Explore the vast range of titles available.

We designed formulations based on minoxidil (MXD) nanoparticles (N-MXD) and examined whether N-MXD can increase drug delivery into the follicles. In addition, we investigated the effect of N-MXD on hair growth in C57BL/6 mice. N-MXD (1%) was prepared as follows: methylcellulose, p-hydroxyalkylbenzoates, mannitol, and MXD were dispersed in purified water and milled using zirconia beads under refrigeration (5500 rpm, 30 s×15 times, intermittent milling). C57BL/6 mice were used to evaluate hair-growth effects. The expression levels of mRNA and protein for vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were determined by real-time PCR and ELISA methods, respectively. The ratio of solid-MXD was approximately 60% in N-MXD, and the MXD nanoparticles (90-300 nm) were oblong in shape. For the design of nanomedicines, usability is important. Therefore, we measured the stability and toxicity after N-MXD treatment. No agglutination of MXD nanoparticles was detected for 2 weeks, and no redness or MXD powder residue was observed in the skin after repetitive applications of N-MXD. Next, we evaluated hair-growth effects by N-MXD treatment. MXD contents in the skin tissue from N-MXD were lower than for commercially available MXD formulations (CA-MXD). Conversely, MXD contents in the hair bulbs were higher for N-MXD than for CA-MXD, and the drug efficacy of N-MXD was also higher than that of CA-MXD. In addition, the mRNA and protein levels of IGF-1 and VEGF were enhanced by the repetitive application of N-MXD and CA-MXD, and the enhanced IGF-1 and VEGF levels were significantly higher for N-MXD than for CA-MXD. We designed a novel nanomedicine based on MXD nanoparticles and showed that N-MXD can deliver MXD into hair bulbs via hair follicles and that the therapeutic efficiency for hair growth is higher than for CA-MXD (solution type).

: Transdermal formulations are widely utilized in the pharmaceutical and cosmetic fields because they enable non-invasive administration and sustained local drug delivery. Conventional ex vivo skin permeation experiments using Franz diffusion cells have limitations in capturing the spatial and temporal dynamics of skin penetration. This study aimed to develop a confocal laser scanning microscopy (CLSM)-based approach to visualize and semi-quantitatively assess the penetration behavior of fluorescent dyes with differing lipophilicities. : Four fluorescent dyes with different Log P values-Rhodamine B (Rho-B), Rhodamine 123 (Rho-123), Fluorescein Sodium (Flu-Na), and Nile Red (NR)-were formulated into lotion-based vehicles and applied to excised human abdominal skin. CLSM imaging was performed from 10 min to 240 min post-application. Fluorescence intensities were extracted from depth-resolved regions (R1-R4, 30-μm intervals) to examine penetration kinetics and distribution. : CLSM imaging demonstrated that Rho-B penetrated through stratum corneum and entered deep into the skin via the hair follicles. Rho-123 and Flu-Na exhibited intercellular and follicular penetration; however, Flu-Na showed only a slight increase in intensity over time; NR showed negligible penetration into the deeper layers. The results of our analysis indicated that moderately lipophilic substances such as Rho-B and Rho-123 diffused deeply into the skin via both transdermal and follicular routes, whereas highly hydrophobic or lipophilic substances remained in the superficial layers. : The CLSM-based approach enabled spatially and temporally resolved, semi-quantitative evaluation of transdermal penetration in a single, non-destructive experiment. Although restricted to fluorescent probes, this approach provides a practical early-stage screening tool for comparing route-specific and time-dependent penetration behaviors of compounds with different lipophilicities.

We previously found that 1% minoxidil (MXD) nanoparticles prepared using a bead mill method led to an increase I n hair follicle delivery and hair growth in C57BL/6 mice. In the present study, we designed a nanoparticle formulation containing 5% MXD (MXD-NPs) using the bead mill method and investigated the hair-growth effect of MXD-NPs and a commercially available MXD solution (CA-MXD). Hair growth and in vivo permeation studies were conducted using C57BL/6 mice. Moreover, we examined the MXD contents in the upper (hair bulge) and the lower hair follicle (hair bulb) and observed the hair follicle epithelial stem cells (HFSC) by immunohistochemical staining using the CD200 antibody. The mean particle size of the MXD in the MXD-NPs was 139.8 nm ± 8.9 nm. The hair-growth effect of the MXD-NPs was higher than that of CA-MXD, and the MXD content in the hair bulge of mice treated with MXD-NPs was 7.4-fold that of the mice treated with CA-MXD. In addition, the activation of HFSC was observed around the bulge in the MXD-NPs-treated mice. We showed that MXD-NPs enable the accumulation of MXD in the upper hair follicles more efficiently than CA-MXD, leading the activation of HFSC and the hair growth.

Amphiphiles composed of two different natural renewable raw materials, amino acid and carbohydrate (chitin), were synthesized, and their colloidal properties were studied. N‐Higher acylated glutamic and aspartic acid were used as amino acid raw materials. Chitin monomer (N‐acetyl glucosamine) and dimer (N,N′‐diacetylchitobiose) were employed as the carbohydrate hydrophilic moiety in the amphiphiles. These surfactants showed a surface tension in the range of 30–36 mN/m at their critical micelle concentration. In the study of colloidal properties, such as surface tension, emulsification, and foaming, the surfactants containing the monosaccharide hydrophilic group showed much better results than those with disaccharide. Biodegradation measurements showed that the tested surfactants are biodegraded by environmental microorganisms to 57–73% of the initial levels in 14 d. Their biodegradation extent depended on neither the saccharide structure nor the kind of amino acid.

Background In this study, we investigated CD20+ TILs in triple-negative breast cancer (TNBC) and their relationship with T lymphocyte subsets (CD4+, CD8+, CD25+, and FOXP3+), including their combined prognostic value using an immunohistochemical staining method. Methods We investigated 107 patients with TNBC for whom a full-face section stained by hematoxylin and eosin between 2006 and 2018 at Dokkyo Medical University Hospital was available. Results The strongest association of infiltrating CD20+ TILs was with CD4+ TILs. There was a significant relationship between CD20+ and CD4+ TILs ( r  = 0.177; p  < 0.001), CD8+ TILs ( r  = 0.085; p  = 0.002), and FOXP3+ TILs ( r  = 0.0043; p  = 0.032). No significant relationships were observed between the CD20+ and CD25+ TILs ( r  = 0.012; p  = 0.264). Multivariate analysis revealed that only the CD20+/FOXP3 ratio was an independent factor for relapse-free survival ( p  < 0.001) and overall survival ( p  < 0.001). Patients with tumors highly infiltrated by CD4+, CD8+, and CD20+ TILs had a good prognosis. In contrast, those with tumors weakly infiltrated by CD20+ TILs but highly infiltrated by CD25+ and FOXP3+ TILs had a poor prognosis. Conclusions CD20+ TILs may support an increase in CD4+ and CD8+ TILs, which altered the anti-tumor response, resulting in a positive prognosis. CD20+ TILs correlated with FOXP3+ Treg lymphocytes, which were reported to be correlated with a poor prognosis. Our study suggested that TIL-B cells have dual and conflicting roles in TIL-T immune reactions in TNBC.

We compute the one-loop vacuum energy in 10-dimensional (10D) super Yang–Mills theory compactified on $\\mathbb {R}^{1,3}\\times (\\mathbb {T}^2)^3$ in the presence of the Abelian magnetic fluxes. Regularization of the infinite Kaluza–Klein (KK) sum is achieved by the use of Barnes $\\zeta$-functions, which can be applied to the case in which the KK mass spectrum has the Landau level structure. We apply the technique to two different models of the 10D super Yang–Mills theory: One is to introduce the magnetic flux background to the 10D super Yang–Mills action. The other is to first embed the 10D super Yang–Mills action into 4D $\\mathcal {N}=1$ superspace and to introduce magnetic fluxes. The two models built result in different KK mass spectra as well as tree level potentials, and we compute the one-loop vacuum energy of each case. Nevertheless, both of the KK mass spectra have the Landau level structure and we can apply the regularization method in the same way. It turns out that the former model shows UV finite one-loop vacuum energy whereas the latter shows UV divergent one-loop potential that vanish when 4D ${\\cal N}=1$ supersymmetry is not broken by magnetic fluxes. We discuss the origin of the differences from a higher-dimensional-supersymmetry viewpoint.

The urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to develop a scoring system for the diagnosis and pretreatment risk assessment of neuroblastoma, incorporating age and other urinary catecholamine metabolite combinations. Urine samples from 227 controls (227 samples) and 68 patients with neuroblastoma (228 samples) were evaluated. First, the catecholamine metabolites vanillactic acid (VLA) and 3‐methoxytyramine sulfate (MTS) were identified as urinary marker candidates through comprehensive analysis using liquid chromatography–mass spectrometry. The concentrations of these marker candidates and conventional markers were then compared among controls, patients, and numerous risk groups to develop a scoring system. Participants were classified into four groups: control, low risk, intermediate risk, and high risk, and the proportional odds model was fitted using the L2‐penalized maximum likelihood method, incorporating age on a monthly scale for adjustment. This scoring model using the novel urine catecholamine metabolite combinations, VLA and MTS, had greater area under the curve values than the model using HVA and VMA for diagnosis (0.978 vs. 0.964), pretreatment risk assessment (low and intermediate risk vs. high risk: 0.866 vs. 0.724; low risk vs. intermediate and high risk: 0.871 vs. 0.680), and prognostic factors ( MYCN status: 0.741 vs. 0.369, histology: 0.932 vs. 0.747). The new system also had greater accuracy in detecting missing high‐risk neuroblastomas, and in predicting the pretreatment risk at the time of screening. The new scoring system employing VLA and MTS has the potential to replace the conventional adjunctive diagnostic method using HVA and VMA.

Abstract We have found a significant error in our result of the vacuum energy computed for the case with 4D $\\mathcal {N}=1$ supersymmetric completions, and after correcting the error, the one-loop vacuum energy coincides with the one obtained in the model without 4D $\\mathcal {N}=1$ supersymmetric completions, particularly the one-loop divergence disappears.

Urine is a complex liquid containing numerous small molecular metabolites. The ability to non-invasively test for cancer biomarkers in urine is especially beneficial for screening child patients. This study attempted to identify neuroblastoma biomarkers by comprehensively analysing urinary metabolite samples from children. A total of 87 urine samples were collected from 54 participants (15 children with neuroblastoma and 39 without cancer) and used to perform a comprehensive analysis. Urine metabolites were extracted using liquid chromatography/mass spectrometry and analysed by Metabolon, Inc. Biomarker candidates were extracted using the Wilcoxon rank sum test, random forest method (RF), and orthogonal partial least squares discriminant analysis (OPLS-DA). RF identified three important metabolic pathways in 15 samples from children with neuroblastoma. One metabolite was selected from each of the three identified pathways and combined to create a biomarker candidate (3-MTS, CTN, and COR) that represented each of the three pathways; using this candidate, all 15 cases were accurately distinguishable from the control group. Two cases in which known biomarkers were negative tested positive using this new biomarker. Furthermore, the predictive value did not decrease in cases with a low therapeutic effect. This approach could be effectively applied to identify biomarkers for other cancer types.