MicroRNAs in human cancer: from research to therapy

Numerous miRNAs are deregulated in human cancers, and experimental evidence indicates that they can play roles as oncogenes or tumor suppressor genes. Similarly to cancer genes that encode proteins, deregulation of miRNA-encoding genes is associated with genetic or epigenetic alterations, such as deletions, amplifications, point mutations and aberrant DNA methylation. The discovery that miRNAs interact with known oncogenes has established further links with molecular pathways implicated in malignant transformation. Finally, miRNAs can be used as diagnostic markers, and their potential as therapeutic molecules has moved miRNAs from the area of basic research to the field of cancer biotechnology

Radionuclides for theranostic applications

High Specific Activity Radionuclides (HSARNs), obtained by either proton, deuteron or alpha cyclotron irradiation, followed by selective radiochemical separation from the irradiated target in No Carrier Added (NCA) form represent a powerful analytical tool in pure and applied sciences and technologicies. One of the main applications of HSARNs concern medical radiodiagnostics and metabolic radiotherapy in the relatively novel theranostic paradigm that involves individual \u201cdual-purpose\u201d radionuclides or radionuclide pairs with emissions suitable for both imaging and therapy in the contest of the age-long dream of personalized medicine. We present some examples of radionuclides produced by deuteron beams irradiation, suitable for theranostics applications

Genomic divergence in swedish warmblood horses selected for equestrian disciplines

The equestrian sport horse Swedish Warmblood (SWB) originates from versatile cavalry horses. Most modern SWB breeders have specialized their breeding either towards show jumping or dressage disciplines. The aim of this study was to explore the genomic structure of SWB horses to evaluate the presence of genomic subpopulations, and to search for signatures of selection in subgroups of SWB with high or low breeding values (EBVs) for show jumping. We analyzed high density genotype information from 380 SWB horses born in the period 2010–2011, and used Principal Coordinates Analysis and Discriminant Analysis of Principal Components to detect population stratification. Fixation index and Cross Population Extended Haplotype Homozygosity scores were used to scan the genome for potential signatures of selection. In accordance with current breeding practice, this study highlights the development of two separate breed subpopulations with putative signatures of selection in eleven chromosomes. These regions involve genes with known function in, e.g., mentality, endogenous reward system, development of connective tissues and muscles, motor control, body growth and development. This study shows genetic divergence, due to specialization towards different disciplines in SWB horses. This latter evidence can be of interest for SWB and other horse studbooks encountering specialized breeding

Genetic Diversity and Signatures of Selection in a Native Italian Horse Breed Based on SNP Data

Horses are nowadays mainly used for sport and leisure activities, and several local breeds, traditionally used in agriculture, have been exposed to a dramatic loss in population size and genetic diversity. The loss of genetic diversity negatively impacts individual fitness and reduces the potential long-term survivability of a breed. Recent advances in molecular biology and bioinformatics have allowed researchers to explore biodiversity one step further. This study aimed to evaluate the loss of genetic variability and identify genomic regions under selection pressure in the Bardigiano breed based on GGP Equine70k SNP data. The effective population size based on Linkage Disequilibrium (Ne) was equal to 39 horses, and it showed a decline over time. The average inbreeding based on runs of homozygosity (ROH) was equal to 0.17 (SD = 0.03). The majority of the ROH were relatively short (91% were ≤ 2Mbp long), highlighting the occurrence of older inbreeding, rather than a more recent occurrence. A total of eight ROH islands, shared among more than 70% of the Bardigiano horses, were found. Four of them mapped to known quantitative trait loci related to morphological traits (e.g., body size and coat color) and disease susceptibility. This study provided the first genome-wide scan of genetic diversity and selection signatures in an Italian native horse breed

Reconstruction of Acinetobacter johnsonii ICE_NC genome using hybrid de novo genome assemblies and identification of the 12α-hydroxysteroid dehydrogenase gene

Aims: The role of a Acinetobacter johnsonii strain, isolated from a soil sample, in the biotransformation of bile acids (BAs) was already described but the enzymes responsible for these transformations were only partially purified and molecularly characterized. Methods and Results: This study describes the use of hybrid de novo assemblies, that combine long-read Oxford Nanopore and short-read Illumina sequencing strategies, to reconstruct the entire genome of A. johnsonii ICE_NC strain and to identify the coding region for a 12α-hydroxysteroid dehydrogenase (12α-HSDH), involved in BAs metabolism. The de novo assembly of the A. johnsonii ICE_NC genome was generated using Canu and Unicycler, both strategies yielded a circular chromosome of about 3.6 Mb and one 117 kb long plasmid. Gene annotation was performed on the final assemblies and the gene for 12α-HSDH was detected on the plasmid. Conclusions: Our findings illustrate the added value of long read sequencing in addressing the challenges of whole genome characterization and plasmid reconstruction in bacteria. These approaches also allowed the identification of the A. johnsonii ICE_NC gene for the 12α-HSDH enzyme, whose activity was confirmed at the biochemical level. Significance and impact or the study: At present, this is the first report on the characterization of a 12α-HSDH gene in an A. johnsonii strain able to biotransform cholic acid into ursodeoxycholic acid, a promising therapeutic agent for several diseases. © 2022 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology

Animal models of hepatocellular carcinoma prevention

Hepatocellular carcinoma (HCC) is a deadly disease and therapeutic efficacy in advanced HCC is limited. Since progression of chronic liver disease to HCC involves a long latency period of a few decades, a significant window of therapeutic opportunities exists for prevention of HCC and improve patient prognosis. Nonetheless, there has been no clinical advancement in instituting HCC chemopreventive strategies. Some of the major challenges are heterogenous genetic aberrations of HCC, significant modulation of tumor microenvironment and incomplete understanding of HCC tumorigenesis. To this end, animal models of HCC are valuable tools to evaluate biology of tumor initiation and progression with specific insight into molecular and genetic mechanisms involved. In this review, we describe various animal models of HCC that facilitate effective ways to study therapeutic prevention strategies that have translational potential to be evaluated in a clinical context © 2019 by the authors. Licensee MDPI, Basel, Switzerland

microRNAs and Inflammatory Immune Response in SARS-CoV-2 Infection: A Narrative Review

The current SARS-CoV-2 pandemic has emerged as an international challenge with strong medical and socioeconomic impact. The spectrum of clinical manifestations of SARS-CoV-2 is wide, covering asymptomatic or mild cases up to severe and life-threatening complications. Critical courses of SARS-CoV-2 infection are thought to be driven by the so-called “cytokine storm”, derived from an excessive immune response that induces the release of proinflammatory cytokines and chemokines. In recent years, non-coding RNAs (ncRNAs) emerged as potential diagnostic and therapeutic biomarkers in both inflammatory and infectious diseases. Therefore, the identification of SARS-CoV-2 miRNAs and host miRNAs is an important research topic, investigating the host–virus crosstalk in COVID-19 infection, trying to answer the pressing question of whether miRNA-based therapeutics can be employed to tackle SARS-CoV-2 complications. In this review, we aimed to directly address ncRNA role in SARS-CoV-2-immune system crosstalk upon COVID-19 infection, particularly focusing on inflammatory pathways and cytokine storm syndromes

Morphological evolution of Bardigiano horse

The Bardigiano horse is a local breed of the province of Parma. Since the institution of the Stud Book in 1977, the breed has improved its diffusion and is currently present with 110 stallions and over 1700 mares in 43 provinces in Italy and beyond that in Germany, Switzerland and Hungary

Effects of a dietary crude fibre concentrate on growth in weaned piglets

Many fibre sources can help the adaptation of piglets at weaning, improving the growth. In this study, the effects of a dietary crude fibre concentrate (CFC) on piglet’s growth was investigated. From 31 to 51 days of age, 108 weaned piglets (D×(Lw×L)), had access to two isofibrous, isoenergetic and isonitrogenous diets, supplemented with 1% of CFC (CFC group) or not (control (CON) group). From days 52 to 64 all piglets received the same starter diet. During the dietary treatment period the CFC group showed higher average daily gain, average daily feed intake and feed efficiency (P<0.001) than CON group. At 64 days of age, BW was higher in CFC group compared with CON group (P<0.001). Blood samples were collected at days 31, 38, 45 and 52 of age. From days 31 to 52 significant differences in the somatotropic axis between groups were observed. In particular, growth hormone levels were higher only at the end of the 1st week of dietary treatment (P<0.05) in CFC group animals compared with CON group animals. The IGF-I trend was similar between groups even if the IGF-I levels were higher in the CFC group than CON group 1 week after starting treatment (P<0.01). The IGF-binding protein 3 (IGFBP-3) levels were higher in the first 2 weeks of dietary treatment and lower in the 3rd week in CON group compared with CFC group (P<0.01). Specifically, the IGFBP-3 profile was consistent with that of IGF-I in CFC group but not in CON group. At the same time, an increase of leptin in CFC compared with CON group was observed (P<0.05). Piglets fed the CFC diet showed a lower diarrhoea incidence (P<0.05) and a lower number of antibiotic interventions (P<0.05) than CON diet from 31 to 51 days of age. Pig-major acute-phase protein plasma level (P<0.01) and interleukin-6 gene expression (P<0.05) were higher in CON group than CFC group at the end of 1st week of dietary treatment. In conclusion, this study showed that CFC diet influences the hormones related to energy balance enhancing the welfare and growth of piglets. Furthermore, the increase in feed intake during 3 weeks of dietary treatment improved the feed efficiency over the entire post-weaning period