The effects of wearing a face mask and of subsequent moisturizer use on the characteristics of sensitive skin.

BACKGROUND: COVID-19 is a serious respiratory disease, and wearing masks has become essential in daily life. Nevertheless, the number of people complaining of skin problems caused by wearing masks is increasing. Therefore, we investigated the characteristics of changes in sensitive skin caused by wearing a mask. MATERIALS AND METHODS: Twenty healthy Korean women with sensitive skin participated in this study. To determine any skin-related changes caused by mask-wearing, we evaluated redness, hydration, transepidermal water loss (TEWL), and moisture at 2.5 mm below the surface before and 4 h after wearing a Korea Filter 94 mask. In addition, we tested whether applying a moisturizer for 30 min after mask removal could reverse any mask-induced changes. RESULTS: Skin redness and TEWL were significantly increased at 4 h after wearing a mask (p < 0.05), otherwise skin hydration and the 2.5 mm moisture were significantly decreased (p < 0.05). After applying the moisturizer, skin redness and TEWL were significantly decreased compared to their values 4 h after wearing masks (p < 0.05), whereas skin hydration and the 2.5 mm moisture were significantly increased (p < 0.05). Moreover, after applying the moisturizer, skin redness and TEWL were significantly reduced compared to the pre-masking baseline (p < 0.05), whereas skin hydration was significantly increased (p < 0.05); the 2.5 mm moisture showed no significant change. CONCLUSION: We observed that wearing masks causes physiological changes in sensitive skin, whereas applying a moisturizer after removing the mask improved skin conditions.

Drosophila PEBP1 inhibits intestinal stem cell aging via suppression of ERK pathway.

The intestine is a high cellular turnover tissue largely dependent on the regenerative function of stem cell throughout life, and a signaling center for the health and viability of organisms. Therefore, better understanding of the mechanisms underlying the regulation of intestinal stem cell (ISC) regenerative potential is essential for the possible intervention of aging process and age-related diseases. Drosophila midgut is a well-established model system for studying the mechanisms underlying ISC regenerative potential during aging. Here, we report the requirement of Drosophila phosphatidylethanolamine binding protein 1 (PEBP1) in ISC regenerative potential. We showed that PEBP1 was strongly expressed in enterocytes (ECs) of guts and its decrease with age and oxidative stress. Furthermore, the downregulation of PEBP1 in ECs accelerates ISC aging, as evidenced by ISC hyper-proliferation, γH2AX accumulation, and centrosome amplification, and intestinal hyperplasia. The decrease in PEBP1 expression was associated with increased extracellular signal-regulated kinase (ERK) activity in ECs. All these phenotypes by EC-specific depletion of PEBP1 were rescued by the concomitant inhibition of ERK signaling. Our findings evidence that the age-related downregulation of PEBP1 in ECs is a novel cause accelerating ISC aging and that PEBP1 is an EC-intrinsic suppressor of epidermal growth factor receptor (EGFR)/ERK signaling. Our study provides molecular insights into the tight regulation of EGFR/ERK signaling in niches for stem cell regenerative potential.

Effect of heterochromatin stability on intestinal stem cell aging in Drosophila.

Chromatin change is one of the crucial causes of aging. Specifically, maintenance of heterochromatin stability is critical for cellular integrity, and its loss induces genomic instability and cellular aging. However, the causes and effects of heterochromatin instability in multicellular tissue aging still remain unclear. Here, in the adult Drosophila midgut, we report age-related loss of heterochromatin stability in enterocytes (ECs) due to the loss and dispersion of tri-methylated histone H3 Lys9 (H3K9me3) and heterochromatin protein 1 (HP1). Our study further shows that EC-specific knockdown of Su(var)3-9, histone lysine methyltransferase for H3K9me3 formation, or HP1a leads to intestinal stem cell (ISC) aging through genomic stress, JNK signaling, and apoptotic death in ECs. Our findings revealed the plausible causes of age-related loss of heterochromatin stability in ECs, including oxidative stress and nutrient-sensing AKT/TOR signaling. Taken together, the loss of heterochromatin stability may be the crucial niche aging mechanism for ISC aging which is the prime determinant of intestinal tissue aging. Furthermore, our study provides new clues on the link between heterochromatin and aging.

Deficiency of Atg6 impairs beneficial effect of metformin on intestinal stem cell aging in Drosophila.

Age-related changes of adult stem cell are crucial for tissue aging and age-related diseases. Thus, clarifying mechanisms to prevent adult stem cell aging is indispensable for healthy aging. Metformin, a drug for type 2 diabetes, has been highlighted for its anti-aging and anti-cancer effect. In Drosophila intestinal stem cell (ISC), we previously reported the inhibitory effect of metformin on age-related phenotypes of ISC. Here, we showed that knockdown of Atg6, a crucial autophagy-related factor, in ISC induces age-related phenotypes of ISC such as hyperproliferation, centrosome amplification, and DNA damage accumulation. Then, we revealed that metformin inhibits ISC aging phenotypes in Atg6-dependent manner. Taken together, our study suggests that Atg6 is required for the inhibitory effect of metformin on ISC aging, providing an intervention mechanism of metformin on adult stem cell aging.

Deficiency in DNA damage response of enterocytes accelerates intestinal stem cell aging in Drosophila.

Stem cell dysfunction is closely linked to tissue and organismal aging and age-related diseases, and heavily influenced by the niche cells' environment. The DNA damage response (DDR) is a key pathway for tissue degeneration and organismal aging; however, the precise protective role of DDR in stem cell/niche aging is unclear. The Drosophila midgut is an excellent model to study the biology of stem cell/niche aging because of its easy genetic manipulation and its short lifespan. Here, we showed that deficiency of DDR in Drosophila enterocytes (ECs) accelerates intestinal stem cell (ISC) aging. We generated flies with knockdown of Mre11, Rad50, Nbs1, ATM, ATR, Chk1, and Chk2, which decrease the DDR system in ECs. EC-specific DDR depletion induced EC death, accelerated the aging of ISCs, as evidenced by ISC hyperproliferation, DNA damage accumulation, and increased centrosome amplification, and affected the adult fly's survival. Our data indicated a distinct effect of DDR depletion in stem or niche cells on tissue-resident stem cell proliferation. Our findings provide evidence of the essential role of DDR in protecting EC against ISC aging, thus providing a better understanding of the molecular mechanisms of stem cell/niche aging.

Folic acid is necessary for proliferation and differentiation of C2C12 myoblasts.

Folic acid, a water soluble B vitamin, plays an important role in cellular metabolic activities, such as functioning as a cofactor in one-carbon metabolism for DNA and RNA synthesis as well as nucleotide and amino acid biosynthesis in the body. A lack of dietary folic acid can lead to folic acid deficiency and result in several health problems, including macrocytic anemia, elevated plasma homocysteine, cardiovascular disease, birth defects, carcinogenesis, muscle weakness, and walking difficulty. However, the effect of folic acid deficiency on skeletal muscle development and its molecular mechanisms are unknown. We, therefore, investigated the effect of folic acid deficiency on myogenesis in skeletal muscle cells and found that folic acid deficiency induced proliferation inhibition and cell cycle breaking as well as cellular senescence in C2C12 myoblasts, implying that folic acid deficiency influences skeletal muscle development. Folic acid deficiency also inhibited differentiation of C2C12 myoblasts and induced deregulation of the cell cycle exit and many cell cycle regulatory genes. It inhibited expression of muscle-specific marker MyHC as well as myogenic regulatory factor (myogenin). Moreover, immunocytochemistry and Western blot analyses revealed that DNA damage was more increased in folic acid-deficient medium-treated differentiating C2C12 cells. Furthermore, we found that folic acid resupplementation reverses the effect on the cell cycle and senescence in folic acid-deficient C2C12 myoblasts but does not reverse the differentiation of C2C12 cells. Altogether, the study results suggest that folic acid is necessary for normal development of skeletal muscle cells.

Overexpression of dJmj differentially affects intestinal stem cells and differentiated enterocytes.

Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 independent function is suggested for Drosophila Jumonji (dJmj). To clarify the function of dJmj during cell differentiation, we used Drosophila adult intestinal stem cell system that allows to follow stem cell behaviors in vivo. Overexpression of dJmj in intestinal stem cells/enteroblasts (ISCs/EBs) induces cell-autonomous ISC proliferation followed by differentiation, that is controlled by the Notch and EGFR pathway. In contrast, overexpression of dJmj in enterocytes (ECs) resulted in activation of the JNK pathway in ECs followed by the induction of apoptosis. Activated JNK increased the level of Yorkie in ECs and induced the reduction of Upd proteins and EGFR ligands, which activated the JAK/STAT and EGFR pathway in both ISCs and EBs to promote ISC proliferation. The Notch signaling pathway appears to be highly activated to support the differentiation of EBs to ECs. Thus, the combination of these signaling pathways caused by ECs-specific dJmj-overexpression induced non-cell-autonomous ISC proliferation and differentiation. Surprisingly, these effects did not relate to H3K27me3 status, likely represented PRC2 activity, in cells that overexpressed dJmj. Instead of this, the disappearance of H3K27me3 in ISC/EB-specific overexpressed dJmj suggested a possible PRC2-independent role of dJmj in regulating chromatin structure.

Functional Profiling of Human MeCP2 by Automated Data Comparison Analysis and Computerized Expression Pathway Modeling.

OBJECTIVES: Methyl-CpG binding protein 2 (MeCP2) is a ubiquitous epigenetic factor that represses gene expression by modifying chromatin. Mutations in the MeCP2 gene cause Rett syndrome, a progressive neurodevelopmental disorder. Recent studies also have shown that MeCP2 plays a role in carcinogenesis. Specifically, functional ablation of MeCP2 suppresses cell growth and leads to the proliferation of cancer cells. However, MeCP2's function in adult tissues remains poorly understood. We utilized a weight matrix-based comparison software to identify transcription factor binding site (TFBS) of MeCP2-regulated genes, which were recognized by cDNA microarray analysis. METHODS: MeCP2 expression was silenced using annealed siRNA in HEK293 cells, and then a cDNA microarray analysis was performed. Functional analysis was carried out, and transcriptional levels in target genes regulated by MeCP2 were investigated. TFBS analysis was done within genes selected by the cDNA microarray analysis, using a weight matrix-based program and the TRANSFAC 6.0 database. RESULTS: Among the differentially expressed genes with a change in expression greater than two-fold, 189 genes were up-regulated and 91 genes were down-regulated. Genes related to apoptosis and cell proliferation (JUN, FOSL2, CYR61, SKIL, ATF3, BMABI, BMPR2, RERE, and FALZ) were highly up-regulated. Genes with anti-apoptotic and anti-proliferative functions (HNRPA0, HIS1, and FOXC1) were down-regulated. Using TFBS analysis within putative promoters of novel candidate target genes of MeCP2, disease-related transcription factors were identified. CONCLUSIONS: The present results provide insights into the new target genes regulated by MeCP2 under epigenetic control. This information will be valuable for further studies aimed at clarifying the pathogenesis of Rett syndrome and neoplastic diseases.

Folic acid promotes the myogenic differentiation of C2C12 murine myoblasts through the Akt signaling pathway.

Folic acid is a water-soluble vitamin in the B-complex group, and an exogenous intake is required for health, growth and development. As a precursor to co-factors, folic acid is required for one-carbon donors in the synthesis of DNA bases and other essential biomolecules. A lack of dietary folic acid can lead to folic acid deficiency and can therefore result in several health problems, including macrocytic anemia, elevated plasma homocysteine levels, cardiovascular disease, birth defects, carcinogenesis, muscle weakness and difficulty in walking. Previous studies have indicated that folic acid exerts a positive effect on skeletal muscle functions. However, the precise role of folic acid in skeletal muscle cell differentiation remains poorly understood. Thus, in the present study, we examined the effects of folic acid on neo-myotube maturation and differentiation using C2C12 murine myoblasts. We found that folic acid promoted the formation of multinucleated myotubes, and increased the fusion index and creatine kinase (CK) activity in a concentration-dependent manner. In addition, western blot analysis revealed that the expression levels of the muscle-specific marker, myosin heavy chain (MyHC), as well as those of the myogenic regulatory factors (MRFs), MyoD and myogenin, were increased in the folic acid-treated myotubes during myogenic differentiation. Folic acid also promoted the activation of the Akt pathway, and this effect was inhibited by treatment of the C2C12 cells with LY294002 (Akt inhibitor). Blocking of the Akt pathway with a specific inhibitor revealed that it was necessary for mediating the stimulatory effects of folic acid on muscle cell differentiation and fusion. Taken together, our data suggest that folic acid promotes the differentiation of C2C12 cells through the activation of the Akt pathway.

Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila.

The stem cell genomic stability forms the basis for robust tissue homeostasis, particularly in high-turnover tissues. For the genomic stability, DNA damage response (DDR) is essential. This study was focused on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adultDrosophila midgut. We explored the role of ATM and ATR, utilizing immunostaining with an anti-pS/TQ antibody as an indicator of ATM/ATR activation, γ-irradiation as a DNA damage inducer, and the UAS/GAL4 system for cell type-specific knockdown of ATM, ATR, or both during adulthood. The results showed that the pS/TQ signals got stronger with age and after oxidative stress. The pS/TQ signals were found to be more dependent on ATR rather than on ATM in ISCs/enteroblasts (EBs). Furthermore, an ISC/EB-specific knockdown of ATR, ATM, or both decreased the number of ISCs and oxidative stress-induced ISC proliferation. The phenotypic changes that were caused by the ATR knockdown were more pronounced than those caused by the ATM knockdown; however, our data indicate that ATR and ATM are both needed for ISC maintenance and proliferation; ATR seems to play a bigger role than does ATM.

Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway.

We delineated the mechanism regulating the inhibition of centrosome amplification by metformin in Drosophila intestinal stem cells (ISCs). Age-related changes in tissue-resident stem cells may be closely associated with tissue aging and age-related diseases, such as cancer. Centrosome amplification is a hallmark of cancers. Our recent work showed that Drosophila ISCs are an excellent model for stem cell studies evaluating age-related increase in centrosome amplification. Here, we showed that metformin, a recognized anti-cancer drug, inhibits age- and oxidative stress-induced centrosome amplification in ISCs. Furthermore, we revealed that this effect is mediated via down-regulation of AKT/target of rapamycin (TOR) activity, suggesting that metformin prevents centrosome amplification by inhibiting the TOR signaling pathway. Additionally, AKT/TOR signaling hyperactivation and metformin treatment indicated a strong correlation between DNA damage accumulation and centrosome amplification in ISCs, suggesting that DNA damage might mediate centrosome amplification. Our study reveals the beneficial and protective effects of metformin on centrosome amplification via AKT/TOR signaling modulation. We identified a new target for the inhibition of age- and oxidative stress-induced centrosome amplification. We propose that the Drosophila ISCs may be an excellent model system for in vivo studies evaluating the effects of anti-cancer drugs on tissue-resident stem cell aging.

Age-related change in γH2AX of Drosophila muscle: its significance as a marker for muscle damage and longevity.

Muscle aging is closely related to unhealthy late-life and organismal aging. Recently, the state of differentiated cells was shown to be critical to tissue homeostasis. Thus, understanding how fully differentiated muscle cells age is required for ensuring healthy aging. Adult Drosophila muscle is a useful model for exploring the aging process of fully differentiated cells. In this study, we investigated age-related changes of γH2AX, an indicator of DNA strand breaks, in adult Drosophila muscle to document whether its changes are correlated with muscle degeneration and lifespan. The results demonstrate that γH2AX accumulation increases in adult Drosophila thoracic and leg muscles with age. Analyses of short-, normal-, and long-lived strains indicate that the age-related increase of γH2AX is closely associated with the extent of muscle degeneration, cleaved caspase-3 and poly-ubiquitin aggregates, and longevity. Further analysis of muscle-specific knockdown of heterochromatin protein 1a revealed that the excessive γH2AX accumulation in thoracic and leg muscles induces accelerated degeneration and decreases longevity. These data suggest a strong correlation between age-related muscle damage and lifespan in Drosophila. Our findings indicate that γH2AX may be a reliable biomarker for assessing muscle aging in Drosophila.

Dlx-2 is implicated in TGF-ß- and Wnt-induced epithelial-mesenchymal, glycolytic switch, and mitochondrial repression by Snail activation.

Epithelial-mesenchymal transition (EMT) and oncogenic metabolism (including glycolytic switch) are important for tumor development and progression. Here, we show that Dlx-2, one of distal-less (Dlx) homeobox genes, induces EMT and glycolytic switch by activation of Snail. In addition, it was induced by TGF-ß and Wnt and regulates TGF-ß- and Wnt-induced EMT and glycolytic switch by activating Snail. We also found that TGF-ß/Wnt suppressed cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, in a Dlx-2/Snail-dependent manner. TGF-ß/Wnt appeared to downregulate the expression of various COX subunits including COXVIc, COXVIIa and COXVIIc; among these COX subunits, COXVIc was a common target of TGF-ß, Wnt, Dlx-2 and Snail, indicating that COXVIc downregulation plays an important role(s) in TGF-ß/Wnt-induced COX inhibition. Taken together, our results showed that Dlx-2 is involved in TGF-ß- and Wnt-induced EMT, glycolytic switch, and mitochondrial repression by Snail activation.

Modulation of biomechanical properties of hyaluronic acid hydrogels by crosslinking agents.

Modulation of both mechanical properties and biocompatibilities of hyaluronic acid (HA) hydrogels is very importance for their applications in biomaterials. Pure HA solution was converted into a hydrogel by using butanediol diglycidyl ether (BDDE) as a crosslinking agent. Mechanical properties of the HA hydrogels have been evaluated by adding up different amount of BDDEs. While the mechanical properties of the obtained HA hydrogels were evaluated by measuring their crosslinking degrees, elastic modulus and viscosity, their in vitro biocompatibilities were done by measuring the degrees of anti-inflammatory reactions, cell viabilities and cytotoxicity. The degrees of anti-inflammatory reactions were determined by measuring the amount of nitric oxides (NOs) released from lipopolysaccharide(LPS)(+)-induced macrophages; cell viability was evaluated by observing differences in the behaviors of fibroblasts covered with the HA hydrogels, compared with those covered with the films of Teflon and Latex. Cytotoxicity of the HA hydrogels was also evaluated by measuring the degrees of viability of the cells exposed on the extracts of the HA hydrogels over those of Teflon, Latex and pure HA solutions by the assays of thiazoly blue tetrazolium bromide (MTT), neutral reds, and bromodeoxyuridine (BrdU). The results showed that employment of BDDEs beyond critical amounts showed lower biocompatibility of the crosslinked HA hydrogels but higher crosslinking degrees and mechanical properties, indicating the importance of controlling the HA concentrations, BDDE amounts and their reaction times for the synthesis of the crosslinked HA hydrogels for their clinical applications as biomaterials.

The combination of ursolic acid and leucine potentiates the differentiation of C2C12 murine myoblasts through the mTOR signaling pathway.

Aging causes phenotypic changes in skeletal muscle progenitor cells that lead to the progressive loss of myogenic differentiation and thus a decrease in muscle mass. The naturally occurring triterpene, ursolic acid, has been reported to be an effective agent for the prevention of muscle loss by suppressing degenerative muscular dystrophy. Leucine, a branched-chain amino acid, and its metabolite, ß-hydroxy-ß-methylbutyric acid, have been reported to enhance protein synthesis in skeletal muscle. Therefore, the aim of the present study was to investigate whether the combination of ursolic acid and leucine promotes greater myogenic differentiation compared to either agent alone in C2C12 murine myoblasts. Morphological changes were observed and creatine kinase (CK) activity analysis was performed to determine the conditions through which the combination of ursolic acid and leucine would exert the most prominent effects on muscle cell differentiation. The effect of the combination of ursolic acid and leucine on the expression of myogenic differentiation marker genes was examined by RT-PCR and western blot analysis. The combination of ursolic acid (0.5 µM) and leucine (10 µM) proved to be the most effective in promoting myogenic differentiation. The combination of ursolic acid and leucine significantly increased CK activity than treatment with either agent alone. The level of myosin heavy chain, a myogenic differentiation marker protein, was also enhanced by the combination of ursolic acid and leucine. The combination of ursolic acid and leucine significantly induced the expression of myogenic differentiation marker genes, such as myogenic differentiation 1 (MyoD) and myogenin, at both the mRNA and protein level. In addition, the number of myotubes and the fusion index were increased. These findings indicate that the combination of ursolic acid and leucine promotes muscle cell differentiation, thus suggesting that this combination of agents may prove to be beneficial in increasing muscle mass.

Increased centrosome amplification in aged stem cells of the Drosophila midgut.

Age-related changes in long-lived tissue-resident stem cells may be tightly linked to aging and age-related diseases such as cancer. Centrosomes play key roles in cell proliferation, differentiation and migration. Supernumerary centrosomes are known to be an early event in tumorigenesis and senescence. However, the age-related changes of centrosome duplication in tissue-resident stem cells in vivo remain unknown. Here, using anti-γ-tubulin and anti-PH3, we analyzed mitotic intestinal stem cells with supernumerary centrosomes in the adult Drosophila midgut, which may be a versatile model system for stem cell biology. The results showed increased centrosome amplification in intestinal stem cells of aged and oxidatively stressed Drosophila midguts. Increased centrosome amplification was detected by overexpression of PVR, EGFR, and AKT in intestinal stem cells/enteroblasts, known to mimic age-related changes including hyperproliferation of intestinal stem cells and hyperplasia in the midgut. Our data show the first direct evidence for the age-related increase of centrosome amplification in intestinal stem cells and suggest that the Drosophila midgut is an excellent model for studying molecular mechanisms underlying centrosome amplification in aging adult stem cells in vivo.

Functional modification of Drosophila intestinal stem cells by ionizing radiation.

Although the diverse effects of ionizing radiation on biological and pathological processes at various levels ranging from molecular to whole body are well studied, the effects on adult stem cells by ionizing radiation remain largely unknown. In this study, we characterized the functional modifications of adult Drosophila midgut intestinal stem cells after ionizing radiation treatment. A dose of 10 Gy of radiation decreased the proliferative capacity of intestinal stem cells. Interestingly, after irradiation at 2 Gy, the intestinal stem cells exhibited increased proliferative activity, misdifferentiation and γH2AvD and 8-oxo-dG levels. In addition, the guts irradiated with 2 Gy showed increased JNK and AKT activities. Furthermore, we showed that 2 Gy of ionizing radiation induced centrosome amplification in intestinal stem cells of adult midguts. Our data gives molecular insights into the effects of ionizing radiation on functional modifications of stem cells. The adult Drosophila midgut intestinal stem cells offer a potentially rich new system for the exploration of the biological effects of ionizing radiation.

A validation study to find highly correlated parameters with visual assessment for clinical evaluation of cosmetic anti-cellulite products.

BACKGROUND/PURPOSE: There has been growing interest in cellulite on parts of the body; however, no objective assessment has been specifically established. This study aims to demonstrate an optimized method by comparing the existing assessments of cellulite. METHODS: In Test 1, for subjects of 20 healthy females who have cellulite, we measured volume and roughness of cellulite using fringe projection method, roughness using replica method, dermo-subcutaneous interface length and subcutaneous thickness using ultrasonography and skin temperature using infrared ray, elasticity and blood flow. In Test 2, we applied an anti-cellulite cosmetic to 28 subjects for 6 weeks and observed if they have any changes. RESULTS: In Test 1, the effective parameter that is the most correlated with visual assessment was volume of skin measured using fringe projection method (r = 0.780). Dermo-subcutaneous interface length (r = 0.355) and subcutaneous thickness (r = 0.502) measured using ultrasonography followed in order. In Test 2, after applying a tested product, the correlation coefficient of volume of skin, of dermo-subcutaneous interface length and of subcutaneous thickness are 0.409 (P = 0.000), 0.275 (P = 0.016) and 0.311 (P = 0.012) respectively. CONCLUSION: We conclude that visual assessment, volume of skin (cavities), dermo-subcutaneous interface length and subcutaneous thickness are optimized methods for assessing an effect of cosmetics on cellulite.

Mechanism of metformin: inhibition of DNA damage and proliferative activity in Drosophila midgut stem cell.

Age-related changes in stem cells could have a profound impact on tissue aging and the development of age-related diseases such as cancer. However, the effects of metformin, a recently recognized anti-cancer drug, on stem cell aging remain largely unknown. In the present study, an experiment was set up to investigate the underlying mechanism of metformin's beneficial effects on age-related changes in intestinal stem cells (ISCs) derived from Drosophila midgut. Results showed that metformin reduced age- and oxidative stress-related accumulation of DNA damage marked by Drosophila γH2AX foci and 8-oxo-dG in ISCs and progenitor cells. Metformin also inhibited age and- oxidative stress-related ISC hyperproliferation as well as intestinal hyperplasia. Our study further revealed that the inhibitory effects of metformin on DNA damage accumulation may be due to the down-regulation of age-related and oxidative stress-induced AKT activity. These data indicate that metformin has beneficial effects on age-related changes in ISCs derived from Drosophila midgut. Further, our results suggest a possible impact of DNA damage on stem cell genomic instability, which leads to the development of age-related diseases. Additionally, our study suggests that Drosophila midgut stem cells can be a suitable model system for studying stem cell biology and stem cell aging.

Analysis of the temporal change in biophysical parameters after fractional laser treatments using reflectance confocal microscopy.

BACKGROUND: Fractional photothermolysis is a popular treatment option for photorejuvenation. Previous literature studies have demonstrated the clinical effectiveness of fractional photothermolysis on cutaneous photoaging; however, the associated changes in biophysical properties of the skin following fractional photothermolysis have not been fully elucidated. This study was conducted to investigate the temporal changes in biophysical parameters after fractional laser treatment on Asian skin. MATERIALS AND METHODS: Eleven female subjects underwent a single treatment with an erbium glass fractional laser. Skin roughness, elasticity, transepidermal water loss (TEWL), dermal thickness were evaluated before and immediately after treatment and 3 days, 1 week, 2 weeks, and 4 weeks after treatment. The changes in the dermal papilla were analyzed using a reflectance confocal microscopy (RCM). RESULTS: Skin roughness showed the greatest improvement at the first week and net elasticity was most improved at the second week. TEWL and the percentage of melanized and active dermal papillae (DP) were mostly increased for 3 days. At 4 weeks after treatment, the number of total dermal papillae showed a significant increase compared with pretreatment. CONCLUSION: This is the first study of the characterization and quantification of dermal papilla reflecting the dermal repair process after fractional photothermolysis through an RCM.