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Injectable hydrogels are promising delivery vehicles for the sustained release of therapeutic proteins. Electrostatic interactions between proteins and hydrogels often increase affinity to decelerate protein release. However, this approach is not suitable for weakly charged proteins. The current study shows that the genetic fusion of a highly charged protein segment (charge booster tag) with proteins can control their interactions with injectable gels. A positive or negative charge booster tag is introduced into urate oxidase (UOX), a therapeutic protein for gout, to generate UOX variants with varying net charges. When a positively‐charged injectable hydrogel is used, both the in vitro release rate and in vivo serum half‐life of UOX are correlated with the net negative charge. This modified delivery approach results in a serum half‐life of over 106 h for the UOX variant, which is substantially longer than that of free UOX (3.3 h). Hence, charge booster tags can be used as a systematic strategy for controlling the release of therapeutic proteins. [ABSTRACT FROM AUTHOR]

Keywords: charge booster tags; injectable gels; serum half-life; therapeutic proteins EN charge booster tags injectable gels serum half-life therapeutic proteins 1 1 1 03/15/23 20230309 NES 230309 B Charge Booster Tags b In article number 2209874, Jaeyun Kim, Inchan Kwon, and co-workers show cars with a booster that deliver the loaded drugs to the goal (blood vessel). Charge booster tags, injectable gels, serum half-life, therapeutic proteins Charge Booster Tags for Controlled Release of Therapeutics from a Therapeutic Carrier (Adv. Funct. [Extracted from the article]

Background: Visitation restrictions due to COVID‐19 kept parents from being with their children who were hospitalized in the PICU and from meeting with professional staff. Aim: This study examined the moderating effect of COVID‐19‐induced visitation restrictions on the relationship between stress and post‐traumatic stress disorder in parents of children admitted to the paediatric intensive care unit. Study Design: We conducted a descriptive, exploratory study involving 93 parents of children hospitalized in the paediatric intensive care unit using the Korean version of the Parental Stressor Scale: Paediatric Intensive Care Unit and the Revised Impact of Events Scale. Descriptive, Pearson's correlation, and logistic regression analyses were used to investigate the data. Self‐reported survey questionnaires were provided for parents to complete in a separate area of the outpatient clinic when they visited for follow‐up care after their children were discharged from the paediatric intensive care unit. Results: Mothers showed significantly higher post‐traumatic stress disorder scores than fathers. The relationship between all the sub‐domains of perceived stress and post‐traumatic stress disorder was statistically significant. Visitation restrictions because of the COVID‐19 pandemic had significant moderating effects on the relationship between perceived parental stress and post‐traumatic stress disorder. Moreover, the moderating effects of COVID‐19 were exhibited when the two sub‐domains—hyperarousal and intrusion—were investigated. Conclusions: Paediatric intensive care unit visitation may be an important intervention for parental post‐traumatic stress disorder. Parental visitation should be enabled, and alternative interventions should be developed in situations where visitation is prohibited. Relevance to Clinical Practice: It is necessary to develop and apply various and effective alternatives visitation that can prepare hospitals for visiting restrictions during pandemic situations which could emerge in the future. [ABSTRACT FROM AUTHOR]

R3680 --> 610.4 --> The central nervous system (CNS) is strongly implicated in cardiovascular disease development including hypertension. In particular, alterations in the subfornical organ (SFO), a forebrain sensory circumventricular nucleus located outside of the blood‐brain‐barrier, is directly associated with hypertension in response to elevations in the hormone angiotensin‐II (Ang‐II). From a circuitry perspective, SFO excitatory neurons that project to the hypothalamic paraventricular nucleus (PVN; hereafter referred to as SFO to PVN) have been suggested to be critical in the development of Ang‐II hypertension. While most investigations have focused on functional mechanisms, little attention has been paid to anatomical synaptic reorganization of SFO to PVN circuits during hypertension development. Thus, we aimed to characterize SFO to PVN synaptic input during hypertension development and further delineate molecular mechanisms involved. Male C57Bl/6J mice were infused with Ang‐II (600 ng/kg/min) for 14 days. Immunohistochemistry in the PVN following Ang‐II infusion revealed elevations in synaptophysin, pointing to overall increases in synaptic innervation of this nucleus (100 ± 1 vs. 112 ± 2 density/area, day 0 vs day 14, n=3/group, p<0.05). Given the strong link between SFO to PVN neurons in cardiovascular regulation, we next focused on the SFO. Our recent work demonstrated a key role for SFO insulin receptors in blood pressure regulation, and therefore, we determined if insulin receptors are expressed on SFO to PVN neurons using retrograde cholera toxin B tracing from the PVN. Immunohistochemistry revealed clear expression of insulin receptors on SFO to PVN neurons. Building on this, we and others have characterized a novel neural tissue‐enriched epidermal growth factor repeat domain containing protein (NELL2) that is involved in axonal projections and synaptic reorganization. Importantly, NELL2 has been suggested to be a downstream signaling molecule of neurotropic receptors, such as insulin receptors. In situ hybridization and immunohistochemistry confirmed the expression of NELL2 in the SFO, and further demonstrated elevated SFO NELL2 during Ang‐II hypertension (100 ± 5 vs. 137 ± 15 density/area, day 0 vs day 14, n=3‐4, p<0.05). Interestingly, co‐immunohistochemistry indicated that the majority of SFO insulin receptor cells express NELL2. Finally, to determine functional crosstalk between insulin receptors and NELL2, we utilized in vitro cell culture experiments. Hippocampal HT22 cells were transfected with a NELL2‐luciferase dependent vector and insulin was administrated into the medium. Insulin stimulated NELL2 gene transcription in a dose‐dependent manner (e.g. 174 and 196% increase relative to vehicle, 100 and 1000 nM insulin respectively, n=3/group, p<0.05). Collectively, these results indicate increased PVN synaptic innervation during hypertension. Moreover, they point to an SFO insulin receptor‐NELL2 network that may be involved in Ang‐II hypertension development, potentially via reorganization of SFO to PVN synaptic circuits. [ABSTRACT FROM AUTHOR]

Background: Ligularia fischeri is a perennial herb isolated from plants of the Asteraceae family. Ligularia fischeri is distributed throughout Korea, Japan, eastern Siberia, and China. Aims: The aim of this study is to examine the intracellular inhibitory effect of Ligularia fischeri ethanol extract on melanin synthesis and expression of tyrosinase and tyrosinase‐related protein 1 and 2. In addition, we analyzed the mitogen‐activated protein kinase signaling pathway and microphthalmia‐associated transcription factor in alpha‐melanocyte‐stimulating hormone‐stimulated B16F10 melanoma cells. Methods: To assess the inhibition of melanogenesis in alpha‐melanocyte‐stimulating hormone‐stimulated B16F10 melanoma cells, the expression of melanogenesis‐related genes was investigated by quantitative real‐time polymerase chain reaction, while western blotting was performed to determine protein expression levels. Results: We confirmed that the ethanol extract of Ligularia fischeri inhibited melanin synthesis in vitro by decreasing tyrosinase and tyrosinase‐related protein 1 and 2 expression. Furthermore, we revealed that tyrosinase expression was regulated by the suppression of microphthalmia‐associated transcription factor expression and activation of extracellular signal‐regulated kinase phosphorylation. The ethanol extract of Ligularia fischeri inhibited melanogenesis by activating extracellular signal‐regulated kinase phosphorylation and suppressing microphthalmia‐associated transcription factor and tyrosinase expression. Conclusions: Ligularia fischeri ethanol extract may be used as an effective skin whitening agent in functional cosmetics. [ABSTRACT FROM AUTHOR]