19 research outputs found

    MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities

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    Ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, markers for disease prediction and prognosis are highly desirable for early diagnosis as well as for helping optimize and personalize treatment. Recently, microRNAs (miRNAs), which consist of short-sequence RNAs that do not encode a protein, have emerged as new biomarkers in the clinical diagnosis and treatment of ovarian cancer. By pairing with bases specific to the target messenger RNA (mRNA), miRNAs cause degradation of the target mRNA or inhibit its translation, thereby regulating various cellular processes including cell proliferation and adhesion. Increasing numbers of studies have shown that miRNA expression abnormality plays an important role in the development of ovarian cancer. In this review, we discuss the mechanisms of miRNA action, current research regarding their role in the suppression or promotion of ovarian cancer, and their use as markers for diagnosis of prognosis or as therapeutic targets for this disease. Finally, we present future perspectives regarding the clinical management of ovarian cancer and the role for miRNAs therein

    Analysis of clinical parameters and echocardiography as predictors of fatal pediatric myocarditis.

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    Pediatric myocarditis symptoms can be mild or as extreme as sudden cardiac arrest. Early identification of the severity of illness and timely provision of critical care is helpful; however, the risk factors associated with mortality remain unclear and controversial. We undertook a retrospective review of the medical records of pediatric patients with myocarditis in a tertiary care referral hospital for over 12 years to identify the predictive factors of mortality. Demographics, presentation, laboratory test results, echocardiography findings, and treatment outcomes were obtained. Regression analyses revealed the clinical parameters for predicting mortality. During the 12-year period, 94 patients with myocarditis were included. Of these, 16 (17%) patients died, with 12 succumbing in the first 72 hours after admission. Fatal cases more commonly presented with arrhythmia, hypotension, acidosis, gastrointestinal symptoms, decreased left ventricular ejection fraction, and elevated isoenzyme of creatine kinase and troponin I levels than nonfatal cases. In multivariate analysis, troponin I > 45 ng/mL and left ventricular ejection fraction < 42% were significantly associated with mortality. Pediatric myocarditis had a high mortality rate, much of which was concentrated in the first 72 hours after hospitalization. Children with very high troponin levels or reduced ejection fraction in the first 24 hours were at higher risk of mortality, and targeting these individuals for more intensive therapies may be warranted

    Protective Efficacy of VP1-Specific Neutralizing Antibody Associated with a Reduction of Viral Load and Pro-Inflammatory Cytokines in Human SCARB2-Transgenic Mice

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    <div><p>Hand-foot-mouth diseases (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16) as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype) or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype). This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.</p></div

    Classification Prediction of Alzheimer’s Disease and Vascular Dementia Using Physiological Data and ECD SPECT Images

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    Alzheimer’s disease (AD) and vascular dementia (VaD) are the two most common forms of dementia. However, their neuropsychological and pathological features often overlap, making it difficult to distinguish between AD and VaD. In addition to clinical consultation and laboratory examinations, clinical dementia diagnosis in Taiwan will also include Tc-99m-ECD SPECT imaging examination. Through machine learning and deep learning technology, we explored the feasibility of using the above clinical practice data to distinguish AD and VaD. We used the physiological data (33 features) and Tc-99m-ECD SPECT images of 112 AD patients and 85 VaD patients in the Taiwanese Nuclear Medicine Brain Image Database to train the classification model. The results, after filtering by the number of SVM RFE 5-fold features, show that the average accuracy of physiological data in distinguishing AD/VaD is 81.22% and the AUC is 0.836; the average accuracy of training images using the Inception V3 model is 85% and the AUC is 0.95. Finally, Grad-CAM heatmap was used to visualize the areas of concern of the model and compared with the SPM analysis method to further understand the differences. This research method can quickly use machine learning and deep learning models to automatically extract image features based on a small amount of general clinical data to objectively distinguish AD and VaD

    Survival of N3 treated hSCARB2-transgenic mice preinfected with 5746.

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    <p>Seven-day old mice preinfected with 1×10<sup>5</sup> pfu of 5746 were given 200 µg N3 at time points of 3 h (▾), 24 h (▴), 48 h (▪), and 48 h twice (•) post infection. Mice injected without N3 (O), with the same amounts of isotype antibody (♦), and mice treated with a low dose of N3 (70 µg) (□) 3 h post infection were included. Mice were monitored daily and survival rates were recorded. Each group consisted of 7 to 10 mice and the results were representative of 2 independent experiments. The Logrank test was used for statistical analysis.</p

    Administration of N3 reduced pro-inflammatory chemokines expression in CNS and muscle tissues of 5746-preinfected hSCARB2-transgenic mice.

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    <p>RNAs were extracted from the brain, spinal cord, and muscle of 5746-infected 7-day old hSCARB2-transgenic mice treated with N3 or isotype antibody, and antibody-untreated mice as described in Fig. 6 and were subjected to quantitative RT-PCR specific to (<b>A</b>) CXCL10, (<b>B</b>) CCL3, and (<b>C</b>) IL-6. The number of PCR cycles (Ct) required for fluorescent detection of target genes was calculated and presented as the relative expression after normalization with the internal control of β-actin expression from the same tissue. Each normalized 2<sup>Ct</sup> value was the ratio to the value from the mean of 2<sup>Ct</sup> obtained from the antibody-untreated tissues. A schematic representation of the target gene expression and the statistical average from 10 mice per group is shown. Unpaired student <i>t</i> test with Welch correction was used for statistical analysis. (*<i>p</i>< = 0.05, **<i>p</i>< = 0.01).</p

    N3 conferred the reduction of hair loss and scurf on E59-preinfected hSCARB2-transgenic mice.

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    <p>(<b>A</b>) and (<b>B</b>) 1-day old hSCARB2-transgenic mice (n = 9–10/group) were preinfected with a HFMD symptom-causing dose of E59 at 1×10<sup>7</sup> pfu subcutaneously. After 3 h of infection, 200 µg of N3 or isotype antibody was injected i.p. Mice without any antibody treatment were included. The Experiments were repeated twice, and 100× magnification of pictures (<b>A</b>) shown the representative data were taken. The graph represents the scoring of severe hair loss and skin scurf (<b>B</b>) from each group of mice. The scores were monitored on a daily basis. One-way ANOVA and the Kruskal-Wallis test were used for statistical analysis (*<i>p</i>< = 0.05, **<i>p</i>< = 0.01).</p

    N3 reduced the pathogenesis of EV71 in the limb muscles and in the intestinal mucosa and villi.

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    <p>(<b>A</b>) Brainstem and (<b>B</b>) limb muscle tissues were isolated from the 1×10<sup>5</sup> pfu of 5746-infected 7-day old hSCARB2-Tg mice which treated i.p. with 200 µg of N3 or isotype antibodies (3 h post infection), and from antibody-untreated mice staining with anti-EV71 antibody on Day 4 post infection. The normal tissues (MOCK) with anti-EV71 staining were also prepared. (<b>C</b>) H/E staining of intestine (>8 days post infection) from the groups of mice described in (<b>A</b>) was shown. Observations were made at a magnification of x200 for (<b>A</b>) and x100 for (<b>B</b>) and (<b>C</b>).</p
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