Mechanism and use strategy of uric acid-lowering drugs on coronary heart disease.

Coronary heart disease (CHD) is a serious cardiovascular illness, for which an elevated uric acid (UA) level presents as a considerable risk factor. This can be treated with UA-lowering drugs such as allopurinol and benzbromarone, which can reduce UA levels by the inhibition of UA production or by promoting its excretion. Such drugs can also be beneficial to CHD in other ways, such as reducing the degree of coronary arteriosclerosis, improving myocardial blood supply and alleviating ventricular remodeling. Different UA-lowering drugs are used in different ways: allopurinol is preferred as a single agent in clinical application, but in absence of the desired response, a combination of drugs such as benzbromarone with ACE inhibitors may be used. Patients must be monitored regularly to adjust the medication regimen. Appropriate use of UA-lowering drugs has great significance for the prevention and treatment of CHD. However, the specific mechanisms of the drugs and individualized drug use need further research. This review article expounds the mechanisms of UA-lowering drugs on CHD and their clinical application strategy, thereby providing a reference for further optimization of treatment.

The protective effects of uric acid against myocardial ischemia via the Nrf2 pathway.

Uric acid (UA) possesses both pro- and anti-oxidative properties in ischemic heart disease, but the underlying mechanism remains unclear. We aimed to investigate UA's protective effect on myocardial ischemia by examining its effects on ECG Ischemic Alterations (EIA) and H2O2-induced oxidative stress in H9C2 myocardial cells. The incidence of EIA decreased over time and was more prevalent among women than men. A U-shaped relationship was observed between UA levels and EIA incidence, with the third quartile exhibiting a protective association. Addition of 237.9 µmol/L UA improved cellular damage and oxidative stress in H2O2-treated H9C2 cells, as determined by cell viability, LDH release, ROS levels, and total antioxidant capacity assays. UA activated the Nrf2 pathway, evidenced by increased expression of Nrf2, GCLC, and HO-1 proteins. By reversing cell cycle blockage, promoting wound healing ability, improving colony-forming capacity, and increasing angiogenesis in H2O2-treated cells, UA exhibited positive effects on cardiomyocyte growth characteristics. Additionally, use of Nrf2 inhibitor ML385 confirmed the involvement of the Nrf2 pathway by negating UA's effects on oxidatively damaged cardiomyocytes. Our findings suggest that UA induces downstream antioxidant factors to ameliorate oxidative stress by activating the Nrf2 pathway, which could be one of the targets responsible for UA's beneficial effects in myocardial ischemia.

Perceptions towards online learning among medical students during the COVID-19 pandemic.

Social distancing has been essential during the COVID-19 pandemic to slow the spread of the disease. Online learning ensures students can participate in learning activities while also maintaining a physical distance from other students. Although online learning was used to prevent the spread of COVID-19, the development of online learning has also been promoted. Here, we sought to explore the perceptions and responses of students to online learning during the pandemic using a cross-sectional study. Electronic questionnaire was used for data collection. Statistical analyses were performed for 1614 valid questionnaires and P < 0.05 was considered statistically significant. Overall, COVID-19 had more effect on female students, such as fear of COVID-19 (2.4 times higher than the number of male students) and length of time spent learning (H = 42.449, P < 0.05). However, the higher the students' grades were, the less the impact of COVID-19. For the style of lessons, all students would prefer shorter lessons (P < 0.05). Female and fifth-grade students were more prefer combined online and face-to-face learning, and male and freshmen students were more likely to prefer face-to-face learning after the pandemic. More than 50% of students thought the main advantage of online learning was convenience, with low efficiency being a disadvantage. The main factors negatively influencing online learning were eyestrain, poor network connections, and poor learning environments at home. In conclusion, synchronous online and face-to-face learning may become more common in future curricula, however the efficiency of online learning and the female students more attentions.

[Retracted] Dracorhodin perchlorate induces the apoptosis of glioma cells.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that certain of the western blotting data appeared to have been duplicated, comparing Fig. 2B with Fig. 4A; furthermore, the flow cytometric data panels featured in Fig. 3A appeared to contain repeated patternings of data within those data panels.  After having conducted an independent investigation in the Editorial Office, the Editor of Oncology Reports has determined that this paper should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in Oncology Reports 35: 2364­2372, 2016; DOI: 10.3892/or.2016.4612].

Epstein-Barr Virus EA-IgA, VCA-IgA, and EBVNA-IgG Antibodies in a Population of Wuhan, China.

The study investigated the distribution of Epstein-Barr virus (EBV) EA-IgA, VCA-IgA, and EBVNA-IgG antibodies in a local population of Wuhan, China. Chemiluminescence immunoassay (CLIA) was used to detect EBV EA-IgA, VCA-IgA, and EBVNA-IgG antibodies in 972 subjects undergoing physical examination in Wuhan, and the results were analyzed. The detection rate of EBV was positively correlated with age. In the 972 cases, there was significant difference between different genders in the positive rate of VCA-IgA and EBVNA-IgG. Moreover, the positive rate of VCA-IgA and EBVNA-IgG was higher in men ≥ 60 years old than in those < 60 but no significant differences were found in three antibodies among various age groups. Our results suggested that the EBV infection should be intensively monitored in elderly people in Wuhan.

Effect of silencing S-phase kinase-associated protein 2 on chemosensitivity to temozolomide of human glioma cells U251.

OBJECTIVE: To examine the effect of silencing SKP2 on chemosensitivity of human glioma cells U251 to temozolomide (TMZ). METHODS: Adenoviruses harbouring shRNA targeting SKP2 (i.e. Ad-shSKP2) and non-targeting scrambled shRNA (i.e. Ad-shNC) were used to infect U251 cells. The transduced cells were then treated with TMZ. Cell viability after treatment was assayed using CCK8; while cell cycle and apoptosis were examined using flow cytometry. To study the effect of silencing SKP2 on autophagy in U251, we co-transduced the cells with Ad-mRFP-LC3 and Ad-shSKP2/Ad-shNC. The expression of autophagy marker LC3 after TMZ treatment was studied using microscopy and Western blotting assays. RESULTS: The cytotoxicity of TMZ (i.e. 20-100 µM) was more significantly seen in Ad-shSKP2-transduced U251 cells than in the Ad-shNC-transduced U251 cells. The IC50 values in shSKP2-U251 were significantly lower than those of the shNC-U251 (P < 0.05). Both TMZ and Ad-shSKP2 alone increased apoptosis and promoted expression of LC3 in U251. Combined treatment of Ad-shSKP2 and TMZ further elevated apoptosis and LC3 expression. CONCLUSION: Silencing SKP2 in U251 cells increased chemosensitivity to TMZ that was accompanied with enhanced apoptosis and autophagy. Targeting SKP2 may be a potential approach to potentiate TMZ treatment in patients with glioma.

Low concentration of quercetin antagonizes the invasion and angiogenesis of human glioblastoma U251 cells.

Glioblastoma is the most aggressive type of brain tumor with a very poor prognosis. Therefore, it is always of great importance to explore and develop new potential treatment for glioblastoma. Quercetin, a flavonoid present in a variety of human foods, has been shown to inhibit various tumor cell proliferation. In this study, we found that treating human glioblastoma U251 cells with 10 µg/mL quercetin for 24 hours, a concentration that was far below the IC50 (113.65 µg/mL) and at which quercetin failed to inhibit cell proliferation, inhibited cell migration (30%) and cell invasion as examined by wound scratch assay and transwell assay, respectively. We further showed that 10 µg/mL quercetin inhibited cell migration and tube formation of human umbilical vein endothelial cells induced by the conditioned medium derived from U251 cell culture. The inhibitory effect of quercetin on migration and angiogenesis is possibly mediated through the downregulation of protein levels of VEGFA, MMP9, and MMP2 as detected by Western blot. Our findings demonstrated that low concentration of quercetin antagonized glioblastoma cell invasion and angiogenesis in vitro.

Effects of quercetin on proliferation and migration of human glioblastoma U251 cells.

Quercetin is a flavonoid that has been shown to have anti-oxidation, anti-inflammation, anti-allergic, anti-viral, and anti-cancer activities. Here, we examined the effects of quercetin on cell viability, cell cycle progression, and migration in U251 cells, a human glioblastoma cell line. We found that quercetin inhibited cell proliferation after treating cells for 24 (IC50 of 113.65µg/ml) or 48h (IC50 of 48.61µg/ml). Quercetin treatment also induced apoptosis via deregulating the expression of apoptotic genes, including Bax and Bcl-2, and arrested cell cycle at G2/M phases. We further found that quercetin impaired cell migration and invasion via downregulating the expression of matrix metallopeptidases MMP9 and MMP2. Our results provide evidences that quercetin has inhibitory effects on glioblastoma cell proliferation and invasion, and suggest a potential clinical application for glioblastoma.

Dracorhodin perchlorate induces the apoptosis of glioma cells.

Dracorhodin perchlorate (Dp), a synthetic analogue of the antimicrobial anthocyanin red pigment, has recently been shown to induce apoptotic cell death in various types of cancer cells. Yet, the inhibitory effect of Dp on human glioma cells remains uninvestigated. Therefore, in the present study, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to detect cell viability and cell cycle progression in glioma U87MG and T98G cells, respectively. Annexin V-FITC/propidium iodide double staining and JC-1 staining were separately applied to determine cellular apoptosis and mitochondrial membrane potential damage in the cells. The expression levels of associated proteins involved in cell cycle progression and apoptosis were measured by western blotting. The activities of caspase­9/-3 were determined by Caspase-Glo-9/3 assay. The results indicated that Dp treatment significantly inhibited cell proliferation in a dose- and time-dependent manner, and blocked cell cycle progression at the G1/S phase in the U87MG and T98G cells via the upregulation of p53 and p21 protein expression, and simultaneous downregulation of Cdc25A, Cdc2 and P-Cdc2 protein expression. Additionally, Dp treatment led to the loss of cellular mitochondrial membrane potential, and the release of cytochrome c, and strongly induced the occurence of apoptosis. Increased expression levels of Bim and Bax protein and the downregulated expression of Bcl-2 protein were observed. Caspase-9/-3 were activated and their activities were elevated after Dp treatment. These findings indicate that Dp inhibits cell proliferation, induces cell cycle arrest and apoptosis in glioma cells, and is a possible candidate for glioma treatment.