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      • Pro-apoptotic role of the MEK/ERK pathway in ursodeoxycholic acid-induced apoptosis in SNU601 gastric cancer cells.

        Lim, Sung-Chul,Duong, Hong-Quan,Parajuli, Keshab Raj,Han, Song Iy National Hellenic Research Foundation 2012 Oncology reports Vol.28 No.4

        <P>Ursodeoxycholic acid (UDCA) has been regarded as a suppressor of gastrointestinal cancer, but the mechanisms underlying its antitumor effects are not fully understood. Previously, we reported the antitumor effect of UDCA by demonstrating that UDCA induces apoptosis of gastric cancer cells. Bile acids are known to activate the ERK pathway and ERK is a representative oncogenic kinase in cancer cells. Here, we investigated the role of ERK in UDCA-induced gastric cancer cell apoptosis. We found that UDCA enhanced the phosphorylation of ERK1/2 and MEK1/2. The prevention of MEK by the pharmacologic inhibitors PD98059 and U0126, resulted in decreased UDCA-induced apoptosis as shown by the reduction of apoptotic body formation, caspase-8 activity, and caspase-3, -6 and PARP cleavage, indicating that ERK exerts pro-apoptotic activity upon exposure to UDCA. In addition, U0126 reduced UDCA-triggered TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2/DR5) expression. In gene silencing studies, we observed that RNA interference of ERK2 decreased apoptosis and reduced DR5 overexpression. Lipid raft disrupting agent, methyl-β-cyclodextrin, blunted the phosphorylation of ERK1/2, indicating that ERK activation is regulated in a lipid raft-dependent manner. On the other hand, tumor-promoting bile acid, deoxycholic acid (DCA), also phosphorylated ERK in SNU601 cells. However, the DCA-triggered ERK pathway exerted anti-apoptotic function in the cells. Suppression of the ERK pathway enhanced DCA-induced apoptosis, and ERK activation was observed to be lipid raft-independently controlled. These results indicated that UDCA and DCA may cause differential responses in gastric cancer cells through the ERK signaling molecule. Thus, ERK activation may be a possible mechanism by which UDCA and DCA represent differential activities in gastrointestinal cancer.</P>

      • Poster Session : PS 0417 ; Infectious Disease ; Biofi lm Production and Antibiotic Resistance Pattern in Clinical Isolates from Indwelling Medical Devices

        ( Shyam K Mishra ),( Prashant Basukala ),( Om Basukala ),( Keshab Parajuli ),( Bharat M Pokhrel ),( Basista P Rijal ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

        Background: Microbial biofilms pose great threat for patients requiring indwelling medical devices (IMDs) as it is difficult to eradicate them. Besides, sublethal concentration of some antibiotics has been shown to induce biofilm in bacteria. It is, therefore, crucial to follow an appropriate and relevant method for the detection of biofi lms and hence the clinician can choose appropriate antibiotic for the treatment. Methods: This prospective analysis included 65 prosthetic samples. After isolation and identifi cation of bacteria following standard methodology, antibiogram of the isolates were produced following Kirby-Bauer disk diffusion method. Detection of biofi lms was done by tube adherence (TA), Congo red agar and tissue culture plate (TCP) methods. Results: Out of 67 clinical isolates from indwelling medical devices, TCP detected 31 (46.3%) biofi lm producers and 36 (53.7%) biofi lm non-producers. Klebsiella pneumoniae, Pseudomonas aeruginosa and Burkholderia cepacia complex were found to be the most frequent biofi lm producers. The TA method correlated well with the TCP method for biofi lm detection. Higher antibiotic resistance was observed in biofi lm producers than in biofi lm non-producers. The most effective antibiotics for biofi lm producing Gram-positive isolates were Vancomycin and Tigecycline, and that for biofi lm producing Gram-negative isolates were Polymyxin B, Colistin Sulphate and Tigecycline. Conclusions: Nearly forty-six percent of the isolates were found to be biofi lm producers. The antibiotic susceptibility pattern in the present study showed Amoxicillin to be an ineffective drug for isolates from the IMDs. For the detection of biofi lm production, TA method can be an economical and effective alternative to TCP method.

      • KCI등재후보

        Risk perception among r esidents l iving n ear i ndustries in Godawari Municipality of Lalitpur, Nepal

        Kshitij Karki,Anish Chaurel,Aashish Kumar Neupane,Keshab Parajuli,Raju Ghimire 환경독성보건학회 2023 환경독성보건학회지 Vol.38 No.4

        The industrial sector stands out as a significant contributor to environmental pollution. Those who reside in close proximity to industrial areas commonly harbor concerns about potential health and environmental hazards. This study aimed to find out the perception of risk and self-reported health impacts among individuals living near industries in Godawari Municipality, Lalitpur, Nepal. Conducted as a community-based cross-sectional study, it involved 270 households. Face-to-face interviews were employed, utilizing a pretested structured questionnaire. The study zone encompassed the communities of Godawari Municipality within a 3-kilometer radius of industrial sites. Specifically, stone mines, stone crushers, and brick kilns were purposefully selected, while study participants were randomly sampled using a random table. Data analysis was performed using IBM SPSS, incorporating both univariate and bivariate techniques. Among those residing near industrial zones, a mere 9.6 % reported experiencing wheezing or whistling in the past 12 months. A substantial 36.3% consistently felt stressed due to industrial activities in their vicinity. Approximately half (51.9 %) of the participants indicated that the contaminated air in the area had adverse effects on human health. Furthermore, a palpable perception of elevated risk was associated with the proximity of industries (p<0.001). Over half of the participants perceived a notable risk stemming from the presence of industries near their homes, largely due to pollutants. These individuals also disclosed various health repercussions and expressed significant apprehension regarding their future well-being in the area. The implications of these findings are substantial, particularly for local-level planning and the development of industrial sites. Addressing the concerns surrounding peoples heightened perception of risk from nearby industries is pivotal in fostering harmonious coexistence and informed decision-making.

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