• Title/Summary/Keyword: Statins

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Rosuvastatin Induces ROS-mediated Apoptosis in Human Prostate Cancer PC-3 Cells (Rosuvastatin이 유도하는 ROS가 전립선암 PC-3 세포주의 세포사멸 유도에 미치는 영향)

  • Choi, Hyeun Deok;Baik, Jong Jin;Kim, Sang Hun;Yu, Sun Nyoung;Chun, Sung Hak;Kim, Young Wook;Nam, Hyo Won;Kim, Kwang Youn;Ahn, Soon Cheol
    • Journal of Life Science
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    • v.26 no.4
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    • pp.398-405
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    • 2016
  • Statins, the inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, are widely used in treatments of hypercholesterolemia and newly known as anti-cancer effect of various cancer cells. Recently, several studies suggested that reactive oxygen species (ROS) play a critical role on cell death signaling. However, mechanism of ROS by rosuvastatin is currently unclear. This study aimed to explore the molecular mechanism of apoptosis by rosuvastatin in human prostate cancer PC-3 cells. Cell viability and apoptosis-related protein expression were measured by MTT assay and western blotting, respectively. In addition, the levels of apoptosis and ROS were analyzed. The results showed that rosuvastatin dramatically reduced cell viability in a dose- and time-dependent manner. We confirmed that rosuvastatin induced apoptosis through reduction of procaspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) in PC-3 cells. In addition, rosuvastatin stimulated ROS production in a dose-dependent manner and pre-treatment with N-acetylcysteine (NAC), a ROS scavenger, significantly recovered rosuvastatin-induced ROS and apoptosis. Thus, we concluded that rosuvastain induces apoptosis through generation of ROS in human prostate cancer PC-3 cells and provides a promising approach to improve the efficacy of cancer therapy.

Advance Understanding and New Treatment of Alopecia Areata (원형탈모증(alopecia areata)의 최신 이해와 치료)

  • Kang, Kyung-Hwa
    • Journal of Life Science
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    • v.26 no.11
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    • pp.1345-1354
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    • 2016
  • Alopecia areata (AA) is a common and tissue-specific autoimmune disease of hair follicle resulting in the loss of hair on the scalp and elsewhere on the body. Hair follicles is a unique organ because it has its own immune system and hormonal milieu and has a different immune state at each hair cycle stage. The collapses of anagen-dependent hair follicle immune privilege arise autoimmune attack, inducing ectopic MHC class I expression in the hair follicle epithelium and autoantigen presentation to autoreactive CD8+T cells, which results in AA. Clinical and experimental studies have pointed that psychological stress may also influence the hair follicle immune/hormone systems and contribute to the induction of AA. The key pathogenesis of AA is associated with immune privilege guardians (including ACTH, ${\alpha}-MSH$, and $TGF-{\beta}$), natural killer group 2D-positive (NKG2D+) cells (including NK and CD8+T cells), and stress hormones (including CRH and substance P). Effective treatments for AA are still demanded. One of the future targets of treatment will be the modification of hair follicle immune privilege including stress. Recent studies have reported that JAK inhibitors and immunomodulators used in other autoimmune disease, such as psoriasis, atopic dermatitis, and rheumatoid arthritis, Tregs, platelet-rich plasma therapy, statins, and prostaglandin anaolgues are effective for AA. Here the article reviews the recent understanding in the pathogenesis associated with perifollicular endocrine/immunology and new treatments of AA.

A Study on the Microflora of the Han River(II) The phytoplanktons and its seasonal variaton in the area of the Chun-chon and the Chung-pyong reservoir of the Han River (한강의 Microflora에 관한 연구 (제2보) 춘천 및 청평정수지를 중심으로 한 한강의 식물성 planktond과 그 계절적 소장)

  • 정영호
    • Journal of Plant Biology
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    • v.11 no.2
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    • pp.1-30
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    • 1968
  • The Han River was investigated monthly from April through September, 1967 at Chun-chon reservoir, Shin-yean, So-yang, Chung-pyong reservoir, Yang-soo-ri and Gi-doo-won to clarify the phytoplankton and to study its seasonal variation. At the same time, vertical distribution of phytoplankton was also studied from June through September at Chun-chon and Chung-pyong reservoir. The results obtained are as follows: As the environmental conditions, water temperature, dissolved oxygen, pH, and transparency were determined. The plankton samples collected from six stations were identified and classified by Engler's classification system. It resulted in 4 phyla, 4 classes, 3 subclasses, 13 orders, 27 families, 5 tribes, 71 genera, 222 species, 1 subspecies, 51 varieties and 2 forms. The total number of phytoplankton identified was 276. Of them, 84 species, 1 subspecies 26 varieties, 2 forms were recorded in this paper for the first time. Considering with the habitat of the total number of phytoplanktons, the highest percentage of Limnoplankton existed in the Chung-pyong reservoir. It suggests that hte Chung-pyong reservoir is becoming to have the character of lake. The planktons appeared commonly during six months at six station belong to Chrysophyta including 22 species in 11 genera. Among these 22 species, Navicula, consists of 6 species, was the most abundant. The number of species identified uniquely at each station were 5 species in the Chun-chon reservoir, 6 in Chung-pyong and Yang-soo-ri, 8 at Shin-yean, 11 at So-yang, and 18 at Gi-doo-won. The number of species occurred at all stations were 29 in spring, 42 in Autumn and during investigation period. The maximum production of total phytoplankton was generally shown in the late spring and the early fall with differences in quantity at six collecting statins. In the Chun-chon reservoir, the high concentration of approximately 1, 190, 000 cells per litter in the months of August and September was due to the increase of Chrysophyte genus, Melosira and the highest concentration of approximately 2, 000, 000 in July at Gi-doo-won was caused Chlorophyte genus, Secenedesmus. The Chun-chon reservoir of three years old was different from the Chung-pyong reservoir of 25 years old with respect to increase in Melosira genus in August and September. After the completion of the Ui-am reservoir, though there was an increase in total density, the number of species of phytoplankton was not changed. It suggests that Ui-am reservoir is similar to the Chun-chon reservoir under the influence of the latter. The density of total phytoplankton was generally high at the depth of 2m to 5m for the two reservoirs.

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Impact of High-Dose Statin Pretreatment in Patients with Stable Angina during Off-Pump Coronary Artery Bypass

  • Youn, Young-Nam;Park, Seong-Yong;Hwang, Yoo-Hwa;Joo, Huyn-Chul;Yoo, Kyung-Jong
    • Journal of Chest Surgery
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    • v.44 no.3
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    • pp.208-214
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    • 2011
  • Background: Periprocedural treatment with high-dose statins is known to have cardioprotective and pleiotropic effects, such as anti-thrombotic and anti-inflammatory actions. We aimed to assess the efficacy of high-dose rosuvastatin loading in patients with stable angina undergoing off-pump coronary artery bypass grafting (OPCAB). Materials and Methods: A total of 142 patients with stable angina who were scheduled to undergo surgical myocardial revascularization were randomized to receive either pre-treatment with 60-mg rosuvastatin (rosuvastatin group, n=71) or no pre-treatment (control group, n=71) before OPCAB. The primary endpoint was the 30-day incidence of major adverse cardiac events (MACEs). The secondary endpoint was the change in the degree of myocardial ischemia as evaluated with creatine kinase-myocardial band (CK-MB) and troponin T (TnT). Results: There were no significant intergroup differences in preoperative risk factors or operative strategy. MACEs within 30 days after OPCAB occurred in one patient (1.4%) in the rosuvastatin group and four patients (5.6%) in the control group, respectively (p=0.37). Preoperative CK-MB and TnT were not different between the groups. After OPCAB, the mean maximum CK-MB was significantly higher in the control group (rosuvastatin group $10.7{\pm}9.75$ ng/mL, control group $14.6{\pm}12.9$ ng/mL, p=0.04). Furthermore, the mean levels of maximum TnT were significantly higher in the control group (rosuvastatin group $0.18{\pm}0.16$ ng/mL, control group $0.39{\pm}0.70$ ng/mL, p=0.02). Conclusion: Our findings suggest that high-dose rosuvastatin loading before OPCAB surgery did not result in a significant reduction of 30-day MACEs. However, high-dose rosuvastatin reduced myocardial ischemia after OPCAB.

The Effects of Simvastatin on Bone Healing in Mandible Fractured Rats. (백서의 하악골 골절 치유에서 Simvastatin이 미치는 영향)

  • Jeong, Jae-Oo;Kwon, Yong-Seok;Kim, Seok-Kwun;Lee, Keun-Cheol
    • Archives of Plastic Surgery
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    • v.36 no.5
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    • pp.525-530
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    • 2009
  • Purpose: The hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are widely used in the treatment of dyslipidemia for the lowering of cholesterol. And studies about simvastatins have been shown to enhance bone formation in vitro and in vivo in rodents. But some other researchers have reported that there was no anabolic effect abouts simvastatins on bone. The peripheral distribution beyond the liver represents a small fraction of an orally administered dose. We hypothesize that this poor peripheral distribution is the likely reason that simvastatins, yield ambiguous results as anabolic agents. We therefore investigated whether the effects of simvastatins on bone may be enhanced by subcutaneous administration, providing better peripheral delivery of these drugs. Methods: 36 rat unilaterally mandible fractured models were prepared and divided into two groups. The simvastatin treated group where 1 mg/kg of simvastatin was daily injected subcutaneously. The same dose of normal saline was injected on the control group. And 3 rats in each group were sacrificed and taken bone samples in each week. Bone sample was evaluated with tensile strength and histological morphology after 1, 2, 3, 4, 5 and 6 weeks. Results: In simvastatin treated group, the fracture healing process, chondrocyte aggregation, collagen formation and trabecular bone formation was rapidly proceeded than the control group in histologically. The tensile strength of the simvastatin treated group was 1.02, 2.25, 3.95, 4.42, 5.49 and $6.00N/mm^2$ by weeks. The control group data was 0.60, 1.05, 2.17, 3.75, 4.15 and $5.17N/mm^2$ by weeks. The average tensile strength was higher by $1.04N/mm^2$ in simvastatin treated group. Conclusion: The currently available data on the effects of simvastatin on bone has done to confirm the finding that simvastatin helps fracture healing. And the potential for simvastatin to be used as anabolic agents for bone when delivered by the subcutaneous route.

Allium tuberosum Reverses PCSK9-Mediated LDLR Degradation by Inhibition of HNF1α (부추 추출물의 PCSK9 억제를 통한 LDL 콜레스테롤 저감 효능)

  • Choi, Hyo-Kyoung;Kim, Hyo Jin;Hwang, Jin-Taek;Chung, Min-Yu
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1278-1285
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    • 2017
  • Accumulation of excess low density lipoprotein (LDL) cholesterol in the blood can initiate and accelerate atherosclerosis. Statins mediate the transactivation of proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn limits their cholesterol-lowering effects via LDL receptor (LDLR) degradation. The objective of this study was to investigate whether or not Allium tuberosum (AT) regulates LDLR and PCSK9. Mice were fed a low fat control diet (LD) or Western diet (WD) supplemented with AT (1%, w/w). AT significantly attenuated total and LDL cholesterol levels in mice fed WD (P<0.05). AT also significantly inhibited hepatic PCSK9 gene expression (P<0.05) while AT maintained hepatic LDLR gene expression. To further investigate AT-mediated PCSK9 regulation, HepG2 cells were treated with 10% delipidated serum (DLPS) in the presence or absence of AT. Non-toxic level of AT dose-dependently increased the LDLR protein level, and AT at $400{\mu}g/mL$ markedly inhibited PCSK9 protein expression. Similarly, AT significantly increased LDLR gene expression, whereas it significantly down-regulated PCSK9 gene expression. AT-mediated reduction of PCSK9 gene expression is likely due to decreased hepatic nuclear factor $1{\alpha}$ ($HNF1{\alpha}$) expression, but not SREBP2 in HepG2 cells under lipid-depleted conditions. AT-mediated PCSK9 inhibition contributed to LDLR protein stabilization via protection against LDLR lysosomal degradation in HepG2 cells under lipid-depleted conditions. Further investigation is warranted to determine the active components of AT and whether or not these components are effective in reducing hypercholesterolemia.