Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging viral pathogen that causes severe morbidity and mortality. Up to date, there is no approved or licensed vaccine or antiviral ...medicines can be used to treat MERS-CoV-infected patients. Here, we analyzed the antiviral activities of resveratrol, a natural compound found in grape seeds and skin and in red wine, against MERS-CoV infection.
We performed MTT and neutral red uptake assays to assess the survival rates of MERS-infected Vero E6 cells. In addition, quantitative PCR, western blotting, and immunofluorescent assays determined the intracellular viral RNA and protein expression. For viral productivity, we utilized plaque assays to confirm the antiviral properties of resveratrol against MERS-CoV.
Resveratrol significantly inhibited MERS-CoV infection and prolonged cellular survival after virus infection. We also found that the expression of nucleocapsid (N) protein essential for MERS-CoV replication was decreased after resveratrol treatment. Furthermore, resveratrol down-regulated the apoptosis induced by MERS-CoV in vitro. By consecutive administration of resveratrol, we were able to reduce the concentration of resveratrol while achieving inhibitory effectiveness against MERS-CoV.
In this study, we first demonstrated that resveratrol is a potent anti-MERS agent in vitro. We perceive that resveratrol can be a potential antiviral agent against MERS-CoV infection in the near future.
Background and Purpose
Oxidative stress is an important pathogenic factor in the development of hypertension. Resveratrol, the main antioxidant in red wine, improves NO bioavailability and prevents ...cardiovascular disease. The aim of this study was to examine whether resveratrol decreases the generation of reactive oxygen species (ROS), thereby reducing BP in rats with fructose‐induced hypertension.
Experimental Approach
Rats were fed 10% fructose with or without resveratrol (10 mg·kg−1·day−1) for 1 week or for 4 weeks with resveratrol treatment beginning at week 2; systolic BP (SBP) was measured by tail‐cuff method. Endogenous in vivo O2− production in the nucleus tractus solitarii (NTS) was determined with dihydroethidium. Real‐time PCR and immunoblotting analyses were used to quantify RNA and protein expression levels.
Key Results
In fructose‐fed rats, ROS levels in the NTS were higher, whereas the NO level was significantly decreased. Also, RNA and protein levels of NADPH oxidase subunits (p67, p22‐phox) were elevated, superoxide dismutase 2 (SOD2) reduced and AMP‐activated PK (AMPK) T172 phosphorylation levels in the NTS were lower in fructose‐fed rats. Treatment with the AMPK activator resveratrol decreased levels of NADPH oxidase subunits and ROS, and increased NO and SOD2 levels in the NTS of fructose‐fed rats. Administration of resveratrol, in combination with fructose at week 0 and later at week 2, significantly reduced the SBP of fructose‐fed rats.
Conclusions and Implications
Collectively, resveratrol decreased BP through the phosphorylation of AMPK, Akt and neuronal NOS in fructose‐fed rats. These novel findings suggest that resveratrol may be a potential pharmacological candidate for the treatment of hypertension.
It was suspected that aristolochic acid‐induced mutations may be associated with hepatitis B virus (HBV), playing an important role in liver carcinogenesis. The purpose of this study was to ...investigate the association between the use of Chinese herbs containing aristolochic acid and the risk of hepatocellular carcinoma (HCC) among HBV‐infected patients. We conducted a retrospective, population‐based, cohort study on patients older than 18 years who had a diagnosis of HBV infection between January 1, 1997 and December 31, 2010 and had visited traditional Chinese medicine clinics before one year before the diagnosis of HCC or the censor dates. A total of 802,642 HBV‐infected patients were identified by using the National Health Insurance Research Database in Taiwan. The use of Chinese herbal products containing aristolochic acid was identified between 1997 and 2003. Each patient was individually tracked from 1997 to 2013 to identify incident cases of HCC since 1999. There were 33,982 HCCs during the follow‐up period of 11,643,790 person‐years and the overall incidence rate was 291.8 HCCs per 100,000 person‐years. The adjusted hazard ratios (HRs) were 1.13 (95% confidence interval CI, 1.11–1.16), 1.21 (95% CI, 1.13–1.29), 1.37 (95% CI, 1.24–1.50) and 1.61 (95% CI, 1.40–1.84) for estimated aristolochic acid of 1–250, 251–500, 501–1,000 and more than 1,000 mg, respectively, relative to no aristolochic acid exposure. Our study found a significant dose–response relationship between the consumption of aristolochic acid and HCC in patients with HBV infection, suggesting that aristolochic acid which may be associated with HBV plays an important role in the pathogenesis of HCC.
What's new?
Aristolochic acid is a known carcinogen, and aristolochic acid‐induced mutations in concert with hepatitis B virus (HBV) are suspected to play an important role in liver carcinogenesis. This study investigated the association between the use of now‐banned herbal medicines containing aristolochic acid and the risk of hepatocellular carcinoma (HCC) among HBV‐infected patients in Taiwan. A significant linear dose–response relationship was found between aristolochic acid consumption and HCC in HBV patients. This suggests that aristolochic acid, which is sometimes associated with HBV infection, plays an important role in HCC pathogenesis, and HBV patients who took those herbs should be followed up.
Inflammation is a common pathophysiological trait found in both hypertension and cardiac vascular disease. Recent evidence indicates that fractalkine (FKN) and its receptor CX3CR1 have been linked to ...inflammatory response in the brain of hypertensive animal models. Here, we investigated the role of CX3CR1-microglia in nitric oxide (NO) generation during chronic inflammation and systemic blood pressure recovery in the nucleus tractus solitarii (NTS).
The hypertensive rat model was used to study the role of CX3CR1-microglia in NTS inflammation following hypertension induction by oral administration of 10% fructose water. The systolic blood pressure was measured by tail-cuff method of non-invasive blood pressure. The CX3CR1 inhibitor AZD8797 was administered intracerebroventricularly (ICV) in the fructose-induced hypertensive rat. Using immunoblotting, we studied the nitric oxide synthase signaling pathway, NO concentration, and the levels of FKN and CX3CR1, and pro-inflammatory cytokines were analyzed by immunohistochemistry staining.
The level of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, FKN, and CX3CR1 were elevated two weeks after fructose feeding. AZD8797 inhibited CX3CR1-microglia, which improved the regulation of systemic blood pressure and NO generation in the NTS. We also found that IL-1β, IL-6, and TNF-α levels were recovered by AZD8797 addition.
We conclude that CX3CR1-microglia represses the nNOS signaling pathway and promotes chronic inflammation in fructose-induced hypertension. Collectively, our results reveal the role of chemokines such as IL-1β, IL-6, and TNF-α in NTS neuroinflammation with the involvement of FKN and CX3CR1.
Climate change has caused numerous disasters around the world. It has also influenced the climate of Taiwan, with urban areas exhibiting a temperature increase by 1 °C between 1998 and 2020. In this ...study, climate change and landslides in Taiwan were statistically analyzed. Cumulative annual precipitation in mountain watersheds in central Taiwan exhibit a declining trend and is lower than that in urban areas. The relatively few typhoons reduced the distribution of rainfall in mountain watersheds and fewer landslides. From 2017 to 2020, typhoon-induced rains caused fewer landslides than did other climate events such as the meiyu front, tropical low pressure, and southwesterly flow events. Three rainfall characteristics of landslide initiation were identified: high rainfall intensity over a short duration (<12 h), high-intensity and prolonged rainfall, and high cumulative rainfall over a long duration (>36 h). Combinations of warning models for landslides in cumulative rainfall–duration plots with rainfall intensity classification and mean rainfall intensity–duration plots with cumulative rainfall classification were presented. In recent (2018–2020) years, climate change has resulted in higher temperatures, less rainfall in mountain watersheds, and a lower rainfall threshold at which landslides are initiated by non-typhoon climate events.
Separated analyses are available for evaluating slope stability after seismic shaking and rainfall. However, the combined effect of seismic shaking and rainfall water seepage on slope stability has ...not yet been well studied. In this study, the stability of the designed 30° and 45° slopes was analyzed under static, rainfall seepage, and seismic conditions. The soil shear strength reduction method was adopted to determine the factor of safety (FS) of the slope through the plane strain model of the finite difference method. The factor of safety and failure mode of the slope were studied for the interaction mechanism of seismic shaking and rainwater seepage. The numerical analysis results indicate that the soil friction angle has stronger effects on the slope stability than the soil cohesion does under the same slope conditions. The failure surface observed for biaxial seismic shaking was different from that observed for uniaxial seismic shaking. The combination effects of multi-axial seismic shaking must be considered when analyzing the failure mode of the slope. Seismic shaking after rainwater seepage results in a low FS and changes the failure mode of the slope. The FS continuously decreased with the biaxial and post-rainwater seepage seismic shaking of the slope. Seismic analysis after rainwater seepage is important for safety evaluation and disaster prevention in landslide-prone areas.
•Extend SDT to a live streaming context to elucidate factors influencing streamers’ continuance broadcasting intentions.•Performance expectancy and website attractiveness have significant effects on ...continuance broadcasting intentions.•This study offers valuable implications and guidelines for management to propose effective mechanism to increase live streamers’ e-loyalty.
Empowered by today’s rich tools for a media generation, the rapid development of the Internet, and collaborative production, live streaming services that allow anyone to launch a stream or watch someone else perform over the Internet have gained great popularity. This study endeavored to ascertain the determinants compelling live streamers to continue broadcasting on Twitch, a live streaming video platform. This novel research model used self-determination theory to investigate different motivational forces (i.e., intrinsic and extrinsic) that drive live streamers’ continuance broadcasting intentions. Both intrinsic and extrinsic motivation significantly influenced live streamers’ performance expectancies, but not their perceived website attractiveness. Efforts to influence perceived website attractiveness must be made via performance expectancies. Performance expectancy and perceived website attractiveness subsequently affect streamers’ continuance of broadcasting intentions on Twitch. This study yields important managerial implications for live streaming platforms to improve their service design and understanding of streamers’ behavioral intentions.
Ovarian cancer is highly metastatic, with a high frequency of relapse, and is the most fatal gynecologic malignancy in women worldwide. It is important to elevate the drug susceptibility and ...cytotoxicity of ovarian cancer cells, thereby eliminating resident cancer cells for more effective therapeutic efficacy. Here, we developed a bispecific antibody (BsAb; mPEG × HER2) that can easily provide HER2
tumor tropism to mPEGylated liposomal doxorubicin (PLD) and further increase the drug accumulation in cancer cells via receptor-mediated endocytosis, and improve the cytotoxicity and therapeutic efficacy of HER2
ovarian tumors. The mPEG × HER2 can simultaneously bind to mPEG molecules on the surface of PLD and HER2 antigen on the surface of ovarian cancer cells. Simply mixing the mPEG × HER2 with PLD was able to confer HER2 specificity of PLD to HER2
ovarian cancer cells and efficiently trigger endocytosis and enhance cytotoxicity by 5.4-fold as compared to non-targeted PLD. mPEG × HER2-modified PLD was able to significantly increase the targeting and accumulation of HER2
ovarian tumor by 220% as compared with non-targeted PLD. It could also significantly improve the anti-tumor activity of PLD (P < 0.05) with minimal obvious toxicity in a tumor-bearing mouse model. We believe that the mPEG × HER2 can significantly improve the therapeutic efficacy, potentially reduce the relapse freqency and thereby achieve good prognosis in ovarian cancer patients.
To classify chest computed tomography (CT) images as positive or negative for coronavirus disease 2019 (COVID-19) quickly and accurately, researchers attempted to develop effective models by using ...medical images. A convolutional neural network (CNN) ensemble model was developed for classifying chest CT images as positive or negative for COVID-19. To classify chest CT images acquired from COVID-19 patients, the proposed COVID19-CNN ensemble model combines the use of multiple trained CNN models with a majority voting strategy. The CNN models were trained to classify chest CT images by transfer learning from well-known pre-trained CNN models and by applying their algorithm hyperparameters as appropriate. The combination of algorithm hyperparameters for a pre-trained CNN model was determined by uniform experimental design. The chest CT images (405 from COVID-19 patients and 397 from healthy patients) used for training and performance testing of the COVID19-CNN ensemble model were obtained from an earlier study by Hu in 2020. Experiments showed that, the COVID19-CNN ensemble model achieved 96.7% accuracy in classifying CT images as COVID-19 positive or negative, which was superior to the accuracies obtained by the individual trained CNN models. Other performance measures (i.e., precision, recall, specificity, and F.sub.1-score) obtained bythe COVID19-CNN ensemble model were higher than those obtained by individual trained CNN models. The COVID19-CNN ensemble model had superior accuracy and excellent capability in classifying chest CT images as COVID-19 positive or negative.
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