• Tuberculosis and Respiratory Diseases
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• v.80 no.2
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• pp.179-186
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• 2017

Background: Although the World Health Organization (WHO) classification of lung squamous cell carcinoma (SCC) was revised in 2015, its clinical implications for lung SCC subsets remain unclear. We investigated whether the morphologic characteristics of lung SCC, including keratinization, were associated with clinical parameters and clinical outcome of patients. Methods: A total of 81 patients who underwent curative surgical resection of diagnosed lung SCC, were enrolled in this study. Attributes such as keratinization, tumor budding, single cell invasion, and nuclear size within the tumor, as well as immunohistochemistry of Bcl-xL and pS6 expressions, were evaluated. Results: The keratinizing and nonkeratinizing subtypes did not differ with respect to age, sex, TNM stage, and morphologic parameters such as nuclear diameter, tumor budding, and single cell invasion at the tumor edge. Most patients with the keratinizing subtype (98.0%) had a history of smoking, whereas the nonkeratinizing group had a relatively higher proportion of never-smokers relative to the keratinizing group (24.0% vs. 2.0%; p=0.008, chi-square test). Expression of pS6 (a surrogate marker of mammalian target of rapamycin complex 1 [mTORC1] signaling that regulates keratinocyte differentiation), and Bcl-xL (a key anti-apoptotic molecule that may inhibit keratinization), did not correlate significantly with the presence of keratinization. Patients with the keratinizing subtype had a significantly shorter overall survival (85.2 months vs. 135.7 months, p=0.010, log-rank test), and a multivariate analysis showed that keratinization was an independent, poor prognostic factor (hazard ratio, 2.389; 95% confidence interval, 1.090-5.233; p=0.030). Conclusion: In lung SCC, keratinization is associated with a poor prognosis, and might be associated with smoking.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.2 s.33
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• pp.47-67
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• 2007

Objective : As a result of increasing amount of ultraviolet ray, skin problems including sunburn, rapid skin aging, melanoma, and even skin cancer continue to rise. In the present study, the effect of oriental herbal extract, Daehwanggo(大黃膏,DH) and Daehwanggogasnagbakpi(大黃膏加桑白皮,DS), as external application, on the skin damage, was investigated. Methods : 30 mice were equally distributed into 3 groups : control, UVB-control and UVB-irradiated and DS-treated group. Also mouse melanoma cell lines were cultured. Tyrosinase inhibition was measured to analyze the UN-protection effect. Melanogenesis in the UV-irradiated melanoma cell lines was compared in DS-treated cell line and control cell line. Sample skin from the ear tissue of the 3 groups were analyzed to observe the inflammatory response, T cell differentiation, apoptosis of keratinocytes. Results : The tyrosinase was more significantly inhibited in the DS group compared to DH group. Antioxidative effects was more prominent in DS group when superoxide dismutase was measured. Both the DS- and DH-treated cell lines showed significantly reduced melanogenesis. The reduction of external skin damage including erythematous papule, eczema, keratinocyte, pyopoiesis was observed in the DS- and DH-treated sample cells. In terms of the effect on the skin damage, sunburn cell, activated skin mast cells, secretion of IL-12, manifestation of HSP70, hyperplasia of epithelial cells, MMP-9 and destruction of the collagen were all significantly improved in the DS-treated sample cells. Melanin cells and the apoptosis in the melanoma cell line were decreased. Conclusion : DH and DS were traditionally applied externally for the scald in the oriental medicine. The present study elucidated the possibility of herbal extracts to be used as ultraviolet protectives. Further investigations are needed to assure the clinical application.

• KSBB Journal
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• v.29 no.1
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• pp.36-41
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• 2014

Skin disease is one of the most common diseases and its incidence is increasing dramatically in modern society. Specially, many attempts have been made to treat chronic skin inflammation diseases, such as psoriasis and atopic dermatitis, but effective therapies for the immune cell-mediated skin diseases, including psoriasis and atopic dermatitis have not been developed. Until recently, several drug candidates which were claimed to be effective for skin diseases have been reported, but most of them are not used to treat chronic skin disease. Especially, Psoriasis is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells and various immune-related cytokines. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators are up-regulated in psoriasis development. Contact- and mediator-dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. TMP and its derivatives themselves effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors. However, TMP and its derivatives induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP and derivatives, a liposomal formulation was prepared and tested for its effectiveness. TMP and derivatives liposomes retained the effectiveness of TMP in vitro while side effects were reduced. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis, with the possibility that use as a psoriasis relief agent.

• Food Science and Preservation
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• v.24 no.2
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• pp.320-324
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• 2017

Eruca sativa is a rocket plant and a member of the Brassicaceae, which is considered to be an important chemo-preventive plant family. Although Eruca sativa has positive biological effects, the effect of Eruca sativa extract (ES) on improvement of skin barrier function has not been reported. In this study, we investigated the applicability of functional materials by examining a variety of physiological activities of Eruca sativa extract. ES showed anti-microbial activities against Bacillus subtilis, Escherichia coli, and Candida albicans. In particular, antimicrobial activities of ES against B. subtilis was the highest. Additionally, immunohistochemical analysis of protein marker related to keratinocyte differentiation was determined. The treatment by ES (50 mg/L) showed a significant increase of involucrin expression compared with treatment by 0.1% DMSO as a control in skin equivalents, the ES-treated group showed similar level in the expression of involucrin compared to the group treated with the same concentration of WY14643 in $EpiDerm^{TM}$, a three-dimensional model of skin equivalents. These results indicate that ES promotes the expression of protein related to barrier properties of the skin. Therefore, ES may be an effective ingredient for skin barrier improvement.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.274-281
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• 2020

Background: Ultraviolet (UV) goes through the epidermis and promotes release of inflammatory cytokines in keratinocytes. Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of the keratinocyte-derived cytokines, regulates proliferation and differentiation of melanocytes. Extracellular signal-regulated kinase (ERK1/2) and protein kinase C (PKC) signaling pathways regulate expression of GM-CSF. Based on these results, we found that ginsenoside Rh3 prevented GM-CSF production and release in UV-B-exposed SP-1 keratinocytes and that this inhibitory effect resulted from the reduction of PKCδ and ERK phosphorylation. Methods: We investigated the mechanism by which ginsenoside Rh3 from Panax ginseng inhibited GM-CSF release from UV-B-irradiated keratinocytes. Results: Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or UV-B induced release of GM-CSF in the SP-1 keratinocytes. To elucidate whether the change in GM-CSF expression could be related to PKC signaling, the cells were pretreated with H7, an inhibitor of PKC, and irradiated with UV-B. GM-CSF was decreased by H7 in a dose-dependent manner. When we analyzed which ginsenosides repressed GM-CSF expression among 15 ginsenosides, ginsenoside Rh3 showed the largest decline to 40% of GM-CSF expression in enzyme-linked immunosorbent assay. Western blot analysis showed that TPA enhanced the phosphorylation of PKCδ and ERK in the keratinocytes. When we examined the effect of ginsenoside Rh3, we identified that ginsenoside Rh3 inhibited the TPA-induced phosphorylation levels of PKCδ and ERK. Conclusion: In summary, we found that ginsenoside Rh3 impeded UV-B-induced GM-CSF production through repression of PKCδ and ERK phosphorylation in SP-1 keratinocytes.

• IMMUNE NETWORK
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• v.23 no.3
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• pp.29.1-29.23
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• 2023

Cholesterol (CL) is required for various biomolecular production processes, including those of cell membrane components. Therefore, to meet these needs, CL is converted into various derivatives. Among these derivatives is cholesterol sulfate (CS), a naturally produced CL derivative by the sulfotransferase family 2B1 (SULT2B1), which is widely present in human plasma. CS is involved in cell membrane stabilization, blood clotting, keratinocyte differentiation, and TCR nanocluster deformation. This study shows that treatment of T cells with CS resulted in the decreased surface expression of some surface T-cell proteins and reduced IL-2 release. Furthermore, T cells treated with CS significantly reduced lipid raft contents and membrane CLs. Surprisingly, using the electron microscope, we also observed that CS led to the disruption of T-cell microvilli, releasing small microvilli particles containing TCRs and other microvillar proteins. However, in vivo, T cells with CS showed aberrant migration to high endothelial venules and limited infiltrating splenic T-cell zones compared with the untreated T cells. Additionally, we observed significant alleviation of atopic dermatitis in mice injected with CS in the animal model. Based on these results, we conclude that CS is an immunosuppressive natural lipid that impairs TCR signaling by disrupting microvillar function in T cells, suggesting its usefulness as a therapeutic agent for alleviating T-cell-mediated hypersensitivity and a potential target for treating autoimmune diseases.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.1
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• pp.43-56
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• 2012

Objective : In this study, we assessed the anti-bacterial effects and epidermal permeability barrier function of red onion juice comparing to yellow onion juice and $Houttuynia$ $cordata$ extract $in$ $vitro$. Methods : 3types of red and yellow onion juice were prepared as antibacterial agent candidates with Houttuynia cordata hot water extract using 4 different bacterial strains ($Escherichia$ $coil$, $Salmonella$ $enterica$ $subsp.$ $enterica$, $Staphylococcus$ $epidermidis$, $Staphylococcus$ $aureus$ $subsp$) by colony counting method. The expression of filaggrin, a marker of keratinocyte differentiation, and serine palmitoyl transferase (SPT), a marker of the formation of the stratum corneum lipid barrier, in human HaCat keratinocytes were analyzed using HaCaT cell line. The expression of COX-2 and AP-1 which is a factor of COX-2 transcription were also analyzed by western blotting method. Results : There was detectable anti-bacterial effects on $Staphylococcus$ $epidermidis$, $Staphylococcus$ $aureus$ $subsp$ among 1%, 5%, 10% extracts of yellow and red onion.(81%-100%) The bacteriocidal effects were not shown on $Escherichia$ $coil$, $Salmonella$ $enterica$ $subsp.$ $enterica$ among $Houttuynia$ $cordata$, yellow onion and red onion extracts. The in vitro results showed the concentration-dependent effects on the expression of both filaggrin and SPT in HaCat cells among 0.01%, 0.05%, 0.1%, 0.5% extracts in Houttuynia cordata and red onion, reflecting the notion that $Houttuynia$ $cordata$ and red onion can induce epidermal keratinocyte differentiation and improve the recovery of skin barrier functions. The concentration-dependent effects also have been shown on the expression of both COX-2 and AP-1 among 0.01%, 0.05%, 0.1%, 0.5% extracts in $Houttuynia$ $cordata$ and red onion, while slight effect in yellow onion. Conclusion : Red onion juice could be a potential candidate enhanser for the skin care and cosmetology.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.29 no.2 s.43
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• pp.205-232
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• 2003

Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ONA are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1 mg/ml UA or 0.1-1 mg/ml ONA after tape stripping, and TEWL (Transepidermal water loss) was measured . The recovery rate increased in those UA or ONA treated groups (0.1 mg/ml UA and 0.5 mg/ml ONA) at 6 h more than $20\%$ compared to vehicle treated group (p<0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/ml per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to vehicle group from f week without TEWL alteration (p<0.005). EM examination using RuO4 and OsO4 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent $(ONA{\geq}UA>Vehicle)$. LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA>ONA>Veh). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via $PPAR\;\alpha$. Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either $ONA\;(10{\mu}M)$ or UA $(10{\mu}M)$ for 24h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via $PPAR\;{\alpha}$. Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.529-535
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• 2016

Atopic dermatitis (AD) results from gene and environment interactions that lead to a range of immunological abnormalities and breakdown of the skin barrier. Protease-activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is expressed in suprabasal layers of the epidermis. PAR2 is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$ and is involved in both epidermal permeability barrier homeostasis and epithelial inflammation. In this study, we investigated the effect of lobaric acid on inflammation, keratinocyte differentiation, and recovery of the skin barrier in hairless mice. Lobaric acid blocked trypsin-induced and SLIGKV-$NH_2$-induced PAR2 activation resulting in decreased mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes. Lobaric acid reduced expression of interleukin-8 induced by SLIGKV-$NH_2$ and thymus and activation regulated chemokine (TARC) induced by tumor necrosis factor-a (TNF-${\alpha}$) and IFN-${\gamma}$ in HaCaT keratinocytes. Lobaric acid also blocked SLIGKV-$NH_2$-induced activation of ERK, which is a downstream signal of PAR2 in normal human keratinocytes (NHEKs). Treatment with SLIGKV-$NH_2$ downregulated expression of involucrin, a differentiation marker protein in HaCaT keratinocytes, and upregulated expression of involucrin, transglutamase1 and filaggrin in NHEKs. However, lobaric acid antagonized the effect of SLIGKV-$NH_2$ in HaCaT keratinocytes and NHEKs. Topical application of lobaric acid accelerated barrier recovery kinetics in a SKH-1 hairless mouse model. These results suggested that lobaric acid is a PAR2 antagonist and could be a possible therapeutic agent for atopic dermatitis.

• Journal of Veterinary Clinics
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• v.26 no.6
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• pp.528-533
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• 2009

In the current study, the mesenchymal stem cells (MSCs) isolated and propagated from the human umbilical cord blood (UCB) were tested for their capabilities of differentiation into chondrocytes in vitro. The mesenchymal progenitor cells (MPCs) collected from UCB were cultured in a low glucose DMEM medium with 10% FBS, L-glutamine and antibiotics. The human MSC colonies were positively stained by PAS reaction. When the immunophenotypes of surface antigens on the MSCs were analyzed by fluorescence-activated cell sorter (FACS) analysis, these cells expressed positively MSC-related antigens of CD 29, CD44, CD 90 and CD105, whereas they did not express antigens of CD14, CD31, CD34, CD45, CD133 and HLA-DR. Following induction these MSCs into chondrocytes in the chondrogenic differentiation medium for 3 weeks or more, the cells were stained positively with safranin O. We clearly confirmed that human MSCs were successfully differentiated into chondrocytes by RT-PCR and immunofluorescent stain of type-II collagen protein. These data also indicate that the isolation, proliferation and differentiation of the hUCB-derived MSCs in vitro can be used for elucidating the mechanisms involved in chondrogenesis. Moreover this differentiation technique can be applied to developing cell-based tissue regeneration or repair damaged tissues.