MicroRNA profiles discriminate among colon cancer metastasis

MicroRNAs are being exploited for diagnosis, prognosis and monitoring of cancer and other diseases. Their high tissue specificity and critical role in oncogenesis provide new biomarkers for the diagnosis and classification of cancer as well as predicting patients' outcomes. MicroRNAs signatures have been identified for many human tumors, including colorectal cancer (CRC). In most cases, metastatic disease is difficult to predict and to prevent with adequate therapies. The aim of our study was to identify a microRNA signature for metastatic CRC that could predict and differentiate metastatic target organ localization. Normal and cancer tissues of three different groups of CRC patients were analyzed. RNA microarray and TaqMan Array analysis were performed on 66 Italian patients with or without lymph nodes and/or liver recurrences. Data obtained with the two assays were analyzed separately and then intersected to identify a primary CRC metastatic signature. Five differentially expressed microRNAs (hsa-miR-21, -103, -93, -31 and -566) were validated by qRT-PCR on a second group of 16 American metastatic patients. In situ hybridization was performed on the 16 American patients as well as on three distinct commercial tissues microarray (TMA) containing normal adjacent colon, the primary adenocarcinoma, normal and metastatic lymph nodes and liver. Hsa-miRNA-21, -93, and -103 upregulation together with hsa-miR-566 downregulation defined the CRC metastatic signature, while in situ hybridization data identified a lymphonodal invasion profile. We provided the first microRNAs signature that could discriminate between colorectal recurrences to lymph nodes and liver and between colorectal liver metastasis and primary hepatic tumor

Tufted hair folliculitis: Complete enduring response after treatment with rifampicin

BACKGROUND:A 47-year-old woman presented with erythematous lesions with papules and pustules on her parieto-occipital region that had been present for 8 months. Areas of sclero-atrophic alopecia were evident, whereas at different points tufted hair shafts were coming out from single dilatated follicular ostia. Before our observation, an antibiotic oral therapy with tetracyclines and local with erythromycin had been administered to the patient, with partial improvement and relapse on its suspension. METHODS: Bacterial culture from pustules showed the development of Staphylococcus aureus. A skin biopsy was done. According to clinical and histopathological findings a diagnosis of tufted hair folliculitis was made and a treatment with oral rifampicin was started at the dosage of 450 mg twice per day. RESULTS: After 3 weeks of therapy, the pustular lesions regressed completely and after a follow-up of 1 year no relapse was observed. CONCLUSIONS: Rifampicin is one of the best active antibiotics against S. aureus, which seems to play a role in the pathogenesis of tufted hair folliculitis. Our results, if further confirmed, may suggest a role for rifampicin either for the control of the pustular phase of this rare disorder or to prevent its relapses for a long time

Electrosteric Activation by using Ion-Tagged Prolines: A Combined Experimental and Computational Investigation

We have recently proposed the empirical concept of electrosteric activation to explain the improved catalytic performances observed for a series of ion-tagged catalysts compared to the parent tag-free structures. Here, the results of a combined experimental and computational investigation on the asymmetric aldol reaction between cyclohexanone and benzaldehyde, catalyzed by a family of tag-free and ionic-tagged prolines, are presented. Whereas diastereo- and enantioselectivities remain very high in all cases examined, the ion-tagged catalyst cis-4-(2-(3-methyl-imidazol-3-ium-1-yl)acetoxy)-proline bistriflimide, cis-7, displays a remarkably high activity compared to its tagged trans analogue and to the tag-free catalysts cis and trans-4-(2-phenylacetoxy)-proline 8. A computational investigation of ion-tagged and tag-free model systems shows that the transition state involving cis-7 is stabilized by a complex interplay of hydrogen bonds (in particular, those involving the counter ion oxygen atoms and the hydrogen atoms of the ionic tag), \u3c0-stacking interactions involving the aldehyde phenyl ring, and similar \u3c0 interactions between the proline carboxyl group and the imidazole ring. The overall effect of these interactions accounts for the observed enhanced activity

Oncosuppressor proteins of fragile sites are reduced in cervical cancer

FHIT and WWOX are tumor suppressor genes that span the common fragile sites FRA3B and FRA16D, respectively. To analyze possible synergisms among these genes in cervical cancer progression, we considered 159 cervical intraepithelial neoplasias, and 58 invasive squamous cell carcinomas of the uterine cervix. All cases were previously selected as high risk HPV. FHIT and WWOX proteins were examined by immunohistochemistry and their expression was inversely correlated with precancerous vs. invasive lesions. Statistics among biological markers indicated an association between FHIT and WWOX. Protein expression of these two genes was also absent or reduced in cancer cell lines. Thus, WWOX may be considered as a novel important genetic marker in cervical cancer and the association between the altered expression of FHIT and WWOX may be a critical event in the progression of this neoplasia. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Trauma- and stressor-related disorders in survivors from a shipwreck: a short report on forensic implications

On January 2012 the Costa Concordia cruise ship sank after hitting an underwater rock off Isola del Giglio, in Tuscany, this resulting in a number of deaths and injuries. After the disaster, several survivors developed psychological disturbances. This led to medico-legal evaluations aimed at assessing the psychiatric sequelae of the accident in order to quantify the permanent biological impairment and the related compensations. In the present manuscript we provide an overview of the results of clinical and medico-legal evaluations performed between 2013 and 2019 on 177 survivors complaining psychological disturbances. The most frequently diagnosed condition was Post-Traumatic Stress Disorder (PTSD; n=90), followed by Acute Stress Disorder (n=37), Adjustment Disorders (n=29) and Generalized Anxiety Disorder (n=5). The results of such evaluations are consistent with evidence indicating the risk of developing PTSD and other trauma- and stressor-related disorders among disaster survivors; further, they highlight the potential relevance in the forensic context of individual elements increasing or decreasing the possibility to develop PTSD among subjects exposed to similar life threatening experiences

sequences and

UCbase & miRfunc: a database of ultraconserve

Abstract LB-241: Silencing of microRNA-31 prevents esophageal neoplasia in zinc deficient rats.

Dietary zinc deficiency (ZD) is implicated in the pathogenesis of human esophageal squamous cell carcinoma (ESCC). microRNA-31 (miR-31) is overexpressed in human ESCC. In the rat a ZD diet promotes esophageal carcinogenesis by inducing cellular proliferation and changes in the expression of microRNA and mRNA, including overexpression of miR-31 and cancer-related proinflammation genes. Here we report that treatment of ZD rats with locked nucleic acid (LNA)-modified inhibitor of miR-31 (LNA-antimiR) prevents the development of a precancerous esophageal phenotype. Weanling rats were fed ZD or zinc-sufficient (ZS) diet for 5 weeks. Simultaneously, ZD rats were administered intravenously (twice a week) LNA-antimiR, LNA-scramble miR-31 or the vehicle saline. ZS rats received saline. Compared to ZS rats, LNA-scramble miR-31-treated or saline-treated ZD rats overexpressed miR-31 and displayed a highly proliferative and inflammatory esophageal phenotype. Treatment of ZD rats with LNA-antimiR reduced miR-31 expression in esophageal epithelia and circulating blood by ~60% and reversed the ZD-induced esophageal pathology, as evidenced by a thinned esophageal epithelium with reduced cell proliferation by PCNA immunohistochemistry and increased apoptosis by caspase-3/7 activity. Transcriptome analyses of esophageal epithelia demonstrated derepression of target mRNAs with miR-31 seed sites. In particular, Stk40 (a negative regulator of NF-κ? signaling) was demonstrated to be a bona fide miR-31 target. Using in situ hybridization and immunohistochemistry, miR-31 overexpression in ZD esophageal sections correlated with downregulation of STK40 protein, as well as with upregulation of an NF-κ? p65 - RAGE-S100A9 inflammatory pathway that in turn, was normalized by miR-31 silencing. Thus, silencing miR-31 prevents esophageal neoplasia. Overexpression of miR-31 promotes ESCC initiation by enhancing inflammation via STK40 - NF-κ? signaling. The data indicate that miR-31 may be a promising therapeutic target for improved ESCC diagnosis and prevention. Funding: National Institutes of Health grants U01 CA152758 to CMC and R01CA118560 & R21CA152505 to LYYF