Genipin-crosslinking polyvinyl alcohol hollow braids degradable tissue engineering scaffolds: Manufacturing techniques and property evaluations

Tissue engineering has been developed with the aim of improving the regeneration and recovery of impaired tissues and organs. Biodegraded scaffolds serve the aforementioned functions and can also be decomposed by means of metabolism. They have no biological toxicity and save patients from injuries by the second surgery, which makes biodegradable scaffolds a new development trend in the tissue engineering. In this study, the textile engineering and chemical crosslinking techniques are employed to produce biodegradable polyvinyl alcohol (PVA) hollow braids, serving as the tissue engineering scaffolds. The process involves two types of products, including the twisted yarns and hollow braids. The twist number of PVA twisted yarns is changed to form different PVA twisted yarns, which are then used to braided into hollow braids via the braiding technology. Therefore, the hollow braids are basically composed three types of PVA twisted yarns. Next, the surface observation, mechanical properties, and degradation of the products are then evaluated. The test results indicate that PVA twisted yarns exhibit the optimal mechanical properties when being twisted with 3 turns/inch. Any higher twist counts result in over twist in the twisted yarns. The optimal hollow braids are composed of PVA twisted yarns with a twist counts being 3 turns/inch. Afterwards, hollow braids are crosslinking with genipin, thereby obtaining greater mechanical strength of 23.6 N and higher decomposition rate of 0.8. The specified hollow braids are suitable for the use as tissue engineering scaffolds.     

Inhibition of Soluble Epoxide Hydrolase Ameliorates Phenotype and Cognitive Abilities in a Murine Model of Niemann Pick Type C Disease

Niemann–Pick type C (NPC) disease is a rare autosomal recessive inherited childhood neurodegenerative disease characterized by the accumulation of cholesterol and glycosphingolipids, involving the autophagy-lysosome system. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxy fatty acids (EpFAs) to 12-diols, exerts beneficial effects in modulating inflammation and autophagy, critical features of the NPC disease. This study aims to evaluate the effects of UB-EV-52, an sEH inhibitor (sEHi), in an NPC mouse model (Npc) by administering it for 4 weeks (5 mg/kg/day). Behavioral and cognitive tests (open-field test (OF)), elevated plus maze (EPM), novel object recognition test (NORT) and object location test (OLT) demonstrated that the treatment produced an improvement in short- and long-term memory as well as in spatial memory. Furthermore, UB-EV-52 treatment increased body weight and lifespan by 25% and reduced gene expression of the inflammatory markers (i.e., Il-1β and Mcp1) and enhanced oxidative stress (OS) markers (iNOS and Hmox1) in the treated Npc mice group. As for autophagic markers, surprisingly, we found significantly reduced levels of LC3B-II/LC3B-I ratio and significantly reduced brain protein levels of lysosomal-associated membrane protein-1 (LAMP-1) in treated Npc mice group compared to untreated ones in hippocampal tissue. Lipid profile analysis showed a significant reduction of lipid storage in the liver and some slight changes in homogenated brain tissue in the treated NPC mice compared to the untreated groups. Therefore, our results suggest that pharmacological inhibition of sEH ameliorates most of the characteristic features of NPC mice, demonstrating that sEH can be considered a potential therapeutic target for this disease.     

Salivary Proteome Changes in Response to Acute Psychological Stress Due to an Oral Exam Simulation in University Students: Effect of an Olfactory Stimulus

The autonomic nervous system (ANS) plays a crucial role both in acute and chronic psychological stress eliciting changes in many local and systemic physiological and biochemical processes. Salivary secretion is also regulated by ANS. In this study, we explored salivary proteome changes produced in thirty-eight University students by a test stress, which simulated an oral exam. Students underwent a relaxation phase followed by the stress test during which an electrocardiogram was recorded. To evaluate the effect of an olfactory stimulus, half of the students were exposed to a pleasant odor diffused in the room throughout the whole session. Saliva samples were collected after the relaxation phase (T0) and the stress test (T1). State anxiety was also evaluated at T0 and T1. Salivary proteins were separated by two-dimensional electrophoresis, and patterns at different times were compared. Spots differentially expressed were trypsin digested and identified by mass spectrometry. Western blot analysis was used to validate proteomic results. Anxiety scores and heart rate changes indicated that the fake exam induced anxiety. Significant changes of α-amylase, polymeric immunoglobulin receptor (PIGR), and immunoglobulin α chain (IGHA) secretion were observed after the stress test was performed in the two conditions. Moreover, the presence of pleasant odor reduced the acute social stress affecting salivary proteome changes. Therefore, saliva proteomic analysis was a useful approach to evaluate the rapid responses associated to an acute stress test also highlighting known biomarkers.     

Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs

In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF_2α and 1,15-PGF_2α lactones, many 1,15-lactones of E₂, E₃, F₂, F₃, A₂, and A₃ were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.     

Thermoset IM-LSI-based C/C-SiC: Influence of flow direction and weld lines on microstructure and mechanical properties

The production of ceramic matrix composites (CMC) based on C/C-SiC is still very cost-intensive and therefore only economical for a few applications. The fabrication of the preforms involves many costs that need to be reduced. In this work, the shaping of the CFRP-preforms is realized by thermoset injection molding, which enables large-scale production. The polymeric matrix used is a multi-component matrix consisting of novolak resin, curing agent and lubricant. Six millimeter chopped carbon fiber with a proportion of 50 wt.% were used as a reinforcement. These ingredients are processed by an industrial equipment for compounding and injection molding in order to manufacture a CFRP demonstrator representing a brake disc. Test specimens are cut out of the demonstrator in different directions in order to investigate influences of flow direction and weld lines on microstructural and mechanical properties. Afterward, the CFRP samples were converted to C/C-SiC composites by the liquid silicon infiltration process. The article addresses the flow behavior of the compound during the injection molding and the building of the weld lines in the demonstrator. In addition, results of the directional dependence of the microstructural and mechanical properties within the fabricated disc in the different production steps are presented.     

Loliolide,a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum

Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed Codium tomentosum, to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells’ exposure to 6-OHDA in the presence of Loliolide led to an increase of cells’ viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential.     

Neuroprotective and Anti-Inflammatory Effects of Evernic Acid in an MPTP-Induced Parkinson’s Disease Model

Oxidative stress, mitochondrial dysfunction, and neuroinflammation are strongly associated with the pathogenesis of Parkinson’s disease (PD), which suggests that anti-oxidative and anti-inflammatory compounds might provide an alternative treatment for PD. Here, we evaluated the neuroprotective effects of evernic aid (EA), which was screened from a lichen library provided by the Korean Lichen Research Institute at Sunchon National University. EA is a secondary metabolite generated by lichens, including Ramalina, Evernia, and Hypogymnia, and several studies have described its anticancer, antifungal, and antimicrobial effects. However, the neuroprotective effects of EA have not been studied. We found that EA protected primary cultured neurons against 1-methyl-4-phenylpyridium (MPP⁺)-induced cell death, mitochondrial dysfunction, and oxidative stress, and effectively reduced MPP⁺-induced astroglial activation by inhibiting the NF-κB pathway. In vivo, EA ameliorated MPTP-induced motor dysfunction, dopaminergic neuronal loss, and neuroinflammation in the nigrostriatal pathway in C57BL/6 mice. Taken together, our findings demonstrate that EA has neuroprotective and anti-inflammatory effects in PD models and suggest that EA is a potential therapeutic candidate for PD.     

Enhancing the Yield Stress in Liquid Polydimethylsiloxane to Allow Its 3D Printing: Hydrogels as Removable Fillers

For manufacturing parts of very soft materials by liquid deposition modeling (e.g., to mimic living soft tissues), formulations of 3D-printable polydimethylsiloxane have been developed, with the aim of increasing the yield stress of the liquid and reducing the final mechanical modulus. In the present work, suspensions of solid-like hydrogel particles, which are easily 3D-printable, are prepared in order to generate yield stress, and the suspended phase is removed after manufacturing by taking advantage of the thermo-reversibility of the hydrogel behavior, resulting in porosity, which reduces the final rigidity. The reported approach is even more efficient than a previous approach based on emulsion formulations.