DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Cytotoxic Potential of a-Azepano- and 3-Amino-3,4-SeCo-Triterpenoids

Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative 11 was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound 11 to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds 3, 4, 7, 8, 9, 11, 15, 16, 19, and 20 showed growth inhibitory (GI₅₀) against the most sensitive cell lines at submicromolar concentrations (0.20–0.94 μM), and their cytotoxic activity (LC₅₀) was also high (1–6 μM). Derivatives 3, 8, 11, 15, and 16 demonstrated a certain selectivity profile at GI₅₀ level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol 3 at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI₅₀ level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group.     

BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides

Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1_NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4^th generation, are reported here for the first time.     

New water-soluble copolymers of 2-methacryloyloxyethyl phosphorylcholine for surface modification

New copolymers of 2-methacryloyloxyethyl phosphorylcholine with 2-Deoxy-2-methacrylamido-D-glucose, N-vinylpyrrolidone, and N-vinyl-N-methylacetamide were synthesized and characterized; the obtained copolymers contained 10–50 mol% of phosphorylcholine moieties, and their molecular masses ranged from 1.05 × 10⁵ to 4.40 × 10⁵. Reactivity ratios of the monomers were estimated. Conformational states of the copolymers in aqueous solutions were studied. The synthesized copolymer was grafted onto the surface of carbon fiber biosorbent using γ-radiation.     

Spontaneous Cell Detachment and Reattachment in Cancer Cell Lines: An In Vitro Model of Metastasis and Malignancy

There is an unmet need for simplified in vitro models of malignancy and metastasis that facilitate fast, affordable and scalable gene and compound analysis. “Adherent” cancer cell lines frequently release “free-floating” cells into suspension that are viable and can reattach. This, in a simplistic way, mimics the metastatic process. We compared the gene expression profiles of naturally co-existing populations of floating and adherent cells in SW620 (colon), C33a (cervix) and HeLa (cervix) cancer cells. We found that 1227, 1367 and 1333 genes were at least 2-fold differentially expressed in the respective cell lines, of which 122 were shared among the three cell lines. As proof of principle, we focused on the anti-metastatic gene NM23-H1, which was downregulated both at the RNA and protein level in the floating cell populations of all three cell lines. Knockdown of NM23-H1 significantly increased the number of floating (and viable) cells, whereas overexpression of NM23-H1 significantly reduced the proportion of floating cells. Other potential regulators of these cellular states were identified through pathway analysis, including hypoxia, mTOR (mechanistic target of rapamycin), cell adhesion and cell polarity signal transduction pathways. Hypoxia, a condition linked to malignancy and metastasis, reduced NM23-H1 expression and significantly increased the number of free-floating cells. Inhibition of mTOR or Rho-associated protein kinase (ROCK) significantly increased cell death specifically in the floating and not the adherent cell population. In conclusion, our study suggests that dynamic subpopulations of free-floating and adherent cells is a useful model to screen and identify genes, drugs and pathways that regulate the process of cancer metastasis, such as cell detachment and anoikis.     

The Mechanism of Mechanochemical Interaction between Amorphous Silicon Dioxide and Pyrocatechol

Silicon - The products of solid-phase mechanochemical interaction between pyrocatechol and silicon dioxide yielding a powdered composite were studied using a number of physicochemical methods. This...     

Rheological and viscoelastic properties of colloidal solutions based on gelatins and chitosan as affected by pH

The objective of this study was to evaluate the influence of pH on rheological and viscoelastic properties of solutions based on blends of type A (GeA) or type B (GeB) gelatin and chitosan (CH). Solutions of GeA, GeB, CH, GeA:CH, and GeB:CH were prepared in several pH (3.5–6.0) and analyzed for determination of zeta-potential. Rheological analyses (stationary and dynamic essays) were carried out with blends allowing to study the effect of pH on shear stress, apparent viscosity, loss (G”) and storage (G’) moduli, and angle phase (Tanδ). Zeta potential of all biopolymers decreased linearly as a function of pH. CH presented higher values, and GeB, the lowest one, being the only having negative values at pH > 5. Overall, the pH influenced the rheological and viscoelastic properties of the colloidal solutions: shear stress and apparent viscosity increased as a function of pH. Other assays were carried out at 3% and 5% strain, for GeA:CH and GeB:CH, respectively. In the sol domain, G’ and G” (1 Hz) increased linearly for GeA:CH. But for GeB:CH, they increased in two linear different regions: one function between pH 3.5 and 5.0 and another one between 5.0 and 6.0, being a more important effect was visible in this last domain probably due to the negative net charge of gelatin, above it pI. An effect in two domains was also visible for Tanδ, explained in the same manner as previously. The GeB:CH blends behaved like diluted solutions, and transition temperatures increased as a function of pH.     

Digestive protection of probiotic Lacticaseibacillus rhamnosus in Ricotta cheese by monoglyceride structured emulsions

This research aimed at studying the potential use of monoglyceride (MG) structured emulsions (MSEs) as delivery and protective systems for probiotic bacteria in Ricotta cheese. To this purpose, a low-fat commercial Ricotta cheese was added with MSEs formulated with milk, as water phase, and sunflower oil (MSE-SO) or anhydrous milk fat (MSE-AMF), as lipid phase. A commercial whole milk Ricotta cheese (W-RC) was considered as reference. A probiotic Lacticaseibacillus rhamnosus strain was inoculated as free cells in W-RC or embedded into the MSEs and added to the low-fat Ricotta at the same reference fat content. After physico-chemical characterisation, L. rhamnosus viability and sample destructuring behaviour upon in vitro digestion were evaluated. At the end of in vitro digestion, both W-RC and sample containing MSE-SO were unable to protect cells. By contrast, sample with AMF ensured a sufficient probiotic viability, even after 14 days of storage at 4 °C. This result was attributed to system composition and structure. During the gastric phase, the presence of caseins and MG-AMF mixed structures induced the formation of clots, entrapping and protecting cells against the acidic pH of the stomach, as confirmed by confocal micrographs and particle size. During the intestinal phase, cell viability was guaranteed by the formation of mixed micelles promoted by MG. It was demonstrated that microbial cells located near MG structures where they found protection.     

COVID-19 crisis impact on the stability between parties in crowdfunding and crowdsourcing

This research reviews challenges in building sustainable relationships between the parties involved in the crowdfunding and crowdsourcing projects, which are running in extreme situations, such as the COVID-19 pandemic. This study aims to solve problems that generate the crowdsourcing concerns and to find better alternatives to increase trust for crowdfunding among donors, as this impacts their strategic sustainability in the conditions of turbulence and COVID-induced financial crisis. It was found that factors influence donor decisions in different ways, yet the common tendency for donor activity is non-monotonicity. Future development in the field of sustainable relationships should focus on creating a donor classification system.

     

Increasing the photocatalytic and fungicide activities of Ag3PO4 microcrystals under visible-light irradiation

The present study reports for the first time the performance of silver phosphate (Ag₃PO₄) microcrystals as photocatalyst (degradation of Rodamine B-RhB) and antifungal agent (against Candida albicans–C. albicans) under visible-light irradiation (455 nm). Ag₃PO₄ microcrystals were synthesized by a simple co-precipitation (CP) method at room temperature. The structural and electronic properties of the as-synthetized Ag₃PO₄ have been investigated before and after 4 cycles of RhB degradation under visible light using X-ray diffraction (XRD), micro-Raman spectroscopy, UV–Vis spectrophotometer and field emission scanning electron microscopy (FE-SEM) images. The antifungal activity was analyzed in planktonic cells and 48h-biofilm of C. albicans by colony forming units (CFU) counting, confocal laser and FE-SE microscopies. Statistical analysis was carried out using SPSS software. Morphological and structural modifications of Ag₃PO₄ were observed upon recycling. After 4 recycles, the material maintained its photodegradation property; an eightfold increase in the efficiency of Ag₃PO₄ was observed in planktonic cells and a two fold increase in biofilm when irradiated under visible light. Thus, higher antifungal effectiveness against C. albicans was obtained when associated with visible-light irradiation.