In vitro and in vivo antitumor effects of acetylshikonin isolated from Arnebia euchroma (Royle) Johnst (Ruanzicao) cell suspension cultures

<p>Abstract</p> <p>Background</p> <p>Shikonin derivatives have cytotoxic and antitumor effects. This study aims to investigate the antitumor effects of acetylshikonin isolated from a Chinese medicinal herb <it>Arnebia euchroma (Royle) Johnst</it>.</p> <p>Methods</p> <p>The 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the <it>in vitro </it>antitumor effects of acetylshikonin on human lung adenocarcinoma cell line A549, human hepatocellular carcinoma cell line Bel-7402, human breast adenocarcinoma cell line MCF-7 and mouse Lewis lung carcinoma (LLC) cell line. C₅₇BL/6 mice with LLC model were used to study the <it>in vivo </it>antitumor effects of acetylshikonin. The expression of bax, bcl-2 and caspase-3 proteins in LLC tissue was determined with immunohistochemical staining.</p> <p>Results</p> <p>In A549, Bel-7402, MCF-7 and LLC cell lines, acetylshikonin inhibited cell growth in a dose-dependent manner. IC50 (means ± SD) were 5.6 ± 0.86 μg/ml, 6.82 ± 1.5 μg/ml, 3.04 ± 0.44 μg/ml and 2.72 ± 0.38 μg/ml respectively. Acetylshikonin suppressed tumor growth in C57BL/6 mice with LLC. The inhibition rate of acetylshikonin (2 mg/kg) was 42.85%. Immunohistochemical staining revealed that in the acetylshikonin groups the expression of bax and caspase-3 increased, whereas the expression of bcl-2 decreased, suggesting that acetylshikonin induced tumor cell apoptosis through activating the pro-apoptotic bcl-2 family and caspase-3.</p> <p>Conclusion</p> <p>Acetylshikonin isolated from <it>Arnebia euchroma (Royle) Johnst </it>cell suspension cultures exhibits specific <it>in vivo </it>and <it>in vitro </it>antitumor effects.</p

Tibetan sheep have a high capacity to absorb and to regulate metabolism of SCFA in the rumen epithelium to adapt to low energy intake

The nutritional intake of Tibetan sheep on the harsh Qinghai-Tibetan Plateau is often under maintenance requirements, especially during the long, cold winter. However, they have adapted well and even thrive under these conditions. The aim of the present study was to gain insight into how the rumen epithelium of Tibetan sheep has adapted to the consumption of low-energy-level diets. For this purpose, we compared Tibetan and small-tailed Han sheep (n 24 of each breed, all wethers and 1 center dot 5 years of age), which were divided randomly into one of four groups and offered ad libitum diets of different digestible energy (DE) densities: 8 center dot 21, 9 center dot 33, 10 center dot 45 and 11 center dot 57 MJ DE/kg DM. The Tibetan sheep had higher rumen concentrations of total SCFA, acetate, butyrate and iso-acids but lower concentrations of propionate than small-tailed Han sheep. The Tibetan sheep had higher absorption capability of SCFA due to the greater absorption surface area and higher mRNA expression of the SCFA absorption relative genes than small-tailed Han sheep. For the metabolism of SCFA in the rumen epithelium, the small-tailed Han sheep showed higher utilisation of the ketogenesis pathway than Tibetan sheep; however, Tibetan sheep had greater regulation capacity in SCFA metabolism pathways. These differences between breeds allowed the Tibetan sheep to have greater capability of absorbing SCFA and better capacity to regulate the metabolism of SCFA, which would allow them to cope with low energy intake better than small-tailed Han sheep

Microbial Intervention as a Novel Target in Treatment of Non-Alcoholic Fatty Liver Disease Progression

Background/Aims: Emerging evidence suggests a close link between gut microbiota and non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the association between gut microbiota and the DNA methylation of adiponectin (an adipocyte-specific adipocytokine) in rats, following diet-induced NAFLD. Methods: 50 male SD rats were randomly divided into five groups with or without a high fat diet (HFD), antibiotics, and probiotics, in order to establish an imbalanced gut microbiota and probiotic treatment model in NAFLD rats. After 13 weeks of treatment, blood, liver, and cecal tissue samples were collected. Serum lipids, liver function indexes by biochemical analyzers, and changes in liver pathology with hematoxylin-eosin (HE) and masson staining were detected. Furthermore, the serum adiponectin by enzyme-linked immunosorbent assay (ELISA) and liver adiponectin methylation levels in the promoter regions by pyrophosphate sequencing were determined. High throughput Illumina sequencing targeted microbial 16S genes, bioinformatics and statistical analysis identified cecal-associated gut microbiota. Results: HFD with antibiotic exposure showed the most severe steatohepatitis and a severe gut microbiota alteration. Reduced bacterial diversity was also seen and the abundances of Firmicutes, Lactobacillus, Cyanobacteria, Acidobacteria, Chlamydiae, Chlamydiales, Rubrobacteria, Verrucomicrobia, Blautia, Shewanella, Bacteroides, Bacteroides acidifaciens, and Bacteroides uniformis, were shown to be partly reversed by probiotic treatment. Decreased serum adiponectin levels and increased DNA methylation levels of adiponectin promoter regions were also markedly associated with the NAFLD progression during gut microbiota alteration. Conclusion: Our results suggested that both gut microbiota alteration and adiponectin variability may be drivers of NAFLD progression and that targeting the gut microbiota, such as via administration of a probiotic, may delay NAFLD progression via adiponectin

An analysis of E-waste flows in China

In Europe, legislation about waste of electrical and electronic equipment (WEEE) recovery and recycling has been introduced in 2002, and corresponding legislation in the EU Member States was in place in August 2005 (EU-EC 2003). In the same period, China has been developing WEEE regulation as well. The main contribution to date to the Chinese legislative framework is the 'Circular Economy Promotion Law of the People's Republic of China' that was approved on August 29, 2008, and came into force as of January 1, 2009. Both these legislative systems contain the Extended Producer Responsibility as a core concept, as well as a formal, and, in the case of China, centralised, recovery system. Given the conceptual similarities of legislation on WEEE, but striking differences in the product recovery systems in China and the EU, it is of interest to investigate if the existing recovery and recycling system in China actually fits the new legislation. Currently, there is anecdotal evidence that, in China, much of the WEEE flows into informal recycling channels such as secondhand market and manual recycling workshops. Not much is known otherwise because a formal governance system and official statistics collection do not exist yet. More particularly, the actual WEEE flow in China, or in particular cities, is virtually unknown, as is the relationship between collection-treatment, re-selling and disposal. This paper suggests a Markov chain model that allows for the analysis of the flow of WEEE through the reverse chain from point of collection through the final disposal. We analyse this sytem in its equilibrium state and investigate the impact of scenarios that reflect key elements of the new WEEE regulation in China. In addition, we offer a qualitative analysis of the various scenarios for the three dimensions of sustainability: people, planet and profit. This research offers specific suggestions to strengthen the Chinese WEEE recovery and recycling system that would bring the actual system more in line with the current policy

Comparable cognitive impairment was detected in MACS and CS and alleviated after remission of hypercortisolism in MACS

ContextFew studies have directly compared the cognitive characteristics of patients with mild autonomous cortisol secretion (MACS) and Cushing’s syndrome (CS). The effect of surgical or conservative treatment on cognitive function in patients with MACS is still unclear.ObjectiveTo compare the differences in cognitive function between patients with MACS and CS and evaluate the effect of surgery or conservative treatment on cognitive function.MethodsWe prospectively recruited 59 patients with nonfunctional adrenal adenoma (NFA), 36 patients with MACS, and 20 patients with adrenal CS who completed the global cognition and cognitive subdomains assessments. Seventeen MACS patients were re-evaluated for cognitive function after a 12-month follow-up period; of these, eleven underwent laparoscopic adrenalectomy and six received conservative treatment.ResultsPatients with MACS and CS performed worse in the global cognition and multiple cognitive domains than those with NFA (all P&lt;0.05). No statistical difference was found in cognitive functions between patients with MACS and CS. Logistic regression analysis showed that patients with MACS (odds ratio [OR]=3.738, 95% confidence intervals [CI]: 1.329–10.515, P=0.012) and CS (OR=6.026, 95% CI: 1.411–25.730, P=0.015) were associated with an increased risk of immediate memory impairment. Visuospatial/constructional, immediate and delayed memory scores of MACS patients were significantly improved at 12 months compared with pre-operation in the surgical treatment group (all P&lt;0.05), whereas there was no improvement in the conservative treatment group.ConclusionPatients with MACS have comparable cognitive impairment as patients with CS. Cognitive function was partially improved in patients with MACS after adrenalectomy. The current data support the inclusion of cognitive function assessment in the clinical management of patients with MACS

Association between urinary excretion of protein-bound uremic toxins and upper urinary tract calculus

Objective·To investigate the relation between urinary excretion of protein-bound uremic toxins (PBUTs) and upper urinary tract calculus.Methods·Residents aged 18‒80 years in the community of Haitou, Danzhou city in Hainan Province were recruited. Basic information and diet for the last 3 d of the subjects were recorded. Their fasting sera and 24-hour urine samples were collected, and they also underwent ultrasound examination of kidneys and ureters. The subjects with upper urinary calculi detected by ultrasound or a clear history of upper urinary calculi were selected as the calculus group, and the others as the non-calculus group. The biochemical indicators related to the formation of calculus in blood and urine were detected, and the levels of PBUTs, including indoxyl sufate (IS), indole-3-acetic acid (IAA), and p-cresol sulfate (PCS) in blood and urine, as well as oxalic acid and citric acid in urine were detected by high-performance liquid chromatography. The related factors of upper urinary tract calculus formation were analyzed by multivariate Logistic regression. The correlations of urine PBUTs with urine uric acid, oxalic acid, and citric acid were analyzed by Spearman correlation test.Results·A total of 117 participants were screened out with 54 people in the calculus group and 63 people in the non-calculus group. There were no significant differences between the two groups in terms of gender, age, serum indicators, and prevalence of complications such as hypertension, diabetes, and hyperuricemia/gout. The 24-hour urine pH, calcium, uric acid, and chlorine in the calculus group were significantly higher than those in the non-calculus group (all P<0.05), while IS was significantly lower than that in the non-calculus group (P<0.05). Multivariate Logistic regression analysis showed that urinary IS (OR=0.929, 95%CI 0.875‒0.986, P=0.016) was related to the calculus formation independently, in addition to urinary calcium. The Spearman correlation analysis results showed that the levels of IAA (r=0.420, P=0.000) and PCS (r=0.307, P=0.001) in 24-hour urine were positively correlated with oxalic acid, PCS was positively correlated with uric acid (r=0.297, P=0.002), and IS was positively correlated with citric acid (r=0.289, P=0.002).Conclusion·In the population, a decrease in urinary excretion of IS may be an independent risk factor for the formation of upper urinary tract calculus, and PBUTs levels are correlated with levels of uric acid, oxalic acid, and citric acid

Color-coded parametric imaging support display of vessel hemorrhage—an in vitro experiment and clinical validation study

BackgroundDigital Subtraction Angiography (DSA) is currently the most effective diagnostic method for vascular diseases, but it is still subject to various factors, resulting in uncertain diagnosis. Therefore, a new technology is needed to help clinical doctors improve diagnostic accuracy and efficiency.PurposeThe objective of the study was to investigate the effect of utilizing color-coded parametric imaging techniques on the accuracy of identifying active bleeding through DSA, the widely accepted standard for diagnosing vascular disorders.MethodsSeveral variables can delay the diagnosis and treatment of active bleeding with DSA. To resolve this, we carried out an in vitro simulation experiment to simulate vascular hemorrhage and utilized five color-coded parameters (area under curve, time to peak, time-of-arrival, transit time, and flow rate of contrast agent) to determine the optimal color coding parameters. We then verified it in a clinical study.ResultsFive different color-coded parametric imaging methods were compared and the time-of-arrival color coding was the most efficient technique for diagnosing active hemorrhage, with a statistically significant advantage (P &lt; 0.001). In clinical study, 135 patients (101 with confirmed bleeding and 34 with confirmed no bleeding) were collected. For patients whose bleeding could not be determined using DSA alone (55/101) and whose no bleeding could not be diagnosed by DSA alone (35/55), the combination of time-of-arrival color parametric imaging was helpful for diagnosis, with a statistically significant difference (P &lt; 0.01 and P = 0.01).ConclusionsThe time-of-arrival color coding imaging method is a valuable tool for detecting active bleeding. When combined with DSA, it improves the visual representation of active hemorrhage and improves the efficiency of diagnosis

Looking under the hood: A comparison of techno-economic assumptions across national and global integrated assessment models

Integrated assessment models are extensively used in the analysis of climate change mitigation and are informing national decision makers as well as contribute to international scientific assessments. This paper conducts a comprehensive review of techno-economic assumptions in the electricity sector among fifteen different global and national integrated assessment models. Particular focus is given to six major economies in the world: Brazil, China, the EU, India, Japan and the US. The comparison reveals that techno-economic characteristics are quite different across integrated assessment models, both for the base year and future years. It is, however, important to recognize that techno-economic assessments from the literature exhibit an equally large range of parameters as the integrated assessment models reviewed. Beyond numerical differences, the representation of technologies also differs among models, which needs to be taken into account when comparing numerical parameters. While desirable, it seems difficult to fully harmonize techno-economic parameters across a broader range of models due to structural differences in the representation of technology. Therefore, making techno-economic parameters available in the future, together with of the technology representation as well as the exact definitions of the parameters should become the standard approach as it allows an open discussion of appropriate assumptions. © 2019 The Author