de Mallorca, Spain (Hospital Son Dureta) and Alexandroupolis, Greece (Sleep Unit, Medical School, Democritus University of Thrace), were evaluated in this study. All underwent …

Background/Aims We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes. Methods Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defined as a focal thickening >1.3 mm. Results Prevalence of high OSA risk was similar in patients refusing or accepting PG (76% vs 68%, p = 0.17). Among those accepting PG, overall OSA prevalence was significantly higher in patients with F2-F4 fibrosis compared to those without (72% vs 44%; p = 0.04). Significant fibrosis was independently associated with mean nocturnal oxygen saturation (SaO2)1 (OR 6.30, 95%C.I. 1.02–12.3; p = 0.01). Conclusions In NAFLD patients with chronically elevated ALT at low prevalence of morbid obesity, OSA was highly prevalent and indexes of SaO2 resulted independently associated with severity of liver fibrosis and carotid atherosclerosis. These data suggest to consider sleep disordered breathing as a potential additional therapeutic target in severe NAFLD patients.