Eugenio Ragazzi

Antiviral effects of Glycyrrhiza species

Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus‐induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV‐1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus.

A history of the therapeutic use of liquorice in Europe

Abstract Liquorice root has been used in Europe since prehistoric times, and is well documented in written form starting with the ancient Greeks. In this review we compare the independent development of medical uses of this botanical drug in several ancient cultures, attempting to show the rationality of specific indications across different ethnic groups with different cultural backgrounds. Identical specific indications in different cultures highlight universally reproducible therapeutic effects that are beyond those of a mere placebo. In the first part of the review, historical sources dealing with liquorice (Scythian, Greek, Roman, and from the Middle Ages in Germany, Italy, Spain, England) have been considered. In the second part, the historical records of diseases treated with liquorice have been presented. Finally, a comparison between traditional use in and outside Europe, with the most important recent scientific studies concerning its use, is presented.

Oestrogens ameliorate mitochondrial dysfunction in Leber’s hereditary optic neuropathy

Lebers hereditary optic neuropathy, the most frequent mitochondrial disease due to mitochondrial DNA point mutations in complex I, is characterized by the selective degeneration of retinal ganglion cells, leading to optic atrophy and loss of central vision prevalently in young males. The current study investigated the reasons for the higher prevalence of Lebers hereditary optic neuropathy in males, exploring the potential compensatory effects of oestrogens on mutant cell metabolism. Control and Lebers hereditary optic neuropathy osteosarcoma-derived cybrids (11778/ND4, 3460/ND1 and 14484/ND6) were grown in glucose or glucose-free, galactose-supplemented medium. After having shown the nuclear and mitochondrial localization of oestrogen receptors in cybrids, experiments were carried out by adding 100 nM of 17β-oestradiol. In a set of experiments, cells were pre-incubated with the oestrogen receptor antagonist ICI 182780. Lebers hereditary optic neuropathy cybrids in galactose medium presented overproduction of reactive oxygen species, which led to decrease in mitochondrial membrane potential, increased apoptotic rate, loss of cell viability and hyper-fragmented mitochondrial morphology compared with control cybrids. Treatment with 17β-oestradiol significantly rescued these pathological features and led to the activation of the antioxidant enzyme superoxide dismutase 2. In addition, 17β-oestradiol induced a general activation of mitochondrial biogenesis and a small although significant improvement in energetic competence. All these effects were oestrogen receptor mediated. Finally, we showed that the oestrogen receptor β localizes to the mitochondrial network of human retinal ganglion cells. Our results strongly support a metabolic basis for the unexplained male prevalence in Lebers hereditary optic neuropathy and hold promises for a therapeutic use for oestrogen-like molecules.

Arthropods in amber from the Triassic Period

The occurrence of arthropods in amber exclusively from the Cretaceous and Cenozoic is widely regarded to be a result of the production and preservation of large amounts of tree resin beginning ca. 130 million years (Ma) ago. Abundant 230 million-year-old amber from the Late Triassic (Carnian) of northeastern Italy has previously yielded myriad microorganisms, but we report here that it also preserves arthropods some 100 Ma older than the earliest prior records in amber. The Triassic specimens are a nematoceran fly (Diptera) and two disparate species of mites, Triasacarus fedelei gen. et sp. nov., and Ampezzoa triassica gen. et sp. nov. These mites are the oldest definitive fossils of a group, the Eriophyoidea, which includes the gall mites and comprises at least 3,500 Recent species, 97% of which feed on angiosperms and represents one of the most specialized lineages of phytophagous arthropods. Antiquity of the gall mites in much their extant form was unexpected, particularly with the Triassic species already having many of their present-day features (such as only two pairs of legs); further, it establishes conifer feeding as an ancestral trait. Feeding by the fossil mites may have contributed to the formation of the amber droplets, but we find that the abundance of amber during the Carnian (ca. 230 Ma) is globally anomalous for the pre-Cretaceous and may, alternatively, be related to paleoclimate. Further recovery of arthropods in Carnian-aged amber is promising and will have profound implications for understanding the evolution of terrestrial members of the most diverse phylum of organisms.

Cord blood metabolomic profiling in intrauterine growth restriction

A number of metabolic abnormalities have been observed in pregnancies complicated by intrauterine growth restriction (IUGR). Metabolic fingerprinting and clinical metabolomics have recently been proposed as tools to investigate individual phenotypes beyond genomes and proteomes and to advance hypotheses on the genesis of diseases. Non-targeted metabolomic profiling was employed to study fetal and/or placental metabolism alterations in IUGR fetuses by liquid chromatography high-resolution mass spectrometry (LC-HRMS) analysis of cord blood collected soon after birth. Samples were collected from 22 IUGR and 21 appropriate for gestational age (AGA) fetuses. Birth weight differed significantly between IUGR and AGA fetuses (p < 0.001). Serum samples were immediately obtained and deproteinized by mixing with methanol at room temperature and centrifugation; supernatants were lyophilized and reconstituted in water for analysis. LC-HRMS analyses were performed on an Orbitrap mass spectrometer linked to a Surveyor Plus LC. Samples were injected into a 1.0 × 150-mm Luna C18 column. Spectra were collected in full-scan mode at a resolution of approximately 30,000. Data were acquired over the m/z range of 50–1,000, with measurements performed in duplicate. To observe metabolic variations between the two sets of samples, LC-HRMS data were analyzed by a principal component analysis model. Many features (e.g., ionic species with specific retention times) differed between the two classes of samples: among these, the essential amino acids phenylalanine, tryptophan, and methionine were identified by comparison with available databases. Logistic regression coupled to a receiver-operating characteristic curve identified a cut-off value for phenylalanine and tryptophan, which gave excellent discrimination between IUGR and AGA fetuses. Non-targeted LC-HRMS analysis of cord blood collected at birth allowed the identification of significant differences in relative abundances of essential amino acids between IUGR and AGA fetuses, emerging as a promising tool for studying metabolic alterations.

New International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosing gestational diabetes compared with former criteria: a retrospective study on pregnancy outcome.

Diabet. Med. 28, 1074–1077 (2011)

A microworld in Triassic amber

Amber provides an effective medium for conservation of soft-bodied microorganisms, but finds older than 135 million years are very rare and have not so far contained any microbial inclusions. Here we describe 220-million-year-old droplets of amber containing bacteria, fungi, algae and protozoans that are assignable to extant genera. These inclusions provide insight into the evolution and palaeoecology of Lower Mesozoic microorganisms: it seems that the basal levels of food webs of terrestrial communities (biocoenoses) have undergone little or no morphological change from the Triassic to the Recent.

Cretaceous African life captured in amber.

Amber is of great paleontological importance because it preserves a diverse array of organisms and associated remains from different habitats in and close to the amber-producing forests. Therefore, the discovery of amber inclusions is important not only for tracing the evolutionary history of lineages with otherwise poor fossil records, but also for elucidating the composition, diversity, and ecology of terrestrial paleoecosystems. Here, we report a unique find of African amber with inclusions, from the Cretaceous of Ethiopia. Ancient arthropods belonging to the ants, wasps, thrips, zorapterans, and spiders are the earliest African records of these ecologically important groups and constitute significant discoveries providing insight into the temporal and geographical origins of these lineages. Together with diverse microscopic inclusions, these findings reveal the interactions of plants, fungi and arthropods during an epoch of major change in terrestrial ecosystems, which was caused by the initial radiation of the angiosperms. Because of its age, paleogeographic location and the exceptional preservation of the inclusions, this fossil resin broadens our understanding of the ecology of Cretaceous woodlands.

Classification of amber based on thermal analysis

The present study considered a possible way of classifying fossil and sub-fossil resins by means of thermal analysis, by using thermogravimetric (TG) and differential thermogravimetric (DTG) profiles. We used samples of resins of different origin and ages, ranging from present-day to Triassic (225 million years ago (Ma)), in order to extend the knowledge of thermal patterns of very ancient resins. Under differential thermogravimetric analysis, all the samples presented a main exothermal event, whose temperature varied among resins of different age. The increasing value of the main exothermal peak varies with the increase of the age of the specimen and a significant linear correlation was found (r=0.701, P<0.01) with a slope of 0.216. Additional information came in relation to paleobotanical origin, lithology and diagenesis of the fossil samples. Thermal analysis of fossil resins appears therefore as a useful method that may improve the characterization of fossil resins and well correlates with the maturation grade.

Low molecular weight proteins in urines from healthy subjects as well as diabetic, nephropathic and diabetic-nephropathic patients : a MALDI study

Urine samples from healthy subjects as well as diabetic, nephropathic and diabetic-nephropathic patients were analyzed by matrix assisted laser desorption/ionization (MALDI) mass spectrometry in order to establish evidence of some possible differences in the peptide profile related to the pathological states. Multivariate analysis suggested the possibility of a distinction among the considered groups of patients. Some differences have been found, in particular, in the relative abundances of three ions at m/z 1912, 1219 and 2049. For these reasons, further investigation was carried out by MALDI/TOF/TOF to determine the sequence of these peptides and, consequently, to individuate their possible origin. By this approach, the peptide at m/z 1912 was found to originate from uromodulin, and its lower expression in the case of nephropathy can be well related to the pathological condition. Ions at m/z 2049 and 1219 originate from the collagen alpha-1(I) chain precursor and from the collagen alpha-5 (IV) chain precursor, respectively, and, also in this case, their different expressions can be related to the pathologies under investigation. The obtained data seem to indicate that urine is an interesting biological fluid to investigate on the peptide profile and to obtain, consequently, information on the dismetabolism activated by specific pathologies.