bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycyrrhizin inactivates toll‐like receptor (TLR) signaling pathway to reduce lipopolysaccharide‐induced acute lung injury by inhibiting TLR2
Authors: Kong Delei , Wang Zanfeng , Tian Jie , Liu Tingwei , Zhou Hui 
Published: September 2018

AbstractObjectiveThis study aimed to explore glycyrrhizin on acute lung injury (ALI) and how glycyrrhizin (GL) attenuated lipopolysaccharide (LPS)‐induced ALI.MethodsBioinformatics analysis was performed to screen the expressed genes in LPS‐induced ALI mice. The enrichment of functions and signaling pathways of deregulated genes were conducted. Combined with DIGSEE and STICH, the target gene for further investigation was chosen. To verify target gene in mice, we performed experiment in vivo. Forty mice were randomized into NC, LPS, LPS + S, and LPS + GL group. Mice in the LPS + GL group received glycyrrhizin l mg and mice in LPS + S received saline. Then, HE and Masson staining detected pathological changes of lung tissues; enzyme‐linked immunosorbent assay analyzed bronchoalveolar lavage fluid concentrations of MIP‐2, mice growth‐related oncogene homologue (KC), IL‐4, IL‐6, GM‐CSF, IFN‐γ, and IgM; western blot analysis determined the expression of toll‐like receptor (TLR) signaling and NF‐κB pathway‐related proteins.ResultsTlr2 which was not only upregulated but also closely related to glycyrrhizin. TLR2 was upregulated in following LPS induced in cells and TLR2 overexpression‐activated TLR signaling pathway to promote ALI. After glycyrrhizin treatment, the expression of TLR2 was reduced. Furthermore, it was found out that the number of inflammatory cells, collagen deposition, MIP‐2, KC, IL‐4, IL‐6, GM‐CSF, and IFN‐γ expression increased in ALI mice and glycyrrhizin mitigated it. Similarly, the expression of TLR signaling pathway and NF‐κB pathway‐related protein also increased.ConclusionGlycyrrhizin functioned as a suppressor in TLR signaling pathway to reduce LPS‐induced ALI by inhibiting TLR2.
HDAC1/2‐mediated regulation of JNK and ERK phosphorylation in bovine mammary epithelial cells in response to TNF‐α
Authors: Romanick Samantha S. , Morrill Kristen , Hostler Andrew , Evans Levi W. , Shen Yiqiu , Matsumura Allison , Piotrowski Haleigh , Silva Lorrayny G. , Faciola Antonio P. , Ferguson Bradley S. 
Published: September 2018

AbstractBovine mammary epithelial cells (MAC‐Ts) are a common cell line for the study of mammary epithelial inflammation; these cells are used to mechanistically elucidate molecular underpinnings that contribute to bovine mastitis. Bovine mastitis is the most prevalent form of disease in dairy cattle that culminates in annual losses of two billion dollars for the US dairy industry. Thus, there is an urgent need for improved therapeutic strategies. Histone deacetylase (HDAC) inhibitors are efficacious in rodent models of inflammation, yet their role in bovine mammary cells remain unclear. HDACs have traditionally been studied in the regulation of nucleosomal DNA, in which deacetylation of histones impact chromatin accessibility and gene expression. Using MAC‐T cells stimulated with tumor necrosis factor α (TNF‐α) as a model for mammary cell inflammation, we report that inhibition of HDACs1 and 2 (HDAC1/2) attenuated TNF‐α‐mediated inflammatory gene expression. Of note, we report that HDAC1/2‐mediated inflammatory gene expression was partly regulated by c‐Jun N‐terminal kinase (JNK) and extracellular signal‐regulated kinase (ERK) phosphorylation. Here, we report that HDAC1/2 inhibition attenuated JNK and ERK activation and thus inflammatory gene expression. These data suggest that HDACs1 and 2 regulate inflammatory gene expression via canonical (i.e., gene expression) and noncanonical (e.g., signaling dependent) mechanisms. Whereas, further studies using primary cell lines and animal models are needed. Our combined data suggest that HDAC1/2‐specific inhibitors may prove efficacious for the treatment of bovine mastitis.
Neratinib augments the lethality of [regorafenib + sildenafil]
Authors: Booth Laurence , Roberts Jane L. , Rais Rumeesa , Cutler Richard E. , Diala Irmina , Lalani Alshad S. , Hancock John F. , Poklepovic Andrew , Dent Paul 
Published: September 2018

AbstractRegorafenib is approved for the treatment of colorectal cancer and hepatocellular carcinoma. In the trial NCT02466802, we have discovered that regorafenib can be safely combined with the phosphodiesterase 5 inhibitor sildenafil in advanced solid tumor patients. The present studies determined whether the approved ERBB1/2/4 and RAS downregulating drug neratinib, could enhance the lethality of [regorafenib + sildenafil]. Neratinib enhanced [regorafenib + sildenafil] lethality in a greater than additive fashion in colon cancer cells. The drug combination reduced the expression of mutant K‐RAS and of multiple histone deacetylase (HDAC) proteins that required autophagosome formation. It caused green fluorescent protein or red fluorescent protein–tagged forms of K‐RAS V12 to localize into large intracellular vesicles. Compared with [regorafenib + sildenafil], the three‐drug combination caused greater and more prolonged activation of the ATM‐AMPK‐ULK‐1 pathway and caused a greater suppression and prolonged inactivation of mammalian target of rapamycin, AKT, and p70 S6K. Approximately 70% of enhanced lethality caused by neratinib required ataxia‐telangiectasia‐mutated (ATM)–AMP‐dependent protein kinase (AMPK) signaling whereas knockdown of Beclin1, ATG5, FADD, and CD95 completely prevented the elevated killing effect. Exposure of cells to [regorafenib + sildenafil] reduced the expression of the checkpoint immunotherapy biomarkers programmed death‐ligand 1, ornithine decarboxylase, and indoleamine 2,3‐dioxygenase‐1 and increased the expression of major histocompatibility complex A (MHCA), which also required autophagosome formation. Knockdown of specific HDAC proteins recapitulated the effects observed using chemical agents. In vivo, using mouse cancer models, neratinib significantly enhanced the antitumor efficacy of [regorafenib + sildenafil]. Our data support performing a new three drug Phase I trial combining regorafenib, sildenafil, and neratinib.
A meta‐analysis identified genes responsible for distinct immune responses to trivalent inactivated and live attenuated influenza vaccines
Authors: Wen Feng , Guo Jinyue , Huang Shujian 
Published: September 2018

AbstractVaccinations are the cornerstone of influenza prevention strategies. We carried out a meta‐analysis of the messenger RNA expression profiles from recipients of trivalent inactivated vaccines (TIV) or live attenuated vaccines (LAIV) to determine the different recipients’ responses to these two types of vaccines, which may provide information to improve the design of future improved vaccines. We executed meta‐analysis on these datasets using a random‐effects model and identified 191 and 195 differentially expressed genes in TIV and LAIV, respectively, with an false discovery rate <0.05. The genes significantly upregulated by TIV were associated with both the innate immune response and the humoral immune response, whereas LAIV mainly activated the innate immune system. The identified genes that responsible for the immune difference between LAIV and TIV might provide new information to improve current vaccines to have better efficacy in children, adults, and the elderly.
A comparative system‐level analysis of the neurodegenerative diseases
Authors: Godini Rasoul , Fallahi Hossein , Ebrahimie Esameil 
Published: September 2018

AbstractNeurodegenerative diseases are disorders in the central nervous system with consequent progressive neurological symptoms including behavioral and cognitive disabilities. Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, Parkinson’s disease, multiple sclerosis, and schizophrenia are the most important and abundant neurodegenerative diseases that affect different parts of the brain. Detailed studies unveiled the molecular mechanisms and pathways affected in each of these disorders. The role of many genes has been documented in the onset and progression of each disease. Although many system‐level approaches have been used to understand the exact cause of these diseases, there is no comparative analysis in this regard. Despite all differences in the molecular basis of these diseases, overlapping symptoms might indicate the involvement of the similar pathways and processes. Here, we have applied a system biology approach to uncover many aspects of main neurodegenerative diseases using microarray data obtained from 118 cases of postmortem brain samples. Our analysis has identified key genes that might contribute to the status of diseases. We have also compared the involved biological process and pathway between different disease to find possible similar mechanisms that exist in all of them. We also predicted potentially important transcription factors in each disease and predicted the core gene regulatory networks. We have provided a list of possible new key regulators that could be further explored and also discussed the role of these hub genes. The results of this study would be useful to develop new diagnostic strategies and also to find new drug targets.
Cardiovascular Risk of Nonsteroidal Anti‐inflammatory Drugs and Classical and Selective Cyclooxygenase‐2 Inhibitors: A Meta‐analysis of Observational Studies
Authors: Martín Arias Luis Hermenegildo , Martín González Antonio , Sanz Fadrique Rosario , Vazquez Esther Salgueiro 
Published: September 2018

AbstractThe purpose of this study was to review the published evidence on the clinical use of nonsteroidal anti‐inflammatory drugs (NSAIDs) and to assess the cardiovascular risk (CVR) of cyclooxygenase‐2 inhibitors (coxibs), excluding aspirin, by means of a meta‐analytic procedure. A search was conducted on MEDLINE and EMBASE databases between October 1999 and June 2018. Cohort and case‐control studies showing CVR as relative risk (RR), odds ratio, hazard ratio, or incidence rate ratio associated with NSAIDs versus no treatment were selected. We estimated the pooled RR and the 95% confidence interval (CI) for all NSAIDs as a whole and individually. Eighty‐seven studies met the inclusion criteria. Overall, NSAIDs were found to be associated with a statistically significantly increased CVR (RR, 1.24 [95%CI, 1.19‐1.28]). The risk was slightly higher for coxibs (RR, 1.22 [95%CI, 1.17‐1.28]) as compared with nonselective NSAIDs (RR, 1.18 [95%CI, 1.12‐1.24]). Data analysis by drug disclosed that rofecoxib (RR, 1.39 [95%CI, 1.31‐1.47]), followed by diclofenac (RR, 1.34 [95%CI, 1.26‐1.42]) and etoricoxib (RR, 1.27 [95%CI, 1.12‐1.43]) were the NSAIDs associated with the highest CVR. Analysis by type of event showed that the highest risk corresponded to vascular events for both coxibs (RR, 2.18 [95%CI, 1.72‐2.78]) and nonselective NSAIDs (RR, 2.46 [95%CI, 2.00‐3.02]). The meta‐analysis results suggest that the use of the marketed coxibs celecoxib and etoricoxib would be related to a statistically significant CVR increase. Etoricoxib CVR could be higher than that for celecoxib. This increment would be similar to classical NSAID CVR.
Synthesis, Characterization, Molecular Modeling, and Biological Evaluation of 1,2,4‐Triazole‐pyridine Hybrids as Potential Antimicrobial Agents
Authors: Ahirwar J. , Ahirwar D. , Lanjhiyana S. , Jha A. K. , Dewangan D. , Badwaik H. 
Published: September 2018

A novel 1,2,4‐triazole‐pyridine hybrid derivatives were synthesized by the reaction of nicotinohydrazide with carbon disulfide to yield potassium‐3‐pyridyl‐dithiocarbazate (I). This was further cyclized with ammonia solution to yield 5‐mercapto‐substituted 1,2,4‐triazole‐pyridine hybrid (II). This was finally reacted with different substituted benzyl derivatives to produce 1,2,4‐triazole‐pyridine hybrid derivatives (III). The purity of the derivatives was confirmed by thin‐layer chromatography and melting point. Structure of these derivatives was set up by determining its infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectroscopy. Further, the synthesized derivatives were evaluated for their in vitro antimicrobial activity against the three Gram‐negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Acinetbacter baumannii), three Gram‐positive bacteria (Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis), and two fungus (Aspergillus clavatus and Candida albicans). Minimal inhibitory concentration was also determined against same microorganism. Out of all synthesized derivatives, two derivatives, that is, 3‐(5‐(2‐bromobenzylthio)‐4H‐1,2,4‐triazol‐3‐yl)pyridine and 3‐(5‐(2,4‐dibromobenzylthio)‐4H‐1,2,4‐triazol‐3‐yl)pyridine showing more potent antibacterial activity.Docking studies were performed by using Argus lab, and all the derivatives exhibited good docking scores between −10.5369 and −11.8477 kcal/mol and were better as compared with standard drug methotrexate against a dihydrofolate reductase protein fragment from E. coli and Lactobacillus (4DFR). Among all compounds, 4h has shown the maximum docking score and found in agreement to in vitro antimicrobial studies.
Ability of inactivated vaccines based on far‐eastern tick‐borne encephalitis virus strains to induce humoral immune response in originally seropositive and seronegative recipients
Authors: Maikova Galina B. , Chernokhaeva Liubov L. , Rogova Yulia V. , Kozlovskaya Liubov I. , Kholodilov Ivan S. , Romanenko Victor V. , Esyunina Mariya S. , Ankudinova Anna A. , Kilyachina Anna S. , Vorovitch Mikhail F. , Karganova Galina G. 
Published: September 2018

Tick‐borne encephalitis (TBE) remains one of the major public health concerns in northern Eurasia, and its’ area is expanding. TBE virus (TBEV) includes three subtypes and several monophyletic groups, cocirculating in Russia. Five inactivated vaccines are used for TBE prophylaxis. The rising number of people subjected to vaccination brings up the issue of the impact of individual recipient characteristics on vaccination efficacy. The present work studies correlations among the vaccination scheme, sex, age, body mass index (BMI), chronic diseases, postvaccinal reaction, pre‐existing anti‐TBEV antibodies, and postvaccinal humoral immunity development. Sera were collected during clinical trials in the TBEV Siberian subtype endemic area. Adult recipients were vaccinated with Tick‐E‐Vac and EnceVir vaccines based on Far‐Eastern TBEV strains. Vaccine ability to induce humoral immunity in different categories of recipients was estimated by seroconversion rates and the percentage of recipients with high neutralizing antibody titers (≥1:500). High immunogenicity of vaccines based on Far‐Eastern TBEV strains in the TBEV Siberian subtype endemic area in all groups of recipients was demonstrated. Impact of pre‐existing contact with the virus and high BMI on humoral immune response development 14 days after the first immunization was evidenced. Nevertheless, the difference was significantly less pronounced 30 days after the first vaccination and undetectable after the second one.
Signaling pathways and therapeutic perspectives related to environmental factors associated with multiple sclerosis
Authors: Tiwari Sneham , Lapierre Jessica , Ojha Chet Raj , Martins Kyle , Parira Tiyash , Dutta Rajib Kumar , Caobi Allen , Garbinski Luis , Ceyhan Yasemin , Esteban‐Lopez Maria , El‐Hage Nazira 
Published: September 2018

AbstractMultiple sclerosis (MS) is an immune‐mediated demyelinating disorder of unknown etiology. Both genetic‐susceptibility and environment exposures, including vitamin D deficiency, Epstein‐Barr viral and Herpesvirus (HHV‐6) infections are strongly implicated in the activation of T cells and MS‐pathogenesis. Despite precise knowledge of how these factors could be operating alone or in combination to facilitate and aggravate the disease progression, it is clear that prolonged induction of inflammatory molecules and recruitment of other immune cells by the activated T cells results in demyelination and axonal damage. It is imperative to understand the risk factors associated with MS progression and how these factors contribute to disease pathology. Understanding of the underlying mechanisms of what factors triggers activation of T cells to attack myelin antigen are important to strategize therapeutics and therapies against MS. Current review provides a detailed literature to understand the role of both pathogenic and non‐pathogenic factors on the impact of MS.
MRI investigation of glymphatic responses to Gd‐DTPA infusion rates
Authors: Ding Guangliang , Chopp Michael , Li Lian , Zhang Li , Davoodi‐Bojd Esmaeil , Li Qingjiang , Zhang Zhenggang , Jiang Quan 
Published: September 2018

AbstractThe glymphatic system is a newly identified waste clearance pathway in brain discovered and investigated predominately using in vivo two‐photon confocal microscopy. Magnetic resonance imaging (MRI), in contrast to two‐photon confocal microscopy, provides dynamic and real‐time pictures of the glymphatic system in whole brain. We employ MRI to investigate the response of the glymphatic system to the rate of infusion of Gd‐DTPA (magnevist). Wistar rats were subjected to a surgery of inserting a tube into the cisterna magna for infusion during MRI. Three infusion rates were chosen for 20 min infusions of diluted magnevist into the cerebrospinal fluid (CSF) of rat brain. Glymphatic response was imaged using dynamic MRI 3D measurement for 5 hr. Robust correlations were found in all ventricles between the peak intensities of image enhancement and infusion rates, with additional correlations between the peak times of MRI image enhancement and infusion rates in the fourth ventricle. An infusion rate of 2.92 μL/min induced an evident accumulation of tracer in the fourth ventricle near the cisterna magna. In hippocampal tissue, image enhancements exhibited low correlation with the infusion rates. However, an infusion rate of 1.67 μL/min provided a high image enhancement, but less tracer accumulation near the cisterna magna. Contrast‐enhanced MRI provides a suitable tool for investigating image contrast infusion rate response of the glymphatic system in rat brain. Considering both T1 and T2* effects in response to the infused magnevist into CSF, the infusion rate of 1.67 μL/min appears suitable for MRI study of the glymphatic system in rat.
Temperature and polarization dependent Raman spectra of liquid H2O and D2O
Authors: Pattenaude Shannon R. , Streacker Louis M. , Ben‐Amotz Dor 
Published: September 2018

AbstractPolarized Raman spectra of liquid H2O and D2O have been measured over the entire 100 to 4,000 cm−1 vibrational frequency range and 280 to 360 K temperature range. The measured spectra are corrected for wavelength‐dependent detector quantum efficiency and are provided in numerical form to facilitate comparisons with theoretical predictions. Self‐modeling curve resolution is used to decompose the measured spectra into a linear combination of two spectral components whose relative intensities change with temperature but whose shapes are approximately temperature independent. The component whose intensity increases with decreasing temperature contains prominent features in both the high‐frequency OH stretch band region and low‐frequency OH⋯O hydrogen bond stretch band region that resemble those observed in single crystal ice Ih and clathrate hydrates.
Effect of drying conditions on the quality of IRGA 424 rice
Authors: Bertotto M Mercedes , Gastón Analía , Sánchez Sarmiento Gustavo , Gove Benedict 
Published: September 2018

AbstractBACKROUNDThe objective of this research was to investigate the effects of drying temperature (40, 50, and 60 °C), tempering time (40, 80, and 120 min), and initial moisture content at onset of tempering (15, 17, and 19% dry basis) on head rice yield, milled rice yield, and total processing time of IRGA 424 rice.RESULTSThe most significant effects were the drying temperature and its interaction with initial moisture content at onset of tempering. The optimum conditions predicted to reach the highest total yield (74.1%) included drying at 46.6 °C, 49 min of tempering time, and initial moisture content at onset of tempering of 19%. To achieve the maximum value of whole grain yield (52.9%), drying at 40 °C, 40 min of tempering, and an initial moisture content of 19% at the initiation of tempering were required. Under these conditions, the grain reached a moisture content of 13% in 84 min.CONCLUSIONWhole‐grain rice yields may be maximized through the optimization of the drying process. This may result in a larger fraction of the crop entering the human food chain, enhancing the value of the crop, and resulting in a smaller fraction of broken grain, which commands a lower market value. © 2018 Society of Chemical Industry
Value of Contrast‐Enhanced Ultrasound in the Diagnosis of Renal Cancer and in Comparison With Contrast‐Enhanced Computed Tomography: A Meta‐analysis
Authors: Zhang Fan , Li Rui , Li Gang , Jin Lifang , Shi Qiusheng , Du Lianfang 
Published: September 2018

ObjectivesThe purpose of this meta‐analysis was to assess the diagnostic accuracy of contrast‐enhanced ultrasound (CEUS) in renal cancer and to compare it with contrast‐enhanced computed tomography (CECT).MethodsA systematic search was performed to recruit eligible original studies published until December 2017. Two reviewers independently extracted data. A meta‐analysis was performed, and the pooled sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values, diagnostic odds ratio, summary receiver operating characteristic curve, and area under the curve were calculated. The extent and potential sources of heterogeneity were further explored. Moreover, a head‐to‐head comparison was also performed to compare the diagnostic value between CEUS and CECT in renal cancer.ResultsTwenty‐two studies were included in this meta‐analysis. The summary sensitivity and specificity of CEUS for detecting renal cancer were 0.96 (95% confidence interval [CI], 0.94–0.97) and 0.82 (95% CI, 0.74–0.88), respectively. The summary diagnostic odds ratio was 102.04 (95% CI, 49.55–210.13). The area under the summary receiver operating characteristic curve was 0.97 (95% CI, 0.95–0.98). In the head‐to‐head comparison, CEUS showed higher diagnostic sensitivity than CECT (0.94 versus 0.85) for renal cancer, whereas the specificities were comparable between CEUS and CECT (0.77 versus 0.75).ConclusionsContrast‐enhanced US has high sensitivity and moderate specificity in the differential diagnosis of renal cancer. The diagnostic sensitivity of CEUS in renal cancer was higher than that of CECT, suggesting that CEUS could be used as a preferred diagnostic tool for renal cancer.