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Exposure to artificial light at night (ALAN) has been reported to be associated with various pathological changes including sleep deprivation, circadian rhythm disruption, and melatonin suppression with increase in various cancers such as breast or prostate cancers. In this study, we sought to elucidate the association between ALAN and prostate cancer in 27 districts within Gwangju City and urban and rural areas from South Jeolla Province in South Korea. We analyzed the correlation between ALAN and the incidence of a range of cancers by Poisson regression analysis, after adjustment for confounding risk factors, such as smoking, drinking, obesity, stress, air pollution (particulate matter <10 μm in diameter), urbanization (proportion of urbanized area), and the cancer screening rate. Interestingly, the incidence of prostate cancer was significantly associated with ALAN (risk ratio = 1.02, p = 0.0369) and urbanization (risk ratio = 1.06, p = 0.0055). In particular, comparing the prostate cancer incidence at 25% and 75% level of ALAN, the risk ratio was 1.726 (12.6 over 7.3, respectively). No significant association was observed between ALAN and other cancers, including stomach, esophageal, liver, pancreatic, laryngeal, lung and tracheal, bladder, and brain and central nervous system cancers, as well as lymphoma and multiple myeloma. In conclusion, this study shows that a high incidence of prostate cancer may be independently associated with light pollution and urbanization, which represent significant factors in the rapid process of industrialization of South Korea. 相似文献
63.
Ganipisetti Srinivasrao Jung-Eun Park Sungmin Kim Mija Ahn Chaejoon Cheong Ky-Youb Nam Pethaiah Gunasekaran Eunha Hwang Nam-Hyung Kim Song Yub Shin Kyung S. Lee Eunkyung Ryu Jeong Kyu Bang 《PloS one》2014,9(9)
Background
Polo-like kinase-1 (Plk1) plays a crucial role in cell proliferation and the inhibition of Plk1 has been considered as a potential target for specific inhibitory drugs in anti-cancer therapy. Several research groups have identified peptide-based inhibitors that target the polo-box domain (PBD) of Plk1 and bind to the protein with high affinity in in vitro assays. However, inadequate proteolytic resistance and cell permeability of the peptides hinder the development of these peptide-based inhibitors into novel therapeutic compounds.Methodology/Principal Findings
In order to overcome the shortcomings of peptide-based inhibitors, we designed and synthesized small molecule inhibitors. Among these molecules, bg-34 exhibited a high binding affinity for Plk1-PBD and it could cross the cell membrane in its unmodified form. Furthermore, bg-34-dependent inhibition of Plk1-PBD was sufficient for inducing apoptosis in HeLa cells. Moreover, modeling studies performed on Plk1-PBD in complex with bg-34 revealed that bg-34 can interact effectively with Plk1-PBD.Conclusion/Significance
We demonstrated that the molecule bg-34 is a potential drug candidate that exhibits anti-Plk1-PBD activity and possesses the favorable characteristics of high cell permeability and stability. We also determined that bg-34 induced apoptotic cell death by inhibiting Plk1-PBD in HeLa cells at the same concentration as PEGylated 4j peptide, which can inhibit Plk1-PBD activity 1000 times more effectively than bg-34 can in in vitro assays. This study may help to design and develop drug-like small molecule as Plk1-PBD inhibitor for better therapeutic activity. 相似文献64.
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Bani Mukhopadhyay Jie Liu Douglas Osei-Hyiaman Grzegorz Godlewski Partha Mukhopadhyay Lei Wang Won-Il Jeong Bin Gao Gregg Duester Ken Mackie Soichi Kojima George Kunos 《The Journal of biological chemistry》2010,285(25):19002-19011
Alcoholism can result in fatty liver that can progress to steatohepatitis, cirrhosis, and liver cancer. Mice fed alcohol develop fatty liver through endocannabinoid activation of hepatic CB1 cannabinoid receptors (CB1R), which increases lipogenesis and decreases fatty acid oxidation. Chronic alcohol feeding also up-regulates CB1R in hepatocytes in vivo, which could be replicated in vitro by co-culturing control hepatocytes with hepatic stellate cells (HSC) isolated from ethanol-fed mice, implicating HSC-derived mediator(s) in the regulation of hepatic CB1R (Jeong, W. I., Osei-Hyiaman, D., Park, O., Liu, J., Bátkai, S., Mukhopadhyay, P., Horiguchi, N., Harvey-White, J., Marsicano, G., Lutz, B., Gao, B., and Kunos, G. (2008) Cell Metab. 7, 227–235). HSC being a rich source of retinoic acid (RA), we tested whether RA and its receptors may regulate CB1R expression in cultured mouse hepatocytes. Incubation of hepatocytes with RA or RA receptor (RAR) agonists increased CB1R mRNA and protein, the most efficacious being the RARγ agonist CD437 and the pan-RAR agonist TTNPB. The endocannabinoid 2-arachidonoylglycerol (2-AG) also increased hepatic CB1R expression, which was mediated indirectly via RA, because it was absent in hepatocytes from mice lacking retinaldehyde dehydrogenase 1, the enzyme catalyzing the generation of RA from retinaldehyde. The binding of RARγ to the CB1R gene 5′ upstream domain in hepatocytes treated with RAR agonists or 2-AG was confirmed by chromatin immunoprecipitation and electrophoretic mobility shift and antibody supershift assays. Finally, TTNPB-induced CB1R expression was attenuated by small interfering RNA knockdown of RARγ in hepatocytes. We conclude that RARγ regulates CB1R expression and is thus involved in the control of hepatic fat metabolism by endocannabinoids. 相似文献
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Ji Hye Huh Song Vogue Ahn Sang Baek Koh Eunhee Choi Jang Young Kim Ki-Chul Sung Eung Ju Kim Jeong Bae Park 《PloS one》2015,10(11)
Background
Although non-alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, its influence on hypertension development is poorly understood. We investigated whether fatty liver disease, as assessed by the fatty liver index, could predict the development of hypertension independently of systemic insulin resistance, inflammatory status and adipokine levels.Methods
Prospective cohort study of 1,521 adults (484 men and 1037 women) aged 40 to 70 years without baseline hypertension examined. An equation was used to calculate fatty liver index and classify patients as follows: fatty liver index <30, no non-alcoholic fatty liver disease; fatty liver index ≥60, non-alcoholic fatty liver disease; and 30≤ fatty liver index <60, intermediate fatty liver index.Results
During an average of 2.6 years of follow-up, 153 subjects (10.06%) developed hypertension. Fatty liver index was positively associated with baseline blood pressure, homeostasis model assessment of insulin resistance, urinary albumin/creatinine excretion, and high sensitivity C-reactive protein. After adjustment for confounding factors, including markers of insulin resistance, systemic inflammation and adiponectin levels, the odds ratio [95% confidence interval] for the incident hypertension increased in a graded manner with fatty liver index (<30 vs. 30–59 vs. ≥60 = 1 vs. 1.83 [1.16~2.88] vs. 2.09 [1.08~4.055], respectively).Conclusions
Non-alcoholic fatty liver disease assessed by fatty liver index was an independent risk factor for hypertension. Our findings suggest that fatty liver index, a simple surrogate indicator of fatty liver disease, might be useful for identifying subjects at high risk for incident hypertension in clinical practice. 相似文献68.
Prevalence of Cryptosporidium Infection among Inhabitants of 2 Rural Areas in White Nile State,Sudan
Seobo Sim Jae-Ran Yu Young-Ha Lee Jin-Su Lee Hoo-Gn Jeong Abd Al Wahab Saed Mohamed Sung-Tae Hong 《The Korean journal of parasitology》2015,53(6):745-747
Cryptosporidium , a protozoan parasite that causes watery diarrhea, is found worldwide and is common in areas with low water hygiene. In February 2014, 866 stool samples were collected from the inhabitants of 2 rural areas in White Nile State, Sudan. These stool samples were assessed by performing modified acid-fast staining, followed by examination under a light microscope. The overall positive rate of Cryptosporidium oocysts was 13.3%. Cryptosporidium oocysts were detected in 8.6% stool samples obtained from inhabitants living in the area having water purification systems and in 14.6% stool samples obtained from inhabitants living in the area not having water purification systems. No significant difference was observed in the prevalence of Cryptosporidium infection between men and women (14.7% and 14.1%, respectively). The positive rate of oocysts by age was the highest among inhabitants in their 60s (40.0%). These findings suggest that the use of water purification systems is important for preventing Cryptosporidium infection among inhabitants of these rural areas in Sudan. 相似文献
69.