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- 저자 : Endale, (검색결과 20 건)
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Torilin Inhibits Inflammation by Limiting TAK1-Mediated MAP Kinase and NF- <i>κ</i> B Activation
Endale, Mehari,Kim, Tae-Hwan,Kwak, Yi-Seong,Kim, Na-Mi,Kim, Seung-Hyung,Cho, Jae Youl,Yun, Bong-Sik,Rhee, Man-Hee Hindawi Publishing Corporation 2017 Mediators of inflammation Vol.2017 No.-
<P>Torilin, a sesquiterpene isolated from the fruits of<I> Torilis japonica,</I> has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin's effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed. Torilin strongly inhibited LPS-induced NO release, iNOS, PGE<SUB>2</SUB>, COX-2, NF-<I>α</I>, IL-1<I>β</I>, IL-6, and GM-CSF gene and protein expressions. In addition, MAPKs were also suppressed by torilin pretreatment. Involvement of ERK1/2, P38<SUP>MAPK</SUP>, and JNK1/2 was further confirmed by PD98059, SB203580, and SP600125 mediated suppression of iNOS and COX-2 proteins. Furthermore, torilin attenuated NF-kB and AP-1 translocation, DNA binding, and reporter gene transcription. Interestingly, torilin inhibited TAK1 kinase activation with the subsequent suppression of MAPK-mediated JNK, p38, ERK1/2, and AP-1 (ATF-2 and c-jun) activation and IKK-mediated I-<I>κ</I>B<I>α</I> degradation, p65/p50 activation, and translocation. Together, the results revealed the suppression of NF-<I>κ</I>B and AP-1 regulated inflammatory mediator and cytokine expressions, suggesting the test compound's potential as a candidate anti-inflammatory agent.</P>
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Endale, Mehari,Kim, Sung Dae,Lee, Whi Min,Kim, Sangseop,Suk, Kyoungho,Cho, Jae Youl,Park, Hwa Jin,Wagley, Yadav,Kim, Suk,Oh, Jae-Wook,Rhee, Man Hee American Physiological Society 2010 American journal of physiology. Cell physiology Vol.298 No.3
<P>Regulator of G protein signaling (RGS) family members, such as RGS2, interact with Gα subunits of heterotrimeric G proteins, accelerating the rate of GTP hydrolysis and attenuating the intracellular signaling triggered by the G protein-coupled receptor-ligand interaction. They are also reported to regulate G protein-effector interactions and form multiprotein signaling complexes. Ischemic stress-induced changes in RGS2 expression have been described in astrocytes, and these changes are associated with intracellular signaling cascades, suggesting that RGS2 upregulation may be an important mechanism by which astrocytes may regulate RGS2 function in response to physiological stress. However, information on the functional roles of stress-induced modulation of RGS2 protein expression in astrocyte function is limited. We report the role of ischemic stress in RGS2 protein expression in rat C6 astrocytoma cells and primary mouse astrocytes. A marked increase in RGS2 occurred after ischemic stress induced by chemicals (sodium azide and 2-deoxyglucose) or oxygen-glucose deprivation (OGD, real ischemia). RGS2 mRNA expression was markedly enhanced by 1 h of exposure to chemical ischemia or 6 h of OGD followed by 2 or 6 h of recovery, respectively. This enhanced expression in primary astrocytes and C6 cells was restored to baseline levels after 12 h of recovery from chemically induced ischemic stress or 4-6 h of recovery from OGD. RGS2 protein was also significantly expressed at 12-24 h of recovery from ischemic insult. Ischemia-induced RGS2 upregulation was associated with enhanced apoptosis. It significantly increased annexin V-positive cells, cleaved caspase-3, and enhanced DNA ladder formation and cell cycle arrest. However, a small interfering RNA (siRNA)-mediated RGS2 knockdown reversed the apoptotic cell death associated with ischemia-induced RGS2 upregulation. Upregulated RGS2 was significantly inhibited by SB-203580, a p38 MAPK inhibitor. Rottlerin, a potent inhibitor of PKCδ, completely abrogated the increased RGS2 expression. We also examine whether ischemia-induced RGS2-mediated apoptosis is affected by siRNA-targeted endogenous PKCδ downregulation or its phosphorylation. Although RGS2 upregulation was not affected, siRNA transfection significantly suppressed endogenous PKCδ mRNA and protein expressions. Ischemia-induced PKCδ phosphorylation and caspase-3 cleavage were dose dependently inhibited by PKCδ knockdown, and this endogenous PKCδ suppression reversed ischemia-induced annexin V-positive cells. This study suggests that ischemic stress increases RGS2 expression and that this condition contributes to enhanced apoptosis in C6 cells and primary astrocytes. The signaling it follows may involve PKCδ and p38 MAPK pathways.</P>
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Mehari Endale,Jae Chan Song,Man Hee Rhee,Kwang-Hyeon Liu,Taek-Kyum Kim,Joong Goo Kwon,Kyung Sik Park,Ki-Myung Chung,Tae Wan Kim 한국실험동물학회 2011 Laboratory Animal Research Vol.27 No.4
Suaeda asparagoides (Miq.) has long been used as a Korean folk herbal medicine for the treatment of functional gastrointestinal disorders. However, reports on its pharmacological activity on gastrointestinal motility are scarce. The present study investigated the effects of Suaeda asparagoides water fraction of the extract (SAWF) on antral motility in vitro. Muscle strips from rat gastric antrum were set up in an organ bath in a circular orientation. SAWF (100 μg/mL) inhibited the spontaneous contraction of antral circular muscle strips. These inhibitory effects were not significantly affected by tetrodotoxin (1 μM), Nω-Nitro-Larginine methyl ester hydrochloride (100 μM), 1H-(1, 2, 4)oxadiazolo(4, 3-a)quinoxalin-1-one (10 μM), ryanodine (10 μM) and phentolamine (10 μM). SAWF-induced inhibition was mostly restored by cyclopiazonic acid (10 μM). Furthermore, the β-adrenergic receptor antagonist, propranolol (10 μM), abolished SAWFinduced inhibition. These results suggest that SAWF may exert its activity on gastrointestinal smooth muscle via â-adrenergic receptors and sarcoplasmic reticulum Ca2+ ATPase.
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Dessiet Oma,Maria Teklemariam,Daniel Seifu,Zelalem Desalegn,Endale Anberbir,Endale Anberbir,Solomon Mequannent,Solomon Tebeje,Wajana Lako Labisso 대한암예방학회 2023 Journal of cancer prevention Vol.28 No.2
The application of immunohistochemistry (IHC) for molecular characterization of breast cancer (BC) is of paramount importance; however, it is not universally standardized, subject to observer variability and quantifying is a challenge. An alternative molecular technology, such as endpoint reverse transcription (RT)-PCR gene expression analysis, may improve observer variability and diagnostic accuracy. This study was intended to compare IHC with the RT-PCR based technique and assess the potential of RT-PCR for molecular subtyping of BC. In this comparative cross-sectional study, 54 BC tissues were collected from three public hospitals in Addis Ababa and shipped to Gynaecology department at Martin-Luther University (Germany) for laboratory analysis. Only 41 samples were qualified for IHC and RT-PCR investigation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 protein expression analysis. Kappa statistics was used to assess the concordance between the two techniques. The overall percent agreement between RT-PCR and IHC was 68.3% for ER (positive percent agreement [PPA] 71.1%; negative percent agreement [NPA] 33.3%), 39.0% for PR (PPA 14.3%; NPA 92.3%), and 82.9% for HER2 (PPA 62.5%; NPA 87.9%). Cohen’s κ-values of 0.018 (< 0.20), 0.045 (< 0.200), and 0.481 (0.41-0.60) were generated for ER, PR, and HER2, respectively. Concordance for molecular subtypes was only 56.1% (23/41) and 0.20 kappa value. IHC and endpoint RTPCR techniques have shown to be discordant for 43% samples. Molecular subtyping using endpoint RT-PCR was fairly concordant with IHC. Thus, endpoint RT-PCR may give an objective result, and can be applied for BC subtyping.
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Degfie Teshome,Endale Milkyas,Tafese Tarekegn,Dekebo Aman,Shenkute Kebede 한국응용생명화학회 2022 Applied Biological Chemistry (Appl Biol Chem) Vol.65 No.6
Hydnora johannis is a medicinal plant traditionally used to treat various ailments. Chemical investigation of the dichloromethane (DCM)/methanol (MeOH) (1:1) roots extract of Hydnora johannis afforded three compounds (1–3), reported herein for the first time from the species. The structures of the isolated compounds 1–3 were elucidated using 1D and 2D NMR spectroscopic analysis and comparison with literature data. The highest zone of inhibition value was measured for DCM/MeOH extract (10.75 ± 0.25 mm) against Staphylococcus aureus at concentration of 0.25 mg/mL, promising in comparison to the standard amoxicillin (16.0 ± 0.0 mm, 0.25 mg/mL). At concentration of 0.25 mg/mL, the largest mean inhibition zone of 12.0 ± 0.0 mm was measured for compound 2 against Pseudomonas aeruginosa, comparable to the standard drug amoxicillin (16.0 ± 0.0 mm, 0.25 mg/mL). Compound 2 displayed better binding affinity with minimum binding energy of − 8.7 kcal/mol (PqsA), − 7.6 kcal/mol (DNA gyrase), and − 7.4 kcal/ mol ( S aureus PK) than amoxicillin (− 7.3, − 6.1, and − 7.0 kcal/mol, respectively). This suggests that compound 2 may act as potential inhibitor of the tested bacterial proteins. Compound 1 satisfies the Lipinski’s rule of five with zero violations. Compound 2 obey the MW (452.4 g/mol) and iLogP (< 5) rules, and compound 3 obey the NHD (4) and NHA (6) rules. Compounds 2 recorded iLogP value less enough than five (1.55), implying its optimal lipophilicity. Compounds 1 and 3 satisfy the veber’s rule (NRB < 12, and TPSA < 140 unit). Compound 2 and 3 exhibited negligible acute toxicity ( LD50 > 5000, Toxicity class > 5. Compound 2 demonstrated maximum scavenging activity (67.87%) with IC50 value of 0.190 μg/mL, compared to ascorbic acid (78.21%) with IC50 value of 0.014 μg/mL at concentration of 12.5 μg/mL. Overall, the in vitro antibacterial activity of the extracts and compounds, molecular docking analysis and radical scavenging activity results of the isolated compounds suggest DCM/MeOH crude extract and compound 2 are promising antibacterial agents whereas compound 2 and 3 are promising antioxidants which corroborates with the traditional uses of the roots of H. johannis. Hydnora johannis is a medicinal plant traditionally used to treat various ailments. Chemical investigation of the dichloromethane (DCM)/methanol (MeOH) (1:1) roots extract of Hydnora johannis afforded three compounds ( 1–3 ), reported herein for the first time from the species. The structures of the isolated compounds 1–3 were elucidated using 1D and 2D NMR spectroscopic analysis and comparison with literature data. The highest zone of inhibition value was measured for DCM/MeOH extract (10.75 ± 0.25 mm) against Staphylococcus aureus at concentration of 0.25 mg/mL, promising in comparison to the standard amoxicillin (16.0 ± 0.0 mm, 0.25 mg/mL). At concentration of 0.25 mg/mL, the largest mean inhibition zone of 12.0 ± 0.0 mm was measured for compound 2 against Pseudomonas aeruginosa , comparable to the standard drug amoxicillin (16.0 ± 0.0 mm, 0.25 mg/mL). Compound 2 displayed better binding affinity with minimum binding energy of − 8.7 kcal/mol (PqsA), − 7.6 kcal/mol (DNA gyrase), and − 7.4 kcal/mol ( S aureus PK) than amoxicillin (− 7.3, − 6.1, and − 7.0 kcal/mol, respectively). This suggests that compound 2 may act as potential inhibitor of the tested bacterial proteins. Compound 1 satisfies the Lipinski’s rule of five with zero violations. Compound 2 obey the MW (452.4 g/mol) and iLogP (< 5) rules, and compound 3 obey the NHD (4) and NHA (6) rules. Compounds 2 recorded iLogP value less enough than five (1.55), implying its optimal lipophilicity. Compounds 1 and 3 satisfy the veber’s rule (NRB < 12, and TPSA < 140 unit). Compound 2 and 3 exhibited negligible acute toxicity (LD 50 > 5000, Toxicity class > 5. Compound 2 demonstrated maximum scavenging activity (67.87%) with IC 50 value of 0.190 µg/mL, compared to ascorbic acid (78.21%) with IC 50 value of 0.014 µg/mL at concentration of 12.5 µg/mL. Overall, the in vitro antibacterial activity of the extracts and compounds, molecular docking analysis and radical scavenging activity results of the isolated compounds suggest DCM/MeOH crude extract and compound 2 are promising antibacterial agents whereas compound 2 and 3 are promising antioxidants which corroborates with the traditional uses of the roots of H. johannis.
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Anteneh Amsalu,Mesfin Worku,Endale Tadesse,Techalew Shimelis 한국역학회 2016 Epidemiology and Health Vol.38 No.-
OBJECTIVES: The aim of this study was to assess the rate of and risk factors for exposure to hepatitis B virus (HBV) and hepatitis C virus (HCV) among medical waste handlers. METHODS: A cross-sectional study was conducted from December 2014 to January 2015. A total of 152 medical waste handlers (MWH) and 82 non-medical waste handlers (NMWH) were studied. Serum samples were collected from participants and screened for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and anti-HCV using rapid immunochromatography assay. MWH were also screened for hepatitis B surface antibody (anti-HBs). RESULTS: The respective prevalence of HBsAg, anti-HBc and anti-HCV was 1.3%, 39.4%, and 0.7% in MWH, compared to 2.4%, 17.1%, and 1.2%, respectively, in NMWH. Among MWH, 58.6% were susceptible to HBV infection. There was a significant difference in the rate of lifetime exposure to HBV in MWH compared with NMWH (odds ratio [OR], 3.17; 95% confidence interval [CI], 1.64 to 6.13). However, there was no significant difference between participant groups with respect to current HBV infection (OR, 0.53; 95%CI, 0.07 to 3.86) or anti-HCV (OR, 0.54; 95%CI, 0.03 to 8.69). Age older than 40 years and working in a hospital laundry were independent predictors of lifetime exposure to HBV infection. Eleven (7.2%) respondents were vaccinated against HBV. CONCLUSIONS: Lifetime exposure to HBV infection was significantly higher in MWH than in NMWH. The majority of MWH was not vaccinated against HBV and thus remains susceptible to contracting the infection. Screening upon hire followed by vaccination of MWH is recommended to reduce the transmission of HBV.
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