Long non-coding RNAs era in liver cancer

Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to high mortality rates in the general population and the sixth most common cancer worldwide. HCC is characterized by deregulation of multiple genes and signalling pathways. These genetic effects can involve both protein coding genes as well as non-coding RNA genes. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt, constituting a subpopulation of ncRNAs. Their biological effects are not well understood compared to small non-coding RNA (microRNAs), but they have been recently recognized to exert a crucial role in the regulation of gene expression and modulation of signalling pathways. Notably, several studies indicated that lncRNAs contribute to the pathogenesis and progression of HCC. Investigating the molecular mechanisms underlying lncRNAs expression opens potential applications in diagnosis and treatment of liver disease. This editorial provides three examples (MALAT-1 metastasis associated lung adenocarcinoma transcript, HULC highly upregulated in liver cancer and HOTAIR HOX transcript antisense intergenic RNA) of well-known lncRNAs upregulated in HCC, whose mechanisms of action are known, and for which therapeutic applications are delineated. Targeting of lncRNAs using several approaches (siRNA-mediated silencing or changing their secondary structure) offers new possibility to treat HCC

Multimodal artistic metaphors: research on a corpus of Sardinian art

The study aims to define an artistic metaphor and highlight the multimodal properties of metaphors in artistic environments. In this research, an artistic metaphor has a relevant aesthetic purpose and it conveys beauty. Interpreting a metaphor in Sardinian art requires time for contemplation, however the cognitive effort of understanding the meaning of an artistic metaphor is rewarded by the delight of those who contemplate it. This metaphor has some characteristics in common with a visual metaphor but differs from other types of images that have been more extensively analyzed in the literature: it is difficult to establish a specific directionality, and consequently, it is not easy to recognize the target and source domains; the way it is expressed makes its interpretation and classification problematic at times. A proposal is presented in the paper to describe artistic metaphors according to universal macro-categories, inspired by the knowledge of Aristotelian and Kantian categories and by studies in the field of aesthetics: (1) time, (2) space, (3) decontextualization of stereotypes, and (4) fusion of forms. These categories are applied to a corpus of artworks by important artists in Sardinia to show that the visual, tactile, and auditory components of the pictures can boost an effective comprehension of figurative meaning. Results suggest that the multimodality of Sardinian artistic metaphors orients the observer toward original possibilities of learning and stimulates knowledge of the “submerged” wealth of symbols and archetypes that characterize insularity

Microglia-derived microvesicles affect microglia phenotype in glioma

Extracellular-released vesicles (EVs), such as microvesicles (MV) and exosomes (Exo) provide a new type of inter-cellular communication, directly transferring a ready to use box of information, consisting of proteins, lipids and nucleic acids. In the nervous system, EVs participate to neuron-glial cross-talk, a bidirectional communication important to preserve brain homeostasis and, when dysfunctional, involved in several CNS diseases. We investigated whether microglia-derived EVs could be used to transfer a protective phenotype to dysfunctional microglia in the context of a brain tumor. When MV, isolated from microglia stimulated with LPS/IFNg were brain injected in glioma-bearing mice, we observed a phenotype switch of tumor associated myeloid cells (TAMs) and a reduction of tumor size. Our findings indicate that the MV cargo, which contains upregulated transcripts for several inflammation-related genes, can transfer information in the brain of glioma bearing mice modifying microglial gene expression, reducing neuronal death and glioma invasion, thus promoting the recovery of brain homeostasis

The treatment of the organic fraction of municipal solid waste (OFMSW) as a possible source of micro- and nano-plastics and bioplastics in agroecosystems: a review

AbstractPlastics fragmentation into smaller debris, namely, micro- and nano-plastics (MPs and NPs), is a matter of global concern because of their wide distribution in terrestrial and marine environments. The latest research has focused mainly on aquatic ecosystems, and fragmentation of bioplastics into micro- and nano-particles (MBPs and NBPs) is not considered. The distribution, concentration, fate and major source of MPs, NPS, MBPs and NBPs in agroecosystems still need to be understood. The use of composts and sewage sludge from the organic fraction of municipal solid waste (OFMSW) treatment plants as soil amendments is likely to represent a major input of these debris. The present review provides insights into the current evidence of pollution from micro- and nano-particles of both fossil- and bio-origin in the OFMSW treatment, and aims at evaluating if the recycling of organic waste and its application as a soil fertilizer outweigh the risk of pollution in terrestrial environments. Huge unpredictability exists due to the limited numbers of data on their quantification in each source of possible solution. Indeed, the major hurdles arise from the difficult to quantify the micro-, especially the nano-, particles and subsequently assess the concentrations in the environments, as well as bioaccumulation risks, and toxic effects on organisms. Graphical Abstrac

Electrocution and containment methods to reduce the activity of red palm weevil (Rhynchophorus ferrugineus, Ol.)

Aim of study: To evaluate the susceptibility of the Rhynchophorus ferrugineus to electric discharges, to eventually use this application in synergy with other methods as part of an integrated control strategy.Area of study: Worldwide.Material and methods: Three different electric voltage intensities were applied to R. ferrugineus to investigate the insect’s susceptibility in both adult and larval stages. The transmission and diffusion of electricity within a portion of the palm tree was tested. In addition, the suitability of containment materials for handling and transportation of plant residues was tested.Main results: The results of adult test showed that the total number of eggs laid per mating couple and the number of larvae born were about 1.5 times higher in the control compared to the electrified samples. The duration of the electric discharge on larvae had a small impact on the mortality rate, while the electric voltage showed a strong impact on mortality (87% for 10 V and 99% for 15 V). The presence of a significant electric current was observed in a viable portion of stem (distance from the source of electricity 10 cm) providing a direct current with 250 V tension. Among the materials tested for the transportation of palm residues, the aluminium net sheet showed the best results in the containment of both larval and adult individuals.Research highlights: Electrocution has proven to be a system which can help in the control of red palm weevil reducing the use of synthetic chemicals

Hormonal Therapy and Chemoprevention.

Hormone replacement therapy (HRT) can increase the quality as well as the length of life, but a prolonged use can also increase the risk of breast cancer. The combination of HRT and a selective estrogen receptor modulator (SERM) such as tamoxifen may retain the benefits while reducing the risks of either agent. A post hoc analysis of the Italian Tamoxifen Prevention Study showed a borderline significant reduction of breast cancer among women who were on HRT continuously and tamoxifen as compared with continuous HRT users who received placebo. Recent studies suggest that the standard dose of tamoxifen may be reduced to one-quarter (i.e., 10 mg every other day) without loss of its beneficial biological effects. Since the endometrial effect of tamoxifen seems to be both dose and time dependent, a dose reduction could substantially reduce the risk of endometrial cancer while retaining its preventive efficacy. On the other hand, the addition of HRT containing progestins could also minimize the risk of endometrial cancer associated with tamoxifen. Moreover, estrogen should reduce the incidence of vasomotor and urogenital symptoms, which are a major reason for tamoxifen withdrawal in prevention studies. Notably, in the National Surgical Adjuvant Breast Project (NSABP) P-1 trial, women ages 50 or younger had no increased incidence of adverse events, including endometrial cancer and venous thromboembolic events. One possible explanation for the lack of toxicity in premenopause is the presence of adequate circulating estrogen levels which prevent tamoxifen to act as an estrogen agonist at these target tissues. Moreover, data from the current Italian tamoxifen prevention trial indicate that the compliance was substantially higher for de novo and current HRT users as compared to women who never received HRT during the study. The combination of HRT and tamoxifen at low doses could thus reduce the risks and side effects while retaining the benefits of either agent

Nasal Microbiota in RSV Bronchiolitis

Respiratory Syncytial Virus (RSV) is the leading cause of bronchiolitis, and the severity may be influenced by the bacterial ecosystem. Our aim was to analyze the nasal microbiota from 48 infants affected by bronchiolitis from RSV virus and 28 infants with bronchiolitis but negative for the virus. Results showed a significantly lower biodiversity in the RSV-positive group with respect to the RSV-negative group, a specific microbial profile associated with the RSV-positive group different from that observed in the negative group, and significant modifications in the relative abundance of taxa in the RSV-positive group, as well as in the RSV-A group, with respect to the negative group. Furthermore, microbial network analyses evidenced, in all studied groups, the presence of two predominant sub-networks characterized by peculiar inter- and intra-group correlation patterns as well as a general loss of connectivity among microbes in the RSV-positive group, particularly in the RSV-A group. Our results indicated that infants with more severe bronchiolitis disease, caused by RSV-A infection, present significant perturbations of both the nasal microbiota structure and the microbial relationships. Patients with a milder bronchiolitis course (RSV-B-infected and patients who have cleared the virus) presented less severe alterations

Short-Term Outcomes of an ESDM Intervention in Italian Children with Autism Spectrum Disorder following the COVID-19 Lockdown

The COVID-19 pandemic caused a temporary lockdown period in Italy, during which the delivery of in-person treatment for children with autism spectrum disorder (ASD) in public health services was discontinued. This occurrence represented a crucial challenge for both families and professionals. We assessed the short-term outcomes of a sample of 18 children who received an early intervention with the Early Start Denver Model (ESDM), delivered at low intensity over one year in the pre-pandemic period, after six months of interruption of in-presence treatment due to lockdown restrictions. Children who received the ESDM treatment maintained their gains in sociocommunicative skills and did not exhibit any developmental regression. Additionally, there was evidence of a decrease in the restrictive and repetitive behavior (RRB) domain. The parents, who were already familiar with the principles of the ESDM, only received telehealth support from therapists that aimed to sustain the gains already achieved. We believe that it is always helpful to support parents in their daily lives by implementing interactional and play skills with their children to integrate and consolidate the results obtained in the individual interventions conducted by experienced therapists

Mo1927 Mucosa-Associated Microbiota and Promoter Methylation Status of Genes Involved in Immune Response in Crohn's Disease Patients

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Enteric Delivery of Regenerating Family Member 3 alpha Alters the Intestinal Microbiota and Controls Inflammation in Mice With Colitis

Background & Aims Paneth cell dysfunction causes deficiencies in intestinal C-type lectins and antimicrobial peptides, which leads to dysbiosis of the intestinal microbiota, alters the mucosal barrier, and promotes development of inflammatory bowel diseases. We investigated whether transgenic (TG) expression of the human regenerating family member 3 alpha gene ( REG3A ) alters the fecal microbiota and affects development of colitis in mice. Methods We performed studies with C57BL/6 mice that express human regenerating family member 3 alpha (hREG3A) in hepatocytes, via the albumin gene promoter. In these mice, hREG3A travels via the bile to the intestinal lumen. Some mice were given dextran sodium sulfate (DSS) to induce colitis. Feces were collected from mice and the composition of the microbiota was analyzed by 16S ribosomal RNA sequencing. The fecal microbiome was also analyzed from mice that express only 1 copy of human REG3A transgene but were fed feces from control mice (not expressing hREG3A) as newborns. Mice expressing hREG3A were monitored for DSS-induced colitis after cohousing or feeding feces from control mice. Colitis was induced in another set of control and hREG3A-TG mice by administration of trinitrobenzene sulfonic acid; some mice were given intrarectal injections of the hREG3A protein. Colon tissues were collected from mice and analyzed by histology and immunohistochemistry to detect mucin 2, as well as by 16S ribosomal RNA fluorescence in situ hybridization, transcriptional analyses, and quantitative polymerase chain reaction. We measured levels of reactive oxygen species (ROS) in bacterial cultures and fecal microbiota using 2′,7′-dichlorofluorescein diacetate and flow cytometry. Results The fecal microbiota of mice that express hREG3A had a significant shift in composition, compared with control mice, with enrichment of Clostridiales (Ruminococcaceae, Lachnospiraceae) and depletion of Bacteroidetes (Prevotellaceae); the TG mice developed less-severe colitis following administration of DSS than control mice, associated with preserved gut barrier integrity and reduced bacterial translocation, epithelial inflammation, and oxidative damage. A similar shift in the composition of the fecal microbiota occurred after a few months in TG mice heterozygous for REG3A that harbored a wild-type maternal microbiota at birth; these mice developed less-severe forms of colitis following DSS administration. Cohoused and germ-free mice fed feces from REG3A- TG mice and given DSS developed less-severe forms of colitis and had reduced lipopolysaccharide activation of the toll-like receptor 4 and increased survival times compared with mice not fed feces from REG3A -TG mice. REG3A TG mice developed only mild colonic inflammation after exposure to 2,4,6-trinitrobenzene sulfonic acid, compared with control mice. Control mice given intrarectal hREG3A and exposed to 2,4,6-trinitrobenzene sulfonic acid showed less colon damage and inflammation than mice not given intrarectal hREG3A. Fecal samples from REG3A- TG mice had lower levels of ROS than feces from control mice during DSS administration. Addition of hREG3A to bacterial cultures reduced levels of ROS and increased survival of oxygen-sensitive commensal bacteria ( Faecalibacterium prausnitzii and Roseburia intestinalis ). Conclusions Mice with hepatocytes that express hREG3A, which travels to the intestinal lumen, are less sensitive to colitis than control mice. We found hREG3A to alter the colonic microbiota by decreasing levels of ROS. Fecal microbiota from REG3A -TG mice protect non-TG mice from induction of colitis. These findings indicate a role for reduction of oxidative stress in preserving the gut microbiota and its ability to prevent inflammation