1,721,052 research outputs found
Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity
No full textHuman high-density lipoproteins (HDL) show a broad spectrum of antiviral activity in terms of anti-infection. Although many reports have pointed out a correlation between a lower serum HDL-C and a higher risk of COVID-19 infection and progression, the in vitro antiviral activity of HDL against SARS-CoV-2 has not been reported. HDL functionality, such as antioxidant and anti-infection, can be impaired by oxidation and glycation and a change to pro-inflammatory properties. This study compared the antiviral activity of native HDL with glycated HDL via fructosylation and native low-density lipoproteins (LDL). After 72 h of fructosylation, glycated HDL showed a typical multimerized protein pattern with an elevation of yellowish fluorescence. Glycated HDL showed a smaller particle size with an ambiguous shape and a loss of paraoxonase activity up to 51% compared to native HDL. The phagocytosis of acetylated LDL was accelerated 1.3-fold by glycated HDL than native HDL. Native HDL showed 1.7 times higher cell viability and 3.6 times higher cytopathic effect (CPE) inhibition activity against SARS-CoV-2 than that of glycated HDL under 60 μg/mL (approximately final 2.2 μM) in a Vero E6 cell. Native HDL showed EC50 = 52.1 ± 1.1 μg/mL (approximately final 1.8 μM) for the CPE and CC50 = 79.4 ± 1.5 μg/mL (around 2.8 μM). The selective index (SI) of native HDL was calculated to be 1.52. In conclusion, native HDL shows potent antiviral activity against SARS-CoV-2 without cytotoxicity, while the glycation of HDL impairs its antiviral activity. These results may explain why patients with diabetes mellitus or hypertension are more sensitive to a COVID-19 infection and have a higher risk of mortality
Gene duplication of type-B ARR transcription factors systematically extends transcriptional regulatory structures in Arabidopsis
Full text linkMany of duplicated genes are enriched in signaling pathways. Recently, gene duplication of kinases has been
shown to provide genetic buffering and functional diversification in cellular signaling. Transcription factors
(TFs) are also often duplicated. However, how duplication of TFs affects their regulatory structures and
functions of target genes has not been explored at the systems level. Here, we examined regulatory and
functional roles of duplication of three major ARR TFs (ARR1, 10, and 12) in Arabidopsis cytokinin
signaling using wild-type and single, double, and triple deletion mutants of the TFs. Comparative analysis of
gene expression profiles obtained from Arabidopsis roots in wild-type and these mutants showed that
duplication of ARR TFs systematically extended their transcriptional regulatory structures, leading to
enhanced robustness and diversification in functions of target genes, as well as in regulation of cellular
networks of target genes. Therefore, our results suggest that duplication of TFs contributes to robustness
and diversification in functions of target genes by extending transcriptional regulatory structures.1341sciescopu
Evaluation of 13-week subchronic toxicity of Platycodon grandiflorus (Jacq.) A.DC. root extract in rats
No full textEthnopharmacological relevance: Platycodi radix is widely used in traditional herbal medicine for bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. However, data on safety of Platycodi radix are insufficient.
Aim of the study: The present study was performed to evaluate the potential subchronic toxicity of Platycodi radix water extract through a 13-week repeated oral dose experiment in Sprague-Dawley rats.
Materials and methods: Forty male and 40 female rats were randomly assigned to four experimental groups: three treatment groups receiving 300, 1000, and 3000 mg/kg/day of Platycodi radix water extract and a vehicle control group receiving sterile distilled water for 13 weeks.
Results: Repeated oral administration of the Platycodi radix water extract to rats resulted in an increased incidence of centrilobular hepatocellular hypertrophy in the liver, diffuse follicular cell hypertrophy in the thyroid gland, and squamous hyperplasia of the limiting ridge in the stomach at dose levels of ≥500 mg/kg/day of both genders. However, these findings are considered be adaptive non-adverse changes because these findings were observed without organ weight change or clinical pathology alterations. No treatment-related effects on clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, and organ weights were observed at any dose tested.
Conclusion: Under the present experimental conditions, the no-observed-adverse-effect level of the Platycodi radix water extract was considered to be ≥ 3000 mg/kg/day in rats, and no target organs were identified.
One-generation reproductive toxicity study of 2-methylbutane in Sprague–Dawley rats
No full textThis study investigated the potential reproductive toxicity of 2-methylbutane in a one-generation reproductive toxicity study using Sprague-Dawley rats. A total of 24 male and female rats per group were given 2-methylbutane by gavage at 0, 100, 300, and 1000 mg/kg/day. Males were dosed for 10 weeks prior to mating and during mating. Females were dosed from 2 weeks before mating to day 21 of lactation. At 1000 mg/kg/day, both genders exhibited an increase in adrenal gland weight, however, a decrease in body weight gain and food intake, an increase in kidney weight, and an increased incidence of histopathological changes of the kidney were also observed in male rats. No treatment-related effects of 2-methylbutane were found in relation to the reproductive capacity of parental animals or the pre- and post-natal development of the F1 generation. There were no treatment-related effects in either gender at ≤300 mg/kg/day. Under these experimental conditions, the no-observed-adverse-effect level of 2-methylbutane was 300 mg/kg/day for general toxicity and 1000 mg/kg/day for reproductive capacity and pup development in rats.open
Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats
No full textThis study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-α and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities.open
Induction of cytochrome P450 3A1 expression by diallyl disulfide: protective effects against cyclophosphamide-induced embryo-fetal developmental toxicity
No full textThe protective effects of diallyl disulfide (DADS) on cyclophosphamide (CP)-induced developmental toxicity and the possible mechanisms involved in this protection were investigated in rats. In order to study the mechanisms involved in the protection, we examined the effects of DADS on the expression of cytochrome P450 (CYP) 3A1 in the maternal liver and placenta and oxidative stress in the maternal hepatic tissues caused by CP. CP caused severe embryo-fetal developmental toxicity and hepatic oxidative stress. In contrast, DADS treatment significantly attenuated CP-induced developmental toxicity and oxidative damage in the maternal liver. DADS also significantly increased expression of CYP3A1 in the maternal liver and placenta. These results indicate that the protective effects of DADS against CP-induced developmental toxicity may be due to its ability to promote detoxification of CP, primarily by inducing CYP3A1 expression in the maternal liver and placenta, and its potent antioxidant effects.open
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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