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.

The DNA methylation status of the serotonin metabolic pathway associated with reproductive inactivation induced by long-light exposure in Magang geese.

BACKGROUND: Domestic geese are seasonal breeders and have the lowest reproductive capacity among all poultry species. Magang geese is a topical short-day breeder, short photoperiod exposure stimulates its reproductive activity while long photoperiod inhibits. To explore epigenetic change that could influence reproductive activity, we performed whole genome bisulfite sequencing and transcriptome sequencing in the hypothalamus at three reproductive stages during long-light exposure in male Magang geese. RESULTS: A total number of 10,602 differentially methylated regions (DMRs) were identified among three comparison groups. We observed that the vast majority of DMRs were enriched in intron regions. By integrating the BS-sequencing and RNA-seq data, the correlation between methylation changes of CG DMRs and expression changes of their associated genes was significant only for genes containing CG DMRs in their intron. A total of 278 DMR-associated DEGs were obtained among the three stages. KEGG analysis revealed that the DMR-associated DEGs were mainly involved in 11 pathways. Among them, the neuroactive ligand-receptor interaction pathway was significantly enriched in both two comparisons (RA vs.RD and RD vs.RI); the Wnt signaling pathway, apelin signaling pathway, melanogenesis, calcium signaling pathway, focal adhesion, and adherens junction were significantly enriched in the RA vs. RI comparison. In addition, the expression level of two serotonin-metabolic genes was significantly altered during reproductive axis inactivation by the methylation status of their promoter region (TPH2) and intron region (SLC18A2), respectively. These results were confirmed by Bisulfite sequencing PCR (BSP), pyrosequencing, and real-time qPCR, indicating that serotonin metabolic signaling may play a key role in decreasing the reproductive activity of Magang geese induced by long-light exposure. Furthermore, we performed a metabolomics approach to investigate the concentration of neurotransmitters among the three stages, and found that 5-HIAA, the last product of the serotonin metabolic pathway, was significantly decreased in the hypothalamus during RI. CONCLUSIONS: Our study reveals that the methylation status of the serotonin metabolic pathway in the hypothalamus is associated with reproductive inactivation, and provided new insight into the effect of DNA methylation on the reproductive regulation of the hypothalamus in Magang geese.

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.

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.

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.

Transdermal Delivery of Salmon Calcitonin Using a Dissolving Microneedle Array: Characterization, Stability, and In vivo Pharmacodynamics.

Salmon calcitonin (sCT) is a polypeptide drug, possessing the ability to inhibit osteoclast-mediated bone resorption. Just like other bioactive macromolecules, sCT is generally administered to the patients by either injection for poor compliance or through nasal spray for low bioavailability, which limits its use as therapeutic drugs. In the present study, to overcome the limitations of the conventional routes, two new dissolving microneedle arrays (DMNAs) based on transdermal sCT delivery systems were developed, namely sCT-DMNA-1 (sCT/Dex/K90E) and sCT-DMNA-2 (sCT/Dex-Tre/K90E) with the same dimension, meeting the requirements of suitable mechanical properties. An accurate and reliable method was established to determine the needle drug loading proportion in sCT-DMNAs. The stability study exhibited that the addition of trehalose could improve the stability of sCT in DMNA under high temperature and humidity. Further, in vivo pharmacodynamic study revealed that DMNA patch could significantly enhanced relative bioavailability to approximately 70%, and the addition of trehalose was found to be beneficial for sCT transdermal delivery. Therefore, sCT-DMNA is expected to replace traditional dosage form, providing a secure, efficient, and low-pain therapeutic strategy for bone disorders.

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.

Constant conflict between Gypsy LTR retrotransposons and CHH methylation within a stress-adapted mangrove genome.

The evolutionary dynamics of the conflict between transposable elements (TEs) and their host genome remain elusive. This conflict will be intense in stress-adapted plants as stress can often reactivate TEs. Mangroves reduce TE load convergently in their adaptation to intertidal environments and thus provide a unique opportunity to address the host-TE conflict and its interaction with stress adaptation. Using the mangrove Rhizophora apiculata as a model, we investigated methylation and short interfering RNA (siRNA) targeting patterns in relation to the abundance and age of long terminal repeat (LTR) retrotransposons. We also examined the distance of LTR retrotransposons to genes, the impact on neighboring gene expression and population frequencies. We found differential accumulation amongst classes of LTR retrotransposons despite high overall methylation levels. This can be attributed to 24-nucleotide siRNA-mediated CHH methylation preferentially targeting Gypsy elements, particularly in their LTR regions. Old Gypsy elements possess unusually abundant siRNAs which show cross-mapping to young copies. Gypsy elements appear to be closer to genes and under stronger purifying selection than other classes. Our results suggest a continuous host-TE battle masked by the TE load reduction in R. apiculata. This conflict may enable mangroves, such as R. apiculata, to maintain genetic diversity and thus evolutionary potential during stress adaptation.

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.

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).

Isolation, characterization, and marker utility of KCRE1, a transcriptionally active Ty1/copia retrotransposon from Kandelia candel.

Transposable elements are key players in eukaryotic genomic diversity. Due to their high abundance, great heterogeneity, and replicative transposition, long terminal repeat (LTR) retrotransposons are well suited as molecular markers for breeding and biodiversity studies, whereas their utilities in non-model organisms have been hindered by the lack of prior sequence knowledge. In this study, a putative complete (5362 bp) LTR retrotransposon was isolated and characterized in the mangrove species Kandelia candel (named KCRE1), and its transcription, insertional polymorphisms and copy number variations were also investigated. KCRE1 has all the features of a typical copia retroelement, and its transcription initiation and termination sites were identified by 5' and 3' rapid amplification of cDNA ends (RACE), respectively. KCRE1 exhibits high sequence similarity with the tomato retroelement Rider and is constitutively expressed in the leaf, root, flower, and hypocotyl tissues of K. candel. Based on KCRE1, sequence-specific amplification polymorphism (SSAP) markers were developed to explore genetic diversity across 30 individuals from three natural populations of K. candel in China. Six primer combinations yielded a total of 204 SSAP bands with an averaged percentage of polymorphic loci of 55.37 and 41.35 % at the species and population levels, respectively. Each individual had a distinct SSAP phenotype, and 14-23 unique bands were observed for each population. Accordingly, KCRE1 was highly abundant in the genome of K. candel and showed considerable copy number variation among the three populations. In conclusion, KCRE1 is the first transcriptionally active retrotransposon reported in K. candel, providing a useful tool for the elucidation of untapped genetic diversity in mangrove genomes.

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).

Crosstalk between histone/DNA modifications and RNA N6-methyladenosine modification.

N6-methyladenosine (m6A) is the most prevalent internal RNA modification in eukaryotic messenger RNAs (mRNAs), regulating gene expression at the transcription and post-transcription levels. Complex interplay between m6A and other well-studied epigenetic modifications, including histone modifications and DNA modification, has been extensively reported in recent years. The crosstalk between RNA m6A modification and histone/DNA modifications plays a critical role in establishing the chromatin state for the precise and specific fine-tuning of gene expression and undoubtedly has profound impacts on both physiological and pathological processes. In this review, we discuss the crosstalk between RNA m6A modification and histone/DNA modifications, emphasizing their sophisticated communications and the mechanisms underlying to gain a comprehensive view of the biological relevance of m6A-based epigenetic network.

Genetic basis of local adaptation in the cold-tolerant mangrove Kandelia obovata.

Understanding the genetic basis of local adaption is crucial in the context of global climate change. Mangroves, as salt-tolerant trees and shrubs in the intertidal zone of tropical and subtropical coastlines, are particularly vulnerable to climate change. Kandelia obovata, the most cold-tolerant mangrove species, has undergone ecological speciation from its cold-intolerant counterpart, Kandelia candel, with geographic separation by the South China Sea. In this study, we conducted whole-genome re-sequencing of K. obovata populations along China's southeast coast, to elucidate the genetic basis responsible for mangrove local adaptation to climate. Our analysis revealed a strong population structure among the three K. obovata populations, with complex demographic histories involving population expansion, bottleneck, and gene flow. Genome-wide scans unveiled pronounced patterns of selective sweeps in highly differentiated regions among pairwise populations, with stronger signatures observed in the northern populations compared to the southern population. Additionally, significant genotype-environment associations for temperature-related variables were identified, while no associations were detected for precipitation. A set of 39 high-confidence candidate genes underlying local adaptation of K. obovata were identified, which are distinct from genes under selection detected by comparison between K. obovata and its cold-intolerant relative K. candel. These results significantly contribute to our understanding of the genetic underpinnings of local adaptation in K. obovata and provide valuable insights into the evolutionary processes shaping the genetic diversity of mangrove populations in response to climate change.

Sign language recognition based on dual-path background erasure convolutional neural network.

Sign language is an important way to provide expression information to people with hearing and speaking disabilities. Therefore, sign language recognition has always been a very important research topic. However, many sign language recognition systems currently require complex deep models and rely on expensive sensors, which limits the application scenarios of sign language recognition. To address this issue, based on computer vision, this study proposed a lightweight, dual-path background erasing deep convolutional neural network (DPCNN) model for sign language recognition. The DPCNN consists of two paths. One path is used to learn the overall features, while the other path learns the background features. The background features are gradually subtracted from the overall features to obtain an effective representation of hand features. Then, these features are flatten into a one-dimensional layer, and pass through a fully connected layer with an output unit of 128. Finally, use a fully connected layer with an output unit of 24 as the output layer. Based on the ASL Finger Spelling dataset, the total accuracy and Macro-F1 scores of the proposed method is 99.52% and 0.997, respectively. More importantly, the proposed method can be applied to small terminals, thereby improving the application scenarios of sign language recognition. Through experimental comparison, the dual path background erasure network model proposed in this paper has better generalization ability.

The DNA methylation status of the vitamin A signaling associated with testicular degeneration induced by long-day photoperiods in Magang geese.

Magang geese are typical short-day breeders whose reproductive behaviors are significantly influenced by photoperiod. Exposure to a long-day photoperiod results in testicular regression and spermatogenesis arrest in Magang geese. To investigate the epigenetic influence of DNA methylation on the seasonal testicular regression in Magang geese, we conducted whole-genome bisulfite sequencing and transcriptome sequencing of testes across 3 reproductive phases during a long-day photoperiod. A total of 250,326 differentially methylated regions (DMR) were identified among the 3 comparison groups, with a significant number showing hypermethylation, especially in intronic regions of the genome. Integrating bisulfite sequencing with transcriptome sequencing data revealed that DMR-associated genes tend to be differentially expressed in the testes, highlighting a potential regulatory role for DNA methylation in gene expression. Furthermore, there was a significant negative correlation between changes in the methylation of CG DMRs and changes in the expression of their associated genes in the testes. A total of 3,359 DMR-associated differentially expressed genes (DEG) were identified; functional enrichment analyses revealed that motor proteins, MAPK signaling pathway, ECM-receptor interaction, phagosome, TGF-beta signaling pathway, and calcium signaling might contribute to the testicular regression process. GSEA revealed that the significantly enriched activated hallmark gene set was associated with apoptosis and estrogen response during testicular regression, while the repressed hallmark gene set was involved in spermatogenesis. Our study also revealed that methylation changes significantly impacted the expression level of vitamin A metabolism-related genes during testicular degeneration, with hypermethylation of STRA6 and increased calmodulin levels indicating vitamin A efflux during the testicular regression. These findings were corroborated by pyrosequencing and real-time qPCR, which revealed that the vitamin A metabolic pathway plays a pivotal role in testicular degeneration under long-day conditions. Additionally, metabolomics analysis revealed an insufficiency of vitamin A and an abnormally high level of oxysterols accumulated in the testes during testicular regression. In conclusion, our study demonstrated that testicular degeneration in Magang geese induced by a long-day photoperiod is linked to vitamin A homeostasis disruption, which manifests as the hypermethylation status of STRA6, vitamin A efflux, and a high level of oxysterol accumulation. These findings offer new insights into the effects of DNA methylation on the seasonal testicular regression that occurs during long-day photoperiods in Magang geese.

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.

Vanadium Oxide Nanozymes with Multiple Enzyme-Mimic Activities for Tumor Catalytic Therapy.

Using tumors containing high concentrations of hydrogen peroxide to design nanozymes is a new and effective strategy, and vanadium-based nanomaterials receive increasing attention. In this paper, four kinds of vanadium oxide nanozymes with different valences of vanadium are synthesized by a simple method to verify the effect of valence on enzyme activity. Vanadium oxide nanozyme-III (Vnps-III) with a low valence of vanadium (V4+) exhibits good peroxidase (POD) and oxidase (OXD) activities, which can effectively produce reactive oxygen species (ROS) in the tumor microenvironment for tumor treatment. In addition, Vnps-III can also consume glutathione (GSH) to reduce ROS consumption. Vanadium oxide nanozyme-I (Vnps-I) containing a high valence of vanadium (V5+) has catalase (CAT) activity, which can catalyze hydrogen peroxide (H2O2) into oxygen (O2), which is beneficial to alleviate the hypoxic environment of solid tumors. Finally, a vanadium oxide nanozyme with both trienzyme simulation activity and GSH consumption ability was screened out by adjusting the ratio of V4+ to V5+ in vanadium oxide nanozymes. In cell and animal experiments, we successfully demonstrate that vanadium oxide nanozymes have excellent antitumor ability and high safety, which may bring great potential for clinical cancer treatment.

Construction of pH-sensitive targeted micelle system co-delivery with curcumin and dasatinib and evaluation of anti-liver cancer.

Nanomedicine delivery systems can achieve precise drug delivery and reduce toxic side effects compared with traditional drug delivery methods, but further development is still needed to eliminate obstacles such as multiple drug co-delivery, uncontrolled drug-release, and drug-resistance. Herein, we designed a dual drug-loaded nanosystem (THCD-NPs) that selectively transports and targets tumor cells for the treatment of liver cancer. In this drug delivery system, hyaluronic acid (HA)-conjugated curcumin (Cur) and d-α-tocopherol acid polyethylene glycolsuccinate (TPGS) were used as selective drug-carrying vehicles to deliver dasatinib (DAS) to cancer cells for combined administration. The mean size of the nanoparticles was approximately 66.14 ± 4.02 nm with good in vitro stability. The nanoparticles were pH sensitive and could accelerate drug release at low pH conditions. In vitro experiments showed that THCD-NPs were significantly cytotoxic to HepG2 cells and could be effectively taken up by these cells. Detailed investigations also demonstrated its pro-apoptotic activity. In vivo NIR fluorescence imaging showed that the nanoparticles could accumulate efficiently at the tumor site. Meanwhile, in vivo experiments showed that THCD-NPs significantly inhibited tumor growth and reduced the toxic side effects of free drugs in a mouse solid tumor model. In short, the nanoparticles we prepared provide a new idea for the treatment of liver cancer.