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Background: Skin pigmentation is modulated by various processes, with melanogenesis playing a key role. Melanin is synthesized by the catalysis of melanogenesis‐related enzymes, such as tyrosinase and tyrosine‐related proteins TRP‐1 and TRP‐2. Paeoniflorin is the main bioactive component of Paeonia suffruticosa Andr., Paeonia lactiflora., or Paeonia veitchii Lynch and has been used for centuries for its anti‐inflammatory, anti‐oxidant, and anti‐carcinogenic properties. Aims & methods: In this study, melanin biosynthesis in mouse melanoma (B16F10) cells was induced using α‐melanocyte‐stimulating hormone (α‐MSH), and then cells were co‐treated with paeoniflorin to evaluate its potential anti‐melanogenic effect. Results: α‐MSH stimulation increased melanin content, tyrosinase activity, and melanogenesis‐related markers in a dose‐dependent manner. However, treatment with paeoniflorin reversed α‐MSH‐induced upregulation of melanin content and tyrosinase activity. Furthermore, paeoniflorin inhibited cAMP response element‐binding protein activation and TRP‐1, TRP‐2, and microphthalmia‐associated transcription factor protein expression in α‐MSH‐stimulated B16F10 cells. Conclusion: Overall, these findings show the potential of paeoniflorin as a depigmenting agent for cosmetic products. [ABSTRACT FROM AUTHOR]

Lung cancer is a leading cause of cancer‐related death worldwide. In this study, we used lung adenocarcinoma cells as a model, as lung adenocarcinoma has the highest mortality rate among all lung cancers. For the past few years, medical treatments or lung cancer have been limited because of chemotherapy resistance. Therefore, understanding the pathogenesis of the development of drug resistance in lung cancer is urgent. Gemcitabine is widely prescribed in the chemotherapeutic treatment of lung cancers. In this study, we developed gemcitabine‐resistant lung adenocarcinoma cells (A549‐GR) from the A549 cell line. The results showed that apoptotic protein expression and reactive oxygen species (ROS) generation were reduced in A549‐GR cells compared to A549 cells. Interestingly, we found that signal transducer and activator of transcription 3 (STAT3) translocated to the nucleus and mitochondria to affect the apoptotic pathway and ROS generation, respectively. Furthermore, treatment with STAT3 small interfering RNA diminished the increase in ROS production, proliferation and antiapoptotic proteins in A549‐GR cells. Taken together, the study demonstrated that STAT3 acts as an essential regulator and moderates apoptosis through two major mechanisms to induce gemcitabine resistance in cells; and these findings provide a potential target for the treatment of gemcitabine‐resistant lung cancer. [ABSTRACT FROM AUTHOR]

Skin pigmentation is resulted from several processes, such as melanin synthesis transportation and abnormal melanin accumulation in keratinocytes. Various studies have suggested that seven traditional Chinese herbal extracts from Atractylodes macrocephala, Paeonia lactiflora, Bletilla striata, Poria cocos, Dictamnus dasycarpus, Ampelopsis japonica and Tribulus terrestris (which we collectively named ChiBai), show several protective effects toward skin‐related diseases. Lactobacillus rhamnosus, a lactic acid bacterium, has been reported to treat skin inflammation and atopic dermatitis. In this study, the broth produced by the cofermentation of ChiBai with Lactobacillus rhamnosus was studied for its effects on skin pigmentation through in vitro and in vitro experiments. In the in vitro experiments, we found that the fermented broth of ChiBai (FB‐ChiBai) suppressed alpha‐melanocyte stimulating hormone (α‐MSH)‐induced melanogenesis in B16F0 murine melanoma cells without any cytotoxicity at a concentration of 0.5%. FB‐ChiBai significantly attenuated melanin production, tyrosinase activities and melanogenesis‐related signaling pathways. Treatment with FB‐ChiBai also reduced the nuclear translocation and promoter binding activities of MITF. In the in vivo experiments, FB‐ChiBai was topically applied to the dorsal skin of C57BL/6J nude mice and concurrently irradiated with UVB, three times a week for 8 weeks. The results indicated that FB‐ChiBai alleviated UVB‐induced hyperpigmentation by reducing epidermal hyperplasia and inhibiting the CREB/MITF/tyrosinase pathway. In conclusion, our data indicated that the anti‐melanogenic effects of FB‐ChiBai are mediated by the inhibition of CREB/MITF/tyrosinase signaling pathway. The findings suggest that FB‐ChiBai can protect against UV‐B irradiation and that it might be used as an agent in cosmetic products to protect against UVB‐induced hyperpigmentation. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) irradiation is a crucial factor that leads to skin photoaging and results in increased DNA damage, oxidative stress, and collagen degradation. Jasmine flowers have been utilized as a traditional medicine in Asia to treat various diseases, including dermatitis, diarrhea, and fever. Furthermore, the fermented broth of Lactobacillus rhamnosus has been reported to exert protective effects on the skin. In the present study, jasmine flower extract was fermented with L. rhamnosus. We investigated the antioxidant and collagen‐promoting effects on UVB/H2O2‐induced HS68 dermal fibroblast cell damage. The results indicated that treatment with the fermented flower extracts of Jasminum sambac (F‐FEJS) could enhance the viability of HS68 cells. Furthermore, the UVB/H2O2‐induced excessive production of reactive oxygen species, degradation of collagen, activation of MAPKs, including P38, ERK, and JNK, and premature senescence were remarkably attenuated by F‐FEJS in dermal fibroblast cells. The nuclear accumulation of p‐c‐jun, which is downstream of MAPK, and the inactivation of p‐smad2/3, which is one of the crucial transcription factors that enhance collagen synthesis, were reversed in response to F‐FEJS treatment in UVB/H2O2‐exposed cells. Notably, the expression of antioxidant genes, such as HO‐1, and the nuclear translocation of Nrf2 were further enhanced by F‐FEJS in UVB/H2O2‐treated cells. Interestingly, the F‐FEJS‐induced increase in ARE luciferase activity indicated the activation of Nrf2/ARE signaling. In conclusion, our findings demonstrated that F‐FEJS can effectively ameliorate UVB/H2O2‐induced dermal cell aging and may be considered a promising ingredient in skin aging therapy. [ABSTRACT FROM AUTHOR]

Galangin, a natural flavonol, has anti‐inflammatory and antioxidative potential. However, the cytoprotective effects of galangin against oxidative‐induced aging in human fibroblasts have not been well studied. IGF‐1 signaling pathway is associated with the control of aging and longevity in human. The goal of this study was to investigate the effects of galangin on human skin fibroblast HS68 cells under H2O2 exposure to induce aging. In this study, we demonstrate that galangin could decrease the levels of pro‐inflammatory proteins and enhanced collagen formation through promoting the IGF‐1R pathway. Furthermore, aging markers such as senescence‐associated β‐galactosidase p53, p21Cip1/WAF1, and p16INK4A were upregulated under H2O2 exposure and galangin could reverse its effects. Taken together, these data indicated that anti‐inflammatory and antiaging activities of galangin may be mediated through the IGF‐1R signaling pathway. These findings may provide the evidence for galangin to develop as an antiwrinkle product on human skin. [ABSTRACT FROM AUTHOR]

Abstract: The physiological regulation of Oestrogen receptor α (ERα) and peroxisome proliferator‐activated receptor alpha (PPARα) in Hepatocellular carcinoma (HCC) remains unknown. The present study we first treat the cells with fenofibrate and further investigated the possible mechanisms of 17β‐estradiol (E2) and/or ERα on regulating PPARα expression. We also found higher PPARα expression in the tumor area than adjacent areas and subsequently compared PPARα expression in four different hepatic cancer cell lines. Hep3B cells were found to express more PPARα than the other cell lines. Using the PPARα agonist fenofibrate, we found that fenofibrate increased Hep3B cell proliferation efficiency by increasing cell cycle proteins, such as cyclin D1 and PCNA, and inhibiting p27 and caspase 3 expressions. Next, we performed transient transfections and immuno‐precipitation studies using the pTRE2/ERα plasmid to evaluate the interaction between ERα and PPARα. ERα interacted directly with PPARα and negatively regulated its function. Moreover, in Tet‐on ERα over‐expressed Hep3B cells, E2 treatment inhibited PPARα, its downstream gene acyl‐CoA oxidase (ACO), cyclin D1 and PCNA expression and further increased p27 and caspase 3 expressions. However, over‐expressed ERα plus 17‐β‐estradiol (10−8 M) reversed the fenofibrate effect and induced apoptosis, which was blocked in ICI/melatonin/fenofibrate‐treated cells. This study illustrates that PPARα expression and function were negatively regulated by ERα expression in Hep3B cells. [ABSTRACT FROM AUTHOR]

Background Doxorubicin (Dox) is an effective anticancer agent. However, its effectiveness is limited by its cardiotoxic effects. It has also been reported that the mitogen-activated protein kinase family and NF-κB can be activated by Dox treatment. DATS has been shown to be a potent antioxidant with cardioprotective effects. We investigate whether Dox induces cardiac apoptosis through JNK- and ERK-dependent NF-κB upregulation that can be reduced by DATS treatment. Methods and Material H9c2 cells were treated with 0.5-1.5 μM Dox for 24 hours. Dox promoted apoptosis and ROS generation and inhibited viability in a dose-dependent manner. Then, the phosphorylation levels of JNK, ERK, and NF-κB evaluated by western blot were elevated. We used inhibitors of JNK, ERK, and NF-κB to determine which of these proteins were involved in Dox-induced apoptosis. Furthermore, Dox-exposed cells were treated with DATS at doses of 1, 5, and 10 μM, and the data demonstrated that ROS generation and apoptotic proteins were decreased and that ERK and NF-κB were downregulated in a dose-dependent manner. Additionally, six-week-old rats were divided into three groups ( n = 6 per group) designed as an eight-week study. Normal, Dox (at dose 3.75 mg/kg by ip) administered with or without DATS (at dose 40 mg/kg by gavage) treatment groups. The results indicate that cardiac dysfunction, apoptosis, and JNK, ERK, and NF-κB activation by Dox were reversed by treatment with DATS. Conclusion DATS appears to suppress Dox-induced cardiomyocyte apoptosis by inhibiting NADPH oxidase-related ROS production and the downstream JNK/ERK/NF-κB signaling pathway; DATS may possess clinical therapeutic potential by blocking Dox-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Human skin aging is a progressive process that includes intrinsic aging and extrinsic photodamage, both of which can cause an accumulation of reactive oxygen species (ROS), resulting in dermal fibrosis dysfunction and wrinkle formation. Galangin is a flavonoid that exhibits anti-inflammatory and antioxidative potential. Previous studies have reported that galangin has antioxidative activity against ROS-mediated stress. The aim of the present study is to determine the antiaging effects of galangin on dermal fibroblasts exposed to H2O2. In this study, we established a hydrogen peroxide-induced inflammation and aging model using human HS68 dermal fibroblasts. Stimulation of fibroblasts with H2O2 is associated with skin aging and increased expression of inflammation-related proteins, along with downregulation of collagen I/III formation and expression of antioxidative proteins. Galangin effectively reduced NF-κB activation, the expression of inflammation-related proteins and cell aging. Galangin also reversed H2O2-activated cell senescence in HS68 cells. Our results reveal that galangin protects human dermal fibroblasts by inhibiting NF-κB activation, decreases the expression of inflammatory factors and upregulates IGF1R/Akt-related proteins, indicating that galangin may be a potential candidate for developing natural antiaging products that protect skin from damage caused by ROS. [ABSTRACT FROM AUTHOR]

ABSTRACT The Warburg effect plays a critical role in tumorigenesis, suggesting that specific agents targeting Warburg effect key proteins may be a promising strategy for cancer therapy. Previous studies have shown that diallyl trisulfide (DATS) inhibits proliferation of breast cancer cells by inducing apoptosis in vitro and in vivo. However, whether the Warburg effect is involved with the apoptosis-promoting action of DATS is unclear. Here, we show that the action of DATS is associated with downregulation of lactate dehydrogenase A (LDHA), an essential protein of the Warburg effect whose upregulation is closely related to tumorigenesis. Interestingly, inhibition of the Warburg effect by DATS in breast cancer cells did not greatly affect normal cells. Furthermore, DATS inhibited growth of breast cancer cells, particularly in MDA-MB-231, a triple-negative breast cancer (TNBC) cell, and reduced proliferation and migration; invasion was reversed by over-expression of LDHA. These data suggest that DATS inhibits breast cancer growth and aggressiveness through a novel pathway targeting the key enzyme of the Warburg effect. Our study shows that LDHA downregulation is involved in the apoptotic effect of DATS on TNBC. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1390-1398, 2017. [ABSTRACT FROM AUTHOR]

In this study, the antitumor activity of KHC-4 was analyzed using human prostate cancer (CaP) cells and the underlining anticancer mechanisms of KHC-4 were identified. KHC-4 inhibited cell proliferation and induced cytotoxicity in the castration-resistant CaP DU145 cell line. The most effective concentration of KHC-4 was 0.1 μM. Cell cycle analysis demonstrated that KHC-4 treatment caused G2/M arrest and a subsequent increase in the sub-G1 population. Furthermore, KHC-4 is up-regulated p21, p27, and p53 in a time- and concentration-dependent manner. The exposure of cells to KHC-4 induced Cdk1/cyclin B1 complex activity, which led to cell cycle arrest. Moreover, KHC-4 inhibited the activities of MMP-2 and MMP-9 to inhibit tumor cell metastasis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1879-1887, 2016. [ABSTRACT FROM AUTHOR]

ABSTRACT Consumption of deep sea minerals (DSM), such as magnesium, calcium, and potassium, is known to reduce hypercholesterolemia-induced myocardial hypertrophy and cardiac-apoptosis and provide protection against cardiovascular diseases. Heart diseases develop as a lethal complication among diabetic patients usually due to hyperglycemia-induced cardiac-apoptosis that causes severe cardiac-damages, heart failure, and reduced life expectancy. In this study, we investigated the potential of DSM and its related cardio-protection to increase the life expectancy in diabetic rats. In this study, a heart failure rat model was developed by using streptozotocin (65 mg kg−1) IP injection. Different doses of DSM-1× (37 mg kg−1 day−1), 2× (74 mg kg−1 day−1) and 3× (111 mg kg−1 day−1), were administered to the rats through gavages for 4 weeks. The positive effects of DSM on the survival rate of diabetes rats were determined with respect to the corresponding effects of MgSO4. Further, to understand the mechanism by which DSM enhances the survival of diabetic rats, their potential to regulate cardiac-apoptosis and control cardiac-dysfunction were examined. Echocardiogram, tissue staining, TUNEL assay, and Western blotting assay were used to investigate modulations in the myocardial contractile function and related signaling protein expression. The results showed that DSM regulate apoptosis and complement the cardiomyocyte proliferation by enhancing survival mechanisms. Moreover DSM significantly reduced the mortality rate and enhanced the survival rate of diabetic rats. Experimental results show that DSM administration can be an effective strategy to improve the life expectancy of diabetic subjects by improving cardiac-cell proliferation and by controlling cardiac-apoptosis and associated cardiac-dysfunction. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 769-781, 2016. [ABSTRACT FROM AUTHOR]

Non-invasive and quantitative estimations for the delineation of sub-surface tumor margins could greatly aid in the early detection and monitoring of the morphological appearances of tumor growth, ensure complete tumor excision without the unnecessary sacrifice of healthy tissue, and facilitate post-operative follow-up for recurrence. In this study, a high-speed, non-invasive, and ultra-high-resolution spectral domain optical coherence tomography (UHR-SDOCT) imaging platform was developed for the quantitative measurement of human sub-surface skin mass. With a proposed robust, semi-automatic analysis, the system can rapidly quantify lesion area and shape regularity by an en-face-oriented algorithm. Various sizes of nylon sutures embedded in pork skin were used first as a phantom to verify the accuracy of our algorithm, and then in vivo, feasibility was proven using benign human angiomas and pigmented nevi. Clinically, this is the first step towards an automated skin lesion measurement system. [ABSTRACT FROM AUTHOR]