Investigating the Role of P311 in the Hypertrophic Scar

The mechanisms of hypertrophic scar formation are not fully understood. We previously screened the differentially expressed genes of human hypertrophic scar tissue and identified P311 gene as upregulated. As the activities of P311 in human fibroblast function are unknown, we examined the distribution of it and the effects of forced expression or silencing of expression of P311. P311 expression was detected in fibroblast-like cells from the hypertrophic scar of burn injury patients but not in peripheral blood mononuclear cells, bone marrow mesenchymal stem cells, epidermal cells or normal skin dermal cells. Transfection of fibroblasts with P311 gene stimulated the expression of alpha-smooth muscle actin (α-SMA), TGF-β1 and α1(I) collagen (COL1A1), and enhanced the contraction of fibroblast populated collagen lattices (FPCL). In contrast, interference of fibroblast P311 gene expression decreased the TGF-β1 mRNA expression and reduced the contraction of fibroblasts in FPCL. These results suggest that P311 may be involved in the pathogenesis of hypertrophic scar via induction of a myofibroblastic phenotype and of functions such as TGF-β1 expression. P311 could be a novel target for the control of hypertrophic scar development

Donated chemical probes for open science.

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project

The Effects of Music Therapy on Pediatric Patients\u27 Pain and Anxiety During Donor Site Dressing Change

The purpose of this study was to assess the effects of music therapy on pain and anxiety in pediatric burn patients during a donor site dressing change. Fourteen subjects were randomly selected to participate in this study. The experiment was conducted in the Reconstructive Unit of Shriners Burns Hospital-Boston. The experimental group\u27s intervention consisted of live music and was compared to a control group whose intervention was verbal interaction. Psychological, behavioral, and physiological data were assessed through the Wong Baker FACES Pain Rating Scale, the Fear Thermometer, the Nursing Assessment of Pain Index, heart rate, and respiration rate. Data were analyzed using the ANCOVA, Mann-Whitney U, and regression analysis. The results were mixed and inconclusive. The members of the experimental group reported anecdotal information about the effects of music on pain and anxiety. An exploration of the limitations of the study and suggestions for further study are discussed

Exploring the Effects of Music Therapy on Pediatric Pain: Phase 1

The purpose of this study was to assess the effects of music therapy on pain and anxiety in pediatric burn patients during nursing procedures. Nine subjects were randomly selected to participate in this study. Qualitative and quantitative data was collected on the patients\u27 pain, anxiety, heart rate, blood oxygenation, and engagement level through measurement tools and interviews. The results from the qualitative and quantitative data indicated that music therapy reduced pain, anxiety, and behavioral distress. The quantitative data were analyzed and an inverse relationship between engagement in music therapy and lower behavioral distress scores was noted. Additionally, a linear relationship between engagement and behavioral distress was noted; significance was found but was moderated by the age of the child. However, no significant relationship was found between heart rate and behavioral distress. The results from the qualitative data from the interviews with the patients, parents, nurses and music therapist indicated that music therapy reduced pain and anxiety, and that engagement in music therapy enhanced relaxation. In addition, music therapy positively affected patients\u27 mood, compliance, and the relaxation level. Finally, parents/guardians and nurses involved in the study reported that music therapy helped them to feel more relaxed as well

Unveiling the attributes of rabbit milk

Increasing the knowledge of rabbit milk can help in breeding practice to solve issues considering the health and growth of rabbit kits. The goal of the study was to perform a broad physicochemical analysis of rabbit milk and examine the effect of the reproductive status of the females on daily milk yield and milk attributes. The study was conducted on a commercial rabbit farm and included three consecutive lactations of Hycole does. It has been observed that the daily milk production increased from the 2nd till the 14th day of lactation when does produced almost 300 g of milk daily. The day of lactation caused a significant variation in the content of total solids, solids-not-fat, total protein, casein, lactose, C18: 2, C18: 3, Somatic Cell Count, and pH. The percentage of fat globules categorised according to their diameter changed with the ongoing lactation as well, and the diameter increased from 5 to 7 µm. The percentage of small milk fat globules decreased with lactation day, causing a possible decrease in the digestions rates of milk. Pregnancy had a negative impact on milk production, kits growth performance, and the content of total protein, solids-not-fat, and lactose in milk. Therefore, we can speculate about the negative impact of overlapping lactations and pregnancies on rabbit kits, as their growth is dependent on milk production and composition

Pervasive Regulatory Functions of mRNA Structure Revealed by High-Resolution SHAPE Probing

mRNAs can fold into complex structures that regulate gene expression. Resolving such structures de novo has remained challenging and has limited our understanding of the prevalence and functions of mRNA structure. We use SHAPE-MaP experiments in living E. coli cells to derive quantitative, nucleotide-resolution structure models for 194 endogenous transcripts encompassing approximately 400 genes. Individual mRNAs have exceptionally diverse architectures, and most contain well-defined structures. Active translation destabilizes mRNA structure in cells. Nevertheless, mRNA structure remains similar between in-cell and cell-free environments, indicating broad potential for structure-mediated gene regulation. We find that the translation efficiency of endogenous genes is regulated by unfolding kinetics of structures overlapping the ribosome binding site. We discover conserved structured elements in 35% of UTRs, several of which we validate as novel protein binding motifs. RNA structure regulates every gene studied here in a meaningful way, implying that most functional structures remain to be discovered

Reductively Responsive Hydrogel Nanoparticles with Uniform Size, Shape, and Tunable Composition for Systemic siRNA Delivery <i>in Vivo</i>

To achieve the great potential of siRNA based gene therapy, safe and efficient systemic delivery <i>in vivo</i> is essential. Here we report reductively responsive hydrogel nanoparticles with highly uniform size and shape for systemic siRNA delivery <i>in vivo</i>. “Blank” hydrogel nanoparticles with high aspect ratio were prepared using continuous particle fabrication based on PRINT (particle replication in nonwetting templates). Subsequently, siRNA was conjugated to “blank” nanoparticles via a disulfide linker with a high loading ratio of up to 18 wt %, followed by surface modification to enhance transfection. This fabrication process could be easily scaled up to prepare large quantity of hydrogel nanoparticles. By controlling hydrogel composition, surface modification, and siRNA loading ratio, siRNA conjugated nanoparticles were highly tunable to achieve high transfection efficiency <i>in vitro</i>. FVII-siRNA conjugated nanoparticles were further stabilized with surface coating for <i>in vivo</i> siRNA delivery to liver hepatocytes, and successful gene silencing was demonstrated at both mRNA and protein levels