Targeting Non-Coding RNAs for the Development of Novel Hepatocellular Carcinoma Therapeutic Approaches.

Hepatocellular carcinoma (HCC) remains a global health challenge, representing the third leading cause of cancer deaths worldwide. Although therapeutic advances have been made in the few last years, the prognosis remains poor. Thus, there is a dire need to develop novel therapeutic strategies. In this regard, two approaches can be considered: (1) the identification of tumor-targeted delivery systems and (2) the targeting of molecule(s) whose aberrant expression is confined to tumor cells. In this work, we focused on the second approach. Among the different kinds of possible target molecules, we discuss the potential therapeutic value of targeting non-coding RNAs (ncRNAs), which include micro interfering RNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). These molecules represent the most significant RNA transcripts in cells and can regulate many HCC features, including proliferation, apoptosis, invasion and metastasis. In the first part of the review, the main characteristics of HCC and ncRNAs are described. The involvement of ncRNAs in HCC is then presented over five sections: (a) miRNAs, (b) lncRNAs, (c) circRNAs, (d) ncRNAs and drug resistance and (e) ncRNAs and liver fibrosis. Overall, this work provides the reader with the most recent state-of-the-art approaches in this field, highlighting key trends and opportunities for more advanced and efficacious HCC treatments.

Potential Application of Small Interfering RNA in Gastro-Intestinal Tumors.

Despite the progress made in the diagnoses and therapy of gastrointestinal cancers, these diseases are still plagued by a high mortality. Thus, novel therapeutic approaches are urgently required. In this regard, small interfering RNA (siRNA), double-stranded RNA molecules able to specifically target the mRNA of pathological genes, have the potential to be of therapeutic value. To be effective in the human body, siRNAs need to be protected against degradation. Additionally, they need to target the tumor, leaving the normal tissue untouched in an effort to preserve organ function. To accomplish these tasks, siRNAs have been formulated with smart delivery systems such has polymers and lipids. While siRNA protection is not particularly difficult to achieve, their targeting of tumor cells remains problematic. Here, after introducing the general features of gastrointestinal cancers, we describe siRNA characteristics together with representative delivery systems developed for gastrointestinal cancers. Afterward, we present a selection of research papers employing siRNAs against upper- and lower- gastrointestinal cancers. For the liver, we also consider papers using siRNAs to combat liver cirrhosis, a relevant risk factor for liver cancer development. Finally, we present a brief description of clinical trials employing siRNAs for gastrointestinal cancers.

Effects of biochar on berseem clover (Trifolium alexandrinum, L.) growth and heavy metal (Cd, Cr, Cu, Ni, Pb, and Zn) accumulation.

Urban soil pollution by heavy metals (HMs) is a pressing problem in the development of urban agriculture (UA). In this context, the use of amendments, such as biochar, and phytoremediation are considered potentially cost-effective alternatives to conventional methods, and can be also combined to improve the remediation of soils from HMs. A pot experiment was performed to investigate the combined effect of berseem clover (Trifolium alexandrinum, L.) and biochar amendment in remediating a sandy soil collected near a shooting range area co-contaminated with Cd, Cr, Cu, Ni, Pb, and Zn. The biochar, obtained from a wood-chip gasifier fed with a mix of Douglas (Pseudotsuga menziesii, Mirb.) and Black Pine (Pinus nigra, J.F.Arnold) wood, was applied at two rates (0.8% and 1.6%, w/w). Eighteen weeks after sowing, all plants were harvested. The roots and aboveground tissues of the crops were separately collected and analyzed. The tested biochar effectively adsorbed the HMs (Cd, Cr, Cu, Ni, Pb, and Zn) from the soil. Biochar increased DW production of aboveground and root tissues. Moreover, biochar significantly reduced the concentration of Cr, Cu, Ni, and Pb in the aboveground tissues of berseem clover, although a significant reduction was not detected for Cd and Zn. Results indicated that berseem clover was a Cr, Ni and Pb excluder. However, this species can be considered suitable for Cu phytoextraction and Cd and Zn phytostabilization of slightly polluted urban soil. Only the Cu levels in the aerial biomass were below the acceptable limit for use as fodder.

Crop suitability assessment in remediation of Zn contaminated soil.

Zinc (Zn) is naturally present in soils and constitutes an essential micronutrient for plants. Mining, industrial, as well as various agricultural activities all contribute to increasing the Zn concentrations in soils to levels that are toxic for plants. The aim of this study was to evaluate the capacity of field crops to remove Zn from contaminated soils. The experimental design included 28 treatments, comprising seven field crops (Hordeum vulgare L., Ricinus communis L., Phaseolus vulgaris L., Brassica juncea Czem., Sorgum vulgare L., Spinacea oleracea L., Solanum lycopersicum L.) and four Zn levels (0, 500, 1000, 1500 mg kg-1) applied to soils. The dry weight (DW) of the aboveground biomass of R. communis and S. lycopersicum increased significantly as the Zn concentration in the soil increased, whereas the DW significantly decreased in P. vulgaris, B. juncea and S. vulgare. Results indicated that S. oleracea was the most efficient in concentrating Zn in the aboveground tissues, followed in decreasing order by H. vulgare, S. lycopersicum, R. communis, S. vulgare, P. vulgaris, and B. juncea. H. vulgare resulted the most efficient in accumulating Zn both in fruit and in leaves and stems, whereas S. lycopersicum resulted the most efficient in accumulating Zn in roots. The BAF and TF values indicated that H. vulgare and S. oleracea resulted being suitable for Zn phytoextraction, whereas the remaining crops being suitable for Zn phytostabilization. These results highlight the phytoremediation potential of the seven analysed crops.

Efficacy of a strict surveillance policy towards inappropriateness of plasma transfusion.

BACKGROUND: Plasma transfusion is not without risks. Despite a limited spectrum of indications, plasma is frequently used as prophylaxis in non-bleeding patients, to correct altered coagulation tests. A high rate of inappropriate use of plasma transfusion is frequently reported, as well as underdosage. STUDY DESIGN AND METHODS: Since 2010 we started an education program that occurred in several phases to disseminate the knowledge of plasma transfusion guidelines. Since 2014 a 'zero tolerance' policy was applied: except for massive bleedings, plasma requests were prospectively evaluated, rejecting those without an appropriate indication. When indicated, at least 10 mL/Kg b.w.were issued. The previous five year period (2005-2009) served as control. RESULTS: The number of patients transfused/year decreased by 67.6% vs the control period (149 vs 460), and the liters of plasma issued/year decreased by 70.4% (233 vs 795). The deepest fall was observed in acute care wards (-70.8%). The mean volume transfused per episode raised from 731 mL ±â€¯70 to 879 mL ±â€¯154. The Prothrombin Time ratio at the moment of transfusion request increased from a mean of 1.35 (Interquartile range 1.20-2.64) in the control period to 1.62 (Interquartile range 1.43-1.98) in the last period (p < 0.001). CONCLUSION: With a proactive educational approach a remarkable reduction of plasma order and administration has been obtained, without any consequence on morbidity and mortality and with an estimated saving since 2014 of 750,000 €. A 'zero tolerance' policy can be effectively implemented only with a thorough workup with the local physicians, including repeated rounds of information and refreshing of the updated transfusion practice and knowledge of the established guidelines over the time.

Phytoextraction of copper from a contaminated soil using arable and vegetable crops.

Copper (Cu) is among the main contaminant of agricultural soil. The reclamation of Cu polluted soils can be achieved with phytoextraction even if, in general, plants are Cu-excluders and uncommon are Cu-accumulators. The research objectives were to establish the Cu removal capacity by arable and vegetable crops and to investigate the distribution of Cu in their roots, stems and leaves, and fruits. Pot trials were conducted for two subsequent years in Tuscany (Italy). Cu was added into soil in four levels (0, 200, 400, 600 mg kg-1 of Cu). At harvesting, the crops roots, stems and leaves, and fruits or seeds were separately collected, oven dried, weighted, milled and separately analyzed. The results show that the GDUs value to reach the physiological maturity for barley, common bean, Indian mustard, and ricinus was significantly positively correlated with Cu concentration in soil in contrast with observed in sorghum, spinach, and tomato. Leaves and stems of spinach and ricinus have a good storage capacity in contrast with common bean, tomato, Indian mustard sorghum and barley. Tomato storage Cu mainly in fruits and roots which show a remarkable concentration of Cu that increases progressively with the increase of Cu concentration in the soil. In addition, the roots of common bean and ricinus showed a very high concentration of Cu. All species can be considered Cu-excluders because of their low capacity to uptake high quantity of Cu. Indian mustard can be considered a plant able to translocate the metal from root to epigeal tissue.

Laparoscopic colectomy for carcinoma of the colon in octogenarians.

BACKGROUND: The incidence of colorectal cancer increases with age; most patients present with resectable disease. Since there is a high morbidity rate in the elderly, the laparoscopic approach, with its lower complication rate, appears to be the ideal choice for treatment of this patient group. In this retrospective study, we aimed to compare the short-term results of laparoscopic (LC) with open (OC) colectomies for carcinoma in patients 80 years of age or older. METHODS: The study comprised 93 patients aged 80 years and over who underwent OC or LC between 2005 and 2008. Demographics and clinical data were compared. RESULTS: The LC group included 47, and the OC included 46 patients. No differences were found between the two groups with regard to mean age, comorbidities, and the extent of the resection. The operative time was shorter in the OC (121 vs. 157 min, P = 0.001). Hospital stay was shorter in the LC (7.6 vs. 8.8 days, P = 0.06). There were more postoperative complications in the OC (35.6%) than in the LC (30.4%), however the difference was not statistically significant (P = 0.6). CONCLUSIONS: LC in the elderly is safe, with a shorter hospital stay, and carries a short-term benefit for selected patients and could be offered to all elderly patients.

[Inflammatory colitis: classification and surgical treatment]. / Le coliti infiammatorie. Classificazione e trattamento chirurgico.

The development of clinical and histopathological criteria for the diagnosis of Crohn's disease (CD) and ulcerative colitis (UC), pushed the scientists to identify a new category: the indeterminate colitis (CI). This term is used when definitive diagnosis of UC or CD has not been made by colonoscopy, colonic biopsy or colectomy. The distinction between these forms has major implications including the choice of medical treatment, timing of surgery, prognosis and disease course. The role of surgery in inflammatory bowel disease differs between the three main forms: in CD is primarily to treat complications of the disease process; in UC surgery is curative for intestinal manifestations and nearly eliminates the risk of future malignancy; in IC is actually discussed: the current guidelines identify in surgery the best treatment for fulminate disease, intractability of disease symptoms or failure of medical therapy. Although there is a few number of studies in the literature, selective criteria for the diagnosis and successful treatment must be revisited. The term CI should be used as a pending tray diagnosis, representing diagnostic inadequacy and not as specific nosological entity. Evidence emerging from the studies of serological markers (ASCA and P-ANCA) suggests that a subgroup of patients initially diagnosed as IC maybe identified as a separate group, and so they need a specific treatment for their disease.

Verocytotoxin-producing Escherichia coli EH 0157:H7 colitis.

0157:H7 is a known etiologic agent of hemorrhagic colitis. The clinical and histologic picture of colitis is largely similar to that of ischemic colitis, with areas of submucosal hemorrhage and edema, erosions, and ulcerations. We present a case report and review of the literature. A 52-year-old HIV-positive man, in apparently good immunologic condition, developed severe hemorrhagic colitis characterized by the onset of multiple colonic perforations and an unfavorable outcome. The diagnosis of 0157:H7 colitis should therefore be considered in all patients with indeterminate hematic diarrhea. Further studies are warranted to verify whether HIV infection may play a determinant role in the clinical course of 0157:H7 infection.