Experimental data based machine learning classification models with predictive ability to select in vitro active antiviral and non-toxic essential oils

In the last decade essential oils have attracted scientists with a constant increase rate of more than 7% as witnessed by almost 5000 articles. Among the prominent studies essential oils are investigated as antibacterial agents alone or in combination with known drugs. Minor studies involved essential oil inspection as potential anticancer and antiviral natural remedies. In line with the authors previous reports the investigation of an in-house library of extracted essential oils as a potential blocker of HSV-1 infection is reported herein. A subset of essential oils was experimentally tested in an in vitro model of HSV-1 infection and the determined IC50s and CC50s values were used in conjunction with the results obtained by gas-chromatography/mass spectrometry chemical analysis to derive machine learning based classification models trained with the partial least square discriminant analysis algorithm. The internally validated models were thus applied on untested essential oils to assess their effective predictive ability in selecting both active and low toxic samples. Five essential oils were selected among a list of 52 and readily assayed for IC50 and CC50 determination. Interestingly, four out of the five selected samples, compared with the potencies of the training set, returned to be highly active and endowed with low toxicity. In particular, sample CJM1 from Calaminta nepeta was the most potent tested essential oil with the highest selectivity index (IC50 = 0.063 mg/mL, SI > 47.5). In conclusion, it was herein demonstrated how multidisciplinary applications involving machine learning could represent a valuable tool in predicting the bioactivity of complex mixtures and in the near future to enable the design of blended essential oil possibly endowed with higher potency and lower toxicity

Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation

Early onset of primary hyperparathyroidism (PHPT) and multiglandular involvement suggest a familial form in which germline mutation of a PHPT-related gene(s) and a somatic event at the same locus can be often demonstrated. We investigated the involvement of multiple endocrine neoplasia type 1 (MEN1) and HRPT2 genes in a 39-year-old man with recurrent PHPT. PHPT was firstly diagnosed at the age of 21 and the patient had two recurrences separated by extended periods of normocalcemia. This unusual history prompted us to investigate other family members and study the MEN1 and HRPT2 genes. An HRPT2 germline missense mutation in exon 3 (R91P) was found in the index case, which was associated with different HRPT2 somatic alterations in each of the three examined parathyroid tumors. These findings are consistent with Knudson's 'two hit' concept of biallelic inactivation of classical tumor suppressor genes. Screening of 15 asymptomatic relatives was negative for the R91P germline mutation. All the three abnormal parathyroid specimens showed cystic features at histology and were negative for parafibromin immunostaining. In one specimen, diffuse parafibromin staining was evident in a rim of normal parathyroid tissue surrounding the adenomatous lesion. Our study shows that different somatic genetic events at the HRPT2 locus are responsible for the asynchronous occurrence of multiple adenomas in a patient carrying an HRPT2 germline mutation. The finding of diffuse parafibromin staining in a rim of normal parathyroid tissue, but not in the contiguous adenomatous lesion, reinforces the concept that loss of parafibromin expression is responsible for the development of parathyroid tumors in this setting

MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: Role of Hsp90 acetylation

Aim: Histone deacetylases (HDACs) regulate the life cycle of several viruses. We investigated the ability of different HDAC inhibitors, to interfere with influenza virus A/Puerto Rico/8/34/H1N1 (PR8 virus) replication in Madin-Darby canine kidney and NCI cells. Results: 3-(5-(3-Fluorophenyl)-3-oxoprop-1-en-1-yl)-1-methyl-1H-pyrrol-2-yl)-N-hydroxyacrylamide (MC1568) inhibited HDAC6/8 activity and PR8 virus replication, with decreased expression of viral proteins and their mRNAs. Such an effect may be related to a decrease in intranuclear content of viral polymerases and, in turn, to an early acetylation of Hsp90, a major player in their nuclear import. Later, the virus itself induced Hsp90 acetylation, suggesting a differential and time-dependent role of acetylated proteins in virus replication. Conclusion: The inhibition of HDAC6/8 activity during early steps of PR8 virus replication could lead to novel anti-influenza strategy

Enalapril reduces proliferation and hyaluronic acid release in orbital fibroblasts

BACKGROUND: Orbital fibroblast proliferation and hyaluronic acid (HA) release are responsible for some of the clinical features of Graves' ophthalmopathy (GO). Thus, inhibition of these processes may be a possible therapeutic approach to this syndrome. Enalapril, a widely used antihypertensive drug, was found to have some inhibitory actions on fibroblast proliferation in cheloid scars in vivo, based on which we investigated its effects in primary cultures of orbital fibroblasts from GO patients and control subjects. METHODS: Primary cultures of GO and control fibroblasts were treated with enalapril or with a control compound (lisinopril). Cell proliferation assays, lactate dehydrogenase release assays (as a measure of cell necrosis), apoptosis assays, and measurement of HA in the cell media were performed. RESULTS: Enalapril significantly reduced cell proliferation in both GO and control fibroblasts. Because enalapril did not affect cell necrosis and apoptosis, we concluded that its effects on proliferation reflected an inhibition of cell growth and/or a delay in cell cycle. Enalapril significantly reduced HA concentrations in the media from both GO and control fibroblasts. CONCLUSIONS: Enalapril has antiproliferative and HA suppressing actions in both GO and control fibroblasts. Clinical studies are needed to investigate whether enalapril has any effects in vivo in patients with GO

Role of HSV-1 in Alzheimer's disease pathogenesis: A challenge for novel preventive/therapeutic strategies

Herpes simplex virus-1 (HSV-1) is a ubiquitous DNA virus able to establish a life-long latent infection in host sensory ganglia. Following periodic reactivations, the neovirions usually target the site of primary infection causing recurrent diseases in susceptible individuals. However, reactivated HSV-1 may also reach the brain resulting in severe herpetic encephalitis or in asymptomatic infections. These have been reportedly linked to neurodegenerative disorders, such as Alzheimer's disease (AD), suggesting antiviral preventive or/therapeutic treatments as possible strategies to counteract AD onset and progression. Here, we provide an overview of the AD-like mechanisms driven by HSV-1-infection in neurons and discuss the ongoing trials repurposing anti-herpetic drugs to treat AD as well as preventive strategies aimed at blocking virus infection

Spectroscopy of geo-neutrinos from 2056 days of Borexino data

We report an improved geo-neutrino measurement with Borexino from 2056 days of data taking. The present exposure is $(5.5\pm0.3)\times10^{31}$ proton$\times$yr. Assuming a chondritic Th/U mass ratio of 3.9, we obtain $23.7 ^{+6.5}_{-5.7} (stat) ^{+0.9}_{-0.6} (sys)$ geo-neutrino events. The null observation of geo-neutrinos with Borexino alone has a probability of $3.6 \times 10^{-9}$ (5.9$\sigma$). A geo-neutrino signal from the mantle is obtained at 98\% C.L. The radiogenic heat production for U and Th from the present best-fit result is restricted to the range 23-36 TW, taking into account the uncertainty on the distribution of heat producing elements inside the Earth.Comment: 4 pages, 4 figure

The Main Results of the Borexino Experiment

The main physical results on the registration of solar neutrinos and the search for rare processes obtained by the Borexino collaboration to date are presented.Comment: 8 pages, 8 figgures, To be published as Proceedings of the Third Annual Large Hadron Collider Physics Conference, St. Petersburg, Russia, 201

Solar neutrino with Borexino: results and perspectives

Borexino is a unique detector able to perform measurement of solar neutrinos fluxes in the energy region around 1 MeV or below due to its low level of radioactive background. It was constructed at the LNGS underground laboratory with a goal of solar $^{7}$Be neutrino flux measurement with 5\% precision. The goal has been successfully achieved marking the end of the first stage of the experiment. A number of other important measurements of solar neutrino fluxes have been performed during the first stage. Recently the collaboration conducted successful liquid scintillator repurification campaign aiming to reduce main contaminants in the sub-MeV energy range. With the new levels of radiopurity Borexino can improve existing and challenge a number of new measurements including: improvement of the results on the Solar and terrestrial neutrino fluxes measurements; measurement of pp and CNO solar neutrino fluxes; search for non-standard interactions of neutrino; study of the neutrino oscillations on the short baseline with an artificial neutrino source (search for sterile neutrino) in context of SOX project.Comment: 15 pages, 4 figure

Measurement of neutrino flux from the primary proton--proton fusion process in the Sun with Borexino detector

Neutrino produced in a chain of nuclear reactions in the Sun starting from the fusion of two protons, for the first time has been detected in a real-time detector in spectrometric mode. The unique properties of the Borexino detector provided an oppurtunity to disentangle pp-neutrino spectrum from the background components. A comparison of the total neutrino flux from the Sun with Solar luminosity in photons provides a test of the stability of the Sun on the 10$^{5}$ years time scale, and sets a strong limit on the power production in the unknown energy sources in the Sun of no more than 4\% of the total energy production at 90\% C.L.Comment: 15 pages, 2 tables, 3 figure