bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomics profiling of Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata extracts using UPLC-Q/TOF-MS
Authors: Zhang Zhaoyan , Yang Liang , Huang Xiaoyan , Gao Yue 
Published: October 2019

Abstract

Background
The side effects caused by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have often appeared globally. There is no research on the changes of endogenous metabolites among PMR- and PMRP-treated rats. The aim of this study was to evaluate the varying metabolomic effects between PMR- and PMRP-treated rats. We tried to discover relevant differences in biomarkers and endogenous metabolic pathways.

Methods
Hematoxylin and eosin staining and immunohistochemistry staining were performed to find pathological changes. Biochemical indicators were also measured, one-way analysis of variance with Dunnett’s multiple comparison test was used for biochemical indicators comparison among various groups. Metabolomics analysis based on ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q/TOF-MS) was performed to find the changes in metabolic biomarkers. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to reveal group clustering trend, evaluate and maximize the discrimination between the two groups. MetaboAnalyst 4.0 was performed to find and confirm the pathways.

Results
PMR extracts exhibited slight hepatotoxic effects on the liver by increasing aspartate and alanine aminotransferase levels. Twenty-nine metabolites were identified as biomarkers, belonging to five pathways, including alpha-linolenic acid metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, arginine and proline metabolism, and primary bile acid biosynthesis.

Conclusion
This study provided a comprehensive description of metabolomic changes between PMR- and PMRP-treated rats. The underlying mechanisms require further research.
A novel egg-shell membrane based hybrid nanofibrous scaffold for cutaneous tissue engineering
Authors: Mohammadzadeh Leila , Rahbarghazi Reza , Salehi Roya , Mahkam Mehrdad 
Published: October 2019

AbstractBackgroundThe main issue in cutaneous regeneration is to develop engineered scaffolds based on natural extracellular matrix to promote dynamics of skin progenitor cells and accelerate differentiation into mature keratinocytes.MethodsIn this study, nanofibrous scaffolds composed of a blend poly (ɛ-caprolactone) (PCL), silk fibroin (SF), soluble eggshell membrane (SESM), andAloe vera (AV) gel were developed by electrospinning method and human basal cells were used to examine differentiation capacity toward keratinocyte-like cells. For this propose, cells were allocated to four distinct groups; control, PCL/SF, PCL/SF/SESM, and PCL/SF/SESM/AV. In all groups, cells were incubated with differentiation medium. Morphology, composition, hydrophilicity and mechanical features of PCL/SF, PCL/SF/SESM and PCL/SF/SESM/AV nanofibers were studied by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), water contact angle and tensile tests. To examine the orientation of basal cells to mature keratinocytes, we performed immunofluorescence analysis by monitoring cytokeratin-19. The expression of genes such as involucrin, keratin-14 and -5 was monitored by real-time PCR assay.ResultsPCL/SF, PCL/SF/SESM, and PCL/SF/SESM/AV had suitable physic chemical indices and biological activities to be applied as biomimetic scaffolds for the restoration cutaneous tissue. Compared to control, we found an increased basal cell proliferation at 7 and 14 days after plating on scaffolds and reach maximum levels in group PCL/SF/SESM/AV on day 14 (p < 0.05). Electron microscopy showed cell flattening, morphological adaptation. An integrated cell-to-cell connection was generated after cell seeding on scaffolds in all groups. Immunofluorescence imaging showed the ability of basal cells to synthesize cytokeratin-19 in PCL/SF, PCL/SF/SESM, and positive control cells after exposure to differentiation medium. However, these values were less in PCL/SF/SESM/AV compared to other groups. Real-time PCR analysis showed the potency of all scaffolds to induce the transcription of involucrin, keratin-14 and -5, especially involucrin in PCL/SF/SESM/AV group compared to the negative control.ConclusionModulation of scaffolds with natural biopolymers could enable us to synthesize structures appropriate for cutaneous regeneration.
Predicting metabolite-disease associations based on KATZ model
Authors: Lei Xiujuan , Zhang Cheng 
Published: October 2019

Abstract

Background
Increasing numbers of evidences have illuminated that metabolites can respond to pathological changes. However, identifying the diseases-related metabolites is a magnificent challenge in the field of biology and medicine. Traditional medical equipment not only has the limitation of its accuracy but also is expensive and time-consuming. Therefore, it’s necessary to take advantage of computational methods for predicting potential associations between metabolites and diseases.

Results
In this study, we develop a computational method based on KATZ algorithm to predict metabolite-disease associations (KATZMDA). Firstly, we extract data about metabolite-disease pairs from the latest version of HMDB database for the materials of prediction. Then we take advantage of disease semantic similarity and the improved disease Gaussian Interaction Profile (GIP) kernel similarity to obtain more reliable disease similarity and enhance the predictive performance of our proposed computational method. Simultaneously, KATZ algorithm is applied in the domains of metabolomics for the first time.

Conclusions
According to three kinds of cross validations and case studies of three common diseases, KATZMDA is worth serving as an impactful measuring tool for predicting the potential associations between metabolites and diseases.
Emerging agents and regimens for hepatocellular carcinoma
Authors: Zhu Xiao-Dong , Sun Hui-Chuan 
Published: October 2019

Abstract
Liver cancer, mostly hepatocellular carcinoma (HCC), is the second leading cause of cancer mortality globally. Most patients need at least one systemic therapy at different phases of their treatment for HCC. Sorafenib was the first agent shown to improve the survival of patients with advanced HCC. A decade after the approval of sorafenib, most agents failed to improve patient survival more than sorafenib. In recent years, treatment practices have changed, with lenvatinib as another first-line treatment choice and regorafenib, ramucirumab, and cabozantinib as second-line treatment options. Anti-PD-1 antibodies, including nivolumab, pembrolizumab, and camrelizumab, have demonstrated promising anti-tumor effects as monotherapy for advanced HCC in phase II clinical trials. The combination of an anti-PD-1 antibody and an anti-angiogenesis agent has shown more potent anti-tumor effects in early phase clinical trials and is now the hotspot in clinical studies. Furthermore, these agents are investigated in combination treatment with surgery or other loco-regional therapies in patients with early or intermediate-stage HCC.
Polo-like kinase 3 inhibits glucose metabolism in colorectal cancer by targeting HSP90/STAT3/HK2 signaling
Authors: Ou Baochi , Sun Hongze , Zhao Jingkun , Xu Zhuoqing , Liu Yuan , Feng Hao , Peng Zhihai 
Published: October 2019

Abstract

Background
Polo-like kinase 3 (PLK3) has been documented as a tumor suppressor in several types of malignancies. However, the role of PLK3 in colorectal cancer (CRC) progression and glucose metabolism remains to be known.

Methods
The expression of PLK3 in CRC tissues was determined by immunohistochemistry. Cells proliferation was examined by EdU, CCK-8 and in vivo analyses. Glucose metabolism was assessed by detecting lactate production, glucose uptake, mitochondrial respiration, extracellular acidification rate, oxygen consumption rate and ATP production. Chromatin immunoprecipitation, luciferase reporter assays and co-immunoprecipitation were performed to explore the signaling pathway. Specific targeting by miRNAs was determined by luciferase reporter assays and correlation with target protein expression.

Results
PLK3 was significantly downregulated in CRC tissues and its low expression was correlated with worse prognosis of patients. In vitro and in vivo experiments revealed that PLK3 contributed to growth inhibition of CRC cells. Furthermore, we demonstrated that PLK3 impeded glucose metabolism via targeting Hexokinase 2 (HK2) expression. Mechanically, PLK3 bound to Heat shock protein 90 (HSP90) and facilitated its degradation, which led to a significant decrease of phosphorylated STAT3. The downregulation of p-STAT3 further suppressed the transcriptional activation of HK2. Moreover, our investigations showed that PLK3 was directly targeted by miR-106b at post-transcriptional level in CRC cells.

Conclusion
This study suggests that PLK3 inhibits glucose metabolism by targeting HSP90/STAT3/HK2 signaling and PLK3 may serve as a potential therapeutic target in colorectal cancer.
A randomized controlled trial comparing lithium plus valproic acid versus lithium plus carbamazepine in young patients with type 1 bipolar disorder: the LICAVAL study
Authors: Missio Giovani , Moreno Doris Hupfeld , Demetrio Frederico Navas , Soeiro-de-Souza Marcio Gerhardt , dos Santos Fernandes Fernando , Barros Vivian Boschesi , Moreno Ricardo Alberto 
Published: October 2019

Abstract

Background
Treatment of bipolar disorder (BD) usually requires drug combinations. Combinations of lithium plus valproic acid (Li/VPA) and lithium plus carbamazepine (Li/CBZ) are used in clinical practice but were not previously compared in a head-to-head trial.

Objective
The objective of this trial was to compare the efficacy and tolerability of Li/VPA versus Li/CBZ in treating type 1 BD in any phase of illness in young individuals.

Methods
LICAVAL was a randomized, unicenter, open-label, parallel-group trial that was conducted from January 2009 to December 2012 in a tertiary hospital in São Paulo, Brazil. Participants were between 18 and 35 years old and were followed up for 2 years. Our primary outcome was the number of participants achieving/maintaining response and remission during the acute and maintenance phases of BD treatment, respectively. Other outcomes assessed were symptom severity and adverse events throughout the study. In the analysis of the primary outcome, we compared groups by using a two-way repeated measures analysis of variance and estimated effect sizes by using Cohen’s d.

Results
Of our 64 participants, 36 were allocated to Li/VPA and 28 to Li/CBZ. Our sample was composed predominantly of females (66.6%) and the average age was 27.8 years. A total of 27 (45.0%) participants had depression, 17 (28.3%) had mania/hypomania, and 16 (26.7%) had a mixed state. We found no between-group differences in CGI-BP (Clinical Global Impression Scale modified for use in bipolar disorder) scores (P = 0.326) or in any other outcome. Side effects differed significantly between groups only in the first week of treatment (P = 0.021), and there were more side effects in the Li/VPA group. Also, the Li/VPA group gained weight (+2.1 kg) whereas the Li/CBZ group presented slight weight loss (−0.2 kg).

Conclusion
Our study suggests that Li/VPA and Li/CBZ have similar efficacy and tolerability in BD but that Li/CBZ might have metabolic advantages in the long term.

Trial registration
ClinicalTrials.gov identifier: NCT00976794. Registered on September 9, 2009.
Protein hydrolysis and fermentation under methanogenic and acidifying conditions
Authors: Duong Thu Hang , Grolle Katja , Nga Tran Thi Viet , Zeeman Grietje , Temmink Hardy , van Eekert Miriam 
Published: October 2019

Abstract

Background
Many kinds of wastewaters contain appreciable quantities of protein. Anaerobic processes are suitable for the treatment of wastewater high in organics to achieve pollution control and recovery of energy as methane and hydrogen, or intermediates for production of biofuels and valuable biochemicals. A distinction between protein hydrolysis and amino acid fermentation, especially for dissolved proteins, is needed to target which one is truly rate-limiting and to effectively harvest bioproducts during anaerobic conversion of these wastewaters. This study explored mesophilic anaerobic hydrolysis and amino acid fermentation of gelatine, as a model for dissolved proteins, at pH 7 and at pH 5.

Results
The results showed that at pH 7, protein hydrolysis (first-order rate of 0.15 h−1) was approximately 5 times faster than acidification of the hydrolysis products (first-order rate of 0.03 h−1), implying that not hydrolysis but acidification was the rate-limiting step in anaerobic dissolved protein degradation. This was confirmed by (temporary) accumulation of amino acids. Nineteen different amino acids were detected during the first 8 incubation hours of gelatine at neutral pH and the total chemical oxygen demand (COD) of these 19 amino acids was up to approximately 40% of the COD of the gelatine that was added. Protein hydrolysis at pH 5 was 2–25 times slower than at pH 7. Shifting the initial pH from neutral to acidic conditions (pH 5) inhibited protein degradation and changed the volatile fatty acids (VFA) product profile. Furthermore, the presence or absence of methanogenic activity did not affect the rates of protein hydrolysis and acidification.

Conclusions
The findings in this study can help to set a suitable solid retention time to accomplish anaerobic degradation of protein-rich wastewaters in continuous reactor systems. For example, if the target is harvesting VFAs, methanogens can be washed-out for a shorter retention time while amino acid fermentation, instead of hydrolysis as assumed previously, will govern the design and solutions to improve the system dealing with dissolved proteins.
Simultaneous upgrading of biomass-derived sugars to HMF/furfural via enzymatically isomerized ketose intermediates
Authors: Wang Wei , Mittal Ashutosh , Pilath Heidi , Chen Xiaowen , Tucker Melvin P. , Johnson David K. 
Published: October 2019

Abstract

Background
Recently, exploring fermentative or chemical pathways that convert biomass-derived sugars to fuels/chemicals has attracted a lot of interest from many researchers. We are investigating a hydrocarbon pathway from mixed sugars via 5-hydroxymethyl furfural (HMF) and furfural intermediates. To achieve this goal, we must first convert glucose and xylose to HMF and furfural in favorable yields. Current processes to produce HMF/furfural generally involve the use of acid catalysts in biphasic systems or solvents such as ionic liquids. However, the yield from transforming glucose to HMF is lower than the yield of furfural from xylose.

Results
In this study, we present an efficient chemical pathway simultaneously transforming glucose and xylose to HMF and furfural via ketose intermediates, i.e., fructose and xylulose, which were generated from glucose and xylose via enzymatic isomerization. In the enzymatic isomerization, by adding sodium borate to complex with the ketoses, xylose conversion reached equilibrium after 2 h with a conversion of 91% and glucose conversion reached 84% after 4 h. By enzymatically isomerizing the aldoses to ketoses, the following dehydration reactions to HMF and furfural could be performed at low process temperatures (i.e., 110–120 °C) minimizing the side reactions of the sugars and limiting the degradation of furfurals to humins and carboxylic acids. At 120 °C, pH 0.5, and 15 min reaction time, mixed ketose sugars were converted to HMF and furfural in yields of 77% and 96%, respectively (based on starting aldose concentrations).

Conclusion
Taken together, our results demonstrate that this combined biological and chemical process could be an effective pathway to simultaneously convert biomass-derived glucose and xylose to HMF and furfural, for use as intermediates in the production of hydrocarbons.
Early treatment with ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA study)
Authors: Pan Zixuan , Marra Alberto M. , Benjamin Nicola , Eichstaedt Christina A. , Blank Norbert , Bossone Eduardo , Cittadini Antonio , Coghlan Gerry , Denton Christopher P. , Distler Oliver , Egenlauf Benjamin , Fischer Christine , Harutyunova Satenik , Xanthouli Panagiota , Lorenz Hanns-Martin , Grünig Ekkehard 
Published: October 2019

Abstract

Objective
The objective of this randomized, placebo-controlled, double-blind, parallel group, trial was to assess the effect of ambrisentan on mean pulmonary arterial pressure (mPAP) in patients with systemic sclerosis (SSc) and mildly elevated pulmonary hypertension (PH).

Methods
Thirty-eight SSc patients with mildly elevated mPAP at rest between 21 and 24 mmHg and/or > 30 mmHg during low-dose exercise were randomly assigned to treatment with either ambrisentan 5–10 mg/day or placebo. Right heart catheterization and further clinical parameters were assessed at baseline and after 6 months. The primary endpoint was the difference of mPAP change at rest between groups.

Results
After 6 months, the two groups did not differ in the primary endpoint (ambrisentan mPAP − 1 ± 6.4 mmHg vs. placebo − 0.73 ± 3.59 mmHg at rest, p = 0.884). However, three patients from the placebo group but none of the ambrisentan group progressed to SSc-associated pulmonary arterial hypertension. Furthermore, ambrisentan treatment showed significant improvements in the secondary endpoints cardiac index (CI) and pulmonary vascular resistance (PVR) at rest (CI 0.36 ± 0.66 l/min/m2 vs. − 0.31 ± 0.71 l/min/m2, p = 0.010; PVR − 0.70 ± 0.78 WU vs. 0.01 ± 0.71 WU, p = 0.012) and during exercise (CI 0.7 ± 0.81 l/min/m2 vs. − 0.45 ± 1.36 l/min/m2, p = 0.015; PVR − 0.84 ± 0.48 WU vs. − 0.0032 ± 0.34 WU, p < 0.0001).

Conclusion
This is the first randomized, double-blind, placebo-controlled study testing the effect of ambrisentan in patients with mildly elevated mPAP and/or exercise PH. The primary endpoint change in mPAP did only tendentially improve in the ambrisentan group, but the significant improvement of other hemodynamic parameters points to a possible benefit of ambrisentan and will be helpful to design future trials.

Trial registration
www.ClinicalTrials.gov, unique identifier NCT: NCT02290613, registered 14th of November 2014.
Hyperhomocysteinemia is an independent risk factor of atherosclerosis in patients with metabolic syndrome
Authors: Piazzolla Giuseppina , Candigliota Mafalda , Fanelli Margherita , Castrovilli Anna , Berardi Elsa , Antonica Gianfranco , Battaglia Stefano , Solfrizzi Vincenzo , Sabbà Carlo , Tortorella Cosimo 
Published: October 2019

Abstract

Background
Metabolic syndrome (MetS) is a clinical condition potentially promoting the development of atherosclerotic disease. To date, the clinical impact of elevated serum homocysteine (Hcy) levels in MetS is still under discussion. The aim of this cross sectional study was to evaluate the relationship between MetS and hyperhomocysteinemia and the potential role of Hcy in the pathogenesis of atherosclerotic complications of MetS.

Methods
We recruited 300 outpatients with MetS. All patients underwent a medical history collection, physical examination, blood sampling and carotid ultrasound echo-color Doppler. According to Hcy levels, MetS patients were divided into two groups: “normal” (< 10.7 μmol/l; n = 140, group 1) and “high” Hcy (≥ 10.7 μmol/l; n = 160, group 2). Comparisons between groups were made by Student’s t-test or Chi-square test. The effects of potential covariates on group differences were evaluated by general linear models. The relationships between continuous variables were assessed by simple or multiple correlation and by linear regression. Multiple regression models were built to evaluate the effects of Hcy, together with other potential risk factors, on carotid atherosclerosis.

Results
Patients with high Hcy were predominantly male and slightly older than group 1 patients. Smokers and non-smokers exhibited similar Hcy levels, nor was a statistical relationship between pack-years and Hcy observed. Group 2 showed lower levels of folic acid, vitamin D, high density lipoprotein (HDL)-cholesterol and glomerular filtration rate (e-GFR) than group 1, but higher levels of C-peptide, uric acid and triglycerides. In all patients, Hcy was positively correlated with C-peptide and uric acid and negatively with folic acid and e-GFR. Intima-media thickness (IMT) and carotid stenosis degree were significantly higher in patients with high Hcy and a positive relationship between Hcy and both IMT and carotid stenosis was detected in all patients. Finally, Hcy atherogenic effects were independent of other well-known atherosclerosis risk factors.

Conclusions
Our results highlight a link between MetS and hyperhomocysteinemia and a direct effect of Hcy on atherogenic process during MetS. Early correction of folic acid levels may contribute to prevent cardiovascular complications in MetS patients.
Effects of comprehensive sexuality education on the comprehensive knowledge and attitude to condom use among first-year students in Arba Minch University: a quasi-experimental study
Authors: Boti Negussie , Hussen Sultan , Shegaze Mulugeta , Shibru Simon , Shibiru Tamiru , Zerihun Eshetu , Godana Wanzahun , Abebe Sintayehu , Gebretsadik Woyinshet , Desalegn Nathan , Temtime Zebene 
Published: October 2019

Abstract

Objective
To assess the effect of comprehensive sexuality education on the comprehensive knowledge and attitude to condom use among first-year students at Arba Minch University.

Results
A total of 832 students participated at a baseline, and 820 students participated at the posttest. This study found that there was a significant effect on changing students’ knowledge and attitude towards a condom. In the education group, the students’ average change of comprehensive condom knowledge score was 0.229 higher than the average score of students’ in the control group (ATE = 0.229, 95% CI 0.132 to 0.328; p < 0.001). The average change of attitude toward condom score of students’ in the education group was 1.834 higher than the average change score of students’ in the control group (ATE = 1.834, 95% CI 1.195 to 2.772; p < 0.001).This study provides further evidence on the effectiveness of comprehensive sexuality education in terms of knowledge and attitude towards a condom. Therefore, the implementation of this education should be strengthened in order the prevent youths from STI/HIV and unintended pregnancies.