Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis

In the last few years, more and more scientists have suggested and confirmed that epigenetic regulators are tightly connected and form a comprehensive network of regulatory pathways and feedback loops. This is particularly interesting for a better understanding of processes that occur in the development and progression of various diseases. Appearing on the preclinical stages of diseases, epigenetic aberrations may be prominent biomarkers. Being dynamic and reversible, epigenetic modifications could become targets for a novel option for therapy. Therefore, in this review, we are focusing on histone modifications and ncRNAs, their mutual regulation, role in cellular processes and potential clinical application.     

Molecular Mechanisms of Bone Metastasis: Which Targets Came from the Bench to the Bedside?

Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteotropic factors. The deep comprehension of the molecular mechanisms of bone metastases may allow the future development of specific anti-tumoral therapies, but so far the approved and effective therapies for bone metastatic disease are mostly based in bone-targeted agents, like bisphosphonates, denosumab and, for prostate cancer, radium-223. Bisphosphonates and denosumab have proven to be effective in blocking bone resorption and decreasing morbidity; furthermore, in the adjuvant setting, these agents can decrease bone relapse after breast cancer surgery in postmenopausal women. In this review, we will present and discuss some examples of applied knowledge from the bench to the bed side in the field of bone metastasis.     

Acute and Delayed Effects of Mechanical Injury on Calcium Homeostasis and Mitochondrial Potential of Primary Neuroglial Cell Culture: Potential Causal Contributions to Post-Traumatic Syndrome

In vitro models of traumatic brain injury (TBI) help to elucidate the pathological mechanisms responsible for cell dysfunction and death. To simulate in vitro the mechanical brain trauma, primary neuroglial cultures were scratched during different periods of network formation. Fluorescence microscopy was used to measure changes in intracellular free Ca²⁺ concentration ([Ca²⁺]_i) and mitochondrial potential (ΔΨm) a few minutes later and on days 3 and 7 after scratching. An increase in [Ca²⁺]_i and a decrease in ΔΨm were observed ~10 s after the injury in cells located no further than 150–200 µm from the scratch border. Ca²⁺ entry into cells during mechanical damage of the primary neuroglial culture occurred predominantly through the NMDA-type glutamate ionotropic channels. MK801, an inhibitor of this type of glutamate receptor, prevented an acute increase in [Ca²⁺]_i in 99% of neurons. Pathological changes in calcium homeostasis persisted in the primary neuroglial culture for one week after injury. Active cell migration in the scratch area occurred on day 11 after neurotrauma and was accompanied by a decrease in the ratio of live to dead cells in the areas adjacent to the injury. Immunohistochemical staining of glial fibrillary acidic protein and β-III tubulin showed that neuronal cells migrated to the injured area earlier than glial cells, but their repair potential was insufficient for survival. Mitochondrial Ca²⁺ overload and a drop in ΔΨm may cause delayed neuronal death and thus play a key role in the development of the post-traumatic syndrome. Preventing prolonged ΔΨm depolarization may be a promising therapeutic approach to improve neuronal survival after traumatic brain injury.     

Inhaled Placental Mesenchymal Stromal Cell Secretome from Two- and Three-Dimensional Cell Cultures Promotes Survival and Regeneration in Acute Lung Injury Model in Mice

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is a common clinical problem, leading to significant morbidity and mortality, and no effective pharmacotherapy exists. The problem of ARDS causing mortality became more apparent during the COVID-19 pandemic. Biotherapeutic products containing multipotent mesenchymal stromal cell (MMSC) secretome may provide a new therapeutic paradigm for human healthcare due to their immunomodulating and regenerative abilities. The content and regenerative capacity of the secretome depends on cell origin and type of cultivation (two- or three-dimensional (2D/3D)). In this study, we investigated the proteomic profile of the secretome from 2D- and 3D-cultured placental MMSC and lung fibroblasts (LFBs) and the effect of inhalation of freeze-dried secretome on survival, lung inflammation, lung tissue regeneration, fibrin deposition in a lethal ALI model in mice. We found that three inhaled administrations of freeze-dried secretome from 2D- and 3D-cultured placental MMSC and LFB protected mice from death, restored the histological structure of damaged lungs, and decreased fibrin deposition. At the same time, 3D MMSC secretome exhibited a more pronounced trend in lung recovery than 2D MMSC and LFB-derived secretome in some measures. Taking together, these studies show that inhalation of cell secretome may also be considered as a potential therapy for the management of ARDS in patients suffering from severe pneumonia, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, their effectiveness requires further investigation.     

Mechanism of energy transfer in Sr2CeO4:Eu phosphor

Blue–white phosphor Sr₂CeO₄ belongs to a particular class of optical materials whose luminescence is governed by optical transitions associated with the electron charge transfer. The originality of its crystallographic structure, a chain-like sequence of luminescent centers, permits an effective transfer of the electronic excitation energy from the host to doped centers. Sr₂CeO₄, рure and doped with Eu³⁺-ions of different concentrations, was synthesized by the Pechini citrate-gel method. The luminescence spectra and luminescence decay curves of Sr₂CeO₄ and Sr₂CeO₄:Eu³⁺ at 300 and 80 K were investigated. The performed experiments revealed the Förster nonradiative energy transfer under the energy migration condition from the crystal host to the doped europium ions.     

Brewing with 100% green malt – process development and key quality indicators

Brewing with undried, germinated (green) malt has the potential to lower energy and water usage in the malting and brewing chain. However, doing so introduces technical and biochemical (flavour) challenges. Beers were brewed using 100% green malt (n = 3) or kilned pilsner malt (n = 3), prepared from the same batch in each case, utilising the pilot brewery at KU Leuven (2.5 hL). Three further pairs of beers were brewed whereby the green malt was pre-steeped under deaerated water for 1 hour; this procedure was previously shown to lower LOX activity in green malt. Six green malt beers were brewed with acceptable specifications in terms of pH, alcohol content, foam stability and colour. No significant taints or obvious defects were detected in green malt beers. Increased S-methyl methionine levels were measured in worts and beers made from green malt, however DMS concentrations in the finished beers did not differ significantly from the reference beers. Furthermore, the results demonstrated promising indicators for flavour stability, such as reduced TBI, lower residual FAN and trihydroxy fatty acid (THFA) levels in brews using untreated green malt. Using re-steep water in green malt brewing (for reasons of water economy), however, increased THFA levels, possibly because oxygen uptake was not adequately controlled at this step. Whilst further process optimisations are undoubtedly required, it is shown that an acceptable lager style beer could be brewed to a specification not dissimilar to that of a kilned malt control beer, using 100% green malt with intact rootlets. © 2020 The Authors. Journal of the Institute of Brewing published by John Wiley & Sons Ltd on behalf of The Institute of Brewing & Distilling     

The role of motives in the content and structure of autobiographical memory.

Findings from 4 studies suggest that differentiation and integration are used by individuals high in agency and communion to structure motive-related information in episodic memory. Studies 1 and 2 demonstrated that agentic and communal individuals recalled more emotional experiences related to their motives, and that agentic individuals used more differentiation whereas communal individuals used more integration to structure these memories. Study 3 showed that agentic and communal individuals used more differentiation and integration to structure memories about social separation and connection, respectively. Study 4 demonstrated a similar pattern of recall in an experimentally controlled retrieval task. For a motive-congruent topic, agentic individuals recognized more differentiated information and had fewer differentiation recognition errors, and communal individuals freely recalled more integration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Octacalcium Phosphate for Bone Tissue Engineering: Synthesis,Modification, and In Vitro Biocompatibility Assessment

Octacalcium phosphate (OCP, Ca₈H₂(PO₄)₆·5H₂O) is known to be a possible precursor of biological hydroxyapatite formation of organic bone tissue. OCP has higher biocompatibility and osseointegration rate compared to other calcium phosphates. In this work, the synthesis of low-temperature calcium phosphate compounds and substituted forms of those at physiological temperatures is shown. Strontium is used to improve bioactive properties of the material. Strontium was inserted into the OCP structure by ionic substitution in solutions. The processes of phase formation of low-temperature OCP with theoretical substitution of strontium for calcium up to 50 at.% in conditions close to physiological, i.e., temperature 35–37 °C and normal pressure, were described. The effect of strontium substitution range on changes in the crystal lattice of materials, the microstructural features, surface morphology and biological properties in vitro has been established. The results of the study indicate the effectiveness of using strontium in OCP for improving biocompatibility of OCP based composite materials intended for bone repair.