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Antioxidant activity is an essential aspect of oxygen-sensitive merchandise and goods, such as food and corresponding packaging, cosmetics, and biomedicine. Technical lignin has not yet been applied as a natural antioxidant, mainly due to the complex heterogeneous structure and polydispersity of lignin. This report presents antioxidant capacity studies completed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The influence of purification on lignin structure and activity was investigated. The purification procedure showed that double-fold selective extraction is the most efficient (confirmed by ultraviolet-visible (UV/Vis), Fourier transform infrared (FTIR), heteronuclear single quantum coherence (HSQC) and 31P nuclear magnetic resonance spectroscopy, size exclusion chromatography, and X-ray diffraction), resulting in fractions of very narrow polydispersity (3.2⁻1.6), up to four distinct absorption bands in UV/Vis spectroscopy. Due to differential scanning calorimetry measurements, the glass transition temperature increased from 123 to 185 °C for the purest fraction. Antioxidant capacity is discussed regarding the biomass source, pulping process, and degree of purification. Lignin obtained from industrial black liquor are compared with beech wood samples: antioxidant activity (DPPH inhibition) of kraft lignin fractions were 62⁻68%, whereas beech and spruce/pine-mixed lignin showed values of 42% and 64%, respectively. Total phenol content (TPC) of the isolated kraft lignin fractions varied between 26 and 35%, whereas beech and spruce/pine lignin were 33% and 34%, respectively. Storage decreased the TPC values but increased the DPPH inhibition.
Here, we present a miR mechanism which is active in the nucleus and is essential for the production of intron included, C-terminal truncated and biologically active proteins, like e.g. Vim3. We exemplified this mechanism by miRs, miR-15a and miR-498, which are overexpressed in clear cell renal carcinoma or oncocytoma. Both miRs directly interact with DNA in an intronic region, leading to transcriptional stop, and therefore repress the full length version of the pre-mRNA, resulting in intron included truncated proteins (Mxi-2 and Vim3). A computational survey shows that this miR:DNA interactions mechanism may be generally involved in regulating the human transcriptome, with putative interaction sites in intronic regions for over 1000 genes. In this work, an entirely new mechanism is revealed how miRs can repress full length protein translation, resulting in C-terminal truncated proteins.
The Fragile X Syndrome (FXS) is one of the most common forms of inherited intellectual disability in all human societies. Caused by the transcriptional silencing of a single gene, the fragile x mental retardation gene FMR1, FXS is characterized by a variety of symptoms, which range from mental disabilities to autism and epilepsy. More than 20 years ago, a first animal model was described, the Fmr1 knock-out mouse. Several other models have been developed since then, including conditional knock-out mice, knock-out rats, a zebrafish and a drosophila model. Using these model systems, various targets for potential pharmaceutical treatments have been identified and many treatments have been shown to be efficient in preclinical studies. However, all attempts to turn these findings into a therapy for patients have failed thus far. In this review, I will discuss underlying difficulties and address potential alternatives for our future research.
Bei Thymian (Thymus vulgaris) handelt es sich um eine sehr varietätenreiche Art, die aufgrund ihres Gehaltes an therapeutisch wirksamen Inhaltsstoffen als Arzneipflanze monographiert ist. Insbesondere das ätherische Öl mit dem Hauptbestandteil Thymol (ca. 50%) hat eine hohe antioxidative Wirkung. Ziel ist es, dieses Potential als nachhaltig produzierte Additive zu nutzen. Hierfür eignen sich antioxidativ bzw. antimikrobiell wirksame sowie UV-absorbierende Substanzen, die das Produkt bei Zusatz vor oxidativem Stress, mikrobiellem Abbau und Qualitätsverlust schützen.
Hierzu werden zunächst sechs Varianten auf verschiedene Parameter analysiert, um die potenteste Variante auszuwählen. Auf diese Variante wird sich die weitere Forschung konzentrieren.
Daher wird das ätherische Öl durch azeotrope Destillation extrahiert und mittels GCMS analysiert. In Extrakten werden zudem das AP und Absorptionsverhalten bestimmt. Auch die chemische Zusammensetzung des Extrakts sowie die flüchtigen Stoffe des Thymians werden untersucht. Generell gibt es wenig qualitative, teilweise jedoch quantitative Unterschiede: Eine Variante weist u.a. einen deutlich höheren Thymolgehalt im Öl (ca. 65 %) und ein hohes hydrophiles AP auf. Somit ist eine vielversprechende Variante für die weitere Entwicklung und Optimierung bioaktiver Additive gefunden.
Polyurethane (PU) coatings were successfully produced using unmodified kraft lignin (KL) as an environmentally benign component in contents of up to 80 wt%. Lignin samples were precipitated from industrial black liquor in aqueous solution working at room temperature and different pH levels (pH 2 to pH 5). Lignins were characterized by UV-Vis, FTIR, pyrolysis-GC/MS, SEC and 31P-NMR. Results show a correlation between pH level, OH number and molecular weight Mw of isolated lignins. Lignin-based polyurethane coatings were prepared in an efficient one step synthesis dissolving lignin in THF and PEG425 in an ultrasonic bath followed by addition of 4,4-diphenylmethanediisocyanate (MDI) and triethylamine (TEA). Crosslinking was achieved under very mild conditions (1 hour at room temperature followed by 3 hours at 35 °C). The resulting coatings were characterized regarding their physical properties including ATR-IR, TGA, optical contact angle, light microscopy, REM-EDX and AFM data. Transparent homogeneous films of high flexibility resulted from lignins isolated at pH 4, possessing a temperature resistance up to 160 °C. Swelling tests revealed a resistance against water. Swelling in DMSO depends on index, pH of precipitation and catalyst utilization for PU preparation. According to AFM studies, surface roughness is between 10 and 28 nm.
Amino acids perform multiple essential physiological roles in humans, and accordingly, their importance to health has been the subject of extensive attention. In this special issue of the Journal of Nutrition and Metabolism, we focus on the various inborn errors of amino acid metabolism, their diagnostic challenges, new treatment approaches, and recent advances in patient monitoring as well as clinical outcomes.
Triple-negative breast cancer (TNBC) lacks targeted therapies and has a worse prognosis than other breast cancer subtypes, underscoring an urgent need for new therapeutic targets and strategies. IRE1 is an endoplasmic reticulum (ER) stress sensor, whose activation is predominantly linked to the resolution of ER stress and, in the case of severe stress, to cell death. Here we demonstrate that constitutive IRE1 RNase activity contributes to basal production of pro-tumorigenic factors IL-6, IL-8, CXCL1, GM-CSF, and TGFβ2 in TNBC cells. We further show that the chemotherapeutic drug, paclitaxel, enhances IRE1 RNase activity and this contributes to paclitaxel-mediated expansion of tumor-initiating cells. In a xenograft mouse model of TNBC, inhibition of IRE1 RNase activity increases paclitaxel-mediated tumor suppression and delays tumor relapse post therapy. We therefore conclude that inclusion of IRE1 RNase inhibition in therapeutic strategies can enhance the effectiveness of current chemotherapeutics.
In 2018, in the US alone, it is estimated that 268,670 people will be diagnosed with breast cancer, and that 41,400 will die from it. Since breast cancers often become resistant to therapies, and certain breast cancers lack therapeutic targets, new approaches are urgently required. A cell-stress response pathway, the unfolded protein response (UPR), has emerged as a promising target for the development of novel breast cancer treatments. This pathway is activated in response to a disturbance in endoplasmic reticulum (ER) homeostasis but has diverse physiological and disease-specific functions. In breast cancer, UPR signalling promotes a malignant phenotype and can confer tumours with resistance to widely used therapies. Here, we review several roles for UPR signalling in breast cancer, highlighting UPR-mediated therapy resistance and the potential for targeting the UPR alone or in combination with existing therapies.
Small Molecules Enhance Scaffold-Based Bone Grafts via Purinergic Receptor Signaling in Stem Cells
(2018)
The need for bone grafts is high, due to age-related diseases, such as tumor resections, but also accidents, risky sports, and military conflicts. The gold standard for bone grafting is the use of autografts from the iliac crest, but the limited amount of accessible material demands new sources of bone replacement. The use of mesenchymal stem cells or their descendant cells, namely osteoblast, the bone-building cells and endothelial cells for angiogenesis, combined with artificial scaffolds, is a new approach. Mesenchymal stem cells (MSCs) can be obtained from the patient themselves, or from donors, as they barely cause an immune response in the recipient. However, MSCs never fully differentiate in vitro which might lead to unwanted effects in vivo. Interestingly, purinergic receptors can positively influence the differentiation of both osteoblasts and endothelial cells, using specific artificial ligands. An overview is given on purinergic receptor signaling in the most-needed cell types involved in bone metabolism-namely osteoblasts, osteoclasts, and endothelial cells. Furthermore, different types of scaffolds and their production methods will be elucidated. Finally, recent patents on scaffold materials, as wells as purinergic receptor-influencing molecules which might impact bone grafting, are discussed.