Adrenomedullin stimulates steroid secretion by the isolated perfused rat adrenal gland in situ: comparison with calcitonin gene-related peptide effects

Adrenomedullin (ADM), a vasodilatatory peptide contained in adrenal medulla, was found to induce a dose-dependent increase in aldosterone (ALDO) and corticosterone (B) release by the in situ perfused rat adrenal gland, along with a rise in the flow rate of the perfusion medium. The minimal effective dose for ALDO response was three and two orders of magnitude less than those able to evoke B and medium flow rate responses. Calcitonin gene-related peptide (CGRP), another vasodilatatory peptide contained in adrenal medulla and showing a slight homology in its amino acid sequence with ADM, elicited similar effects. CGRP (8-37), a specific antagonist of CGRP1 receptors, annulled all the effects of both ADM and CGRP, whereas l-alprenolol, a beta-adrenoceptor antagonist, partially reversed only ALDO response to the peptides. In light of these findings the following conclusions are drawn: i) ADM and CGRP stimulate rat adrenals in vivo to release B by raising blood flow rate; ii) ADM and CGRP enhance ALDO secretion via an indirect mechanism probably requiring the release of catecholamines by medullary chromaffin cells; and iii) the effects of ADM and CGRP on the rat adrenal gland are mediated by a common receptor of the CGRP1 subtype.     

MS-275 (Entinostat) Promotes Radio-Sensitivity in PAX3-FOXO1 Rhabdomyosarcoma Cells

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. About 25% of RMS expresses fusion oncoproteins such as PAX3/PAX7-FOXO1 (fusion-positive, FP) while fusion-negative (FN)-RMS harbors RAS mutations. Radiotherapy (RT) plays a crucial role in local control but metastatic RMS is often radio-resistant. HDAC inhibitors (HDACi) radio-sensitize different cancer cells types. Thus, we evaluated MS-275 (Entinostat), a Class I and IV HDACi, in combination with RT on RMS cells in vitro and in vivo. MS-275 reversibly hampered cell survival in vitro in FN-RMS RD (RASmut) and irreversibly in FP-RMS RH30 cell lines down-regulating cyclin A, B, and D1, up-regulating p21 and p27 and reducing ERKs activity, and c-Myc expression in RD and PI3K/Akt/mTOR activity and N-Myc expression in RH30 cells. Further, MS-275 and RT combination reduced colony formation ability of RH30 cells. In both cell lines, co-treatment increased DNA damage repair inhibition and reactive oxygen species formation, down-regulated NRF2, SOD, CAT and GPx4 anti-oxidant genes and improved RT ability to induce G2 growth arrest. MS-275 inhibited in vivo growth of RH30 cells and completely prevented the growth of RT-unresponsive RH30 xenografts when combined with radiation. Thus, MS-275 could be considered as a radio-sensitizing agent for the treatment of intrinsically radio-resistant PAX3-FOXO1 RMS.     

Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.     

Dietary intakes in infertile women a pilot study

Background  

The reproductive axis is closely linked to nutritional status. The purpose of this study was to compare the nutritional status in two groups of young infertile women, without clinically overt eating disorders: hypothalamic amenorrhea (HA) and polycystic ovary syndrome (PCOS).     

Numerical simulation of coherent transport in quantum wires for quantum computing

A solid-state implementation of a universal set of gates for quantum computation is proposed and analysed using a time-dependent 2D Schrödinger solver. The qubit is defined as the state of an electron propagating along a couple of quantum wires. The wires are suitably coupled through a potential barrier with variable height and/or width. It is shown how a proper design of the system allows the implementation of any one-qubit transformation. The two-qubit gate is realized through a Coulomb coupler able to entangle the quantum states of two electrons running in two wires of two different qubits. The simulated devices are GaAs—AlGaAs heterostructures that should be on the borderline of present semiconductor technology. An estimate of decoherence effects due to phonon scattering is also presented.     

Congenital diarrheal disorders: an updated diagnostic approach

Congenital diarrheal disorders (CDDs) are a group of inherited enteropathies with a typical onset early in the life. Infants with these disorders have frequently chronic diarrhea of sufficient severity to require parenteral nutrition. For most CDDs the disease-gene is known and molecular analysis may contribute to an unequivocal diagnosis. We review CDDs on the basis of the genetic defect, focusing on the significant contribution of molecular analysis in the complex, multistep diagnostic work-up.     

A combination of modified atmosphere and antimicrobial packaging to extend the shelf-life of beefsteaks stored at chill temperature

An antimicrobial polyethylene (PE) film was obtained by coating a nisin-based antimicrobial solution. PE sheets were coated on both sides and were used for the packaging of beefsteaks to be stored in air or modified atmosphere packaging (MAP, 60% O(2)-40% CO(2)). Microbial populations, species diversity, headspace volatile organic compounds, colour and sensory properties were monitored after 0, 1, 7 and 12days of storage at 4°C. The viable counts showed that there was an effect of MAP and antimicrobial film on the development of all the spoilage associated microbial populations. Carnobacterium spp., Brochothrix thermosphacta, Pseudomonas fragi and Rhanella aquatilis were found in most of the samples. C. maltaromaticum was identified in MRS bulk cells from samples stored in air as well as MAP. Quantitative data of headspace-SPME-GC/MS analysis showed that during storage the production of volatile organic compounds (VOCs) was affected by the use of the treated film and the MAP storage. Compounds such as phenylethylalcohol, nonanal, decanal and ethylbutanoate were produced only from 7 to 12day of storage and only in the samples stored in air. In agreement with the microbiological and VOCs data, the meat stored in active packaging scored the best rankings in the sensory evaluation. Principal component analysis of microbial, sensory and instrumental data showed that beefsteaks stored with the combination of MAP and active packaging for 12days at 4°C differed from the other samples that were more associated to high microbial loads, VOCs concentration and meat off odour perception. In conclusion, the antimicrobial sheets in combination with MAP storage at 4°C were effective for the storage of beefsteaks by retarding the growth of spoilage bacteria, determining lower concentration of VOCs and keeping acceptable levels of colour and other sensory parameters for more than 10days.     

Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

Hypoxia is a key component of the tumor microenvironment (TME) and promotes not only tumor growth and metastasis, but also negatively affects infiltrating immune cells by impairing host immunity. Dendritic cells (DCs) are the most potent antigen-presenting cells and their biology is weakened in the TME in many ways, including the modulation of their viability. RNASET2 belongs to the T2 family of extracellular ribonucleases and, besides its nuclease activity, it exerts many additional functions. Indeed, RNASET2 is involved in several human pathologies, including cancer, and it is functionally relevant in the TME. RNASET2 functions are not restricted to cancer cells and its expression could be relevant also in other cell types which are important players in the TME, including DCs. Therefore, this study aimed to unravel the effect of hypoxia (2% O₂) on the expression of RNASET2 in DCs. Here, we showed that hypoxia enhanced the expression and secretion of RNASET2 in human monocyte-derived DCs. This paralleled the HIF-1α accumulation and HIF-dependent and -independent signaling, which are associated with DCs’ survival/autophagy/apoptosis. RNASET2 expression, under hypoxia, was regulated by the PI3K/AKT pathway and was almost completely abolished by TLR4 ligand, LPS. Taken together, these results highlight how hypoxia- dependent and -independent pathways shape RNASET2 expression in DCs, with new perspectives on its implication for TME and, therefore, in anti-tumor immunity.     

Automatic process control for stable bio-hythane production in two-phase thermophilic anaerobic digestion of food waste

The paper reports the results of a long term (310 days) pilot-scale trial where food waste as sole substrate was treated in a two-phase thermophilic anaerobic digestion process. This was optimized for concurrent hydrogen and methane production. First phase's optimization for hydrogen production was obtained recirculating the effluent coming from the methanogenic phase and without the addition of external chemicals. A drawback of such approach is the recirculation of ammonia into the first phase reactor for hydrogen production with possibility of consequent inhibition.     

Manufacturing of 3D-Printed Microfluidic Devices for the Synthesis of Drug-Loaded Liposomal Formulations

Microfluidic technique has emerged as a promising tool for the production of stable and monodispersed nanoparticles (NPs). In particular, this work focuses on liposome production by microfluidics and on factors involved in determining liposome characteristics. Traditional fabrication techniques for microfluidic devices suffer from several disadvantages, such as multistep processing and expensive facilities. Three-dimensional printing (3DP) has been revolutionary for microfluidic device production, boasting facile and low-cost fabrication. In this study, microfluidic devices with innovative micromixing patterns were developed using fused deposition modelling (FDM) and liquid crystal display (LCD) printers. To date, this work is the first to study liposome production using LCD-printed microfluidic devices. The current study deals with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes with cholesterol (2:1) prepared using commercial and 3D-printed microfluidic devices. We evaluated the effect of microfluidic parameters, chip manufacturing, material, and channel design on liposomal formulation by analysing the size, PDI, and ζ-potential. Curcumin exhibits potent anticancer activity and it has been reported that curcumin-loaded liposomes formulated by microfluidics show enhanced encapsulation efficiency when compared with other reported systems. In this work, curcumal liposomes were produced using the developed microfluidic devices and particle sizing, ζ-potential, encapsulation efficiency, and in vitro release studies were performed at 37 °C.