12/02/2024


Ketamine has become a popular recreational drug due to its neuronal anesthesia effect and low price. The process of learning and memory is part of the distinctive high-level neural activities in animals. We investigated the effects of subanesthetic and anesthetic doses of ketamine on the learning and memory-related signal transduction mechanisms. We used the Morris water maze test to execute rats' learning and memory ability and detected changes of Arc mRNA and Arc, cAMP-response element-binding protein (CREB), phospho-CREB (p-CREB), extracellular signal-regulated kinase (ERK), and phospho-ERK (p-ERK) protein expression in the hippocampus 10 min and 24 h after administration. Ten min after ketamine injection, the Arc gene and the protein expression levels increased in all groups; p-ERK only increased in the chronic subanesthetic dose group. After 24 h, the Arc gene and the protein expression levels of the subanesthetic dose group increased, but those of the chronic subanesthetic dose group and anesthetic dose group decreased. However, p-ERK increased in all groups. A chronic subanesthetic dose of ketamine could increase learning and memory ability through ERK, CREB, and Arc in a short time, and the high body temperature after the subanesthetic dose of ketamine injection was the main factor leading to changes in Arc. The subanesthetic dose of ketamine regulated learning and memory through ERK, CREB, and ARC 24 h after injection.A synthetic route for redox-sensitive and non-sensitive core multi-shell (CMS) carriers with sizes below 20 nm and narrow molecular weight distributions was established. Cyclic voltammetric measurements were conducted characterizing the redox potentials of reduction-sensitive CMS while showcasing its reducibility through glutathione and tris(2-carboxyethyl)-phosphine as a proof of concept. Measurements of reduction-initiated release of the model dye Nile red by time-dependent fluorescence spectroscopy showed a pronounced release for the redox-sensitive CMS nanocarrier (up to 90% within 24 h) while the non-sensitive nanocarriers showed no release in PBS. Penetration experiments using ex vivo human skin showed that the redox-sensitive CMS nanocarrier could deliver higher percentages of the loaded macrocyclic dye meso-tetra (m-hydroxyphenyl) porphyrin (mTHPP) to the skin as compared to the non-sensitive CMS nanocarrier. Encapsulation experiments showed that these CMS nanocarriers can encapsulate dyes or drugs with different molecular weights and hydrophobicity. A drug content of 1 to 6 wt% was achieved for the anti-inflammatory drugs dexamethasone and rapamycin as well as fluorescent dyes such as Nile red and porphyrins. These results show that redox-initiated drug release is a promising strategy to improve the topical drug delivery of macrolide drugs.The debate regarding the actual cardiovascular burden in metabolically healthy obese or metabolically unhealthy non-obesity individuals is ongoing. Accumulating data have suggested a unique pathophysiological role of pro-inflammatory cytokines in mediating metabolic and cardiovascular disorders by dysregulated visceral adiposity. To compare the burden of visceral adiposity, the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the prevalent atherosclerotic burden in metabolically healthy obese (MHO) or metabolically unhealthy (MU) populations, were compared to those of metabolically healthy non-obesity subjects (MHNO). https://www.selleckchem.com/products/nvp-dky709.html Coronary artery calcification score (CACS) and visceral fat, including pericardial fat (PCF)/thoracic peri-aortic fat (TAT), were quantified in 2846 asymptomatic subjects using a CT dataset. A cross-sectional analysis comparing CACS, inflammatory marker hs-CRP, and visceral fat burden among four obesity phenotypes (MHNO, metabolically unhealthy non-obesity (MUNO), MHO, and metabolically unhealthy obese (MUO)) was performed. Both MUNO and MUO demonstrated significantly higher hs-CRP and greater CACS than MHNO/MHO (adjusted coefficient 25.46, 95% confidence interval (CI) 5.29-45.63; 43.55, 95% CI 23.38-63.73 for MUNO and MUO (MHNO as reference); both p less then 0.05). Visceral fat (PCF/TAT) was an independent determinant of MU and was similarly higher in the MUNO/MHO groups than in the MHNO group, with the MUO group having the largest amount. PCF/TAT, obesity, and MU remained significantly associated with higher CACS even after adjustment, with larger PCF/TAT modified effects for MU and diabetes in CACS (both pinteraction less then 0.05). MU tightly linked to excessive visceral adiposity was a strong and independent risk factor for coronary atherosclerosis even in lean individuals, which could be partially explained by its coalignment with pathological pro-inflammatory signaling.Lactic acid bacteria (LAB) potential in the food industry and in the biotechnological sector is a well-established interest. LAB potential in counteracting especially food-borne infections has received growing attention, but despite being a road full of promises is yet poorly explored. Furthermore, the ability of LAB to produce antimicrobial compounds, both by ribosomal synthesis and by decrypting them from proteins, is of high value when considering the growing impact of multidrug resistant strains. The antimicrobial potential of 14 food-derived lactic acid bacteria strains has been investigated in this study. Among them, four strains were able to counteract Listeria monocytogenes growth Lactococcus lactis SN12 and L. lactis SN17 by high lactic acid production, whereas L. lactis 41FLL3 and Lactobacillus sakei I151 by Nisin Z and Sakacin P production, respectively. Strains Lactococcus lactis MG1363, Lactobacillus rhamnosus 17D10 and Lactobacillus helveticus 4D5 were tested and selected for their potential attitude to hydrolyze caseins. All the strains were able to release bioactive peptides with already known antimicrobial, antihypertensive and opioid activities. These features render these strains or their bioactive molecules suitable for use in food as biocontrol agents, or as nutraceutical supplements to treat mild disorders such as moderate hypertension and children insomnia. These results highlight once again that LAB potential in ensuring food safety, food nutraceutical value and ultimately in favoring human health is still underexplored and underexploited.