Strangejenkins2388

Reports on the long-term survival effect of edaravone, which was approved for the treatment of amyotrophic lateral sclerosis (ALS) in 2015 in Japan, are rare. Herein, we report our retrospective analysis of 45 consecutive patients with ALS who initially visited our hospital between 2013 and 2018. Of these, 22 patients were treated with edaravone for an average duration of 26.6 (range, 2-64) months, whereas the remaining patients were not treated with edaravone and comprised the control group. There were no differences in baseline demographics between the two groups. The primary endpoint was tracheostomy positive-pressure ventilation (TPPV) or death, and the follow-up period ended in December 2020. The survival rate was significantly better in the edaravone group than in the control group based on the Kaplan-Meier analysis, which revealed that the median survival durations were 49 (9-88) and 25 (8-41) months in the edaravone and control groups, respectively (p = 0.001, log-rank test). There were no serious edaravone-associated adverse effects during the study period. Crenolanib Overall, the findings of this single-center retrospective study suggest that edaravone might prolong survival in patients with ALS.TrkB is a tyrosine kinase receptor that is activated upon binding to brain-derived neurotrophic factor (BDNF). To date, the search for low-molecular-weight molecules mimicking BDNF's action has been unsuccessful. Several molecules exerting antidepressive effects in vivo, such as 7,8-DHF, have been suggested to be TrkB agonists. However, more recent publications question this hypothesis. In this study, we developed a set of experimental procedures including the evaluation of direct interactions, dimerization, downstream signaling, and cytoprotection in parallel with physicochemical and ADME methods to verify the pharmacology of 7,8-DHF and other potential reference compounds, and perform screening for novel TrkB agonists. 7,8 DHF bound to TrkB with Kd = 1.3 μM; however, we were not able to observe any other activity against the TrkB receptor in SN56 T48 and differentiated SH-SY5Y cell lines. Moreover, the pharmacokinetic and pharmacodynamic effects of 7,8-DHF at doses of 1 and 50 mg/kg were examined in mice after i.v and oral administration, respectively. The poor pharmacokinetic properties and lack of observed activation of TrkB-dependent signaling in the brain confirmed that 7,8-DHF is not a relevant tool for studying TrkB activation in vivo. The binding profile for 133 molecular targets revealed a significant lack of selectivity of 7,8-DHF, suggesting a distinct functional profile independent of interaction with TrkB. Additionally, a compound library was screened in search of novel low-molecular-weight orthosteric TrkB agonists; however, we were not able to identify reliable drug candidates. Our results suggest that published reference compounds including 7,8-DHF do not activate TrkB, consistent with canonical dogma, which indicates that the reported pharmacological activity of these compounds should be interpreted carefully in a broad functional context.Extracellular vesicles (EVs) are increasingly studied as vectors for drug delivery because they can transfer a variety of molecules across biological barriers. SerpinB3 is a serine protease inhibitor that has shown a protective anti-apoptotic function in a variety of stressful conditions. The aim of this study was to evaluate protection from oxidative stress-induced damage, using extracellular vesicles that overexpress SerpinB3 (EVs-SB3) in order to enhance the effect of extracellular vesicles on cellular homeostasis. EVs-SB3s were obtained from HepG2 cells engineered to overexpress SerpinB3 and they revealed significant proteomic changes, mostly characterized by a reduced expression of other proteins compared with EVs from non-engineered cells. These EV preparations showed a significantly higher protection from H2O2 induced oxidative stress in both the hepatoma cell line and in primary cardiomyocytes, compared to cells treated with naïve EVs or SerpinB3 alone, used at the same concentration. In conclusion, the induction of SerpinB3 transgene expression results in the secretion of EVs enriched with the protein product that exhibits enhanced cytoprotective activity, compared with naïve EVs or the nude SerpinB3 protein.Sensitive skin is characterized by symptoms of discomfort when exposed to environmental factors. Peptides are used in cosmetics for sensitive skin and stand out as active ingredients for their ability to interact with skin cells by multiple mechanisms, high potency at low dosage and the ability to penetrate the stratum corneum. This study aimed to analyze the composition of 88 facial cosmetics for sensitive skin from multinational brands regarding usage of peptides, reviewing their synthetic pathways and the scientific evidence that supports their efficacy. Peptides were found in 17% of the products analyzed, namely acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, acetyl tetrapeptide-15, palmitoyl tripeptide-5, acetyl hexapeptide-49, palmitoyl tetrapeptide-7 and palmitoyl oligopeptide. Three out of seven peptides have a neurotransmitter-inhibiting mechanism of action, while another three are signal peptides. Only five peptides present evidence supporting their use in sensitive skin, with only one clinical study including volunteers having this condition. Noteworthy, the available data is mostly found in patents and supplier brochures, and not in randomized placebo-controlled studies. Peptides are useful active ingredients in cosmetics for sensitive skin. Knowing their efficacy and synthetic pathways provides meaningful insight for the development of new and more effective ingredients.Chelidonium majus L. is a perennial herbaceous plant that has various medicinal properties. However, the genomic information about its carotenoid biosynthesis pathway (CBP), xanthophyll biosynthesis pathway (XBP), and apocarotenoid biosynthesis pathway (ABP) genes were limited. Thus, the CBP, XBP, and ABP genes of C. majus were identified and analyzed. Among the 15 carotenoid pathway genes identified, 11 full and 4 partial open reading frames were determined. Phylogenetic analysis of these gene sequences showed higher similarity with higher plants. Through 3D structural analysis and multiple alignments, several distinct conserved motifs were identified, including dinucleotide binding motif, carotene binding motif, and aspartate or glutamate residues. Quantitative RT-PCR showed that CBP, XBP, and ABP genes were expressed in a tissue-specific manner; the highest expression levels were achieved in flowers, followed by those in leaves, roots, and stems. The HPLC analysis of the different organs showed the presence of eight different carotenoids. The highest total carotenoid content was found in leaves, followed by that in flowers, stems, and roots. This study provides information on the molecular mechanisms involved in CBP, XBP, and ABP genes, which might help optimize the carotenoid production in C. majus. The results could also be a basis of further studies on the molecular genetics and functional analysis of CBP, XBP, and ABP genes.This study evaluated if specific light quality (LQ) regimes (white fluorescent, FL; full-spectrum, FS; red-blue, RB) during plant growth modified morphological and photosynthetic traits of Solanum lycopersicum L. 'Microtom' plants irradiated at the dry seed stage with 25 Gy 48Ca ions (IR). The irradiation reduced plant size while it increased leaf dry matter content (LDMC) and relative water content (RWC) compared to the control. FS and RB light regimes determined a decrease of plant height and a rise of RWC compared to FL plants. The irradiation under FS and RB regimes favoured the development of dwarf plants and improved the leaf water status. Under the FL regime, irradiated plants showed reduced photosynthesis and stomatal conductance. The opposite behavior was observed in RB irradiated plants in which gas exchanges were significantly stimulated. RB regime enhanced Rubisco expression in irradiated plants also inducing anatomical and functional adjustments (i.e., increase of leaf thickness and incidence of intercellular spaces). Finally, 48Ca ions did not prevent fruit ripening and the achievement of the 'seed-to seed' cycle, irrespective of the LQ regime. Overall, the present study evidenced that RB light regime was the most effective in optimising growth and photosynthetic efficiency of 'Microtom' irradiated plants. These outcomes may help to develop proper cultivation protocols for the growth of dwarf tomato in Controlled Ecological Life Support Systems (CELSS).Yams (Dioscorea spp.) are cultivated and consumed as edible tubers, while their leaves are discarded as waste or burned with negative environmental impact. Herein, the metabolites of two yam species (Danma, DAN; Dunggeunma, DUN), harvested in June, July, and August, were profiled using GC-TOF-MS and UHPLC-LTQ-Orbitrap-MS/MS and the antioxidant activity of the extracts was evaluated to stimulate the utilization of yam leaves as a by-product. We observed that the relative levels of amino acids, organic acids, sugars, and saponins decreased linearly with prolonged harvest time, while fatty acid, phenanthrene, and flavonoid levels gradually increased. Furthermore, the leaf extracts obtained in August exhibited the highest antioxidant activity. To determine the antioxidant-contributing metabolites, OPLS-DA was performed for the leaf metabolites of DAN and DUN leaves harvested in August. Hydroxytyrosol-glucoside, apigenin-rhamnoside, and rutin were more abundant in DUN, while luteolin, phenanthrene derivatives, epicatechin, and kaempferide were relatively higher in DAN and their respective metabolites were positively correlated with the antioxidant activity. Moreover, secondary metabolites were more abundant in the leaves than in the roots, and consequently, the antioxidant activity of the former was also higher. Overall, the potential value of yam leaves as a renewable source of bioactive compounds is proposed.This study demonstrates the indirect effects of non-thermal ambient air plasmas (NTP) on seed germination and plant growth. It investigates the effect of plasma-activated water (PAW) on 3-day-old seedlings of two important farm plants-barley and pea. Applying different types of PAW on pea seedlings exhibited stimulation of amylase activity and had no inhibition of seed germination, total protein concentration or protease activity. Moreover, PAW caused no or only moderate oxidative stress that was in most cases effectively alleviated by antioxidant enzymes and proved by in situ visualization of H2O2 and ˙O2-. In pea seedlings, we observed a faster turn-over from anaerobic to aerobic metabolism proved by inhibition of alcohol dehydrogenase (ADH) activity. Additionally, reactive oxygen/nitrogen species contained in PAW did not affect the DNA integrity. On the other hand, the high level of DNA damage in barley together with the reduced root and shoot length and amylase activity was attributed to the oxidative stress caused by PAW, which was exhibited by the enhanced activity of guaiacol peroxidase or ADH. Our results show the glow discharge PAW at 1 min activation time as the most promising for pea. However, determining the beneficial type of PAW for barley requires further investigation.