Skin aging is a process of structural and compositional remodeling that can be manifested by wrinkling and sagging. Remarkably, the dermis plays a dominant role in the aging process. Recent studies suggest that microR...Skin aging is a process of structural and compositional remodeling that can be manifested by wrinkling and sagging. Remarkably, the dermis plays a dominant role in the aging process. Recent studies suggest that microRNAs are implicated in the regulation of gene expression during aging. However, studies about age-related microRNAs and how they modulate skin aging remain limited. In the present work, a complex of hydrolyzed natural yeast proteins (Saccharomyces cerevisiae) and hydrolyzed natural soya bean was developed and showed the ability to modulate the expression of telomere-binding protein TRF2, which is a key factor for telomere protection and to prevent cellular senescence in vitro and DNA damage. The aim of the study was to identify microRNAs specifically modulated after application of the ingredient complex to cultured fibroblasts, and their possible involvement in remodeling of the human extracellular matrix and fibroblast senescence. Consequently, human skin fibroblasts were cultured and treated with 1% of the ingredient complex for 48 h before analyzing microRNA modulation by RT-qPCR. The use of bioinformatics allowed us to predict the target genes for modulated microRNAs. Results show that the ingredient complex modulated a pattern of microRNAs including the down-regulation of miR-29a-3p, miR-30a-5p and miR-34a-5p, which are associated with fibroblast senescence and remodeling of the human dermal extracellular matrix. In conclusion, our results indicate that miR-29a-3p, miR-30a-5p and miR-34a-5p possibly represent key microRNAs that impact human fibroblast senescence and remodeling of the dermal extracellular matrix.展开更多
As human skin is daily exposed to oxidative stress causing various unesthetical abnormalities, the road to effective anti-aging substances is being widely investigated. 20S proteasome is a key pathway in the breakdown...As human skin is daily exposed to oxidative stress causing various unesthetical abnormalities, the road to effective anti-aging substances is being widely investigated. 20S proteasome is a key pathway in the breakdown of oxidized proteins. But its activity declines dramatically in aging cells. Nrf2 inducers -lipoic acid (LA) and sulforaphane (SFN) have been described in the dietary industries for their antioxidant effects on various cell lines. However, since little is yet known about LA’s capacity to protect skin cells from premature and extrinsic aging;our aim was to demonstrate the beneficial effect of LA on the cellular detoxification systems. On this purpose, we evaluated its effects against injuries induced by H2O2 in NHDF and its likely positive effect on the chymotrypsin-like (CT-like) activity of 20S proteasome, using SFN as a reference. The cellular content in proteins was measured, as well as the production of Reactive Oxygen Species (ROS). Also, the induction of the proteasomal protein expression was investigated. The results show that after 48 h treatment, LA significantly decreased the percentage of ROS positive cells. Also, LA decreased the level of H2O2-induced carbonylated proteins and increased the proteasomal activity. Furthermore, LA upregulated the expression of the 20S proteasome ß-subunit responsible for the CT-like activity (PSMB5). Overall, both molecules enhanced cell proliferation over 8 days. So, our investigation found evidence of the higher capacity of LA to induce 20S proteasome activity with less toxicity in human fibroblasts compared to reference molecule SFN. These results tend to demonstrate that the induction of the proteasomal activity might be a part of the antioxidant potential of LA. To our knowledge, this is the first study to elucidate the capacity of LA to activate detoxification systems in human cell lines through the induction of 20S proteasome.展开更多
Objective:Hypertrophic scars(HS)are a variety of skin tissue fibrosis disease that occurs in human skin,the effective therapeutic method of which is still inaccessible up to now.As a bioactive constituent of a well-kn...Objective:Hypertrophic scars(HS)are a variety of skin tissue fibrosis disease that occurs in human skin,the effective therapeutic method of which is still inaccessible up to now.As a bioactive constituent of a well-known medical plant,Salvia miltiorrhiza(Danshen in Chinese),tanshinone Ⅱ_(A)(TSA)is reported to inhibit cell proliferation in HS.Therefore,the aim of this study was to prepare TSA self-soluble microneedles to strengthen its dermal retention and break through the difficulty of significantly thickening epidermal connective tissue and stratum corneum at the HS site.The possible mechanism of action in suppressing HS was studied using human skin fibroblasts(HSF).Methods:Tanshinone Ⅱ_(A) self-dissolving microneedles(TSA-MN)was prepared using a negative mold casting method.The prescription process of microneedle was optimized by Box-Behnken effect surface method.Different media were selected to investigate the ability of transdermal absorption and in vitro release.Furthermore,according to Cell Counting Kit-8(CCK8)method as well as the Western blot method,the effect of TSA-MN on the biological characteristics of HSF was investigated.Results:With remarkable slow release effect and dermal retention,the release and transdermal properties of TSA-MN in vitro were better than both TSA and ordinary dosage forms.Its effect of HSF confirmed the essential decrease in cell motility during cell proliferation and cell migration in vitro,which plays a significant role in down-regulating the secretion of transforming growth factor-β1(TGF-β1)in HSF and increasing the expression level of Smad7.Conclusion:The prepared TSA self-soluble microneedles is helpful in solving the problem of hypertrophic scars,with a stable dermal retention effect after process optimization.展开更多
Skin aging shows an imbalance between synthesis and degradation of the extracellular matrix. The overproduction of degradative enzymes (MMPs) during the chronology- and photo-induced aging leads to a degradation of th...Skin aging shows an imbalance between synthesis and degradation of the extracellular matrix. The overproduction of degradative enzymes (MMPs) during the chronology- and photo-induced aging leads to a degradation of the elastic and collagen networks. In a model of collagen and elastin destruction, we showed that the gingival fibroblast was able to preserve these macromolecules by inhibiting the overproduction of metalloproteinases by overproduction of TIMP-1 and modulation of the inflammatory cytokines activity. The objective of this study is to evaluate the effect of the gingival fibroblasts on human skin. The results in vitro and ex vivo show that the gingival fibroblast protects the skin collagen and elastic network by the inhibition of MMPs which leads to an overproduction of the TIMP-1. Moreover, the gingival fibroblast modulates the activity of some enzymes responsible for the inflammation;they inhibit the IL-1β and stimulate the production of TGF-β1. In vivo studies with a duration of six months and 50 women with pronounced wrinkles show that the culture supernatant of gingival fibroblasts diluted to 5% leads to a statistically significant decrease in the number and length of wrinkles.展开更多
A study on the effect of the solar ultra-violet radiation on the human skin fibroblast cells revealed that the production of matrix metalloproteinase-2 was inhibited by the radiation.A CO2 incubator connected by optic...A study on the effect of the solar ultra-violet radiation on the human skin fibroblast cells revealed that the production of matrix metalloproteinase-2 was inhibited by the radiation.A CO2 incubator connected by optical fibers to a reflector telescope for collecting the solar light was built at Syowa station by the 49th Japanese Antarctica Research Expedition.The direction of the telescope was continuously controlled by a sun-tracker to follow the movement of the Sun automatically.The intensity of the collected light was monitored by a portable spectrophotometer housed inside.The human skin fibroblast cells were incubated in the CO2 chamber to investigate the effect of the solar radiation at Syowa station and were compared with those reference experiments at a laboratory in Japan.The results showed cell damage by strong UV radiation.The production of matrix metalloproteinase-2 was prompted by the moderate UV-B,but was inhibited by the strong UV-B radiation,as studied under laboratory conditions in Japan.The effect of strong solar radiation at Syowa station involving the radiation of UV-B region was estimated to be of the same extent of the radiation caused by an artificial UV-B light with the intensity more than 50 mJ/cm2.展开更多
文摘Skin aging is a process of structural and compositional remodeling that can be manifested by wrinkling and sagging. Remarkably, the dermis plays a dominant role in the aging process. Recent studies suggest that microRNAs are implicated in the regulation of gene expression during aging. However, studies about age-related microRNAs and how they modulate skin aging remain limited. In the present work, a complex of hydrolyzed natural yeast proteins (Saccharomyces cerevisiae) and hydrolyzed natural soya bean was developed and showed the ability to modulate the expression of telomere-binding protein TRF2, which is a key factor for telomere protection and to prevent cellular senescence in vitro and DNA damage. The aim of the study was to identify microRNAs specifically modulated after application of the ingredient complex to cultured fibroblasts, and their possible involvement in remodeling of the human extracellular matrix and fibroblast senescence. Consequently, human skin fibroblasts were cultured and treated with 1% of the ingredient complex for 48 h before analyzing microRNA modulation by RT-qPCR. The use of bioinformatics allowed us to predict the target genes for modulated microRNAs. Results show that the ingredient complex modulated a pattern of microRNAs including the down-regulation of miR-29a-3p, miR-30a-5p and miR-34a-5p, which are associated with fibroblast senescence and remodeling of the human dermal extracellular matrix. In conclusion, our results indicate that miR-29a-3p, miR-30a-5p and miR-34a-5p possibly represent key microRNAs that impact human fibroblast senescence and remodeling of the dermal extracellular matrix.
文摘As human skin is daily exposed to oxidative stress causing various unesthetical abnormalities, the road to effective anti-aging substances is being widely investigated. 20S proteasome is a key pathway in the breakdown of oxidized proteins. But its activity declines dramatically in aging cells. Nrf2 inducers -lipoic acid (LA) and sulforaphane (SFN) have been described in the dietary industries for their antioxidant effects on various cell lines. However, since little is yet known about LA’s capacity to protect skin cells from premature and extrinsic aging;our aim was to demonstrate the beneficial effect of LA on the cellular detoxification systems. On this purpose, we evaluated its effects against injuries induced by H2O2 in NHDF and its likely positive effect on the chymotrypsin-like (CT-like) activity of 20S proteasome, using SFN as a reference. The cellular content in proteins was measured, as well as the production of Reactive Oxygen Species (ROS). Also, the induction of the proteasomal protein expression was investigated. The results show that after 48 h treatment, LA significantly decreased the percentage of ROS positive cells. Also, LA decreased the level of H2O2-induced carbonylated proteins and increased the proteasomal activity. Furthermore, LA upregulated the expression of the 20S proteasome ß-subunit responsible for the CT-like activity (PSMB5). Overall, both molecules enhanced cell proliferation over 8 days. So, our investigation found evidence of the higher capacity of LA to induce 20S proteasome activity with less toxicity in human fibroblasts compared to reference molecule SFN. These results tend to demonstrate that the induction of the proteasomal activity might be a part of the antioxidant potential of LA. To our knowledge, this is the first study to elucidate the capacity of LA to activate detoxification systems in human cell lines through the induction of 20S proteasome.
基金supported by the National Natural Science Foundation of China(No.82173982,2021)the Guangdong Natural Science Project(No.2018A0303130234)Excellent Young Teachers Training Project in Higher Education of Guangdong(No.YQ2015099).
文摘Objective:Hypertrophic scars(HS)are a variety of skin tissue fibrosis disease that occurs in human skin,the effective therapeutic method of which is still inaccessible up to now.As a bioactive constituent of a well-known medical plant,Salvia miltiorrhiza(Danshen in Chinese),tanshinone Ⅱ_(A)(TSA)is reported to inhibit cell proliferation in HS.Therefore,the aim of this study was to prepare TSA self-soluble microneedles to strengthen its dermal retention and break through the difficulty of significantly thickening epidermal connective tissue and stratum corneum at the HS site.The possible mechanism of action in suppressing HS was studied using human skin fibroblasts(HSF).Methods:Tanshinone Ⅱ_(A) self-dissolving microneedles(TSA-MN)was prepared using a negative mold casting method.The prescription process of microneedle was optimized by Box-Behnken effect surface method.Different media were selected to investigate the ability of transdermal absorption and in vitro release.Furthermore,according to Cell Counting Kit-8(CCK8)method as well as the Western blot method,the effect of TSA-MN on the biological characteristics of HSF was investigated.Results:With remarkable slow release effect and dermal retention,the release and transdermal properties of TSA-MN in vitro were better than both TSA and ordinary dosage forms.Its effect of HSF confirmed the essential decrease in cell motility during cell proliferation and cell migration in vitro,which plays a significant role in down-regulating the secretion of transforming growth factor-β1(TGF-β1)in HSF and increasing the expression level of Smad7.Conclusion:The prepared TSA self-soluble microneedles is helpful in solving the problem of hypertrophic scars,with a stable dermal retention effect after process optimization.
文摘Skin aging shows an imbalance between synthesis and degradation of the extracellular matrix. The overproduction of degradative enzymes (MMPs) during the chronology- and photo-induced aging leads to a degradation of the elastic and collagen networks. In a model of collagen and elastin destruction, we showed that the gingival fibroblast was able to preserve these macromolecules by inhibiting the overproduction of metalloproteinases by overproduction of TIMP-1 and modulation of the inflammatory cytokines activity. The objective of this study is to evaluate the effect of the gingival fibroblasts on human skin. The results in vitro and ex vivo show that the gingival fibroblast protects the skin collagen and elastic network by the inhibition of MMPs which leads to an overproduction of the TIMP-1. Moreover, the gingival fibroblast modulates the activity of some enzymes responsible for the inflammation;they inhibit the IL-1β and stimulate the production of TGF-β1. In vivo studies with a duration of six months and 50 women with pronounced wrinkles show that the culture supernatant of gingival fibroblasts diluted to 5% leads to a statistically significant decrease in the number and length of wrinkles.
基金fnancially supported partly by the Grand-In-Aid for Scientifc Research(C)18510022 and (C)21510032 of Japan Society for the promotion of Science
文摘A study on the effect of the solar ultra-violet radiation on the human skin fibroblast cells revealed that the production of matrix metalloproteinase-2 was inhibited by the radiation.A CO2 incubator connected by optical fibers to a reflector telescope for collecting the solar light was built at Syowa station by the 49th Japanese Antarctica Research Expedition.The direction of the telescope was continuously controlled by a sun-tracker to follow the movement of the Sun automatically.The intensity of the collected light was monitored by a portable spectrophotometer housed inside.The human skin fibroblast cells were incubated in the CO2 chamber to investigate the effect of the solar radiation at Syowa station and were compared with those reference experiments at a laboratory in Japan.The results showed cell damage by strong UV radiation.The production of matrix metalloproteinase-2 was prompted by the moderate UV-B,but was inhibited by the strong UV-B radiation,as studied under laboratory conditions in Japan.The effect of strong solar radiation at Syowa station involving the radiation of UV-B region was estimated to be of the same extent of the radiation caused by an artificial UV-B light with the intensity more than 50 mJ/cm2.
