Search

Inoue et al develop a non-invasive method of analyzing human skin mRNA using RNA in skin surface lipids collected with oil-blotting films. The authors outline the validation of this methodology and describe an application to determine transcriptome in skin surface lipids in patients with atopic dermatitis versus healthy skin.

Abstract To accurately simulate human physiology and thermal comfort, certain human physiological and comfort models categorize the human body into multiple parts. Most of these body parts are normally clothed, which must be quantified in the simulation. However, existing databases of clothing evaporative resistance only characterize the evaporative resistance of the whole body and not those of individual body parts. This implies that each body part has the same level of clothing evaporative resistance. In this research, we measure the local clothing insulation and evaporative resistance. Here, we present the local thermal characteristic values as well as the values for the whole body.

Background. Docetaxel (DOC) was the first regimen that increased the survival and became the standard-of-care in patients with metastatic castration-resistant prostate cancer (mCRPC). However, it is unclear whether switching to second-line chemotherapy or optimal sequencing of cabazitaxel (CBZ) ensures better clinical outcomes. We aimed to evaluate the efficacy of sequential therapy with DOC and CBZ and the effect of the number of prior DOC cycles on oncological outcomes in patients with mCRPC. Methods. We retrospectively included 46 mCRPC patients who received DOC followed by CBZ at quaternary hospitals in Japan between February 2015 and March 2019. Participants received intravenous DOC (40–75 mg/m2) every 3–4 weeks; CBZ (15–25 mg/m2) was administered every 3–4 weeks. Androgen-deprivation therapy and prednisolone 5 mg (twice daily) were administered throughout both regimens. The primary endpoints were overall (OS) and progression-free survival (PFS). The secondary endpoints were the rates of ≥30% and ≥50% reduction in prostate-specific antigen (PSA) levels at chemotherapy initiation. Results. Participants were divided into two groups according to DOC cycles (Groups A and B: ≤6 and ≥7 DOC cycles, respectively). The rates of ≥30% and ≥50% reduction in PSA levels were higher in Group B than in Group A, but there were no significant differences in both groups. Median OS in Groups A and B was 12.7 and 71.0 months, respectively P

Pelvic lymphoceles are an infrequent complication after pelvic surgery and develop shortly after the surgery in most cases. We experienced a case of delayed infection of a lymphocele 6 months after robot-assisted radical prostatectomy (RARP) and pelvic lymphadenectomy. In this case, antimicrobial chemotherapy and percutaneous drainage were effective, and there was no recurrence of the disease. Most urologists do not recognize that infected lymphoceles can develop a long time after surgery; thus, infected lymphoceles should be kept in mind in patients with nonspecific infectious symptoms, regardless of the length of time after surgery.

A unified total synthesis of stemoamide-type alkaloids is reported. Our synthetic approach features the chemoselective convergent assembly of five-membered building blocks via stemoamide as the common precursor to tetracyclic natural products. The synthesis consists of two successive coupling reactions of the three five-membered building blocks. The first coupling reaction is the vinylogous Michael addition/ reduction sequence, which enables the gram-scale synthesis of stemoamide. The second coupling reaction is a chemoselective nucleophilic addition to stemoamide. While the lactoneselective nucleophilic addition to stemoamide affords saxor-umamide and isosaxorumamide, the lactam-selective reductive nucleophilic addition leads to the formation of stemonine. Both chemoselective nucleophilic additions enable direct modification of stemoamide, resulting in highly concise and efficient total syntheses of the stemoamide-type alkaloids. [ABSTRACT FROM AUTHOR]

The immune-regulatory compound histamine is involved in the metabolism of the essential skin component hyaluronan (HA). We previously reported that histamine up-regulates the expression of hyaluronan-binding protein involved in hyaluronan depolymerization (HYBID, aka CEMIP or KIAA1199), which plays a key role in HA degradation. However, no information is available about histamine's effects on HA synthase (HAS) expression, the molecular sizes of the HAs produced, and histamine receptors and their signaling pathways in skin fibroblasts. Moreover, histamine's effects on photoaged skin remain elusive. Here, we show that histamine increases HA degradation by up-regulating HYBID and down-regulating HAS2 in human skin fibroblasts in a dose- and time-dependent manner and thereby decreases the total amounts and sizes of newly produced HA. Histamine H1 blocker abrogated the histamine effects on HYBID up-regulation, HAS2 suppression, and HA degradation. Histamine H1 agonist exhibited effects on HA levels, composition, and breakdown similar to those of histamine. Of note, blockade of protein kinase Cδ (PKCδ) or PI3K-AKT signaling abolished histamine-mediated HYBID stimulation and HAS2 suppression, respectively. Immunohistochemical experiments revealed a significant ~2-fold increase in tryptase-positive mast cells in photoaged skin, where HYBID and HAS2 expression levels were increased and decreased, respectively, compared with photoprotected skin. These results indicate that histamine controls HA metabolism by up-regulating HYBID and down-regulating HAS2 via distinct signaling pathways downstream of histamine receptor H1. They further suggest that histamine may contribute to photoaged skin damage by skewing HA metabolism toward degradation. [ABSTRACT FROM AUTHOR]

Regulation of hyaluronan (HA) synthesis and degradation is essential to maintenance of extracellular matrix homeostasis. We recently reported that HYBID (HYaluronan-Binding protein Involved in hyaluronan Depolymerization), also called KIAA1199, plays a key role in HA depolymerization in skin and arthritic synovial fibroblasts. However, regulation of HA metabolism mediated by HYBID and HA synthases (HASs) under stimulation with growth factors remains obscure. Here we report that TGF-β1, basic FGF, EGF, and PDGF-BB commonly enhance total amount of HA in skin fibroblasts through up-regulation of HAS expression, but molecular size of newly producedHAis dependent on HYBID expression levels. Stimulation of HAS1/2 expression and suppression of HYBID expression by TGF-β1 were abrogated by blockade of theMAPKand/orSmadsignaling and the PI3K-Akt signaling, respectively. In normal human skin, expression of the TGF-β1 receptors correlated positively with HAS2 expression and inversely with HYBID expression. On the other hand, TGF-β1 upregulated HAS1/2 expression but exerted only a slight suppressive effect on HYBID expression in synovial fibroblasts from the patients with osteoarthritis or rheumatoid arthritis, resulting in the production of lower molecular weight HA compared with normal skin and synovial fibroblasts. These data demonstrate that although TGF-β1, basic FGF, EGF, and PDGF-BB enhance HA production in skin fibroblasts,TGF-β1mostefficiently contributes to production of high molecular weight HA by HAS up-regulation and HYBID down-regulation and suggests that inefficient downregulation of HYBID by TGF-β1 in arthritic synovial fibroblasts may be linked to accumulation of depolymerized HA in synovial fluids in arthritis patients. [ABSTRACT FROM AUTHOR]