Increased iron uptake by splenic hematopoietic stem cells promotes TET2-dependent erythroid regeneration.

Hematopoietic stem cells (HSCs) are capable of regenerating the blood system, but the instructive cues that direct HSCs to regenerate particular lineages lost to the injury remain elusive. Here, we show that iron is increasingly taken up by HSCs during anemia and induces erythroid gene expression and regeneration in a Tet2-dependent manner. Lineage tracing of HSCs reveals that HSCs respond to hemolytic anemia by increasing erythroid output. The number of HSCs in the spleen, but not bone marrow, increases upon anemia and these HSCs exhibit enhanced proliferation, erythroid differentiation, iron uptake, and TET2 protein expression. Increased iron in HSCs promotes DNA demethylation and expression of erythroid genes. Suppressing iron uptake or TET2 expression impairs erythroid genes expression and erythroid differentiation of HSCs; iron supplementation, however, augments these processes. These results establish that the physiological level of iron taken up by HSCs has an instructive role in promoting erythroid-biased differentiation of HSCs.

310 nm UV-LEDs attenuate imiquimod-induced psoriasis-like skin lesions in C57BL/6 mice and inhibit IL-22-induced STAT3 expression in HaCaT cells.

Ultraviolet light-emitting diodes (UV-LEDs) are a novel light source for phototherapy. This study aimed to evaluate the therapeutic effects of UV-LEDs on psoriasis. Importantly, 310 nm UV-LEDs have not been studied in psoriasis in vitro and in vivo. Effects due to 310 nm UV-LED and 311 nm narrowband ultraviolet B (NBUVB) irradiation were compared for suppressing IL-22-induced activation of STAT3 expression using cell viability assay, western blotting, and immunocytochemistry. C57BL/6 mice were topically treated with imiquimod (IMQ) for 6 consecutive days and degenerative changes were observed. Test groups were irradiated with a 310 nm UV-LED and 311 nm NBUVB. Phenotypic observations, histopathological examinations, and ELISA were conducted with skin and blood samples. STAT3-dependent IL-22 signalling and effects in keratinocytes are negatively regulated by the 310 nm UV-LED, which significantly ameliorated IMQ-induced psoriasis-like dermatitis development and reduced Th17 cytokine levels (IL-17A, IL-22) in serum and dorsal skin. Histopathological findings showed decreases in epidermal thickness and inflammatory T-cell infiltration in the UV-LED-irradiated groups. Quantitative PCR confirmed a UV radiation energy-dependent decrease in IL-17A and IL-22 mRNA levels. The results demonstrated that UV-LEDs had anti-inflammatory and immunoregulatory effects. So, UV-LED phototherapy inhibits psoriasis development by suppressing STAT3 protein and inflammatory cytokines and could be useful in treating psoriasis.

Prospective, preclinical comparison of the performance between radiofrequency microneedling and microneedling alone in reversing photoaged skin.

BACKGROUND: There is a tremendous demand for dermal rejuvenation with minimal invasiveness and patient downtime. AIMS: In this study, we evaluated the performance of nonfractional monopolar radiofrequency for the improvement of photoaged skin texture and wrinkles. METHODS: In total, 32 6-week-old female hairless mice were randomized into four groups of eight mice each: (a) healthy control, (b) UVB-exposed, (c) UVB + microneedling, and (d) UVB + microneedle RF. After applying each treatment modality, skin surface was globally investigated and histologically evaluated senile skin change. Immunohistochemistry was tested with the primary antibody to collagen type I and III. RESULTS: After UVB exposure, the Ra value was significantly increased, leading to clinical development of wrinkles with xerotic scales. Depth and number of wrinkles showed gradual improvement in RF-treated mice. The mean Ra value of the RF-treated group decreased significantly. The RF-treated group showed decreased epidermal thickness, suppression of dermal inflammatory cell infiltration, and increased density of collagen fibers and amount of elastic fibers. CONCLUSIONS: Microneedle RF treatment alleviates photoaged skin texture and wrinkles in this mouse model. To the best of our knowledge, our results provide the first evidence that a nonfractional monopolar microneedle radiofrequency device may contribute to the treatment of UV-damaged skin.

Boehmite enhances hair follicle growth via stimulation of dermal papilla cells by upregulating ß-catenin signalling.

Hair growth, a complex process, has long been the subject of intense research. Recent developments in material technology have revealed boehmite as a new therapeutic modality for use in wound healing and scar reduction, indicating its beneficial effects. Nonetheless, the biological bases of the beneficial effects of boehmite remain unknown. We investigated the hair growth properties of boehmite in vitro and in vivo and observed dose-dependent proliferation of human dermal papilla cells (hDPCs) in vitro and hair regrowth in a mouse model. To investigate the effects of boehmite on the promotion of cell transition to the anagen phase, we evaluated hDPC viability, alkaline phosphatase (ALP) activity, protein expression and vascular endothelial growth factor (VEGF) secretion in vitro and assessed the anagen-promoting effects of boehmite via gross observation and histological analysis in a mouse model. Boehmite increased hDPC viability, ALP activity, AKT/GSK3ß/ß-catenin pathway activity, anagen-related gene expression and VEGF secretion; moreover, it accelerated hair regrowth in a catagen-anagen transition model via upregulation of ß-catenin signalling and follicular cell proliferation. Collectively, our results indicate that boehmite accelerates hair growth, partly via its effects on critical events in the active phase of the hair follicle cycle, including the promotion of the proliferation of hDPCs and their immediate progeny to the follicle base.

Cangfu daotan decoction for polycystic ovary syndrome: A protocol of systematic review and meta-analysis.

BACKGROUNDS: Polycystic ovary syndrome (PCOS) is common endocrine disorder in women and can lead to serious social burdens associated with various reproductive and metabolic abnormalities. Existing therapy is controversial in its effectiveness including side effects. In traditional Korean Medicine, Cangfu Daotan Decoction (CDD), also known as Changbudodam-tang, is used for PCOS patients who are in the type of stagnation of phlegm and dampness. In this study, we aimed to evaluate the efficacy and safety of CDD for PCOS as alternative treatment. METHODS: Two researchers will search the following databases from their inception to February 2019 for relevant randomized controlled trials (RCTs): The Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure Database (CNKI), and 5 Korean medical databases (Korean Studies Information Service System, KoreaMed, DBPIA, Oriental Medicine Advanced Searching Integrated System, and Research Information Service System). The primary outcome will be the scales that assessed drug efficacy including total response rate, sex hormone level (LH, FSH, Testosterone, LH/FSH ratio), BMI, ovulation rate, and pregnancy rate. Adverse events will be assessed as the secondary outcome. Study selection, data extraction, and assessment of risk of bias will be conducted by 2 researchers independently. Statistical analysis will be performed by using the Cochrane Review Manager (RevMan 5.3) software. RESULTS AND CONCLUSION: This review will provide the latest knowledge and evidence on the efficacy and safety of CDD for PCOS women through the analysis of various evaluation scales. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval and will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019134270.

Biostimulatory effects of polydioxanone, poly-d, l lactic acid, and polycaprolactone fillers in mouse model.

BACKGROUND: Numerous fillers are increasingly used for augmentation of volume loss and relaxation of facial wrinkles. Collagen stimulators are the latest next-generation dermal fillers that can induce neocollagenesis. To investigate biophysical characteristics, safety, and efficacy of newly developed polydioxanone (PDO) filler in comparison with poly-l lactic acid (PLLA) and polycaprolactone (PCL) fillers. METHODS: In vitro assay, morphology of particles, and rheological property of fillers were measured. A total of 24 female hairless mice (SKH1-Hrhr ) were randomly divided into three groups and injected with PDO, PLLA, or PCL fillers. Durability of fillers was assessed at 0, 3 days, and 1, 4, 8, 12 weeks after injection using folliscope and PRIMOS. To determine biocompatibility and neocollagenesis, histologic evaluation was performed at 1, 4, 8, and 12 weeks after injection. Efficacy was also evaluated based on skin surface roughness changes using PRIMOS in a hairless mouse photoaging model. RESULTS: In the particle morphology test, PDO microspheres had an irregular surface and were spherical and uniformly sized. PDO filler demonstrated similar neocollagenesis and inflammatory response to other collagen stimulators. PDO filler showed better biodegradability than PLLA and PCL fillers. In the hairless mouse photoaging model, there was a statistically significant decrease in skin surface roughness after PDO filler injection. CONCLUSIONS: Our data suggest that newly developed collagen stimulating PDO filler might be a safe and effective option for correction of volume loss and rejuvenation of photoaging skin.

Effects of Intradermal Radiofrequency Treatment and Intense Pulsed Light Therapy in an Acne-induced Rabbit Ear Model.

Acne vulgaris is a common condition that can have psychologically deleterious effects. Since current treatments carry the risks of antibiotic resistance or teratogenicity, novel treatment modalities are under investigation. Our study investigated the efficacy of intradermal radiofrequency treatment (RF) and intense pulsed light (IPL) in the treatment of acne vulgaris in a rabbit ear model. We evaluated the effectiveness of IPL, RF, and a combination treatment on cultured Cuticobacterium acnes strains in an induced rabbit ear model, according to clinical outcomes as well as histological and immunological approaches. We found that RF treatment markedly decreases papule volume, while IPL appears to have an immunomodulatory effect. In combination, the two have an additive effect in treatment. These findings suggest that combination of RF and IPL may be an effective therapeutic option for the treatment of acne vulgaris.

Effects on skin of Stichopus japonicus viscera extracts detected with saponin including Holothurin A: Down-regulation of melanin synthesis and up-regulation of neocollagenesis mediated by ERK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Stichopus japonicus (sea cucumber), edible traditional food in Asia, and its extracts are renowned for their wound healing, pain relieving, and cosmetic effects in traditional medicine. Holothurins, toxins isolated from sea cucumber, are thought to be active components for their beneficial effects. However, researchers have yet to outline specific mechanisms thereof. AIM OF THE STUDY: The present study was designed to evaluate the anti-melanogenic and anti-wrinkle properties of S. japonicus viscera extracts (VF) on the skin via in vitro and ex vivo experiments and to assess the anti-aging effects of S. japonicus viscera extracts in relation to known wound healing and cosmetic processes. MATERIALS AND METHODS: The viscera of live S. japonicus specimens were freeze dried and ground into a powder. Aqueous extracts were subsequently prepared from the concentrated powder using a water extraction method. To investigate the inhibitory effects of VF on melanogenesis, mushroom tyrosinase activity assay and melanin assay were performed on Melan-A cells. To further delineate the anti-melanogenic properties of VF, western blot analysis for tyrosinase, TRP-1, TRP-2, MITF, and ERK was conducted. Changes in collagen synthesis in human dermal fibroblast (HDF) were evaluated via CCK-8 assay and immunocytochemistry to determine the anti-wrinkle effects of VF. Finally, anti-aging properties were examined in a human skin equivalent ex vivo model. RESULTS: In Melan-A cells, VF treatment reduced melanin contents in a concentration-dependent manner. The anti-melanogenic effects of VF appeared to be due to enzymatic inhibition of tyrosinase. In CCK-8 assay, VF also significantly increased the viability of HDFs in a concentration-dependent manner. Immunoblot analysis revealed phosphorylation of ERK in HDFs treated with VF. In a human skin equivalent ex vivo model (Neoderm®-ED), VF treatment at a concentration of 50 µg/ml enhanced collagen type IV and Ki-67 expression and downregulated MMP-9 expression. CONCLUSION: This study demonstrated that aqueous extracts from S. japonicus viscera are effective whitening and anti-aging agents that stimulate ERK signaling to inhibit melanin synthesis and promote collagen synthesis.

The complete chloroplast genome of the medicinal plant Angelica decursiva (Apiaceae) in Peucedani Radix.

Angelica decursiva (Miquel) Franchet & Savatier (Apiaceae) has been used as a significant medicinal plant in East Asia. We determined its complete chloroplast genome for the first time in this study. The complete chloroplast was circularized and had a typical quadripartite structure genome of 146 719 bp long including the large single copy region (LSC) of 93 256 bp, the small single copy region (SSC) of 17 497 bp and duplicated inverted regions (IRs) of 17 983 bp each. The total GC content was 37.56% and for the four structures it was 35.98% (LSC), 31.06% (SSC), and 44.83% (for each IR). There were a total of 113 genes, comprising four rRNAs, 29 tRNAs and 80 protein coding genes. In the phylogenetic analysis, A. decursiva was grouped with Seseli montanum. This study may contribute to authenticating the plant's correct use as medicine for health and provide an important genetic resource for phylogeny with related species.

The complete chloroplast genome sequence of Ostericum koreanum (Apiaceae).

Ostericum koreanum Kitagawa is an important herbal medicine, whose taxonomic status has been changed to Angelica reflexa as a new species. This study generated the complete chloroplast genome sequence of O. koreanum, and reconsidered its molecular taxonomic status in Angelica by comparing it with related species. The length of the complete chloroplast genome was 147,282 bp, and there were four structures that included the large single copy region (93,185 bp), the small single copy region (17,663 bp) and the duplicated inverted regions (18,217 bp of each). Based on its phylogenetic trees, O. koreanum was grouped by high bootstrap value with the Angelica species. This result proved that O. koreanum is included in Angelica. Therefore, this chloroplast genome data generated for the first time a valuable genetic resource for the discrimination of herbal materials, phylogeny, and evolution.

The complete chloroplast genome sequence of the medicinal plant, Angelica gigas (Apiaceae).

The complete chloroplast genome sequence of Angelica gigas, a traditional herbal plant used in treating diseases, was obtained by de novo assembly using illumina sequencing data (Illumina Inc., San Diego, CA). The circular molecule of the genome was constructed of four parts, with a size of 146,916 bp in total - a large single copy (LSC) region of 93,118 bp, a small single copy (SSC) region of 17,582 bp and two inverted repeat (IRa and IRb) regions of 18,108 bp each. There were a total of 113 annotated genes, including 80 protein-coding genes, 29 tRNA genes and four rRNA genes. The phylogenetic result acquired through maximum parsimony analysis showed that A. gigas is closely related with A. decursiva and Seseli montanum.

Design and Application of Rolling Circle Amplification for a Tumor-Specific Drug Carrier.

It is challenging to design rolling circle amplification (RCA) for tumor-selective delivery of drugs. Here, we devise a doxorubicin nanocarrier composed of RCA products, cholesterol-DNA, and folate-DNA conjugates. RCA products, designed to contain tandem repeats of short hairpin DNA, employ the repeated sequences complementary to both DNA conjugates, and thus RCA products/cholesterol-DNA/folate-DNA complexes, generated via sequential base pairing processes, acquire the amphiphilic properties that facilitate self-assembly into the highly condensed nanoparticles (RCA nanoparticles). Doxorubicin-loaded RCA nanoparticles, especially with high cargo capacity, release drugs to the environment with the aid of acidity and show selective cytotoxicity to cancer cells. Particularly, the condensed structures enable RCA nanoparticles to be resistant to nucleases in the blood. These results show that RCA nanoparticles have great potential as a doxorubicin carrier for targeted cancer therapy, and furthermore, our strategy provides an alternative tool to exploit RCA techniques on drug delivery systems.

Quantitative analysis of marker compounds in Angelica gigas, Angelica sinensis, and Angelica acutiloba by HPLC/DAD.

Although Danggui is the root of Angelica gigas NAKAI in the Korean Pharmacopoeia, it is determined that Danggui is also the root of Angelica sinensis (OLIV.) DIELS in China and Hong Kong, as well as the root of Angelica acutiloba KITAGAWA in Japan. Accordingly, we tried to develop an identification method using the main compounds in A. gigas, A. sinensis, and A. acutiloba through HPLC/diode-array detector (DAD). This method was fully validated for linearity, accuracy, precision, recovery, and robustness. Multivariate analysis was also implemented after pattern analysis and monitoring. As a result, each compound pattern of A. gigas, A. sinensis, and A. acutiloba was identified, making it possible to distinguish them from each other.

Cytotoxicity and anti-inflammatory effects of root bark extracts of Acanthopanax henryi.

AIM: To investigate the cytotoxicity, anti-inflammatory activity, and action mechanism of root bark extracts of Acanthopanax henryi. METHOD: The hot methanol extract of the root bark of A. henryi was subjected to XAD-4 column chromatography eluting with a gradient of methanol in water. The cytotoxicity and anti-inflammatory effects of the MeOH fractions were evaluated on the inhibition on lipopolysaccharide (LPS)-induced nitric oxide, prostaglandin E2, interleukin-1ß, and interleukin-6 production in RAW 264.7 macrophages. RESULTS: The 80% MeOH fraction was a better inhibitor of LPS-induced NO, PGE2, IL-1ß, and IL-6 production, and expression of inducible nitric oxide synthase (iNOS) at the protein levels in a concentration-dependent manner. CONCLUSION: The 80% MeOH fraction of A. henryi root bark has significant anti-inflammatory activity. This provides a pharmacological basis for clinical application for the treatment of inflammation.

Youngia denticulata protects against oxidative damage induced by tert-butylhydroperoxide in HepG2 cells.

Improvement of liver function is one of the most popular commercial health claims of functional foods in Asian countries, including Korea. After examining the potential of several traditional Korean wild vegetables for enhancing liver function, we found that Youngia denticulata Kitam. has strong hepatoprotective effects against oxidative stress induced by tert-butylhydroperoxide (t-BHP). We are the first to report that the extract and ethyl acetate fractions of Y. denticulata have radical scavenging activities and inhibit oxidative stress-induced cell death and DNA damage in HepG2 cells. The extract and ethyl acetate fractions significantly decreased cellular reactive oxygen species production and apoptosis induced by t-BHP in HepG2 cells. In addition, they prevented the depletion of cellular glutathione, which is an important defense molecule against oxidizing xenobiotics. Chlorogenic acid and 3,5-dicaffeoylquinic acid were found to be major active components responsible for the activity of Y. denticulata and could serve as marker compounds for standardization. These data suggest that Y. denticulata could be promoted as a potential antioxidative functional food candidate, particularly for hepatoprotection against oxidative stress.

Apoptosis induction of human lung carcinoma cells by Chan Su (Venenum Bufonis) through activation of caspases.

Chan Su is a traditional Chinese medicine prepared from the dried white secretion of the auricular and skin glands of toads, and has been used as an oriental drug for the treatment of a number of diseases, including cancer. In this study, the potential of Chan Su (skin of Venenum Bufonis) to induce apoptosis in human lung carcinoma A549 cells was investigated. Treatment of A549 cells with skin of Venenum Bufonis resulted in the inhibition of cell growth and viability and the induction of apoptosis, which was shown by trypan blue counts, MTT assay, DAPI staining and flow cytometry analysis. The increase in apoptosis that was induced by skin of Venenum Bufonis was correlated with down-regulation of anti-apoptotic Bcl-2 expression, up-regulation of pro-apoptotic Fas ligand and death receptor 4, and a decrease in the mitochondrial membrane potential. Skin of Venenum Bufonis treatment induced the proteolytic activation of caspases and a concomitant degradation of poly(ADP-ribose)-polymerase and beta-catenin protein. Cleavage of Bid and a down-regulation of the inhibitor of apoptosis family proteins were also observed in skin of Venenum Bufonis-treated A549 cells. Data from this study indicates that SVB induces the apoptosis of A549 cells through a signaling cascade of death receptor-mediated extrinsic and mitochondria-mediated intrinsic caspase pathways.

Regulation and quality control of herbal drugs in Korea.

Korea has a great diversity in resources of medicinal plants. The traditional herbal medicines and their preparations have been widely used in Korea as well as in China and Japan for thousands of years. One of the characteristics of Korean herbal medicine preparations is that all the herbal medicines are incorporated into an extractor at the same time and extracted with boiling water during the decoction process. In this process, a variety of interactions between the active components of several herbal medicines may occur. This is the main reason why quality control of oriental herbal drug is more difficult than that of western herbal drug. In this paper, we would like to present an overview of the characteristics of regulation and quality control of herbal medicines in Korea.