bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide (ChIP-seq) Identification of Target Genes Regulated by WRKY33 During Submergence Stress in Arabidopsis
Authors: Junlin Zhang , bao Liu , Yan Song , yang Chen , jiao Fu , Jianquan Liu , Tao Ma , Zhenxiang Xi , Huanhuan Liu 
Published: December 2020

Abstract
Background: Hypoxia induced by flooding causes significant losses to crop production almost every year. However, the molecular network of hypoxia signaling pathway is still poorly understood. According to previous studies, transgenic plants overexpressing the WRKY33 gene showed enhanced resistance to submergence stress. Thus, the transcription factor WRKY33 may regulate a series of target genes in response to submergence. Here, to determine the putative downstream targets of WRKY33 at a genome-wide scale in Arabidopsis thaliana, we performed the chromatin immunoprecipitation sequencing (ChIP-seq) using 35S:FLAG-WRKY33 overexpression transgenic lines (WRKY33-OE) upon 24 hours of submergence treatment.Results: Using ChIP-seq data, we identified a total of 104 WRKY33-binding genes under submergence treatment (WRKY33BGHs). Most of the WRKY33BGHs are involved in the oxidation-reduction process, programmed cell death in response to reactive oxygen species, lipid biosynthesis process, and other processes related to stress responses. Moreover, the major motif identified in the WRKY33BGHs promoters is a new cis-element, TCTCTC (we named it as “TC box”). This cis-element is different from the previously known W box for WRKY33. Further qPCR experiments verified that genes carrying this motif in their promoters could be regulated by WRKY33 upon submergence treatment.Conclusions: Our study has identified a new putative binding motif of WRKY33 and recovered numerous previously unknown target genes of WRKY33 during submergence stress. The WRKY33 gene positively participates in flooding response probably by transcriptional regulation of the downstream hypoxia-related target genes via a “TC box”.
Comparative Effect of Statin Intensity Between Prediabetes and Type 2 Diabetes Mellitus After Implanting Newer-generation Drug-eluting Stents in Korean Acute Myocardial Infarction Patients: a Retrospective Observational Study
Authors: Kim Yong Hoon , Her Ae-Young , Jeong Myung Ho , Kim Byeong-Keuk , Hong Sung-Jin , Kim Seunghwan , Ahn Chul-Min , Kim Jung-Sun , Ko Young-Guk , Choi Donghoon , Hong Myeong-Ki , Jang Yangsoo 
Published: December 2020

Abstract
Background: Comparative studies regarding the long-term clinical outcomes of statin intensity between acute myocardial infarction (AMI) patients with prediabetes and those with type 2 diabetes mellitus (T2DM), after successful implantation of newer-generation drug-eluting stents (DES) with statin treatment, are limited. We compared the 2-year clinical outcomes between these patients. Methods: A total of 11612 AMI patients were classified as statin users (n = 9893) and non-users (n = 1719). Thereafter, statin users were further divided into high-intensity (n = 2984) or low-moderate-intensity statin (n = 6909) treatment groups. Those in these two groups were further classified into patients with normoglycemia, prediabetes, and T2DM. The major outcomes were the occurrence of major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (Re-MI), or any repeat coronary revascularization. Results: After adjusting for both high-intensity and low-moderate-intensity statin users, the cumulative incidences of MACE (p = 0.737, p = 0.062, respectively), all-cause death, Re-MI, and any repeat revascularization were similar between the prediabetes and T2DM groups. In the total study population, both high-intensity and low-moderate-intensity statin treatments showed comparable results. However, the beneficial effects of high-intensity compared to low-moderate-intensity statin therapy were more apparent in the normoglycemia group than hyperglycemia group, as it reduced the cumulative incidences of MACE (aHR: 1.903; 95% CI: 1.203-3.010; p = 0.006) and any repeat revascularization (aHR: 3.248; 95% CI: 1.539-6.854; p = 0.002). Conclusions: In this retrospective registry study, prediabetes and T2DM groups showed comparable clinical outcomes, after administering both high-intensity and low-moderate-intensity statin treatments. Trial registration: Retrospectively registered
Polymorphisms of the Glucocorticoid Receptor Gene and Adrenal Suppression in Patients with Chronic Obstructive Pulmonary Disease Treated with Glucocorticoids for Acute Exacerbations
Authors: Sivapalan Pradeesh , Borresen Stina W. , Eklöf Josefin , Klose Marianne , Holm Freja S. , Feldt-Rasmussen Ulla , Rossing Maria , Jørgensen Niklas R. , Marvig Rasmus L. , Saeed Mohamad Isam , Wilcke Torgny , Seersholm Niels , Mathioudakis Alexander G. , Vestbo Jørgen , Jensen Jens-Ulrik Stæhr 
Published: December 2020

Abstract
Background: Single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) gene NR3C1 have been associated with an altered sensitivity to glucocorticoids (GC), and thus may affect the therapeutic effects of GCs. We investigated the prevalence of adrenal suppression after treatment with GCs and evaluated whether GR SNPs were associated with the risk of adrenal suppression and metabolic disorders in patients with chronic obstructive pulmonary disease (COPD). Methods: In an observational prospective cohort study, we recruited 77 patients with severe COPD receiving five days GC treatment for an exacerbation of COPD. 49% of patients also received regular inhaled corticosteroids. Adrenal function was evaluated with a corticotropin test 30 days after the exacerbation. Patients were genotyped for Bcl1, N363S, ER22/23EK and 9β SNPs. Results: The prevalence of adrenal suppression (corticotropin-stimulated plasma-cortisol ≤ 420 nmol/L) 1 month after GC treatment was 4/77 (5%). There was no correlation between high-sensitivity (p-value 0.79) or low-sensitivity (p-value 0.26) GR haplotypes and stimulated cortisol levels for COPD patients treated with GCs. There was no difference between adrenal suppression and metabolic disorders in COPD patients stratified for high vs. low GC-sensitivity GR haplotypes plus wild type (p-value > 0.05). Corticotropin stimulated P-cortisol did not differ between carriers and non-carriers for Bcl1, 9β, ER22/23K and N363S. For carriers of the high sensitivity GR gene haplotype, the association between inhaled corticosteroid dose and stimulated P-cortisol concentrations was more inverse (slope –0.25 vs. -0.10) than in patients with the low sensitivity haplotype. Conclusions: Five percent of patients had an insufficient adrenal function. The Bcl1 and N363S polymorphisms do not seem to increase the risk of adrenal suppression or metabolic disorders in adults treated with corticosteroids for COPD exacerbations.Trial Registration: The trial was registered at clinicaltrials.gov (NCT03140761) at May 4, 2017 with URL https://clinicaltrials.gov/ct2/show/NCT03140761.
Muscle Pathological Features and Extra-Muscle Involvement in Idiopathic Inflammatory Myopathies With Anti-Mitochondrial Antibody
Authors: Zhang Lu , Yang Hanbo , Lei Jieping , Peng Qinglin , Yang Hongxia , Wang Guochun , Lu Xin 
Published: December 2020

Abstract
BackgroudAnti-mitochondrial antibodies (AMAs) can be detected in some idiopathic inflammatory myopathy (IIM) patients. We aimed to investigate the clinical features of IIM patients with AMAs.Methods We retrospectively analysed consecutive 1,167 patients with IIM for AMAs-associated myositis and compared them to age- and sex-matched AMA-negative patients. ResultsTwenty-nine patients (2.5%) were identified with AMAs-positive myositis; eight of them had primary biliary cholangitis (PBC). There were no significant differences in skin rash, dysphagia, interstitial lung disease, and muscle strength between AMAs-positive patients and disease controls. 12/23(52.2%) cases showed immune-mediated necrotizing myopathy (IMNM)-like pathological features. Among AMAs-positive patients, 11 of 16 patients with isolated anti-AMA were classified as IMNM which was significantly higher than that of patients with coexistent anti-AMAs and myositis-specific antibodies (p=0.026). Moreover, AMAs-positive patients had a significantly higher cardiac involvement ratio (P<0.001) compared to controls. Comparsion in AMAs-positive IIM patients show the incidence of abnormal echocardiography findings was significantly higher in patients without primary biliary cholangitis (PBC) than in patients with PBC(P=0.009). Patients without heart abnormalities took significantly less time to achieve disease remission and prednisone tapering to <10 mg than patients with heart abnormalities (P<0.001 and P=0.001, respectively).ConclusionsIMNM was a major histopathological finding in IIM patients with isolated anti-AMAs antibody. AMAs was significantly associated with cardiac involvement in IIM. PBC seemed to be a protective factor for abnormal echocardiography findings in AMAs-positive patients. Patients without heart involvement took less time to achieve disease remission and prednisone tapering off.
Commiphora Myrrha (Nees) Engl. Resin Extracts Induce Phase-I Cytochrome P450 2C8, 2C9, 2C19, and 3A4 Isoenzyme Expressions in Human Hepatocellular Carcinoma (HepG2) Cells
Authors: Alehaideb Zeyad , Alatar Ghada , Nehdi Atef , Albaz Abeer , Al-Eidi Hamad , Almutiri Mansour , Hawsa Esraa , Alshuail Nora , Matou-Nasri Sabine 
Published: December 2020

Abstract
Background: Commiphora myrrha (Nees) Engl. (C. myrrha) resin is one of the oldest Middle Eastern herbal medicine used for treatment and prevention of numerous diseases. This resin is prepared in different methods and widely consumed among Saudi Arabian patients. Despite its popularity, no studies have been done on potential modulation effects of C. myrrha resin extracts on human cytochrome P450 (CYP) drug-metabolizing enzyme expression.Methods: The C. myrrha extracts were prepared by two different methods of sonication and boiling resembling the most popular traditional preparations of maceration and decoction, respectively. Both extracts were fingerprinted using high-performance liquid chromatography equipped with ultra-violet detector (HPLC-UVD). The viability of HepG2 cells treated with aqueous extracts was determined using Promega CellTiter-Glo® assay in order to select the efficient and non-toxic resin extract concentrations for phase-I metabolic isoenzyme expression analysis. The isoenzyme gene and protein expression levels of CYP 2C8, 2C9, 2C19, and 3A4 were measured using reverse transcription-quantitative polymerase chain reaction and Western blot technologies, respectively. Results: The HPLC-UVD fingerprinting revealed different chromatograms for C. myrrha extracts indicating possible differences in their modulation effects on CYP expression. Both aqueous extracts were toxic to HepG2 cells when tested at concentrations exceeding 150 µg/ml of dry crude extract. The CYP 2C8, 2C9, and 2C19 mRNA expression levels increased up to 4.0-fold after cell treatment with concentrations ranging from 1 to 30 µg/ml C. myrrha extracts, as compared with the untreated cells. However, the modulation of CYP3A4 mRNA expression levels was only significant at 30 µg/ml of crude extract exceeding the 2.0-fold cutoff. The up-regulation of CYP mRNA expression levels induced by C. myrrha extracts was confirmed at the CYP protein expression levels as well. Conclusions: The C. myrrha aqueous extracts modulate CYP 2C8, 2C9, 2C19, and 3A4 gene expression at clinically-relevant concentrations regardless of preparation methods. Further in vitro and in vivo experiments are required for the establishment of herb-drug interaction profile for these traditional medicinal resin extracts.
Comparison of the Reductions in LDL-C and non-HDL-C Induced by the Red Yeast Rice Extract Xuezhikang between Fasting and Nonfasting States in Patients with Coronary Heart Disease
Authors: Zhu Li-Yuan , Wen Xing-Yu , Xiang Qun-Yan , Guo Li-Ling , Xu Jin , Zhao Shui-Ping , Liu Ling 
Published: December 2020

Abstract
Background: Xuezhikang, an extract of red yeast rice, effectively lowers fasting blood lipid levels. However, the influence of Xuezhikang on the nonfasting levels of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) has not been explored in Chinese patients with coronary heart disease (CHD).Methods: Fifty CHD patients were enrolled and randomly divided into two groups (n = 25 each) to receive 1200 mg/d of Xuezhikang or a placebo for six weeks as routine therapy. Blood lipids were repeatedly measured before and after six weeks of treatment at 0, 2, 4 and 6 hour (h) after a standard breakfast containing 800 kcal and 50 g of fat.Results: The serum LDL-C levels significantly decreased, from a fasting level of 3.88 mmol/L to nonfasting levels of 2.99, 2.83 and 3.23 mmol/L at 2, 4 and 6 h, respectively, after breakfast (P < 0.05). However, no significant difference was found in the total cholesterol (TC) levels between the fasting value and values at any nonfasting time points. The serum non-HDL-C level slightly increased from a fasting level of 4.29 mmol/L to nonfasting levels of 4.32, 4.38 and 4.34 mmol/L at 2, 4 and 6 h postprandially, respectively, and the difference reached statistical significance only at 4 and 6 h after breakfast (P < 0.05). No difference was observed in the fasting and nonfasting blood lipids between the two groups at baseline. After six weeks of Xuezhikang treatment, the patients had significantly lower fasting and nonfasting serum levels of LDL-C and non-HDL-C (P < 0.05) than at pretreatment. The LDL-C levels were reduced by 27.8%, 28.1%, 26.2% and 25.3% at 0, 2, 4 and 6 h, respectively, and the non-HDL-C levels were reduced by 27.6%, 28.7%, 29.0% and 28.0% at 0, 2, 4 and 6 h, respectively, after breakfast. No significant difference was found in the percent reductions in the LDL-C and non-HDL-C levels among the four different time points.Conclusions: Six weeks of Xuezhikang treatment significantly decreased LDL-C and non-HDL-C levels, with similar percent reductions in the fasting and nonfasting states in CHD patients, indicating that the percent change in nonfasting LDL-C or non-HDL-C could replace that in the fasting state for evaluation of the efficacy of cholesterol control in CHD patients who are unwilling or unable to fast.
Optimization of Zinc Application Rates With and Without Arbuscular Mycorrhizal Fungi for the Improvement in Maize Growth, Gas Exchange Attributes and Yield in Zinc Deficient Soil
Authors: Danish Subhan , Saboor Abdul , Ali Muhammad Arif , Ahmed Niaz , Skalicky Milan , Fahad Shah , Datta Rahul , Hassan Mohamed M. , Brestic Marian , Sabagh Ayman EL 
Published: December 2020

Abstract
Zinc (Zn) concentration in soil varies from deficient to toxic. Its deficiency, as well as toxicity through imbalance application, can reduce maize growth and yield. Therefore, balanced application of Zn is a necessity of time to save resources and to achieve optimum growth and yield in maize. Arbuscular mycorrhiza fungi (AMF) can provide tolerance to host plant against Zn induced stress. Inoculation of AMF not only helps in balance uptake of Zn but also enhance growth and yield of crops. That’s why in the current efficacious function of AMF, i.e., Glomus specie was assed. Different application rates of Zn (0, 20, 40, 60, 80, 100 and 120 mg Zn/kg) were applied with AMF (AM) and without AMF (NM). Results showed that root colonization level was 45% higher in AMF inoculated plants as compared with non-inoculated plants. A significant increase in plant height (15%), number of leaves (35.4%), cob weight (4.39%), 1000 grains weight (10.5%) and biological yield (42.2%) signified the efficacious functioning of Zn20+AM over sole inoculation of AM. We also observed that AMF inoculation with Zn20 helped in improved photosynthesis, transpiration and stomatal conductance. Furthermore, both Zn20+AM and Zn20+AM were significantly better for the improvement in total soluble protein over AM in maize. Higher application rates of zinc, i.e., Zn80 and Zn120 induced Zn toxicity with (AM) and without (NM) AMF. In conclusion, Zn20+AM is an effective amendment to achieve better growth and yield of maize without Zn deficiency or toxicity.
Dynamics of T Lymphocyte Phenotypes Between the Periphery and the Brain From the Acute to the Chronic Phase Following Ischemic Stroke in Mice
Authors: Jeon Myung-Shin , Kim Minha , Kim So-Dam , Kim Kyoung-In , Jeon Eun Hae , Kim Min Gee , Lim Yu-Ree , Lkhagva-Yondon Enkhmaa , Oh Yena , Na Kwangmin , Chung Young Cheul , Jin Byung Kwan , Song Yun Seon 
Published: December 2020

Abstract
BackgroundT lymphocytes are involved in infarct size at the early stage of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well-analyzed from the acute to the chronic phase of stroke.MethodsA 45 min transient middle cerebral artery occlusion mouse model was used. The phenotypes of T lymphocytes in the thymus, spleen, blood, and brain were determined using the neurological severity score (NSS) and body weights during the 6-month follow-up. ResultsImpairment of thymocyte numbers, development, proliferation, and apoptosis was observed for up to 2 weeks. The number of mature T cells in the spleen and blood decreased and showed less interferon- production for up to 2 weeks. Increased numbers of CD44+CD62L- effector T cells and CD4-CD8-CD3+ double negative T cells were observed in mouse brains in the early phase of stroke, while interleukin (IL)-10+Foxp3+ regulatory T cell levels increased for 1 week during the chronic phase. These phenotypes were correlated with body weight and the NSS. Conclusions﻿The recovery of T lymphocyte numbers and increased IL-10+Foxp3+ regulatory T lymphocytes may be important for the improvement of long-term neurological outcomes. Dynamic changes in T lymphocytes from the acute and chronic phase may play different roles, such as pathological and recovery roles, respectively. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs from the acute to the chronic phase of stroke.
Analyzing the Multi-target Pharmacological Mechanism of Folium Artemisiae Argyi Acting on Breast Cancer: A Network Pharmacology Approach
Authors: Wang Jinlu , Wang Xiuli , Zhang Han , Lu Minghui , Niu Xingjian , Yin Lei , Wang Yiran , Gu Yucui , Li Dongbo , Ji Hongfei , Zhang Qingyuan 
Published: December 2020

Abstract
Background: Folium Artemislae Argyl (FAA) is a traditional Chinese herb medicine widely used in clinic. However, the underlying mechanisms of its anticancer effects have not been fully understood. Methods: In this study, we applied a network pharmacology approach to dig out the potential mechanisms of FAA against breast cancer.Results: We obtained 9 active ingredients and 236 potential targets from FAA in total to construct a network, which showed that quercetin served as the major ingredient in FAA. AKT1 (RAC-alpha serine/threonine-protein kinase), MYC (Myc proto-oncogene protein), CASP3 (Caspase-3), EGFR (Epidermal growth factor receptor), JUN (Transcription factor AP-1), CCND1 (G1/S-specific cyclin-D1), VEGFA (Vascular endothelial growth factor A), ESR1 (Estrogen receptor), MAPK1 (Mitogen-activated protein kinase 1) and EGF (Pro-epidermal growth factor) were identified as key targets of FAA in the treatment of breast cancer. The protein protein interaction (PPI) cluster demonstrated that AKT1 was the seed in this cluster, indicating that AKT1 played a crucial role in connecting other nodes in the PPI network. This enrichment demonstrated that FAA was highly related to signal transduction, endocrine system, replication and repair, cell growth and death. The enrichment results also verified that the underlying mechanisms of FAA against breast cancer might be attributed to coordinated regulation of several cancer-related pathways, such as MAPK signaling pathway, mammalian target of rapamycin (mTOR) signaling pathway, among of others.Conclusions: To summarize, this study aimed to identify the potential targets and pathways of FAA as a treatment against breast cancer using the network pharmacology approach, and systematically elucidate the mechanisms of FAA in the treatment of breast cancer.
Assessment of Fluralaner Treatment in Eliminating Dermanyssus Gallinae Infestation From Commercial Layer Farms, and the Potential for Derived Benefits of Improved Bird Welfare and Productivity.
Authors: Petersen Ivo , Johannhörster Katharina , Pagot Eric , Escribano Damian , Zschiesche Eva , Thomas Emmanuel 
Published: December 2020

Abstract
Background. Infestations with the poultry red mite (PRM), Dermanyssus gallinae, can result in anaemia, stress-related behaviours linked to reduced laying hen welfare, and impaired productivity. A study was conducted to investigate the potential welfare benefits of PRM elimination following fluralaner treatment.MethodsA single poultry house was selected on each of two layer farms, one free-range, one aviary, containing 5,400 Lohmann LSL hens and 42,400 Lohmann Brown hens, respectively. Fluralaner (Exzolt®; 0.5 mg/kg body weight) was administered twice, seven days apart (Weeks 0 and 1). Mite populations were regularly monitored by traps left in place for one to two days. Infra-red cameras monitored night-time hen behaviours weekly, beginning five weeks pre-treatment, continuing for five and six weeks post-treatment on the free-range and aviary farms, respectively. Weekly daytime behaviours were recorded on the free-range farm. On the aviary farm, blood samples were collected from 50 randomly selected hens during Weeks -3, -1 and 5. On the free-range farm, eggs were randomly collected for corticosterone analysis during Weeks -6, 0 and 6, and on the aviary farm during Weeks -3, -1 and 5. Production parameters were assessed using farm records.ResultsFluralaner efficacy on the free-range farm was >99% following the first administration, and on the aviary farm was 100% at Week 1 and at all subsequent mite counts. On both farms, treatment was followed by significant reductions in night-time preening, head scratching, head shaking, and activity, and on the aviary farm in vertical wing shaking and gentle feather pecking. On the free-range farm there were significant daytime reductions in head scratching, head shaking and preening. Post-treatment increases in egg and plasma corticosterone were suggestive of stress factors extra to mite infestation. Red blood cell counts and haematocrit increased following treatment. On the free range farm, relative to standard production parameters for LSL hens, the decline in laying rate with increasing bird age was less than expected, and the increase in egg weight greater than expected. ConclusionFluralaner treatment eliminated mite challenge, leading to improved hen welfare and health, based on reductions in stress-related behaviours, and restoration of the anaemia-inducing effects of mite blood feeding.