Control of the Autophagy Pathway in Osteoarthritis: Key Regulators,Therapeutic Targets and Therapeutic Strategies

Autophagy is involved in different degenerative diseases and it may control epigenetic modifications, metabolic processes, stem cells differentiation as well as apoptosis. Autophagy plays a key role in maintaining the homeostasis of cartilage, the tissue produced by chondrocytes; its impairment has been associated to cartilage dysfunctions such as osteoarthritis (OA). Due to their location in a reduced oxygen context, both differentiating and mature chondrocytes are at risk of premature apoptosis, which can be prevented by autophagy. AutophagomiRNAs, which regulate the autophagic process, have been found differentially expressed in OA. AutophagomiRNAs, as well as other regulatory molecules, may also be useful as therapeutic targets. In this review, we describe and discuss the role of autophagy in OA, focusing mainly on the control of autophagomiRNAs in OA pathogenesis and their potential therapeutic applications.     

OXIDATIVE CRACKING OF LINEAR HYDROCARBONS AT LOW TEMPERATURES

This work describes the oxidative cracking of n-alkanes with molecular oxygen at low temperatures (below 473 K) in an autoclave reactor. An increase of the oxygen consumption rate with increasing hydrocarbon size was observed. Data for n-hexadecane indicate that oxidative cracking is an autocatalytic reaction. The oxidation rate increased with the progress of the reaction. Low molecular weight compounds were formed as the main products. CG and CG-MS analyses of the liquid products found homologous series of oxygen compounds (acids, ketones, and ethers) and short-chain n-alkanes. Our results strongly suggest that oxidative cracking can be employed for processing heavy materials such as polymers and petroleum residues.     

Nanofilled polyols for viscoelastic polyurethane foams

The use of polyether polyols is common in polyurethane industry, particularly in soft PU applications. In particular, viscoelastic foams, characterized by slow recovery after compression, are obtained using poly(ethylene oxide) (PEO) polyols. Nanofilled polyols can be used for the production of viscoelastic foams with improved fire resistance properties. The high polarity of polyether polyols is responsible of a poor affinity with the organic modifiers used in commercial organically modified montmorillonite (omMMT). In this work, organically modified montmorillonites were prepared, having an improved affinity with the polyether polyols used for the production of soft PU foams. The montmorillonite was modified by using polyetheramines with different ethyleneoxide/propyleneoxide amounts. A strongly intercalated/exfoliated structure was obtained after mixing the polyol with the omMMT. The viscosity increased by three orders of magnitude and the diffraction angles of the MMT measured by x‐ray analysis decreased to values lower than 1.5°. The intercalated structure was preserved after the curing stage, when the isocyanate was added to the polyol/omMMT. The resulting polyurethane had an irregular open cell structure, and was characterized by a mechanical properties comparable to those of unfilled polyurethane. Copyright © 2009 Society of Chemical Industry     

GBA Mutations Influence the Release and Pathological Effects of Small Extracellular Vesicles from Fibroblasts of Patients with Parkinson’s Disease

Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme glucocerebrosidase (GCase), are the strongest known genetic risk factor for Parkinson’s disease (PD). The molecular mechanisms underlying the increased PD risk and the variable phenotypes observed in carriers of different GBA mutations are not yet fully elucidated. Extracellular vesicles (EVs) have gained increasing importance in neurodegenerative diseases since they can vehiculate pathological molecules potentially promoting disease propagation. Accumulating evidence showed that perturbations of the endosomal–lysosomal pathway can affect EV release and composition. Here, we investigate the impact of GCase deficiency on EV release and their effect in recipient cells. EVs were purified by ultracentrifugation from the supernatant of fibroblast cell lines derived from PD patients with or without GBA mutations and quantified by nanoparticle tracking analysis. SH-SY5Y cells over-expressing alpha-synuclein (α-syn) were used to assess the ability of patient-derived small EVs to affect α-syn expression. We observed that defective GCase activity promotes the release of EVs, independently of mutation severity. Moreover, small EVs released from PD fibroblasts carrying severe mutations increased the intra-cellular levels of phosphorylated α-syn. In summary, our work shows that the dysregulation of small EV trafficking and alpha-synuclein mishandling may play a role in GBA-associated PD.     

The HEPD particle detector of the CSES satellite mission for investigating seismo-associated perturbations of the Van Allen belts

CSES(China Seismo-Electromagnetic Satellite) is a mission developed by CNSA(Chinese National Space Administration) and ASI(Italian Space Agency), to investigate the near-Earth electromagnetic, plasma and particle environment, for studying the seismo-associated disturbances in the ionosphere-magnetosphere transition zone. The anthropogenic and electromagnetic noise,as well as the natural non-seismic electromagnetic emissions is mainly due to tropospheric activity. In particular, the mission aims to confirming the existence of possible temporal correlations between the occurrence of earthquakes for medium and strong magnitude and the observation in space of electromagnetic perturbations, plasma variations and precipitation of bursts with highenergy charged particles from the inner Van Allen belt. In this framework, the high energy particle detector(HEPD) of the CSES mission has been developed by the Italian LIMADOU Collaboration. HEPD is an advanced detector based on a tower of scintillators and a silicon tracker that provides good energy and angular resolution and a wide angular acceptance, for electrons of 3–100 Me V, protons of 30–200 Me V and light nuclei up to the oxygen. CSES satellite has been launched on February 2~(nd), 2018 from the Jiuquan Satellite Launch Center(China).     

Bone Health in Children with Rheumatic Disorders: Focus on Molecular Mechanisms,Diagnosis, and Management

Bone is an extremely dynamic and adaptive tissue, whose metabolism and homeostasis is influenced by many different hormonal, mechanical, nutritional, immunological and pharmacological stimuli. Genetic factors significantly affect bone health, through their influence on bone cells function, cartilage quality, calcium and vitamin D homeostasis, sex hormone metabolism and pubertal timing. In addition, optimal nutrition and physical activity contribute to bone mass acquisition in the growing age. All these factors influence the attainment of peak bone mass, a critical determinant of bone health and fracture risk in adulthood. Secondary osteoporosis is an important issue of clinical care in children with acute and chronic diseases. Systemic autoimmune disorders, like juvenile idiopathic arthritis, can affect the skeletal system, causing reduced bone mineral density and high risk of fragility fractures during childhood. In these patients, multiple factors contribute to reduce bone strength, including systemic inflammation with elevated cytokines, reduced physical activity, malabsorption and nutritional deficiency, inadequate daily calcium and vitamin D intake, use of glucocorticoids, poor growth and pubertal delay. In juvenile arthritis, osteoporosis is more prominent at the femoral neck and radius compared to the lumbar spine. Nevertheless, vertebral fractures are an important, often asymptomatic manifestation, especially in glucocorticoid-treated patients. A standardized diagnostic approach to the musculoskeletal system, including prophylaxis, therapy and follow up, is therefore mandatory in at risk children. Here we discuss the molecular mechanisms involved in skeletal homeostasis and the influence of inflammation and chronic disease on bone metabolism.     

Increased Prevalence of Unstable HLA-C Variants in HIV-1 Rapid-Progressor Patients

HIV-1 infection in the absence of treatment results in progression toward AIDS. Host genetic factors play a role in HIV-1 pathogenesis, but complete knowledge is not yet available. Since less-expressed HLA-C variants are associated with poor HIV-1 control and unstable HLA-C variants are associated with higher HIV-1 infectivity, we investigated whether there was a correlation between the different stages of HIV-1 progression and the presence of specific HLA-C allotypes. HLA-C genotyping was performed using allele-specific PCR by analyzing a treatment-naïve cohort of 96 HIV-1-infected patients from multicentric cohorts in the USA, Canada, and Brazil. HIV-1-positive subjects were classified according to their different disease progression status as progressors (Ps, n = 48), long-term non-progressors (LTNPs, n = 37), and elite controllers (ECs, n = 11). HLA-C variants were classified as stable or unstable according to their binding stability to β2-microglobulin/peptide complex. Our results showed a significant correlation between rapid progression to AIDS and the presence of two or one unstable HLA-C variants (p-value: 0.0078, p-value: 0.0143, respectively). These findings strongly suggest a link between unstable HLA-C variants both at genotype and at allele levels and rapid progression to AIDS. This work provides further insights into the impact of host genetic factors on AIDS progression.     

Supercritical Fluid Chromatography × Ultra-High Pressure Liquid Chromatography for Red Chilli Pepper Fingerprinting by Photodiode Array,Quadrupole-Time-of-Flight and Ion Mobility Mass Spectrometry (SFC × RP-UHPLC-PDA-Q-ToF MS-IMS)

The coupling of normal phase and reversed phase liquid chromatography (NP-LC × RP-LC) is one of the most effective ways to increase orthogonality in two-dimensional comprehensive separations, being the two retention mechanisms truly independent. However, such coupling is not straightforward to implement, due to immiscibility of the mobile phases, poor peak focusing at the head of the secondary column (²D), signal interferences and peak deterioration. In this research, supercritical fluid chromatography (SFC) was used in the first dimension (¹D), coupled to ultra high pressure LC (UHPLC), to alleviate incompatibility issues and provide a number of advantages related to the use of supercritical CO₂. An on-line SFC × RP-UHPLC system was implemented in an automated fashion, around two 2-position, six-port switching valves equipped with octadecyl silica cartridges for effective trapping and focusing of the analytes eluted from ¹D. A water make-up flow added to the SFC effluent permitted to efficiently focus the solutes on the sorbent material and to reduce interferences of the expanded CO₂ on the ²D separation. In addition to photodiode array and quadrupole-time-of-flight mass spectrometry detection, ion mobility separation based on analyte mass, shape and size added a fourth separation dimension for carotenoid fingerprinting in a red chilli pepper sample.     

Seed coat tannins and bruchid resistance in stored cowpea seeds

Seeds of wild species and varieties of Vigna were screened for their tannins and α‐amylase inhibitor contents as defensive compounds against cowpea weevil. Seed coats contained condensed tannins that were positively correlated to their colour but not to their resistance against the insect. The α‐amylase inhibitors were present in different amount in cotyledons of all species analysed. Amongst the cultivated lines assayed, Vigna unguiculata TVu 2027, an accession identified as moderately resistant, was found to contain the higher amount of α‐amylase inhibitor. When wild species were considered, V luteola and V vexillata (two resistant species) showed the highest content of α‐amylase inhibitors. In addition, two cultivated accessions (Vita 7 and IT 84E‐1‐108) of cowpea seeds, both classified as susceptible accessions, showing a different degree of bruchid damage in storage, were also analysed. No α‐amylase inhibitory activity was found in cotyledons of undamaged Vita 7 seeds, while the seed coat tannin content was found to be 13 times higher in undamaged Vita 7 seeds than in IT 84E‐1‐108 infested seeds. These latter results support the hypothesis that seed coat tannins must also be considered in biochemical defence mechanisms, which can deter, poison or starve bruchid larvae that feed on cowpea seeds. Copyright © 2004 Society of Chemical Industry