Mixture of Corni Fructus and Schisandrae Fructus improves testosterone-induced benign prostatic hyperplasia through regulating 5α-reductase 2 and androgen receptor

BACKGROUND/OBJECTIVES@#Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosteroneinduced BPH.MATERIALS/METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. @*RESULTS@#Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. @*CONCLUSIONS@#Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.

Induction of apoptotic cell death in human bladder cancer cells by ethanol extract of Zanthoxylum schinifolium leaf, through ROS-dependent inactivation of the PI3K/Akt signaling pathway

BACKGROUND/OBJECTIVES@#Zanthoxylum schinifolium is traditionally used as a spice for cooking in East Asian countries. This study was undertaken to evaluate the anti-proliferative potential of ethanol extracts of Z. schinifolium leaves (EEZS) against human bladder cancer T24 cells.MATERIALS/METHODS: Subsequent to measuring the cytotoxicity of EEZS, the anti-cancer activity was measured by assessing apoptosis induction, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). In addition, we determined the underlying mechanism of EEZS-induced apoptosis through various assays, including Western blot analysis. @*RESULTS@#EEZS treatment concentration-dependently inhibited T24 cell survival, which is associated with apoptosis induction. Exposure to EEZS induced the expression of Fas and Fas-ligand, activated caspases, and subsequently resulted to cleavage of poly (ADPribose) polymerase. EEZS also enhanced the expression of cytochrome c in the cytoplasm by suppressing MMP, following increase in the ratio of Bax:Bcl-2 expression and truncation of Bid. However, EEZS-mediated growth inhibition and apoptosis were significantly diminished by a pan-caspase inhibitor. Moreover, EEZS inhibited activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and the apoptosis-inducing potential of EEZS was promoted in the presence of PI3K/Akt inhibitor. In addition, EEZS enhanced the production of ROS, whereas N-acetyl cysteine (NAC), a ROS scavenger, markedly suppressed growth inhibition and inactivation of the PI3K/Akt signaling pathway induced by EEZS. Furthermore, NAC significantly attenuated the EEZS-induced apoptosis and reduction of cell viability. @*CONCLUSIONS@#Taken together, our results indicate that exposure to EEZS exhibits anticancer activity in T24 bladder cancer cells through ROS-dependent induction of apoptosis and inactivation of the PI3K/Akt signaling pathway.

Suppression of Lipopolysaccharide-Induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid in RAW 264.7 Macrophages and Zebrafish Larvae

In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro- inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

Schisandrae Fructus ethanol extract attenuates particulate matter 2.5-induced inflammatory and oxidative responses by blocking the activation of the ROS-dependent NFκB signaling pathway

BACKGROUND/OBJECTIVES@#Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages.MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E2 (PGE2 ), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. @*RESULTS@#The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE2 , which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. @*CONCLUSIONS@#Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.

Auranofin Enhances Sulforaphane-Mediated Apoptosis in Hepatocellular Carcinoma Hep3B Cells through Inactivation of the PI3K/Akt Signaling Pathway

The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.

Corni Fructus attenuates testosterone-induced benign prostatic hyperplasia by suppressing 5α-reductase and androgen receptor expression in rats

BACKGROUND/OBJECTIVES: Benign prostatic hypertrophy (BPH) is a major cause of abnormal overgrowth of the prostate mainly in the elderly. Corni Fructus has been reported to be effective in the prevention and treatment of various diseases because of its strong antioxidant effect, but its efficacy against BPH is not yet known. This study was designed to evaluate the therapeutic efficacy of Corni Fructus water extract (CF) in testosterone-induced BPH rats. MATERIALS/METHODS: To induce BPH, rats were intraperitoneal injected with testosterone propionate (TP). Rats in the treatment group were orally administered with CF with TP injection, and finasteride, which is a selective inhibitor of 5α-reductase type 2, was used as a positive control. RESULTS: Our results showed that the increased prostate weight and histopathological changes in BPH model rats were suppressed by CF treatment. CF, similar to the finasteride-treated group, decreased the levels of testosterone and dihydrotestosterone by TP treatment in the serum, and it also reduced 5α-reductase expression and concentration in prostate tissue and serum, respectively. In addition, CF significantly blocked the expression of the androgen receptor (AR), AR co-activators, and proliferating cell nuclear antigen in BPH rats, and this blocking was associated with a decrease in prostate-specific antigen levels in serum and prostate tissue. CONCLUSIONS: These results suggest that CF may weaken the BPH status through the inactivation of at least 5α-reductase and AR activity and may be useful for the clinical treatment of BPH.

Circumscribed Palmar Hypokeratosis Showing Bowenoid Change Secondary to Human Papilloma Virus / 대한피부과학회지

Circumscribed palmar or plantar hypokeratosis is a rare condition characterized by the occurrence of an erythematous, well-circumscribed, and depressed macule or patch on the palms or soles. Histopathologically, it is characterized by sharp, stair-like abrupt thinning of the horny layer between the affected and unaffected skin. The pathogenesis of this condition remains unclear. Recently, the human papilloma virus has been implicated as a possible etiological contributor. Circumscribed palmar or plantar hypokeratosis usually shows a benign course. Previous reports have not described malignant changes in these lesions. However, its association with actinic keratosis has been reported in a previous case. We report a case of circumscribed palmar hypokeratosis showing bowenoid epidermal change with expression of the human papilloma virus types 6 and 16 in a patient who was successfully treated with ingenol mebutate gel and cryotherapy.

Reactive oxygen species-dependent apoptosis induction by water extract of Citrus unshiu peel in MDA-MB-231 human breast carcinoma cells

BACKGROUND/OBJECTIVES: Although several recent studies have reported the anti-cancer effects of extracts or components of Citrus unshiu peel, which has been used for various purposes in traditional medicine, the molecular mechanisms for their effects remain unclear. In the present study, the anti-cancer activity of a water-soluble extract of C. unshiu peel (WECU) in MDA-MB-231 human breast carcinoma cells at the level of apoptosis induction was investigated. MATERIALS/METHODS: Cytotoxicity was evaluated using the MTT assay. Apoptosis was detected using DAPI staining and flow cytometry analyses. Mitochondrial membrane potential, reactive oxygen species (ROS) assay, caspase activity and Western blotting were used to confirm the basis of apoptosis. RESULTS: The results indicated that WECU-induced apoptosis was related to the activation of caspase-8, and -9, representative initiator caspases of extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3 accompanied by proteolytic degradation of poly(ADP-ribose) polymerase and down-regulation of the inhibitors of apoptosis protein family members. WECU also increased the pro-apoptotic BAX to anti-apoptotic BCL-2 ratio, loss of mitochondrial membrane potential and cytochrome c release from mitochondria to cytoplasm. Furthermore, WECU provoked the generation of ROS, but the reduction of cell viability and induction of apoptosis by WECU were prevented when ROS production was blocked by antioxidant N-acetyl cysteine. CONCLUSIONS: These results suggest that WECU suppressed proliferation of MDA-MB-231 cells by activating extrinsic and intrinsic apoptosis pathways in a ROS-dependent manner.

Erratum: Folliculotropic Mycosis Fungoides in 20 Korean Cases: Clinical and Histopathologic Features and Response to Ultraviolet A-1 and/or Photodynamic Therapy

In the originally published version of this article, complete anonymity was not achieved.

Folliculotropic Mycosis Fungoides in 20 Korean Cases: Clinical and Histopathologic Features and Response to Ultraviolet A-1 and/or Photodynamic Therapy

BACKGROUND: Folliculotropic mycosis fungoides (FMF) is a variant of mycosis fungoides (MF) that is characterized clinically by variable types of skin eruptions, including plaques, acneiform lesions, and alopecic patches. Histopathologically, FMF is characterized by folliculotropic infiltrates. OBJECTIVE: This study was conducted to scrutinize the clinical and histopathologic features of FMF in Koreans and the responses to phototherapy. METHODS: Twenty Koreans diagnosed with MF who had histopathologic evidence of folliculotropism were enrolled. RESULTS: Eighteen patients had head-and-neck-region infiltration, while five had solitary lesion. In all patients, the atypical lymphocytic infiltrate had a perifollicular distribution. Twelve patients were treated with ultraviolet A (UVA)-1. Eleven of these 12 patients with early-stage FMF experienced >80% improvement (8: complete remission; 3: partial remission). Four patients, including 2 who relapsed after UVA-1, were treated with photodynamic therapy (PDT), reaching complete remission after PDT. CONCLUSION: As FMF has variable clinical presentations, skin biopsy is required to confirm the diagnosis. And both UVA-1 and methyl aminolevulinate-PDT are clinically effective in treatment of early-stage FMF.

A Case of Papular Eruption Associated with Clonorchiasis / 대한피부과학회지

No abstract available.

The Efficacy and Safety of Continuous Intravenous Infusion of Low-dose Epinephrine in Patients with Severe Acute Urticaria Who Do Not Achieve Sufficient Responses to Conventional Treatments: An 8-year Retrospective Study / 대한피부과학회지

BACKGROUND: Acute urticaria sometimes accompanies severe systemic reactions that can be potentially life-threatening. Some patients do not achieve sufficient responses to conventional treatments. There has been no previous study on the effect of continuous intravenous infusion of epinephrine in patients with severe acute urticaria. OBJECTIVE: This study investigated the efficacy and safety of continuous intravenous infusion of low-dose epinephrine in patients with severe acute urticaria who did not achieve a sufficient response to conventional treatments. METHODS: We retrospectively reviewed the medical records of 74 patients with severe acute urticaria who were treated with continuous intravenous infusion of low-dose epinephrine between November 2008 and December 2016. One milligram (1 mL) of 1:1000 epinephrine was diluted in 1 L of saline to yield a concentration of 1 µg/mL. The solution was infused at 0.67 µg/min (40 mL/h). Vital signs were checked at 0, 30, 60, and 90 minutes after infusion of epinephrine. Epinephrine was discontinued after one symptom-free day. RESULTS: Clinical symptoms initially resolved within 24.8 hours on average and symptoms were completely resolved within 73.4 hours on average. Twenty-four adverse events, including palpitation, chest discomfort, hand tremor, increased blood pressure, and elevated cardiac markers, were observed in 19 patients (25.7%). Most adverse events were mild and regressed spontaneously without further management. Four patients (5.4%) stopped the infusion due to adverse events, but all events regressed spontaneously after stopping epinephrine. Six weeks after completion of intravenous infusion of epinephrine, 68 patients (91.9%) were symptom-free and six patients required antihistamines. CONCLUSION: This study suggests that continuous intravenous infusion of low-dose epinephrine is a safe and effective treatment in patients with severe acute urticaria who do not achieve a sufficient response to conventional treatments.

Primary Cutaneous Nocardiosis Caused by Nocardia takedensis

Nocardia species are aerobic, gram-positive, filamentous, partially acid-fast actinomycetes which are found worldwide in soil and decaying organic plant matter. When they infect human beings, they generally enter through the respiratory tract and then disseminate systemically. Rarely has a primary infection occurred as the result of direct inoculation. Isolation of Nocardia from clinical specimens and identification of species are difficult. But, with the introduction of new genetic technologies, reports of novel species of Nocardia have increased. We describe a case of cutaneous nocardiosis caused by Nocardia takedensis in an 87-year-old woman who was diagnosed by bacterial culture and 16S ribosomal RNA sequencing. N. takedensis has been described as a new species. This report describes the first clinical isolate of N. takedensis from a skin specimen in Korea.

Degos-Like Lesions Associated with Systemic Lupus Erythematosus

Degos disease, also referred to as malignant atrophic papulosis, was first described in 1941 by Köhlmeier and was independently described by Degos in 1942. Degos disease is characterized by diffuse, papular skin eruptions with porcelain-white centers and slightly raised erythematous telangiectatic rims associated with bowel infarction. Although the etiology of Degos disease is unknown, autoimmune diseases, coagulation disorders, and vasculitis have all been considered as underlying pathogenic mechanisms. Approximately 15% of Degos disease have a benign course limited to the skin and no history of gastrointestinal or central nervous system (CNS) involvement. A 29-year-old female with history of systemic lupus erythematosus (SLE) presented with a 2-year history of asymptomatic lesions on the dorsum of all fingers and both knees. The patient had only skin lesions and no gastrointestinal or CNS vasculitis symptoms. Her skin lesions were umbilicated, atrophic porcelain-white lesions with a rim of erythema. On the basis of clinical, histologic, and laboratory findings, a diagnosis of Degos-like lesions associated with SLE was made. The patient had been treated for SLE for 7 years. Her treatment regimen was maintained over a 2 month follow-up period, and the skin lesions improved slightly with no development of new lesions.

A Clinical Study using Quadrivalent Human Papilloma Virus (HPV) Vaccine for Treatment of Recalcitrant Wart / 대한피부과학회지

BACKGROUND: Although several traditional treatments have been applied for recalcitrant viral warts, these treatments have rarely resulted in complete recovery. To treat the recalcitrant viral wart, alternative therapies are required. OBJECTIVE: This study aimed to evaluate the efficacy and safety of quadrivalent HPV vaccine for recalcitrant wart treatment. METHODS: From 2012 to 2014, 17 patients who provided informed consent were enrolled. All patients received 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months, respectively. During clinic visits, doctors checked the grade of improvement, patient satisfaction, and treatment side effects. After completion of the 3 doses, the patients were followed up for 5 months with outpatient visits and telephone inquiries. RESULTS: After the third dose, 58.8% of patients showed complete remission and 41.2% showed no response after 5 months. There were no statistically significant differences in sex, age, disease duration, number, anatomic site, and previous treatment between the complete remission group and the no-response group. An adverse effect (syncope) was observed in one patient. CONCLUSION: Compared with traditional aggressive therapies, quadrivalent HPV vaccine is a simple method and does not usually interfere with the patient's work or social life. Quadrivalent HPV vaccine is an effective and safe alternative treatment for recalcitrant warts.

Mycobacterium abscessus Skin Infection Following the Embedding Therapy in a Oriental Clinic / 대한피부과학회지

No abstract available.

Cutaneous and Systemic Plasmacytosis Associated with Renal Amyloidosis

Cutaneous and systemic plasmacytosis (CSP) is a rare disorder of unknown etiology characterized by cutaneous polyclonal plasma cell infiltrates associated with various extracutaneous involvement and polyclonal hypergammaglobulinemia. Here, we report on a 54-year-old male patient with chronic renal insufficiency who presented with disseminated reddish-brown macules and plaques on the face and trunk. In our evaluation, he was found to have lymphadenopathy, polyclonal hypergammaglobulinemia; benign plasma cell infiltration involving the skin, bone marrow, and retroperitoneal area; and renal amyloidosis. To the best of our knowledge, this is the first reported case of CSP associated with renal amyloidosis.

Squamous Cell Carcinoma Originating from Frostbite-induced Osteomyelitis / 대한피부과학회지

Squamous cell carcinoma commonly originates from recalcitrant wound sites, including burn scars, pressure sores, stasis ulcers, osteomyelitis, and sites of frostbite. A 62-year-old male was referred to the dermatology department for skin necrosis of his right great toe and walking difficulty. He had a history of smoking, drinking alcohol, and frostbite of his right great toe 9 years prior, which deteriorated into osteomyelitis due to poor care. Although a skin biopsy was recommended before amputation, the two procedures were performed simultaneously due to a lack of toe function due to severe osteolysis. Biopsy of the amputated toe tip showed many lobules consisting of atypical keratinocytes with hyperchromatic nuclei, and severe dermal pleomorphism. After evaluation for distant metastasis, including a (99m) Tc-MDP bone scan, 18F-FDG positron emission tomography scan, computed tomography, and ultrasound, no metastasis was detected.

Eccrine Syringofibroadenoma Arising from Nevus Sebaceous / 대한피부과학회지

Eccrine syringofibroadenoma (ESFA) is a rare, benign adnexal neoplasm of eccrine differentiation. It is typically located on the limbs and presents as a plaque or a solitary hyperkeratotic nodule in an adult. However, there are several clinical subtypes, ranging from a solitary papule or nodule to multiple lesions with linear or diffuse distribution. Despite the diverse clinical presentation, ESFA is histologically similar. It commonly shows proliferation of anastomosing cords and strands of cuboidal epithelial cells with or without lumina embedded in a fibrovascular stroma. Herein, we report an unusual case of ESFA with verrucous surfaced plaque present on the scalp since birth in a 22-year-old man.

Complete Remission of Recalcitrant Plantar Wart Treated with Quadrivalent Human Papilloma Virus Vaccine / 대한피부과학회지

No abstract available.