Summary
Background
Abnormal deposition of melanin may cause an aesthetic skin problem; therefore, the control of unwanted excessive melanin synthesis is the major goal of cosmetic research.
...Objectives
To identify novel tyrosinase (TYR) inhibitors from marine plants and examine their cellular antimelanogenic effects.
Methods
The extracts of 50 marine plants endemic to Korea were screened against human TYR. Active constituents were then isolated from the selected plant extracts that showed potential and their chemical structures elucidated. Furthermore, their antimelanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEM).
Results
Among the tested extracts, that of Phyllospadix iwatensis Makino exhibited the strongest human TYR inhibitory activity. The active constituents were purified from the butanol fraction of the P. iwatensis extract and identified as hispidulin 7‐sulfate and luteolin 7‐sulfate. Luteolin 7‐sulfate inhibited human TYR more strongly than hispidulin 7‐sulfate, luteolin, hispidulin and arbutin. Furthermore, luteolin 7‐sulfate showed lower cytotoxicity than luteolin in both B16/F10 cells and HEM. Luteolin 7‐sulfate attenuated cellular melanin synthesis more effectively in B16/F10 cells and HEM stimulated by α‐melanocyte‐stimulating hormone and l‐tyrosine than arbutin.
Conclusions
This study demonstrates that luteolin 7‐sulfate isolated from P. iwatensis is a human TYR inhibitor with advantageous antimelanogenic properties, and would be useful for development as a therapeutic agent for the control of unwanted skin pigmentation.
What's already known about this topic?
Previous efforts to develop antimelanogenic agents have investigated the activity of various plants against mushroom tyrosinase. However, this approach is not appropriate because of the inherent differences between mushroom and human tyrosinases.
What does this study add?
This study screened 50 marine plants for human tyrosinase inhibitory effects and found that Phyllospadix iwatensis extract and its constituent, luteolin 7‐sulfate, inhibited human tyrosinase activity and attenuated melanin synthesis in B16/F10 cells and human epidermal melanocytes.
What is the translational message?
Marine plants have attracted attention as under‐researched resources for bioactive compounds, and this study demonstrates that luteolin 7‐sulfate isolated from Phyllospadix iwatensis Makino, a kind of seagrass, is a more potent and safer inhibitor of cellular melanin synthesis than luteolin.
If these findings are confirmed by clinical studies, the flavonoid sulfate may be useful for the control of unwanted skin pigmentation due to excessive melanin synthesis.
Linked Comment: Khotimchenko. Br J Dermatol 2016; 175:457–458.
Structural growth, feed consumption, rumen development, metabolic response, and immune response were studied in Holstein calves fed milk through either a conventional method or a step-down (STEP) ...method. In the conventional method, calves (n = 20) were fed colostrum and then milk at a rate of 10% of their BW for the entire period of 44 d. In the STEP method, calves (n = 20) were given colostrum and then milk at a rate of 20% of their BW for 23 d, which was reduced (between d 24 to 28) to 10% of their BW for the remaining 16 d. The calves on both methods were weaned gradually by diluting milk with water between d 45 and 49. After weaning, feed consumption, structural growth, and body weight gain were monitored until calves were 63 d of age. At d 63, twelve calves (6/treatment) were euthanized and rumen papillae length, papillae width, rumen wall thickness, and emptied forestomach weight were recorded. At wk 4, 7, and 9, ruminal contents were collected to enumerate rumen metabolites. The STEP-fed calves consumed a greater amount of milk than conventionally fed calves during the pre-STEP (d 1 to 28), post-STEP (d 29 to 49), and preweaning (d 1 to 49) periods. Consumption of starter and hay was greater during the pre-STEP period and lesser during the post-STEP and postweaning (d 50 to 63) periods in calves on the conventional method than on the STEP method. Body weight gain and structural growth measurements of calves were greater on the STEP method than on the conventional method. A hypophagic condition caused by greater milk consumption depressed solid feed intake of STEP-fed calves during the pre-STEP period, and a hyperphagic response caused by a reduced nutrient supply from milk triggered their consumption of solid feed during the post-STEP and postweaning periods. Ruminal pH and concentrations of ammonia, total volatile fatty acids, acetate, propionate, butyrate, and plasma β-hydroxybutyrate were higher in calves on the STEP method and at weaning and postweaning (d 63) were lower in calves on the conventional method. Emptied weight of the forestomach, rumen wall thickness, papillae length, papillae width, and papillae concentration were higher in calves on the STEP method than in those on the conventional method. Blood glucose was lower, and blood urea nitrogen and β-hydroxybutyrate at weaning and postweaning were higher in STEP-fed calves. Serum IgG, IgA, and triglycerides for 1, 2, and 3 wk of age were higher in calves on the STEP method than in those on the conventional method. In conclusion, greater feed consumption, BW gain, and structural growth, and a more metabolically and physically developed rumen were observed in calves on the STEP method than in those on the conventional method.
Summary
Background Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated.
Objectives To evaluate ...the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥ 5% body surface area in children or measuring ≥ 20 cm in adults.
Methods In total, 131 patients with GCMN were enrolled, with a mean age of 10·3 years (range: birth–70 years).
Results The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients < 4 years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6‐year‐old girl, a 14‐year‐old girl and a 70‐year‐old man), and the incidence rate was 990 per 100 000 person‐years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma.
Conclusions We should be aware of melanoma development from GCMN, and lifelong follow‐up is required due to the risk of melanoma arising in GCMN.
Although laparoscopic donor hepatectomy is increasingly common, few centers with substantial experience have reported the results of pure laparoscopic donor right hepatectomy (PLDRH). Here, we report ...the experiences of 60 consecutive liver donors undergoing pure laparoscopic donor hepatectomy (PLDH), with most undergoing right hepatectomy. None of the 60 donors who underwent PLDH had intraoperative complications and none required transfusions, reoperation, or conversion to open hepatectomy. Forty‐five donors who underwent PLDRH between November 2015 and December 2016 were compared with 42 who underwent conventional donor right hepatectomy (CDRH) between May 2013 and February 2014. The total operation time was longer (330.7 vs 280.0 minutes; P < .001) and the percentage with multiple bile duct openings was higher (53.3% vs 26.2%; P = .010) in the PLDRH group. However, the length of postoperative hospital stay (8.4 vs 8.2 days; P = .495) and rate of complications (11.9% vs 8.9%; P = .733) and re‐hospitalizations (4.8% vs 4.4%; P = 1.000) were similar in both groups. PLDH, including PLDRH, is feasible when performed by a highly experienced surgeon and transplant team. Further evaluation, including long‐term results, may support these preliminary findings of comparative outcomes for donors undergoing PLDRH and CDRH.
Compared with the open approach, pure laparoscopic donor hepatectomy, primarily right hepatectomy, is a feasible procedure when performed by a highly experienced surgeon and transplantation team.
Summary Objective Cartilage regenerative procedures using the cell-based tissue engineering approach involving mesenchymal stem cells (MSCs) have been receiving increased interest because of their ...potential for altering the progression of osteoarthritis (OA) by repairing cartilage lesions. The aim of this study was to investigate the clinical and magnetic resonance imaging (MRI) outcomes of MSC implantation in OA knees and to determine the association between clinical and MRI outcomes. Design Twenty patients (24 knees) who underwent arthroscopic MSC implantation for cartilage lesions in their OA knees were evaluated at 2 years after surgery. Clinical outcomes were evaluated according to the International Knee Documentation Committee (IKDC) score and the Tegner activity scale, and cartilage repair was assessed according to the MRI Osteoarthritis Knee Score (MOAKS) and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Results The clinical outcomes significantly improved ( P < 0.001 for both). The cartilage lesion grades (as described in MOAKS grades for size of cartilage-loss area and percentage of full-thickness cartilage loss) at follow-up MRI were significantly better than the preoperative values ( P < 0.001 for both). The clinical outcomes at final follow-up were significantly correlated with the MOAKS and MOCART score at follow-up MRI ( P < 0.05 for all). Conclusions Considering the encouraging clinical and MRI outcomes obtained and the significant correlations noted between the clinical and MRI outcomes, MSC implantation seems to be useful for repairing cartilage lesions in OA knees. However, a larger sample size and long-term studies are needed to confirm our findings.
Summary
Background Blue and red light have been reported to have beneficial effects on acne. However, there has been no double‐blind, randomized study of acne treatment for combined blue and red ...light‐emitting diode (LED) devices, and the associated molecular mechanisms have rarely been investigated.
Objectives To evaluate the efficacy, safety and histological changes of combined blue and red LED phototherapy for acne vulgaris.
Methods Thirty‐five patients with mild‐to‐moderate acne were randomly assigned to either a home‐use irradiation group using an LED device, or a control group using a sham device. The treatment group was instructed to serially irradiate their forehead and cheeks with 420‐nm blue light and 660‐nm red light for 2·5 min twice daily for 4 weeks.
Results At the final visit at 12 weeks, both inflammatory and noninflammatory acne lesions had decreased significantly, by 77% and 54%, respectively, in the treatment group. No significant difference was observed in the control group. In the treatment group, sebum output reduction, attenuated inflammatory cell infiltrations and a decreased size of the sebaceous gland were found. The immunostaining intensities for interleukin (IL)‐8, IL‐1α, matrix metalloproteinase‐9, toll‐like receptor‐2, nuclear factor‐κB, insulin‐like growth factor‐1 receptor and sterol response element binding protein (SREBP)‐1 were reduced concomitantly. Messenger RNA expression of SREBP‐1c was also decreased. No severe adverse reactions were reported.
Conclusions This LED phototherapy was safe and effective for treating not only inflammatory but also noninflammatory acne lesions, with good compliance. The experimental results correlated well with clinical results, partly elucidating the related molecular mechanisms.
What’s already known about this topic?
•
Standard acne treatments have demonstrated modest efficacy, but they may cause various side‐effects and discomforts.
•
It has been reported that the beneficial effects of blue and red light on acne result from different, distinct mechanisms. However, there has been no double‐blind, randomized study for phototherapy with a combination of blue and red light‐emitting diodes (LEDs).
•
Previous clinical research has rarely elucidated the molecular interactions between visible light and active acne lesions.
What does this study add?
•
A 12‐week, double‐blind, randomized sham‐device‐controlled study demonstrated that home‐use combination phototherapy with blue and red LEDs was quite effective for safely treating not only inflammatory, but also noninflammatory acne lesions.
•
Sebum output and the average size of the sebaceous gland decreased, and the histopathological findings correlated well with clinical results, partly elucidating the associated molecular mechanisms.
•
This novel phototherapy appears to be safe and effective for the treatment of acne.
Human embryonic stem (hES) cells are pluripotent cell lines established from the explanted inner cell mass of human blastocysts. Despite their importance for human embryology and regenerative ...medicine, studies on hES cells, unlike those on mouse ES (mES) cells, have been hampered by difficulties in culture and by scant knowledge concerning the regulatory mechanism. Recent evidence from plants and animals indicates small RNAs of approximately 22 nucleotides (nt), collectively named microRNAs, play important roles in developmental regulation. Here we describe 36 miRNAs (from 32 stem-loops) identified by cDNA cloning in hES cells. Importantly, most of the newly cloned miRNAs are specifically expressed in hES cells and downregulated during development into embryoid bodies (EBs), while miRNAs previously reported from other human cell types are poorly expressed in hES cells. We further show that some of the ES-specific miRNA genes are highly related to each other, organized as clusters, and transcribed as polycistronic primary transcripts. These miRNA gene families have murine homologues that have similar genomic organizations and expression patterns, suggesting that they may operate key regulatory networks conserved in mammalian pluripotent stem cells. The newly identified hES-specific miRNAs may also serve as molecular markers for the early embryonic stage and for undifferentiated hES cells.
Abstract Aim The aim of this study was to evaluate the effects of adherence to National Comprehensive Cancer Network (NCCN) guidelines on survival outcomes in patients with early-stage epithelial ...ovarian cancer. Methods Our institutional cancer registry data on 266 patients with Stage I epithelial ovarian cancer was reviewed retrospectively and compliance with treatment guidelines for surgery and adjuvant treatment was determined. Patients were categorized according to adherence or non-adherence. The primary endpoints were recurrence-free survival and disease-specific survival. Hazard ratios (HRs) for survival were estimated with a Cox proportional hazards model. Results Of the 266 patients, 71 (26.7%) underwent adequate surgical staging in accordance with the guidelines. The guidelines for adjuvant chemotherapy were followed adequately in all 71 patients that were adherent to surgical staging and in 163 of the 195 patients with non-adherence to surgical staging (83.6%). Multivariate analysis, adjusted for prognostic factors, identified higher recurrence-free survival (HR, 0.36; 95% CI, 0.15–0.88) and disease-specific survival (HR, 0.42; 95% CI, 0.16–1.12) among patients whose treatment adhered to both surgical and chemotherapy guidelines, although disease-specific survival was not statistically significant. When excluding clear cell histology from the cohort, the guideline-adherent group had significantly better disease-specific survival than the non-adherent group (HR, 0.13; 95% CI, 0.02–0.94). Conclusion The results of this study suggest that adherence to NCCN guidelines may improve survival outcomes in patients with early-stage epithelial ovarian cancer, particularly in cases other than clear cell histology.
The effect of single or repeated restraint stress on several signal molecules in the hypothalamus was studied in ICR mice. Single restraint stress was induced for 30, 60, and 120 min. A repeated ...restraint stress was induced for 2 h daily during four consecutive days, and then induced in the same time course on the fifth day. In the immunoblot assay, we observed that the signal molecules c-Fos, phosphorylated extracellular cell-regulated protein kinase (pERK), phosphorylated calcium/calmodulin dependent protein kinase II (pCaMKII) and phosphorylated cyclic-AMP response element binding protein (pCREB) in the hypothalamus were increased by single restraint, and the increased c-Fos and pERK levels were attenuated by repeated restraint stress. However, pCaMKII and pCREB levels were increased by both single and repeated restraint stress. We also observed in the immunohistochemistry study that immunoreactivities (IR) of these signal molecules were changed in paraventricular (PVN) and arcuate nuclei (ArcN) of the hypothalamus in accordance with immunoblot results. Furthermore, in confocal immunofluorescence, the pCaMKII and pCREB up-regulated by repeated restraint stress were co-localized within many neurons of PVN and ArcN. In addition, we found that c-Fos and pCaMKII IR in locus coeruleus (LC) were increased by single restraint, and were attenuated by repeated restraint stress. However, the pERK and pCREB IR were increased by both single and repeated restraint stress. The confocal study revealed that pERK and pCREB up-regulated by repeated restraint stress were co-localized within many neurons of LC. Our results suggest that single and repeated restraint stress differentially triggers the induction and phosphorylation of several signal molecules in the PVN, ArcN, and LC. In addition, single and repeated stress stimuli elicited the brain-region specific changes of signal molecules examined. Furthermore, the upstream signal molecule activating CREB may be also brain-region specific, especially in repeated stress stimuli.
Highlights ► We examined the mechanism of mitochondrial swelling and axonal degeneration. ► Energy failure occurred prior to mitochondrial swelling and axonal degeneration. ► Energy repletion ...prevented mitochondrial swelling and microtubule depolymerization. ► Perturbing microtubule dynamics enhanced axonal degeneration and mitochondrial swelling. ► Calcium was not related to mitochondrial swelling and microtubule depolymerization.
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