miR-1246-overexpressing exosomes improve UVB-induced photoaging by activating autophagy via suppressing GSK3ß.

Stem cell paracrine has shown potential application in skin wound repair and photoaging treatment. Our previous study demonstrated that miR-1246-overexpressing Exosomes (OE-EXs) isolated from adipose-derived stem cells (ADSCs) showed superior photo-protecting effects on UVB-induced photoaging than that of the vector, however, the underlying mechanism was unclear. The simultaneous bioinformatics analysis indicated that miR-1246 showed potential binding sites with GSK3ß which acted as a negative regulator for autophagy. This study was aimed to explore whether OE-EXs ameliorate skin photoaging by activating autophagy via targeting GSK3ß. The results demonstrated that OE-EXs significantly decreased GSK3ß expression, enhanced autophagy flux and autophagy-related proteins like LC3II, while suppressed p62 expression. Meanwhile, OE-EXs markedly reversed the levels of intracellular ROS, MMP-1, procollagen type I and DNA damage in human skin fibroblasts caused by UVB irradiation, but the ameliorating effects were significantly inhibited when 3-Methyladenine (3-MA) was introduced to block the autophagy pathway. Further, OE-EXs could reverse UVB-induced wrinkles, epidermal hyperplasia, and collagen fibers reduction in Kunming mice, nevertheless, the therapeutical effects of OE-EXs were attenuated when it was combinative treated with 3-MA. In conclusion, OE-EXs could cure UVB induced skin photoaging by activating autophagy via targeting GSK3ß.

Protective effect of Salvia plebeia R. Br ethanol extract on UVB-induced skin photoaging in vitro and in vivo.

BACKGROUND: UV exposure is one of the primary factors responsible for photoaging, causing the increase in matrix metalloproteinases (MMPs) and the reduction in collagen. Salvia plebeia R. Br (SP), as an herbaceous plant, contains abundant flavonoids and possesses excellent anti-inflammatory and antioxidant activities. This study aimed to investigate the photoprotective effects of SP on UVB-induced photodamage in immortalized human keratinocytes (HaCaTs) and Kunming mice, as well as its main active components such as homoplantaginin (HP). METHODS: CCK-8 was applied to detect the cell viability in UVB-irradiated or non-irradiated HaCaTs. Commercial kits were used to evaluate the levels of ROS, MDA, SA-ß-Gal, MMP-1, and IL-6. The expression of MAPK and TGF-ß/Smad pathways was detected by western blot. HE and Masson's trichrome staining were performed to examine the epidermis thickness and collagen degradation of Kunming mice. RESULTS: Our results found that SP and HP notably decreased UVB-induced ROS, MDA, and SA-ß-Gal production, and inhibited MMP-1 and IL-6 secretion by inhibiting the MAPK signaling pathway. In addition, SP and HP significantly promoted type I procollagen synthesis by activation of TGF-ß/Smad pathway. Consistently, the in vivo experiments also indicated that SP and HP had a photoprotective effect, which significantly reversed UVB-induced epidermis thickness and collagen degradation. CONCLUSION: This study demonstrated that SP effectively could protect skin from UVB-induced photoaging, while HP acted as the active substance in SP. All these findings provided a new strategy for skin photoaging treatment.

Long Non-coding RNA H19-Overexpressing Exosomes Ameliorate UVB-Induced Photoaging by Upregulating SIRT1 Via Sponging miR-138.

UVB-induced photoaging is characterized by wrinkle formation, slackness and senile plaques, affecting the health and beauty of human being. Our previous study revealed that exosomes derived from adipose-derived stem cells (ADSCs) could efficiently alleviate UVB-induced photodamage. However, the functional ingredients in exosomes were undefined. LncRNA H19, one of the well-researched lncRNAs in exosomes, exhibits multiple physiological effects. This study aims to demonstrate the photo-protective role of lncRNA H19 on skin photoaging in UVB-irradiated human skin fibroblasts cells (HSFs) and Kunming mice. LncRNA H19-overexpressing exosomes (H19-Exo) were isolated from the supernatant of ADSCs infected with lncRNA H19-loaded lentivirus. The results showed that H19-Exo significantly inhibited MMPs production, DNA damage and ROS generation while enhancing procollagen type I synthesis in UVB-irradiated HSFs. Meanwhile, H19-Exo markedly reversed epidermal thickening and collagen degradation in UVB-irradiated mice. Furthermore, luciferase reporter assays indicated that lncRNA H19 acted as a sponge for miR-138 expression, and SIRT1 was targeted by miR-138. Evidence from both in vitro and in vivo studies also revealed that H19-Exo could enhance SIRT1 expression by knocking down miR-138. In conclusion, lncRNA H19 served as a therapeutic candidate in treating UVB-induced skin photoaging by upregulation of SIRT1 via miR-138.

miR-221/222 Promote Endothelial Differentiation of Adipose-Derived Stem Cells by Regulation of PTEN/PI3K/AKT/mTOR Pathway.

Adipose-derived stem cells (ADSCs) are a type of adult mesenchymal stem cell that show a repair effect on ischemic tissues owing to their capacity for endothelial differentiation. MicroRNA-221/222 (miR-221/222) has been extensively studied in endothelial cells (ECs). However, the mechanism that regulates ADSCs differentiation into ECs remains unknown. In this study, we investigated the effects of miR-221/222-overexpression/silence in ADSCs on endothelial differentiation by constructing lentiviral vectors. Differentiation capacity was assessed by measuring the expression of endothelial markers (CD31, CD34, and CD144). In addition, low-density lipoprotein (LDL) uptake and tube-like formation were performed for evaluation of functional characterization. The PTEN/PI3K/AKT/mTOR signaling pathway was investigated using western blotting to clarify the action mechanism of this gene. The revascularization of miR-221/222-transfeted ADSCs was further verified in a rat hind limb ischemia model. The results confirmed that transfection with miR-221/222 promoted the expression of endothelial markers, LDL uptake, and tube-like formation. As expected, the PI3K/AKT signaling pathway was effectively activated when ADSCs showed high expression of miR-221/222 during endothelial differentiation. Furthermore, injection of miR-221/222 transfected ADSCs significantly improved rat hindlimb ischemia, as evidenced by increased blood flow and structural integrity and reduce inflammatory infiltration. The results of this study suggest that miR-221/222 is essential for endothelial differentiation of ADSCs and provides a novel strategy for modulating vascular formation and ischemic tissue regeneration.

miR-1246-overexpressing exosomes suppress UVB-induced photoaging via regulation of TGF-ß/Smad and attenuation of MAPK/AP-1 pathway.

Stem cell therapy is widely employed for the treatment of skin diseases, especially in skin rejuvenation. Exosomes derived from stem cells have been demonstrated to possess anti-photoaging effects; however, the precise components within exosomes that are responsible for this effect remain unknown. Previously, miR-1246 was found to be one of the most abundant nucleic acids in adipose-derived stem cells (ADSCs)-derived exosomes. This study examined whether miR-1246 was the major therapeutic agent employed by ADSCs to protect against UVB-induced photoaging. Lentivirus infection was used to obtain miR-1246-overexpressing ADSCs and exosomes. We then determined the anti-photoaging effects of miR-1246-overexpressing exosomes (OE-EX) on both UVB-irradiated human skin fibroblasts (HSFs) and Kunming mice. The results showed that OE-EX could significantly decrease MMP-1 by inhibiting the MAPK/AP-1 signaling pathway. Meanwhile, OE-EX markedly increased procollagen type I secretion by activating the TGF-ß/Smad pathway. OE-EX also exhibited an anti-inflammatory effect by preventing the UVB-induced degradation of IκB-α and NF-κB overexpression. Animal experiments demonstrated that OE-EX could reduce UVB-induced wrinkle formation, epidermis thickening, and the loss of collagen fibers reduction in Kunming mice. The combined results suggested that miR-1246 is the key component within ADSCs-derived exosomes that protects against UVB-induced skin photoaging.

Identification of Chinese green tea (Camellia sinensis) marker metabolites using GC/MS and UPLC-QTOF/MS.

Tea is one of the most widely consumed aromatic beverages in the world because of its taste and flavor, as well as due to many potential health beneficial properties. Metabolomics focuses on an in-depth analysis of all metabolites in living organisms. In this study, 29 primary metabolites and 25 secondary metabolites were identified using GC/MS and UPLC-QTOF/MS, respectively. Further, PCA analysis showed conspicuous discrimination for the ten varieties of green tea with metabolite profiling. Among them, organic acids, amino acids, flavan-3-ols, and flavonol glycosides varied greatly through checking the VIP values of the PLS-DA model. Moreover, the intrinsic and/or extrinsic factors characterizing each type of green tea were also discussed. The chemical component marker derived here should be used as an important detection index, while evaluating the tea quality, as well as while establishing the tea quality standard. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00970-4.

Effects of phenylethanol glycosides from Orobanche cernua Loefling on UVB-Induced skin photodamage: a comparative study.

Previous study has found that Orobanche cernua Loefling(OC) and its main ingredient, acteoside, possess excellently anti-photo-aging effect. In addition to acteoside, crenatoside, isoacteoside and 2'-acetylacteoside were also identified as the main phenylethanol glycosides (PhGs) in OC. To screen optimum effective substance and further clarify the photoprotective ingredients of OC, the effects of four major PhGs in OC were compared using UVB-irradiated HaCaT cells. Results indicated that acteoside, isoacteoside and 2'-acetylacteoside effectively decreased UVB-induced MMP-1 expression and stimulated type I procollagen synthesis through inhibition of MAPK/AP-1 and activation of TGF-ß/Smad pathway. Moreover, acteoside and 2'-acetylacteoside significantly reduced UVB-induced ROS and TARC secretion, which is involved in the inhibition of NF-κß/Iκßα and stimulation of Nrf2 antioxidant defense system. However, crenatoside did not show any effect on the regulation of signal cascades mentioned above. Together, our results suggested that 2'-acetylacteoside and isoacteoside also served as efficient agents against UV radiation-induced skin damage. Among them, acteoside and 2'-acetylacteoside showed a higher efficiency than that of isoacteoside, which possessed great potential in treating skin photo-damage.

Combination and efficiency: preparation of dissolving microneedles array loaded with two active ingredients and its anti-pigmentation effects on guinea pigs.

Hyperpigmentation is a common skin disorder caused by excessive melanogenesis and uneven dispersion of melanin in the skin. To combine multiple active agents with an efficient transdermal drug delivery system is an effective strategy to combat UV induced skin pigmentation. In this work, Arbutin (Arb) and Vitamin C (Vc) mixed in 1:1 were found to have the greatest inhibition effects on melanogenesis and tyrosinase activity in B16 murine melanoma cells. And hyaluronic acid (HA) based dissolving microneedles array (DMNA) was employed to overcome the skin barriers for improved topical drug delivery, which exhibited the most desirable features, including morphology, mechanical properties, dissolving ability, and the highest drug loading. Furthermore, DMNA could greatly increase the stability of Vc during storage without adding any antioxidant which is an important issue for Vc administration. Pharmacodynamics study showed that DMNA loaded with Arb and Vc could synergistically suppress UVB-induced hyperpigmentation in guinea pig skin. This work provides a promising treatment strategy and solution for skin pigmentation and other skin problems.

Correction: Icariin and icaritin recover UVB-induced photoaging by stimulating Nrf2/ARE and reducing AP-1 and NF-κB signaling pathways: a comparative study on UVB-irradiated human keratinocytes.

Correction for 'Icariin and icaritin recover UVB-induced photoaging by stimulating Nrf2/ARE and reducing AP-1 and NF-κB signaling pathways: a comparative study on UVB-irradiated human keratinocytes' by Eunson Hwang et al., Photochem. Photobiol. Sci., 2018, 17, 1396-1408.

Icariin and icaritin recover UVB-induced photoaging by stimulating Nrf2/ARE and reducing AP-1 and NF-κB signaling pathways: a comparative study on UVB-irradiated human keratinocytes.

Icariin (ICA) and icaritin (ICT) exhibit many pharmacological functions including anti-osteoporosis, anti-cardiovascular, and anti-cancer activities; however, there are few comprehensive studies that track the detailed effects on UVB-induced photoaging. The recovery effects of ICA and ICT were investigated in UVB-irradiated human keratinocytes (HaCaTs). The results indicated that ICT and ICA showed strong radical scavenging activity, and the reactive oxygen species (ROS) scavenging activity of ICT was superior. UVB-induced matrix metalloproteinase-1 (MMP-1) expression was blocked by ICA via the inhibition of mitogen-activated protein kinase/activator protein 1 (MAPK/AP-1), which directly reduced extracellular matrix (ECM) degradation. ICT activated nuclear factor erythroid 2 related factor 2 (Nrf2) to improve the anti-oxidative stress capacity and suppress nuclear factor-κB (NF-κB) activation, decreasing vascular endothelial growth factor (VEGF) protein, and inflammatory cytokines induced ECM degrading enzyme secretion. Moreover, ICT was more advantageous to improve transforming growth factor beta 1 (TGF-ß1) and procollagen type I expression than ICA, promoting the synthesis of collagen. Therefore, ICA and ICT have potential to treat UVB-induced oxidative stress, inflammation and photoaging, and will be posited as a novel strategy to alleviate photodamage.

Rubus idaeus L. (red raspberry) blocks UVB-induced MMP production and promotes type I procollagen synthesis via inhibition of MAPK/AP-1, NF-κß and stimulation of TGF-ß/Smad, Nrf2 in normal human dermal fibroblasts.

Chronic exposure to ultraviolet (UV) radiation causes photo-oxidation, which in turn results in the upregulation of matrix metalloproteinases (MMPs) and loss of collagen. Rubus idaeus L. (RI), also called red raspberry, is an important cash crop that contains abundant antioxidant compounds. Sanguiin H-6 and lambertianin C are the major ingredients presented in the extracts. Here, we studied the protective effect of RI on UVB-induced photoaging in normal human dermal fibroblasts (NHDFs). We found that RI notably reduced UVB-induced MMPs secretion and pro-inflammatory mediators production, and significantly suppressed UVB-induced activation of mitogen-activated protein kinase (MAPK), nuclear factor-κß, as well as activator protein 1. Additionally, treatment of NHDFs with the ERK inhibitor (PD98059) and JNK inhibitor (SP600125) resulted in the reduction of UVB-induced MMP-1 and IL-6 expressions, which demonstrated that the inhibition of MMP-1 and IL-6 by RI is associated with the MAPK pathway. Furthermore, we also found that RI accelerated procollagen type I synthesis by activating the transforming growth factor-ß/Smad pathway and enhanced the expression of cytoprotective antioxidants such as heme oxygenase-1 and NHD(P)H quinone oxidoreductase 1 by promoting nuclear factor E2-related factor 2 nuclear transfer. Overall, these findings demonstrated that RI was potentially effective in preventing UVB induced skin photoaging.

Paracoccus pueri sp. nov., isolated from Pu'er tea.

A Gram-stain negative, aerobic, short rod-shaped, motile by flagella bacterial strain (THG-N2.35T), was isolated from Pu'er tea. Growth occurred at 10-40 °C (optimum 28 °C), at pH 4-7 (optimum 7) and at 0-5% NaCl (optimum 1%). Based on 16S rRNA gene sequence analysis, the near phylogenetic neighbours of strain THG-N2.35T were identified as Paracoccus hibisci KACC 18632T (99.0%), Paracoccus tibetensis CGMCC 1.8925T (98.7%), Paracoccus beibuensis CGMCC 1.7295T (98.2%), Paracoccus aestuarii KCTC 22049T (98.2%), Paracoccus rhizosphaerae LMG 26205T (98.1%), Paracoccus zeaxanthinifaciens ATCC 21588T (97.1%), Paracoccus marcusii DSM 11574T (97.0%). Levels of similarity between strain THG-N2.35T and other Paracoccus species were lower than 97.0%. DNA-DNA hybridization values between strain THG-N2.35T and P. hibisci KACC 18632T, P. tibetensis CGMCC 1.8925T, P. beibuensis CGMCC 1.7295T, P. aestuarii KCTC 22049T, P. rhizosphaerae LMG 26205T, P. zeaxanthinifaciens ATCC 21588T, P.marcusii DSM 11574T were 47.5% (42.3%, reciprocal analysis), 36.1% (32.3%), 24.7% (22.1%), 19.2% (16.3%), 11.3% (8.8%), 11.1% (10.8%), 6.1% (5.8%), respectively. The DNA G+C content of strain THG-N2.35T was 62.3 mol%. The polar lipids were diphosphatidylglycerol, phosphatidyl-N-methylethanolamine, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine. The quinone was ubiquinone-10 (Q-10). The major fatty acids were C10:0 3OH, C16:0, C18:0 and C18:1 ω7ϲ. On the basis of the phylogenetic analysis, chemotaxonomic data, physiological characteristics and DNA-DNA hybridization data, strain THG-N2.35T represent a novel species of the genus Paracoccus, for which the name Paracoccus pueri sp. nov. is proposed. The type strain is THG-N2.35T (= KACC 18934T = CCTCC AB 2016177T).

Orobanche cernua Loefling Attenuates Ultraviolet B-mediated Photoaging in Human Dermal Fibroblasts.

UV radiation is the primary cause of skin photoaging, which results in an increase in matrix metalloproteinases and degradation of collagen. Developing new natural antioxidant as photoprotective agents has become a popular area of research. Orobanche cernua Loefling is a parasitic plant that is rich in phenylethanoid glycosides (PhGs). This study investigated the photoprotective effects of the ethanolic extract of Orobanche cernua Loefling (OC) and its principal component acteoside on UVB-induced photoaging as well as their underlying molecular mechanisms in normal human dermal fibroblasts (NHDFs). Biological testing demonstrated that OC and acteoside possessed significant photoprotective activities, reducing MMP and IL-6 levels while improving type-I procollagen synthesis in UVB-irradiated NHDFs. Further study showed that the protective mechanisms were the improvement of transcription factor Nrf2-mediated antioxidant defensive system, suppression of MAPK/AP-1 and activation of the TGF-ß/Smad pathway. Together, our results suggested that OC might be a promising antiphotoaging agent against UV radiation-induced skin damage.

Enhancement of Protective Effects of Radix Scutellariae on UVB-induced Photo Damage in Human HaCaT Keratinocytes.

Radix Scutellariae (RS) has long been used in the treatment of inflammatory and allergic diseases. Its main flavonoids, baicalin (BG) and wogonoside (WG), can be hydrolyzed into their corresponding aglycones, baicalein (B) and wogonin (W). In this study, we developed a safe and effective method of transforming these glycosides using Peclyve PR. The transformation rate of BG and WG reached 98.5 and 98.1%, respectively, with 10% enzyme at 40 °C for 60 h. Furthermore, we compared the anti-photoaging activity of RS before and after enzyme treatment, as well as their respective main components, in UVB-irradiated HaCaT cells. Results found that enzyme-treated RS (ERS) appeared to be much better at preventing UVB-induced photoaging than RS. ERS significantly inhibited the upregulation of matrix metalloproteinase-1 and IL-6 caused by UVB radiation by inactivating the MAPK/AP-1 and NF-κB/IκB-α signaling pathways. ERS treatment also recovered UVB-induced reduction of procollagen type I by activating the TGF-ß/Smad pathway. In addition, ERS exhibited an excellent antioxidant activity, which could increase the expression of cytoprotective antioxidants such as HO-1 and NQ-O1, by facilitating Nrf2 nuclear transfer. These findings demonstrated that the photoprotective effects of RS were significantly improved by enzyme-modified biotransformation.

Complete (1)H-NMR and (13)C-NMR spectral assignment of five malonyl ginsenosides from the fresh flower buds of Panax ginseng.

BACKGROUND: Ginsenosides are the major effective ingredients responsible for the pharmacological effects of ginseng. Malonyl ginsenosides are natural ginsenosides that contain a malonyl group attached to a glucose unit of the corresponding neutral ginsenosides. METHODS: Medium-pressure liquid chromatography and semipreparative high-performance liquid chromatography were used to isolate purified compounds and their structures determined by extensive one-dimensional- and two-dimensional nuclear magnetic resonance (NMR) experiments. RESULTS: A new saponin, namely malonyl-ginsenoside Re, was isolated from the fresh flower buds of Panax ginseng, along with malonyl-ginsenosides Rb1, Rb2, Rc, Rd. Some assignments for previously published (1)H- and (13)C-NMR spectra were found to be inaccurate. CONCLUSION: This study reports the complete NMR assignment of malonyl-ginsenoside Re, Rb1, Rb2, Rc, and Rd for the first time.

Niastellahibisci sp. nov., isolated from rhizosphere soil of mugunghwa, the Korean national flower.

A Gram-stain-negative, aerobic, non-motile, long rods with no flagellum strain, designated THG-YS3.2.1T, was isolated from rhizosphere soil of mugunghwa, collected from Kyung Hee University, Yongin, South Korea. Growth occurred at 10-40 °C (optimum 28 °C), at pH 6.0-8.0 (optimum pH 7.0) and with 0-1.0 % NaCl (optimum 1.0 %). The predominant menaquinone was menaquinone-7 (MK-7). The major cellular fatty acids were anteiso-C12 : 0, iso-C14 : 0, iso-C15 : 0, anteiso-C15 : 0, iso-C15 : 1 G, anteiso-C15 : 1 A, C15 : 0 2-OH, C16 : 0, iso-C16 : 0, C16 : 0 3-OH, iso-C16 : 0 3-OH, iso-C16 : 1 G, C17 : 0 2-OH, iso-C17 : 0 3-OH, C17 : 1ω6c, C18 : 3ω6c (6, 9, 12), C18 : 0, summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH). The major polar lipids were phosphatidylmethylethanolamine), phosphatidylethanolamine, five unidentified aminolipids and three unidentified lipids. The DNA G+C content of strain THG-YS3.2.1T was 45.3 mol%. Based on 16S rRNA gene sequence analysis, the nearest phylogenetic neighbours of strain THG-YS3.2.1T were Niastella populi KCTC 22560T (98.7 % 16S rRNA gene sequence similarity), Niastella gongjuensis KACC 17399T (96.9 %), Niastella vici KCTC 42474T (96.2 %), Niastella yeongjuensis KACC 11466T (95.5 %) and Niastella koreensis KACC 11465T (95.1 %). DNA-DNA hybridization values between strain THG-YS3.2.1T and N. populi KCTC 22560T, N. gongjuensis KACC 17399T, N.vici KCTC 42474T, N. yeongjuensis KACC 11466T and N. koreensis KACC 11465Twere 55.8±1.0, 39.5±0.5, 35.2±0.1, 17.6±0.3 and 12.5±1.2 %, respectively. On the basis of the phylogenetic analysis, chemotaxonomic data, physiological characteristics and DNA-DNA hybridization data, strain THG-YS3.2.1T represents a novel species of the genus Niastella, for which the name Niastellahibisci sp. nov. is proposed. The type strain is THG-YS3.2.1T (=KCTC 52084T=CCTCC AB 2015356T).