Both iontophoresis (IP) and electroporation (EP) can be utilized to increase the penetration of relatively high molecular pharmaceutical and/or cosmeceutical compounds into the stratum corneum (SC), ...the uppermost layer of the skin. However, few reports exist on which molecular weights are capable of penetrating the SC, although low molecular compounds of less than 500 Da have been found to readily permeate the skin barrier. In our investigation, we applied fluorescein amine-labeled sodium hyaluronate to porcine aural skin after treatment by IP alone or EP + IP. Each layer of the SC was then tape stripped several times. The stripped SC sheets were observed using a confocal laser scanning microscope to determine the relative amounts of sodium hyaluronate present. The results confirmed that the molecular weight of sodium hyaluronate that penetrated the SC was higher with EP + IP than with IP alone. A high correlation was also established between the quantity of sodium hyaluronate that penetrated and its molecular weight following combined EP + IP treatment.
To successfully engineer large-sized tissues, establishing vascular structures is essential for providing oxygen, nutrients, growth factors and cells to prevent necrosis at the core of the tissue. ...The diameter scale of the biofabricated vasculatures should range from 100 to 1,000 µm to support the mm-size tissue while being controllably aligned and spaced within the diffusion limit of oxygen. In this review, insights regarding biofabrication considerations and techniques for engineered blood vessels will be presented. Initially, polymers of natural and synthetic origins can be selected, modified, and combined with each other to support maturation of vascular tissue while also being biocompatible. After they are shaped into scaffold structures by different fabrication techniques, surface properties such as physical topography, stiffness, and surface chemistry play a major role in the endothelialization process after transplantation. Furthermore, biological cues such as growth factors (GFs) and endothelial cells (ECs) can be incorporated into the fabricated structures. As variously reported, fabrication techniques, especially 3D printing by extrusion and 3D printing by photopolymerization, allow the construction of vessels at a high resolution with diameters in the desired range. Strategies to fabricate of stable tubular structures with defined channels will also be discussed. This paper provides an overview of the many advances in blood vessel engineering and combinations of different fabrication techniques up to the present time.
Cooking can change the polyphenol contents of eggplant. This study elucidated the effects of grilling on total polyphenol content (TPC), antioxidant capacity, and the inner structures of eggplant. ...After identical hollowing, cylindrical eggplant samples were prepared and were then grilled until their center temperatures (CT) respectively reached 50, 65, 75, 85, and 95 °C. Chemical assays and observations of the inner structures clarified that TPC and 1, 1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging activity decreased as CT increased when CT was below 65 °C. Results also showed that TPC and DPPH radical scavenging activity increased as CT increased when CT was between 65 °C and 95 °C. For CT 65 °C, the samples retained polyphenol oxidase (PPO) activity up to 40% of the raw state activity. The 3 grilled eggplant models, chlorogenic acid, chlorogenic acid—sugar and chlorogenic acid—amino acid model, yielded results showing that phenol functional groups on chlorogenic acid were thermally stable and that phenol functional groups on chlorogenic acid reacted neither with sugar nor with amino acids. Results show that PPO activity is a primary reason for the decrease of the 2 indices. Optical microscopic and scanning electron microscopic observations revealed collapsed cells and inter‐tissue cracks around the surface area for CT 85 and 95 °C. Scanning electron microscopic observations clarified that intercellular bonds for CT 85 and 95 °C became thinner than those for CT 75 °C around the middle area. The phenomena explained above are reasons for the increase of TPC and DPPH radical scavenging activity.
Practical Application
The findings of this research can support the development of healthier cooking practices that directly benefit consumers. The results of this research are expected to be illustrative to investigators of academic and commercial sectors who are interested in heat‐induced changes that occur in eggplant during grilling. Moreover, the results reported herein can facilitate understanding of the heating effects and changes occurring in other cooked vegetables.
This study aims to investigate the accuracy of a fine-tuned deep convolutional neural network (CNN) for evaluating responses to the pentagon copying test (PCT). To develop a CNN that could classify ...PCT images, we fine-tuned and compared the pre-trained CNNs (GoogLeNet, VGG-16, ResNet-50, Inception-v3). To collate our training dataset, we collected 1006 correct PCT images and 758 incorrect PCT images drawn on a test sheet by dementia suspected patients at the Osaka City Kosaiin Hospital between April 2009 and December 2012. For a validation dataset, we collected PCT images from consecutive patients treated at the facility in April 2020. We examined the ability of the CNN to detect correct PCT images using a validation dataset. For a validation dataset, we collected PCT images (correct, 41; incorrect, 16) from 57 patients. In the validation testing for an ability to detect correct PCT images, the fine-tuned GoogLeNet CNN achieved an area under the receiver operating characteristic curve of 0.931 (95% confidence interval 0.853-1.000). These findings indicate that our fine-tuned CNN is a useful method for automatically evaluating PCT images. The use of CNN-based automatic scoring of PCT can potentially reduce the burden on assessors in screening for dementia.
Obesity is a risk factor for knee osteoarthritis (KOA). Neuromedin U (NMU) and NMU receptors (NMUR1 and NMUR2) are associated with obesity-related disorders and found in mast cells (MCs), which are ...elevated in osteoarthritis. However, NMU/NMUR expression was not examined in the synovial membrane (SM) or synovial MCs of obese osteoarthritis patients. We compared expression of NMU, NMUR1, NMUR2, and the mast cell (MC) marker, CPA3, in the SM of KOA patients categorized as normal weight (NW; BMI < 25 kg/m2, n = 79), overweight (OW; BMI ≥ 25 and <30 kg/m2, n = 87), and obese (OB; ≥30 kg/m2, n = 40). To study NMU/NMUR expression in MCs, we compared the MC-rich fraction (MC-RF), CD88(+) MC-RF, and CD88(−) MC-RF, extracted using magnetic isolation, with the MC-poor fraction (MC-PF). While NMU and NMUR2 expression were comparable, NMUR1 was significantly elevated in OW and OB compared to NW. Moreover, CPA3 levels were significantly greater in OB than NW. NMUR1 and CPA3 expression were significantly higher in both the CD88(+) and CD88(−) MC-RF than MC-PF. Therefore, NMUR1 expression was elevated in the SM of OB KOA patients, and its expression was found in MCs. Further investigation to analyze the NMU/NMUR1 pathway in MC may provide a link between obesity and KOA pathology.
Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their ...derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease.
Research suggests that vascular endothelial growth factor (VEGF) levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively correlated with KOA severity. The relationship ...between synovial VEGF levels and pain in human KOA patients is not fully understood, and the role of VEGF in the pain pathway remains unclear.
We harvested synovial membrane (SM) from 102 patients with radiographic evidence of KOA (unilateral Kellgren/Lawrence K/L grade 2-4) during total knee arthroplasty. Patients scored their pain on a 0 to 10 cm visual analog scale (VAS). VEGF levels in the SM of KOA patients with strong/severe (VAS ≥ 6) and mild/moderate pain (VAS < 6) were compared. Correlations between VAS and VEGF mRNA expression were investigated. To investigate a possible mechanism for VEGF-induced pain, the distribution of VEGF and the neuropeptide apelin was determined by immunohistochemical analyses. To investigate the role of VEGF in regulating apelin expression, SM cells were exposed to VEGF.
VEGF expression in the VAS ≥ 6 group was significantly greater than expression in the VAS < 6 group. Expression levels of VEGF were also positively correlated with VAS. VEGF-positive cells were identified in the lining of the SM. Expression of apelin mRNA and protein were significantly elevated in SM cells treated with exogenous VEGF compared to those treated with vehicle.
Synovial VEGF may be involved in pain pathways in KOA and its action may be mediated by apelin.
Abstract
We investigated the differences in outcomes after total hip arthroplasty (THA) for hip osteoarthritis (HOA) between patients with and without central sensitivity syndromes (CSSs) other than ...fibromyalgia (FM). After excluding two patients with FM, we compared the clinical data of 41 patients with CSSs and 132 patients without CSSs. Clinical data included scores on the central sensitization inventory, visual analog scale for pain (VAS pain), and Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ). VAS pain was significantly higher at 3 and 6 months after THA in patients with CSSs than in those without CSSs (3 and 6 months, P < 0.001). Satisfaction, pain, and mental JHEQ scores were lower in patients with CSSs than in those without CSSs (satisfaction, P < 0.001; pain, P = 0.011; mental, P = 0.032). Multiple regression analyses indicated that one and ≥ 2 CSS diagnoses significantly impacted the satisfaction score (one CSS, β = − 0.181, P = 0.019; ≥ 2 CSSs, β = − 0.175, P = 0.023). Two or more CSSs were the only factor influencing the pain score (β = − 0.175, P = 0.027). Pain in patients with CSSs reflects central sensitization, which may adversely affect post-operative outcomes. Surgeons should pay attention to patients with a history of CSSs diagnoses who undergo THA for HOA.
School screening for scoliosis is a powerful tool that can be used to identify children who may have scoliosis. There have been no reports on the recent prevalence of idiopathic scoliosis in Japan ...since 1988.
A 5-year epidemiologic study was performed to determined the prevalence of idiopathic scoliosis, the curve magnitude, the distribution of this magnitude, and the sex ratio in school children. Between 2003 and 2007, a total of 255,875 children aged 11-14 years were screened.
A total of 3,424 children were found to be positive as a result of Moiré topography. With radiographic examination, 2,225 (65.0%) children with a Cobb angle of 10° or more were detected. The overall prevalence rate in schoolchildren 11-14 years of age with Cobb angles of 10° or more was 0.87%. The prevalence rate in girls increased from 0.78% at the age of 11-12 years to 2.51% at the age of 13-14 years. For boys, the prevalence rates were 0.04% at the age of 11-12 years and 0.25% at the age of 13-14 years. The overall ratio of girls to boys with scoliosis was 11:1. The ratio of girls to boys was 17:1 at the age of 11-12 years and 10:1 at the age of 13-14 years.
The majority of the curves fell in the range of 10°-19°. There was a slight increase in the prevalence rates of children with a curve of high magnitude (≥20°) as compared to the prevalence rate in 1988. We suggest that school screening for scoliosis is effective for early detection; however, it is first necessary to review and optimize the target groups.
Pain, the primary symptom of osteoarthritis (OA), reduces both the quality and quantity of life for patients. The pathophysiology of OA pain is complex and often difficult to explain solely by ...radiological structural changes. One reason for this discrepancy is pain sensitization (peripheral sensitization PS and central sensitization CS) in OA. Thus, an understanding of pain sensitization is important when considering treatment strategies and development for OA pain. In recent years, pro-inflammatory cytokines, nerve growth factors (NGFs), and serotonin have been identified as causative agents that induce peripheral and central sensitization and are becoming therapeutic targets for OA pain. However, the characteristics of the clinical manifestations of pain sensitization elicited by these molecules remain unclear, and it is not well understood who among OA patients should receive the therapeutic intervention. Thus, this review summarizes evidence on the pathophysiology of peripheral and central sensitization in OA pain and the clinical features and treatment options for this condition. While the majority of the literature supports the existence of pain sensitization in chronic OA pain, clinical identification and treatment of pain sensitization in OA are still in their infancy, and future studies with good methodological quality are needed.
PDF
