AHAs are organic acids with one hydroxyl group attached to the alpha position of the acid. AHAs including glycolic acid, lactic acid, malic acid, tartaric acid, and citric acid are often used extensively in cosmetic formulations. AHAs have been used as superficial peeling agents as well as to ameliorate the appearance of keratoses and acne in dermatology. However, caution should be exercised in relation to certain adverse reactions among patients using products with AHAs, including swelling, burning, and pruritus. Whether AHAs enhance or decrease photo damage of the skin remains unclear, compelling us to ask the question, is AHA a friend or a foe of the skin? The aim of this manuscript is to review the various biological effects and mechanisms of AHAs on human keratinocytes and in an animal model. We conclude that whether AHA is a friend or foe of human skin depends on its concentration. These mechanisms of AHAs are currently well understood, aiding the development of novel approaches for the prevention of UV-induced skin damage.

Epithelial-mesenchymal transition (EMT) is considered a critical event in the pathogenesis of lung fibrosis and tumor metastasis. During EMT, the expression of differentiation markers switches from cell-cell junction proteins such as E-cadherin to mesenchymal markers such as fibronectin. Although nickel-containing compounds have been shown to be associated with lung carcinogenesis, the role of nickel in the EMT process in bronchial epithelial cells is not clear. The aim of this study was to examine whether nickel contributes to EMT in human bronchial epithelial cells. We also attempted to clarify the mechanisms involved in NiCl₂-induced EMT. Our results showed that NiCl₂ induced EMT phenotype marker alterations such as up-regulation of fibronectin and down-regulation of E-cadherin. In addition, the potent antioxidant N-acetylcysteine blocked EMT and expression of HIF-1α induced by NiCl₂, whereas the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine restored the down-regulation of E-cadherin induced by NiCl₂. Promoter hypermethylation of E-cadherin, determined by quantitative real time methyl-specific PCR and bisulfate sequencing, was also induced by NiCl₂. These results shed new light on the contribution of NiCl₂ to carcinogenesis. Specifically, NiCl₂ induces down-regulation of E-cadherin by reactive oxygen species generation and promoter hypermethylation. This study demonstrates for the first time that nickel induces EMT in bronchial epithelial cells.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are newly discovered long-chain fatty acids. However, the major endogenous FAHFAs in healthy human circulation, their correlation with cardiovascular (CV) biomarkers, and their anti-inflammatory effects have not been investigated and remain unclear. In the present study, a total of 57 healthy subjects were recruited. Liquid chromatography–mass spectrometry (LC-MS) was developed for the simultaneous determination of seven FAHFAs, four long-chain fatty acids, and four non-traditional circulating CV-related biomarkers. We found two major types of FAHFAs in healthy human circulation, palmitoleic acid ester of 9-hydroxystearic acid (9-POHSA), and oleic acid ester of 9-hydroxystearic acid (9-OAHSA). Both 9-POHSA and 9-OAHSA had a strong positive correlation with each other and were negatively correlated with fasting blood glucose, S-adenosyl-l-homocysteine (SAH), and trimethylamine N-oxide (TMAO), but not with l-homocysteine. 9-POHSA was also positively correlated with l-carnitine. Moreover, we confirmed that both 9-POHSA and 9-OAHSA exhibited an anti-inflammatory effect by suppressing LPS stimulated cytokines, including IL-1β and IL-6 in RAW 264.7 cells. In addition, palmitoleic acid also had a positive correlation with 9-POHSA and 9-OAHSA. As far as we know, this is the first report showing the major endogenous FAHFAs in healthy subjects and their CV protection potential which might be correlated with SAH and TMAO reduction, l-Carnitine elevation, and their anti-inflammatory effects.

Background: Chronic exposure to ultraviolet (UV) rays causes severe skin damage by inducing oxidative stress and inflammation. Identifying a safe and natural substance for skin protection is a crucial research goal. Objective: The aim of this study was to clarify the effects of genistein on skin inflammation and photoaging by using 3 models (humans: skin parameters; animals: wrinkle formation; and cells: anti-inflammatory effects). Methods: Food frequency questionnaire data and serum and skin parameter data from 120 volunteers (a group with a genistein-rich diet [RG group] and a control group). Human keratinocytes were pretreated with genistein before ultraviolet B (UVB) irradiation. Genistein was topically applied to the dorsal skin of rats. Results: The blood samples of the RG group had lower serum uric acid levels and blood urea nitrogen levels. The dynamic elasticity level in the RG group was higher than that in the controls. Genistein pretreatment suppressed the expression of proinflammatory cytokines (CXCL1, IL-1, MIF, and PLANH1) and the proteins released by UVB-treated keratinocytes. Topical application of genistein to the dorsal skin of rats reduced the severity of UVB-induced wrinkling. Both intake and topical application of genistein combated UVB-induced inflammation and aging. Conclusions: Genistein could be used as a safe and natural compound for use in novel anti-inflammatory agents for topical application. Graphical The experimental design procedure, including the skin parameter and blood serum measurements of 137 participants. Genistein-rich compounds provide protection against UVB-induced inflammation, as determined using in vitro and in vivo animal model experiments.

Ultraviolet-B exposure causes an inflammatory response, photoaged skin, and degradation of extracellular matrix proteins including collagen and elastin. The regulation of these genes was suggested as an important mechanism to attenuate skin aging. Glycolic acid (GA) is commonly present in fruits and recently used to treat dermatological diseases. We reported that GA slows down cell inflammation and aging caused by UVB. Little is known about GA retarding the skin premature senescence or how to impede these events. To investigate the potential of GA to regulate the expression of MMPs and collagen, GA was topically applied onto human keratinocytes and the C57BL/6J mice dorsal skin. In the present study, we demonstrated that GA reduced UVB-induced type-I procollagen expression and secretory collagen levels. GA reverted and dose-dependently increased the level of aquaporin-3 (AQP3), the expression of which was down-regulated by UVB. The UV-induced MMP-9 level and activity were reduced by GA pre-treatment. Concomitantly, GA reverted mitogen-activated protein kinase (MMP-9) activation and inhibited the extracellular signal-regulated kinase activation (p38, pERK) triggered by UVB. The animal model also presented that GA attenuated the wrinkles caused by UVB on the mouse dorsal skin. Finally, GA triggers the transient receptor potential vanilloid-1 (TRPV-1) channel to initiate the anti-photoaging mechanism in keratinocytes. These findings clearly indicated that the mechanisms of GA promote skin protection against UVB-induced photoaging and wrinkle formation. GA might be an important reagent and more widely used to prevent UVB-induced skin aging.