Background and Purpose
This study aimed to evaluate the anti‐hepatitis C virus (HCV) activity of andrographolide, a diterpenoid lactone extracted from Andrographis paniculata, and to identify the ...signalling pathway involved in its antiviral action.
Experimental Approach
Using HCV replicon and HCVcc infectious systems, we identified anti‐HCV activity of andrographolide by measuring protein and RNA levels. A reporter activity assay was used to determine transcriptional regulation of anti‐HCV agents. A specific inhibitor and short hairpin RNAs were used to investigate the mechanism responsible for the effect of andrographolide on HCV replication.
Key Results
In HCV replicon and HCVcc infectious systems, andrographolide time‐ and dose‐dependently suppressed HCV replication. When combined with IFN‐α, an inhibitor targeting HCV NS3/4A protease (telaprevir), or NS5B polymerase (PSI‐7977), andrographolide exhibited a significant synergistic effect. Andrographolide up‐regulated the expression of haeme oxygenase‐1 (HO‐1), leading to increased amounts of its metabolite biliverdin, which was found to suppress HCV replication by promoting the antiviral IFN responses and inhibiting NS3/4A protease activity. Significantly, these antiviral effects were attenuated by an HO‐1‐specific inhibitor or HO‐1 gene knockdown, indicating that HO‐1 contributed to the anti‐HCV activity of andrographolide. Andrographolide activated p38 MAPK phosphorylation, which stimulated nuclear factor erythroid 2‐related factor 2 (Nrf2)–mediated HO‐1 expression, and this was found to be associated with its anti‐HCV activity.
Conclusions and Implications
Our results demonstrate that andrographolide has the potential to control HCV replication and suggest that targeting the Nrf2–HO‐1 signalling pathway might be a promising strategy for drug development.
Chronic hepatitis C virus (HCV) infection is the leading risk factor for hepatocellular carcinoma (HCC) and chronic liver disease worldwide. Green tea, in addition to being consumed as a healthy ...beverage, contains phenolic catechins that have been used as medicinal substances. In the present study, we illustrated that the epicatechin isomers (+)-epicatechin and (-)-epicatechin concentration-dependently inhibited HCV replication at nontoxic concentrations by using in vitro cell-based HCV replicon and JFH-1 infectious systems. In addition to significantly suppressing virus-induced cyclooxygenase-2 (COX-2) expression, our results revealed that the anti-HCV activity of the epicatechin isomers occurred through the down-regulation of COX-2. Furthermore, both the epicatechin isomers additively inhibited HCV replication in combination with either interferon-α or viral enzyme inhibitors 2'-C-methylcytidine (NM-107) or telaprevir. They also had prominent anti-inflammatory effects by inhibiting the gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inducible nitrite oxide synthase as well as the COX-2 in viral protein-expressing hepatoma Huh-7 cells. Collectively, (+)-epicatechin and (-)-epicatechin may serve as therapeutic supplements for treating HCV-related diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Data Mining for Internet of Things: A Survey Tsai, Chun-Wei; Lai, Chin-Feng; Chiang, Ming-Chao ...
IEEE Communications surveys and tutorials,
01/2014, Letnik:
16, Številka:
1
Journal Article
Recenzirano
It sounds like mission impossible to connect everything on the earth together via internet, but Internet of Things (IoT) will dramatically change our life in the foreseeable future, by making many ..."impossibles" possible. To many, the massive data generated or captured by IoT are considered having highly useful and valuable information. Data mining will no doubt play a critical role in making this kind of system smart enough to provide more convenient services and environments. This paper begins with a discussion of the IoT. Then, a brief review of the features of "data from IoT" and "data mining for IoT' is given. Finally, changes, potentials, open issues, and future trends of this field are addressed.
Internet of Things (IoT) and its relevant technologies have been attracting the attention of researchers from academia, industry, and government in recent years. However, since the requirements of ...the IoT are quite different from what the Internet today can offer, several innovative techniques have been gradually developed and incorporated into IoT, which is referred to as the Future Internet of Things (FIoT). Among them, how to extract “data” and transfer them into “knowledge” from sensing layer to application layer has become a vital issue. This paper begins with an overview of IoT and FIoT, followed by discussions on how to apply data mining and computational intelligence to FIoT. An intelligent data management framework inspired by swarm optimization will then given. Finally, open issues and future trends of this field will be addressed.
Inter- and intra-subject variability pose a major challenge to decoding human brain activity in brain-computer interfaces (BCIs) based on non-invasive electroencephalogram (EEG). Conventionally, a ...time-consuming and laborious training procedure is performed on each new user to collect sufficient individualized data, hindering the applications of BCIs on monitoring brain states (e.g. drowsiness) in real-world settings. This study proposes applying hierarchical clustering to assess the inter- and intra-subject variability within a large-scale dataset of EEG collected in a simulated driving task, and validates the feasibility of transferring EEG-based drowsiness-detection models across subjects. A subject-transfer framework is thus developed for detecting drowsiness based on a large-scale model pool from other subjects and a small amount of alert baseline calibration data from a new user. The model pool ensures the availability of positive model transferring, whereas the alert baseline data serve as a selector of decoding models in the pool. Compared with the conventional within-subject approach, the proposed framework remarkably reduced the required calibration time for a new user by 90% (18.00 min–1.72 ± 0.36 min) without compromising performance (p = 0.0910) when sufficient existing data are available. These findings suggest a practical pathway toward plug-and-play drowsiness detection and can ignite numerous real-world BCI applications.
•A novel subject-transfer framework for reducing calibration time in brain state decoding.•Feasibility of cross-subject model transferring inferred from hierarchical clustering.•Robust decoding performance supported by large-scale existing data.•Significant decrease in calibration time using baseline brain activity.
Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening ...adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs.
We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids.
Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%-62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN.
The anti-TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs.
ClinicalTrials.gov NCT01276314.
Ministry of Science and Technology of Taiwan.
Drowsy driving is one of the major causes that lead to fatal accidents worldwide. For the past two decades, many studies have explored the feasibility and practicality of drowsiness detection using ...electroencephalogram (EEG)based brain-computer interface (BCI) systems. However, on the pathway of transitioning laboratory-oriented BCI into real-world environments, one chief challenge is to obtain high-quality EEG with convenience and long-term wearing comfort. Recently, acquiring EEG from non-hair-bearing (NHB) scalp areas has been proposed as an alternative solution to avoid many of the technical limitations resulted from the interference of hair between electrodes and the skin. Furthermore, our pilot study has shown that informative drowsiness-related EEG features are accessible from the NHB areas. This study extends the previous work to quantitatively evaluate the performance of drowsiness detection using cross-session validation with widely studied machine-learning classifiers. The offline results showed no significant difference between the accuracy of drowsiness detection using the NHB EEG and the whole-scalp EEG across all subjects (p = 0.31). The findings of this study demonstrate the efficacy and practicality of the NHB EEG for drowsiness detection and could catalyze explorations and developments of many other real-world BCI applications.
Human papillomavirus (HPV) is the well‐established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high‐grade cervical intraepithelial neoplasia ...(HG‐CIN). We conducted an observational study for long‐term outcomes and HPV genotype changes after conization for HG‐CIN. Between 2008 and 2014, patients with newly diagnosed HG‐CIN before conization (surveillance new SN group) and those who had undergone conization without hysterectomy (surveillance previous SP group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG‐CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non‐surveillance (non‐S) group. For the S group (n = 493), the median follow‐up period was 74.3 months. Eighty‐four cases had recurrent CIN Grade 2 or worse (CIN2+) (5‐year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type‐specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9‐valent vaccine types. Among the 7397 non‐S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non‐S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type‐specific HPV infections, effective therapeutic vaccines are an unmet medical need.
What's new?
High‐grade cervical intraepithelial neoplasia (HG‐CIN), a cervical carcinoma precursor, frequently is caused by high‐risk human papillomavirus (hr‐HPV) infection. HG‐CIN can be treated by cervical conization, though the procedure does not eradicate hr‐HPV, potentially enabling CIN recurrence. Here, in Taiwanese patients, investigation of HPV genotype changes in relation to HG‐CIN status after conization shows that 77.4 percent of patients with recurrent CIN 2 grade or worse (CIN2+) after conization had persistent type‐specific HPV infections. Vaccination against the remaining high‐risk HPVs prevented recurrent CIN2+ in only 8.3 percent of patients, revealing an unmet need for effective therapeutic vaccines.
Big data analytics: a survey Tsai, Chun-Wei; Lai, Chin-Feng; Chao, Han-Chieh ...
Journal of big data,
1/10, Letnik:
2, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The age of big data is now coming. But the traditional data analytics may not be able to handle such large quantities of data. The question that arises now is, how to develop a high performance
...platform
to efficiently analyze big data and how to design an appropriate
mining algorithm
to find the useful things from big data. To deeply discuss this issue, this paper begins with a brief introduction to data analytics, followed by the discussions of big data analytics. Some important open issues and further research directions will also be presented for the next step of big data analytics.
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life‐threatening cutaneous conditions. However, studies of pediatric SJS/TEN are limited. To investigate the causes, clinical ...course, outcomes and complications of SJS and TEN in children. This retrospective study included 47 pediatric patients (aged < 18 years) with SJS, SJS/TEN, or TEN treated at Chang Gung Memorial Hospital, Taiwan, between January 2009 and December 2019. ALDEN scores and serological tests were used to assess causes and SCORTEN scores were applied to evaluate disease severity. Forty‐seven patients, including 30 with SJS, 6 with SJS/TEN, and 11 with TEN were included. Median age was 8 years (range 1–17 years); 51.1% were male. Thirty‐three cases (70.2%) were caused by drugs and infectious pathogens were suspected in 14 cases (29.8%). Oxcarbazepine (5/47, 10.6%) and amoxicillin (5/47, 10.6%) were the most often‐implicated drugs, and Mycoplasma infection (9/47, 19.1%) was the predominant infectious cause. Only one TENS patient died (mortality rate 1/47, 2.1%) due to septic shock with ARDS, acute renal failure and cardiopulmonary shock. Median hospital stay was 15.5 (3–42) days. Pulmonary involvement (2/39, 5.1%), including pneumonia and ARDS, was noted in acute stage. Long‐term sequelae were ocular involvement (6/39, 15.4%), nail dystrophy (4/39, 10.3%) and post‐inflammatory hypo‐/hyperpigmentation (3/39, 7.7%). In the present study, pediatric patients with SJS, SJS/TEN, or TEN have good outcomes with few long‐term complications and low mortality. Mycoplasma is the most common infectious cause in pediatric SJS/TEN. Ocular discomfort, nail dystrophy and skin dyschromia are common long‐term sequelae requiring regular follow‐up.
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