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Donald Lavelle Yogen Saunthararajah Kestis Vaitkus Mahipal Singh Virryan Banzon Pasit Phiasivongsva Sanjeev Redkar Sarath Kanekal David Bearss Chongtie Shi Roger Inloes Joseph DeSimone 《Journal of translational medicine》2010,8(1):1-8
Background
Apoptosis is an early event involved in cardiomyopathy associated with diabetes mellitus. Toll-like receptor (TLR) signaling triggers cell apoptosis through multiple mechanisms. Up-regulation of TLR4 expression has been shown in diabetic mice. This study aimed to delineate the role of TLR4 in myocardial apoptosis, and to block this process through gene silencing of TLR4 in the myocardia of diabetic mice.Methods
Diabetes was induced in C57/BL6 mice by the injection of streptozotocin. Diabetic mice were treated with 50 μg of TLR4 siRNA or scrambled siRNA as control. Myocardial apoptosis was determined by TUNEL assay.Results
After 7 days of hyperglycemia, the level of TLR4 mRNA in myocardial tissue was significantly elevated. Treatment of TLR4 siRNA knocked down gene expression as well as diminished its elevation in diabetic mice. Apoptosis was evident in cardiac tissues of diabetic mice as detected by a TUNEL assay. In contrast, treatment with TLR4 siRNA minimized apoptosis in myocardial tissues. Mechanistically, caspase-3 activation was significantly inhibited in mice that were treated with TLR4 siRNA, but not in mice treated with control siRNA. Additionally, gene silencing of TLR4 resulted in suppression of apoptotic cascades, such as Fas and caspase-3 gene expression. TLR4 deficiency resulted in inhibition of reactive oxygen species (ROS) production and NADPH oxidase activity, suggesting suppression of hyperglycemia-induced apoptosis by TLR4 is associated with attenuation of oxidative stress to the cardiomyocytes.Conclusions
In summary, we present novel evidence that TLR4 plays a critical role in cardiac apoptosis. This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene. 相似文献203.
Kliucinskas M Nadisauskiene RJ Minkauskiene M 《Gynecologic and obstetric investigation》2006,62(3):173-180
AIMS: To investigate the prevalence, persistence and risk factors of high oncogenic risk human papillomavirus (HPV) among urban and rural women of reproductive age coming to consult a gynaecologist. METHODS: A prospective cohort study in urban (Kaunas) and rural (Marijampole) regions of Lithuania. The data were collected in 8 healthcare institutions from women seeking consultation of gynaecologists using a questionnaire for finding out demographic, social, behavioural and biomedical factors. HPV DNA was determined by molecular hybridization method (hybrid capture version II) determining HPV of high oncogenic risk. RESULT: 1,120 women participated in the study. The prevalence of high-risk HPV among the studied women was 25.1%. It was higher among the urban women than among the rural women. The prevalence of high-risk HPV was increased if the subjects had 2 or more sexual partners during the last 12 months (OR 2.81; 95% CI 1.83-4.32), were 19 years of age or younger (OR 2.68; 95% CI 1.47-4.91), were smoking (OR 1.81; 95% CI 1.16-2.81), and had secondary or lower education level (OR 1.43; 95% CI 1.01-2.04). This infection was obviously associated with high- and low-grade squamous intraepithelial changes of the cervix (OR 1.66, 95% CI = 1.08-2.53). CONCLUSION: The incidence rate for cervical cancer in Lithuania is one of the highest in comparison with other European countries. HPV infection was also particularly common in the studied population. About one-fourth of the women were infected with high-risk HPV infection. Young and less educated women were found to be the group that was most exposed to HPV, and therefore public health interventions and education seem to be essential in programs aimed at reducing the incidence of cervical cancer. 相似文献
204.
205.
Julija iaukait Ieva Puleikyt Simonas Jesmanas Giedr Jurkevi
ien Antanas Vaitkus Daiva Rastenyt 《Clinical Case Reports》2021,9(8)
Creutzfeldt‐Jakob disease (CJD) is a rare rapidly progressive fatal neurodegenerative disease. Neuroleptic malignant syndrome (NMS) is a complication of antipsychotic medications which may be used to treat neuropsychiatric symptoms of CJD. We present a case of a 51‐year‐ old woman with CJD who developed NMS after being prescribed quetiapine. 相似文献