Systematic Review: Adipose-Derived Mesenchymal Stem Cells,Platelet-Rich Plasma and Biomaterials as New Regenerative Strategies in Chronic Skin Wounds and Soft Tissue Defects

The number of clinical trials evaluating adipose-derived mesenchymal stem cells (AD-MSCs), platelet-rich plasma (PRP), and biomaterials efficacy in regenerative plastic surgery has exponentially increased during the last ten years. AD-MSCs are easily accessible from various fat depots and show intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. AD-MSCs have been used in the treatment of soft tissue defects and chronic wounds, employed in conjunction with a fat grafting technique or with dermal substitute scaffolds and platelet-rich plasma. In this systematic review, an overview of the current knowledge on this topic has been provided, based on existing studies and the authors’ experience. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, PRP, and biomaterials used in soft tissue defects and chronic wounds. Of the 2136 articles initially identified, 422 articles focusing on regenerative strategies in wound healing were selected and, consequently, only 278 articles apparently related to AD-MSC, PRP, and biomaterials were initially assessed for eligibility. Of these, 85 articles were excluded as pre-clinical, experimental, and in vitro studies. For the above-mentioned reasons, 193 articles were selected; of this amount, 121 letters, expert opinions, commentary, and editorials were removed. The remaining 72 articles, strictly regarding the use of AD-MSCs, PRP, and biomaterials in chronic skin wounds and soft tissue defects, were analyzed. The studies included had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design (PICOS) approach. The information analyzed highlights the safety and efficacy of AD-MSCs, PRP, and biomaterials on soft tissue defects and chronic wounds, without major side effects.     

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.     

κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance

Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance.     

Plant Copper Amine Oxidases: Key Players in Hormone Signaling Leading to Stress-Induced Phenotypic Plasticity

Polyamines are ubiquitous, low-molecular-weight aliphatic compounds, present in living organisms and essential for cell growth and differentiation. Copper amine oxidases (CuAOs) oxidize polyamines to aminoaldehydes releasing ammonium and hydrogen peroxide, which participates in the complex network of reactive oxygen species acting as signaling molecules involved in responses to biotic and abiotic stresses. CuAOs have been identified and characterized in different plant species, but the most extensive study on a CuAO gene family has been carried out in Arabidopsis thaliana. Growing attention has been devoted in the last years to the investigation of the CuAO expression pattern during development and in response to an array of stress and stress-related hormones, events in which recent studies have highlighted CuAOs to play a key role by modulation of a multilevel phenotypic plasticity expression. In this review, the attention will be focused on the involvement of different AtCuAOs in the IAA/JA/ABA signal transduction pathways which mediate stress-induced phenotypic plasticity events.     

Implication of the NLRP3 Inflammasome in Bovine Age-Related Sarcopenia

Sarcopenia is defined as the age-related loss of skeletal muscle mass, quality, and strength. The pathophysiological mechanisms underlying sarcopenia are still not completely understood. The aim of this work was to evaluate, for the first time, the expression of NLRP3 inflammasome in bovine skeletal muscle in order to investigate the hypothesis that inflammasome activation may trigger and sustain a pro-inflammatory environment leading to sarcopenia. Samples of skeletal muscle were collected from 60 cattle belonging to three age-based groups. Morphologic, immunohistochemical and molecular analysis were performed to assess the presence of age-related pathologic changes and chronic inflammation, the expression of NLRP3 inflammasome and to determine the levels of interleukin-1β, interleukin-18 and tumor necrosis factor alpha in muscle tissue. Our results revealed the presence of morphologic sarcopenia hallmark, chronic lymphocytic inflammation and a type II fibers-selective NLRP3 expression associated to a significant decreased number of immunolabeled-fibers in aged animals. Moreover, we found a statistically significant age-related increase of pro-inflammatory cytokines such as interleukin-1β and interleukin-18 suggesting the activation of NLRP3 inflammasome. Taken together, our data suggest that NLRP3 inflammasome components may be normally expressed in skeletal muscle, but its priming and activation during aging may contribute to enhance a pro-inflammatory environment altering normal muscular anabolism and metabolism.     

Effects of spinosad and spinetoram on larval mortality,adult emergence,progeny production and mating in Cadra cautella (Walk.) (Lepidoptera: Pyralidae)

The bacterial formulations, spinosad and spinetoram, were evaluated for their efficacy in suppressing development and mating success in Cadra cautella (Walk.) (Lepidoptera: Pyralidae), the almond moth. A dilution series of spinosad and spinetoram was sprayed on rice flour. Rice flour samples sprayed with water served as the control. Late instar C. cautella larvae were introduced onto spinosad-, spinetoram-, or water-treated rice flour. The first experiment tested the effects of spinosad and spinetoram on larval mortality, as well as emergence of adults and progeny at different insecticide concentrations. In the second experiment, the mating success of C. cautella adults that had emerged from larvae exposed to spinosad was tested inside a cubicle. Both spinosad and spinetoram increased larval mortality, whereas both compounds reduced adult emergence and progeny production. Natural mating was reduced in the presence of the synthetic sex pheromone (Z,E)-9,12-tetradecadienyl acetate. However, exposure of C. cautella larvae to spinosad did not alter mating in adult progeny. Spinosad was more effective than spinetoram at suppressing C. cautella development. The study concludes that both spinosad and spinetoram suppress the development of immatures of C. cautella to the adult stage as well as mating. Thus, the both compounds can be used to protect stored grains from infestation by C. cautella.     

A model- and simulation-based approach for tolerancing and verifying the functional capability of micro/nano-structured workpieces

The evaluation of functional features of manufactured workpieces is based on GO- and NO-GO-test results, which are obtained by comparing measured geometric characteristics with nominal dimensions and tolerances specified by the designer. These geometrical specifications are based on a tolerancing system, which was originally defined for the function mating capability. Against the background of upcoming lots of other new functions (like reduction of flow resistance, light absorption, reduction of friction, diffraction of light, self-cleaning or mass transmission) are to be realized with our products – particularly by micro- and nano scaled features. If the verification process will deliver the prediction of the achievable degree of functionality, the usability of a part can be assessed more accurately and in consequence quality and economics can be improved. So, a new principle for tolerancing and verifying turns out to be necessary. In this paper the fundamental deficit of the actual tolerancing and specification systems GPS and ASME Y14.5 is derived and the path for enlarging the system by preposing a functional model is shown. To verify the functional capability of the workpieces an approach based on simulations done with the parameterized mathematical–physical model of the function is suggested. Advantages of this approach will be discussed and demonstrated by examples with microstructured inking rolls, crankshafts and injection valves.     

Chemistry of multifunctional polymers based on bis-MPA and their cutting-edge applications

Polymers play an important role in the advancement of materials for use in cutting-edge applications. A direct consequence of an increased demand for more sophisticated materials has been a drive toward developing polymers that exhibit a higher level of structural control, especially in terms of the number and type of functionalities provided within the polymer framework. A family of polymers that meets such a challenge is based on the readily available AB₂ monomer 2,2-bismethylolpropionic acid (bis-MPA) building block. Due to the ease with which the monomers can be synthesized, an array of multifunctional polymers have been produced including monodisperse dendrimers and dendrons and well-defined linear polymers as well as linear-dendritic hybridizations. This review outlines the evolution of the synthetic strategies for developing novel polymeric architectures based on bis-MPA and their assessment in both solution and substrate-based innovative applications.     

Formation of high-density scintillation ceramic from LuAG:Ce + Lu2O3 powders obtained by co-precipitation method

The results of formation of the high density effective scintillation ceramics consisting of two compounds of the cubic symmetry, LuAG:Ce and Lu₂O₃ (LuAG:Ce + Lu₂O₃), are described. Powders of a novel material LuAG:Ce + Lu₂O₃ were synthesized by co-precipitation method. The introduction of Lu₂O₃ into LuAG:Ce was shown to increase the density of the ceramics obtained and modify its scintillation properties.