bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endurance training prevents inflammation and apoptosis in hypothalamic neurons of obese mice
Authors: Marinho Rodolfo , Munõz Vitor R. , Pauli Luciana S. S. , Ropelle Eloize C. C. , de Moura Leandro P. , Moraes Juliana C. , Moura‐Assis Alexandre , Cintra Dennys E. , da Silva Adelino S. R. , Ropelle Eduardo R. , Pauli José R. 
Published: August 2018

This study investigated the effects of exercise training in regulating inflammatory processes, endoplasmic reticulum stress, and apoptosis in hypothalamic neurons of obese mice. Swiss mice were distributed into three groups: Lean mice (Lean), sedentary animals fed a standard diet; obese mice (Obese), sedentary animals fed a high‐fat diet (HFD); trained obese mice (T. Obese), animals fed with HFD and concurrently subjected to an endurance training protocol for 8 weeks. In the endurance training protocol, mice ran on a treadmill at 60% of peak workload for 1 hr, 5 days/week for 8 weeks. Twenty‐four hours after the last exercise session, the euthanasia was performed. Western blot, quantitative real‐time polymerase chain reaction, and terminal deoxynucleotide transferase biotin‐dUTP nick end‐labeling (TUNEL) techniques were used for the analysis of interest. The results show exercise training increased phosphorylation of leptin signaling pathway proteins (pJAK2/pSTAT3) and reduced the content of tumor necrosis factor α, toll‐like receptor 4, suppressor of cytokine signaling 3, protein–tyrosine phosphatase 1B as well as the phosphorylation of IkB kinase in the hypothalamus of T. Obese animals. A reduction of macrophage activation and phosphorylation of eukaryotic initiation factor 2α, and protein kinase RNA‐like endoplasmic reticulum kinase (PERK) were also observed in exercised animals. Furthermore, exercise decreased the expression of the proapoptotic protein (PARP1) and increased anti‐inflammatory (IL‐10) and antiapoptotic (Bcl2) proteins. Using the TUNEL technique, we observed that the exercised animals had lower DNA fragmentation. Finally, physical exercise preserved pro‐opiomelanocortin messenger RNA content. In conclusion, exercise training was able to reorganize the control of the energy balance through anti‐inflammatory and antiapoptotic responses in hypothalamic tissue of obese mice.
Ferritinophagy/ferroptosis: Iron‐related newcomers in human diseases
Authors: Tang Mingzhu , Chen Zhe , Wu Di , Chen Linxi 
Published: August 2018

Nuclear receptor coactivator 4 mediated ferritinophagy is an autophagic phenomenon that specifically involves ferritin to release intracellular free iron. Ferritinophagy is implicated in maintaining efficient erythropoiesis. Notably, ferritinophagy also plays a central role in driving some pathological processes, including Parkinson’s disease (PD) and urinary tract infections. Some evidence has demonstrated that ferritinophagy is critical to induce ferroptosis. Ferroptosis is a newly nonapoptotic form of cell death, characterized by the accumulation of iron‐based lipid reactive oxygen species. Ferroptosis plays an important role in inhibiting some types of cancers, such as hepatocellular carcinoma, pancreatic carcinoma, prostate cancer, and breast cancer. Conversely, the activation of ferroptosis accelerates neurodegeneration diseases, including PD and Alzheimer’s disease. Therefore, in this review, we summarize the regulatory mechanisms related to ferritinophagy and ferroptosis. Moreover, the distinctive effects of ferritinophagy in human erythropoiesis and some pathologies, coupled with the promotive or inhibitory role of tumorous and neurodegenerative diseases mediated by ferroptosis, are elucidated. Obviously, activating or inhibiting ferroptosis could be exploited to achieve desirable therapeutic effects on diverse cancers and neurodegeneration diseases. Interrupting ferritinophagy to control iron level might provide a potentially therapeutic avenue to suppress urinary tract infections.
Nine hub genes as the potential indicator for the clinical outcome of diabetic nephropathy
Authors: Song Xiaoping , Gong Min , Chen Yanping , Liu Hui , Zhang Jun 
Published: August 2018

Diabetic nephropathy (DN) is one of the most serious and dangerous chronic complications caused by diabetes mellitus, and the identification and development of novel biomarkers could be beneficial for the diagnosis and prognosis of DN patients. This study focused on researching the differently expressed pattern of the DN samples from glomeruli and tubulointerstitium. Significance analysis of microarrays (SAM) was used to identify differentially regulated genes in 44 microdissected human kidney samples. Functional enrichment analysis was used to analyze the functions these genes are mostly enriched in. Besides, protein–protein interaction (PPI) network was used to select the hub genes that were associated with DN. The gene expression pattern of DN samples from glomeruli and tubulointerstitium was found to be quite different. It showed that the recurrence rate of DN originating from glomeruli and control samples was lower than that from tubulointerstitium and control samples. A total of 332 differentially expressed genes were identified between glomeruli tissues and tubulointerstitium tissues. PPI network analysis was performed on these 332 genes. Finally, nine hub genes were selected as the most potential biomarkers in the occurrence of DN. In conclusion, a total of 332 genes were found to be related to DN, and these genes were found to be mostly enriched in pathways such as immunity, inflammatory, and vascular pathways. Three genes VAV1, LCK, and Plk had the potential to serve as indicators for the occurrence and development of DN in clinical management.
Estrogen‐related receptor γ negatively regulates osteoclastogenesis and protects against inflammatory bone loss
Authors: Kim Hyun‐Ju , Kim Bo Kyung , Ohk Boram , Yoon Hye‐Jin , Kang Woo Youl , Cho Seungil , Seong Sook Jin , Lee Hae Won , Yoon Young‐Ran 
Published: August 2018

Estrogen‐related receptor γ (ERRγ) is an orphan nuclear receptor that plays an important role in various metabolic processes under physiological and pathophysiological conditions. Here, we report that ERRγ functions as a negative regulator in receptor activator of nuclear factor κΒ ligand (RANKL)–induced osteoclast differentiation. We observed that ERRγ was strongly expressed in osteoclast precursors, bone marrow–derived macrophages (BMMs) while its expression was significantly reduced by RANKL during osteoclastogenesis. Overexpression of ERRγ in BMMs suppressed the formation of multinucleated osteoclasts and attenuated the induction of c‐Fos and nuclear factor of activated T cells c1, which are critical modulators in osteoclastogenesis. Similarly, the treatment of ERRγ agonists, N‐(4‐(diethylaminobenzylidenyl)‐N'‐(4‐hydroxybenzoyl)‐hydrazine (DY131) or GSK4716, also inhibited osteoclast generation and the expression of these key modulators. On the other hand, shRNA‐mediated knockdown of ERRγ accelerated the formation of bone‐resorbing cells and the expression of osteoclastogenic markers. Forced expression of ERRγ blocked RANKL‐stimulated phosphorylation of the nuclear factor κB (NF‐κB) inhibitor IκBα and suppressed NF‐κB transcriptional activity induced by RANKL or the NF‐κB subunit p65. Furthermore, by employing a pharmacological approach, we showed that the ERRγ agonist DY131 protected against inflammatory bone loss induced by lipopolysaccharide in vivo. Together, our findings reveal that ERRγ is a pivotal regulator in RANKL‐mediated osteoclastogenesis and suggest that ERRγ may have potential as a therapeutic target for pathological bone loss.
The predictive value of a preoperative systemic immune‐inflammation index and prognostic nutritional index in patients with esophageal squamous cell carcinoma
Authors: Zhang Hongdian , Shang Xiaobin , Ren Peng , Gong Lei , Ahmed Ashique , Ma Zhao , Ma Rong , Wu Xianxian , Xiao Xiangming , Jiang Hongjing , Tang Peng , Yu Zhentao 
Published: August 2018

Growing evidence indicates that systemic inflammation response and malnutrition status are correlated with survival in certain types of solid tumors. The aim of this study is to evaluate the association between the systemic immune‐inflammation index (SII) and prognostic nutritional index (PNI) and overall survival (OS) in patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. A consecutive series of 655 patients with resected ESCC who underwent esophagectomy were enrolled in the retrospective study. The preoperative SII was defined as platelet × neutrophil/lymphocyte counts. The PNI was calculated as albumin concentration (g/L) + 5 × total lymphocyte count (109/L). The optimal cut‐off values of SII, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and PNI were determined by receiver operating characteristic analysis. Survival analysis was performed using the Kaplan–Meier method with a log‐rank test, followed by a multivariate Cox proportional hazards model. A high SII was significantly related to tumor size, histological type, invasion depth, and TNM stage (p < 0.05). A low PNI was significantly associated with age, tumor size, invasion depth, lymph node metastasis, and TNM stage (p < 0.05). Univariate analysis revealed that age, smoking history, tumor size, invasion depth, lymph node metastasis, SII, NLR, PLR, and PNI were predictors of OS (p < 0.05). Multivariate analysis identified age (p = 0.041), tumor size (p = 0.016), invasion depth (p < 0.001), lymph node metastasis (p < 0.001), SII (p = 0.033), and PNI (p = 0.022) as independent prognostic factors correlated with OS. There was a significant inverse relationship between the SII and PNI (r = 0.309; p < 0.001). The predictive value increased when the SII and PNI were considered in combination. Our results demonstrate that the preoperative high SII and low PNI are powerful indicators of aggressive biology and poor prognosis for patients with ESCC. The combination of SII and PNI can enhance the accuracy of prognosis.
Characterization of ulcerative colitis‐associated constipation syndrome (proximal constipation)
Authors: James Sally L , van Langenberg Daniel R , Taylor Kirstin M , Gibson Peter R 
Published: August 2018

BackgroundThe syndrome of constipation with other abdominal symptoms (“proximal constipation”) in ulcerative colitis (UC) is commonly recognized by practitioners but is poorly described, with no recognized definition and little understanding with regard to prevalence and effect of therapies on disease outcomes. This study aimed to address these issues in a cross‐sectional, consecutive series of patients with UC.MethodsA working definition of proximal constipation was established. Consecutive patients were recruited, and their disease activity, recent medications, and investigations plus abdominal symptoms were assessed at a study visit. Relevant clinical data were also extracted from medical records.ResultsOf 125 patients with UC, (mean age 47, range 14–84 years, 61 male), 58 (46%) fulfilled the definition of proximal constipation. The main symptoms were reduced stool frequency (69%), hard stools (43%), abdominal pain (40%), excessive flatus (29%), straining (24%), and sensation of incomplete emptying (14%). Proximal constipation was associated with female gender (OR 3.45 [1.45–8.24]), left‐sided (OR 2.84 [1.14–7.11]) and concurrently active disease (OR 5.56 [1.96–16.67]), but not age, disease duration or therapy. A total of 88% had an increase in anti‐inflammatory therapy, with the use of laxatives or fiber supplements in 63% compared with 1.4% of those without proximal constipation.ConclusionsProximal constipation is common, and its risk increases in active and distal disease, especially in women. Validation of its definition and evaluation of therapeutic strategies are needed. A new term “ulcerative colitis‐associated constipation syndrome” is proposed to more accurately depict its nature.
Response to neoadjuvant chemoradiotherapy for locally advanced rectum cancer: Texture analysis of dynamic contrast‐enhanced MRI
Authors: Zou Hai‐hua , Yu Jing , Wei Yun , Wu Jiang‐fen , Xu Qing 
Published: August 2018

BackgroundTumor heterogeneity can be assessed by texture analysis (TA). TA has been applied using diffusion‐weighted imaging and apparent diffusion coefficient maps to predict pathological responses to preoperative chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC).PurposeTo evaluate the texture parameters obtained from K
trans maps derived from dynamic contrast‐enhanced (DCE)‐MRI for predicting pathological responses to preoperative CRT for LARCs.Study TypeRetrospective.PopulationAltogether, 83 patients (26 women, 57 men) with rectal cancer met the inclusion criteria.Field Strength/Sequence3.0T/T1‐weighted DCE‐MRI sequence.AssessmentAfter CRT, each tumor was assessed by a pathologist who assigned a tumor regression grade (TRG), thereby identifying pathologically complete responders (pCR; TRG 1) and good responders (GR; TRG1 + TRG2). TA was then applied to the DCE‐MRI K
trans maps. The K
trans value, several TA parameters, and tumor volumes were calculated.Statistical TestsThe Shapiro–Wilk test was used to verify that the data had normal distribution. Results of parameters measured before and after CRT were compared using paired‐sample t‐tests. Value changes of each parameter in the combined pCR/GR group were compared using independent sample t‐tests. Receiver operating characteristic curves and areas under the curve (AUC) were calculated to assess the diagnostic performance of each parameter related to CRT effectiveness.ResultsThere were 15 pCR (16.9%) and 21 GR (25.3%) patients. Tumor volume, mean K
trans, entropy, and correlation decreased and energy values increased significantly in these groups compared with those of the non‐PCR and non‐GR groups. ΔCorrelation (Δcorrelation = postcorrelation – precorrelation) was found to be a valuable parameter for identifying pCR/GR patients (AUC 0.895, sensitivity 86.7%, specificity 81.8%).Data ConclusionTA parameters from the DCE‐MRI K
trans map can predict the efficacy of CRT for treating LARCs. Also, Δcorrelation may be useful for identifying patients who will be responsive to CRT.Level of Evidence: 4Technical Efficacy: Stage 3J. Magn. Reson. Imaging 2019;49:885–893.
Novel vacuum stable ketone‐based matrices for high spatial resolution MALDI imaging mass spectrometry
Authors: Yang Junhai , Norris Jeremy L. , Caprioli Richard 
Published: August 2018

AbstractWe describe the use of aromatic ketones and cinnamyl ketones that have high vacuum stability for analyzing tissue sections using matrix‐assisted laser desorption/ionization imaging mass spectrometry. Specifically, the matrix, (E)‐4‐(2,5‐dihydroxyphenyl)but‐3‐en‐2‐one (2,5‐cDHA) provides high sensitivity and high vacuum stability while producing small size crystals (1‐2 μm). A high throughput and highly reproducible sample preparation method was developed for these matrices that first involves using an organic spray solution for small matrix crystal seeding followed by spraying of the matrix in a 30% acetonitrile/70% water solution on the tissue surface to obtain a homogeneous coating of small crystals, suitable for high spatial resolution imaging.
Droplet‐digital polymerase chain reaction for detection of clinical hepatitis B virus DNA samples
Authors: Yang Deping , Hu Tingting , Wu Xuan , Li Ke , Zhong Qi , Liu Weiwei 
Published: August 2018

This study aimed to establish a quantitative droplet‐digital polymerase chain reaction (ddPCR) detection system for clinical hepatitis B virus (HBV) DNA in samples from patients with HBV infection with the aim of monitoring fluctuations and planning future antiviral treatments. Primers and probes for the conserved region of HBV DNA sequence (GenBank: AB554017.1) were designed by sequence alignment with the HBV DNA sequence in GenBank. The PUC57 plasmid containing the gene fragment was then synthesized according to the fragment amplified by the primer. Linear DNA templates were obtained by digestion of the PUC57 plasmid with EcoRI. Primer specificity was verified by electrophoresis and sequencing, and the plasmid was used to verify the performance of ddPCR. Serum levels of HBV DNA were then detected in 103 HBV patients by ddPCR and real‐time quantitative polymerase chain reaction (qPCR), and the consistency of the two methods was compared. The accuracy of the ddPCR assays showed good linear correlation (R2 = 0.9952). The ddPCR coefficient of variance (CV) for intrarun replicates reached 2.0%, and the CV value for inter‐run replicates reached 3.6%. The ddPCR could detect as little as one copy of the template, as demonstrated by continuous dilution. This assay system provided a novel and specific platform with a linear range of detection from 1 to 105 copies/µL. Serum samples were collected from 103 HBV patients, and HBV DNA levels quantiﬁed by ddPCR and qPCR showed good concordance based on the Bland‐Altman analysis. The 95% limits of agreement were log10: 0.29 ± 0.55 copies/μL. Our ﬁndings demonstrated that ddPCR can improve the detection level of nucleic acid and quantify the nucleic acid concentration, which is suitable for the clinical detection of HBV DNA.
Early Hypophosphatemia in High‐Risk Preterm Infants: Efficacy and Safety of Sodium Glycerophosphate From First Day on Parenteral Nutrition
Authors: Bustos Lozano Gerardo , Soriano‐Ramos María , Pinilla Martín María Teresa , Chumillas Calzada Silvia , García Soria Carmen Elia , Pallás‐Alonso Carmen Rosa 
Published: August 2018

AbstractBackgroundEarly hypophosphatemia is common in premature infants ≤1250 g. The aim of this study was to assess the frequency and severity of hypophosphatemia after sodium glycerophosphate supplementation from first day of life in parenteral nutrition and to address the safety of this practice.MethodsProspective cohort study of infants ≤1250 g birth weight born in a tertiary‐care level neonatal intensive care unit and supplied with sodium glycerophosphate from the first day of life. Primary outcome was the presence of hypophosphatemia (<4 mg/dL) on the first week. Data were compared with our 2014 prospective subcohort of infants ≤1250 g receiving phosphate after 48 hours of life and morbidity with that of our 2016 retrospective cohort of ≤1250 g.ResultsFifty‐four neonates were included. The frequency of hypophosphatemia was 29.6%. Only 1 patient presented hypophosphatemia <2 mg/dL. Mild hypokalemia was found in 8 patients (50%). No cases of hypernatremia were observed. Patients with hypophosphatemia had significantly lower gestational age (27.4 vs 28.8 weeks, P = .032) and lower z‐score birth weight (−1.68 vs −0.47; P = .001). When compared with the 2014 subcohort, we found a lower frequency of hypophosphatemia (29.6% vs 69.2%; P = .008) and a lower rate of samples with hypophosphatemia (20.4% vs 51.4%; P = .0002) and critical hypophosphatemia (0.68% vs 11.4%, P = .0005). No differences were found in morbidity or mortality.ConclusionsSodium glycerophosphate supplementation in parenteral nutrition from the first day of life significantly decreased the frequency of hypophosphatemia. No adverse events were reported.
Innate lymphoid cells are present in gingivitis and periodontitis
Authors: Kindstedt Elin , Koskinen Holm Cecilia , Palmqvist Py , Sjöström Mats , Lejon Kristina , Lundberg Pernilla 
Published: August 2018

AbstractBackgroundInnate lymphoid cells (ILCs) are the most recently identified leukocytes of the immune system and these cells are increasingly acknowledged to play important roles in host defence and tissue repair. ILCs are also contributors of inflammatory diseases such as asthma and colitis. We analyzed the presence and relative proportions of the different ILC subsets (ILC1, ILC2 and ILC3) in gingivitis and periodontitis. Further, we investigated if ILCs express receptor activator of nuclear factor kappa‐B ligand (RANKL), a cytokine crucial for osteoclast differentiation and bone resorption.MethodsWe collected gingivitis and periodontitis soft tissue and characterized ILC subsets including RANKL expression in single‐cell suspensions using flow cytometry.ResultsILCs were detected both in gingivitis and periodontitis. The majority of ILCs, in both conditions, were ILC1s. Furthermore, RANKL expression was detected on a fraction of the ILC1s.ConclusionsOur discovery of the presence of ILCs both in gingivitis and periodontitis and concomitant expression of RANKL on a fraction of the ILC1 population suggest that these cells may be of importance in periodontal disease. In addition, our findings provide a new insight into the field of oral immunology.
Solid‐phase extraction of drugs with cuttlefish bone powder as a sorbent
Authors: Khazri Hassen , Ghorbel‐Abid Ibtissem , Debrauwer Laurent , Kalfat Rafik , Trabelsi‐Ayadi Malika 
Published: August 2018

AbstractWe investigated cuttlefish bone powder for the solid‐phase extraction of naproxen, ibuprofen, and carbamazepine. The basic principles controlling the extraction are presented to aid in the choice of the nature and quantity of the extracting phase according to the sample matrix and the solute properties, based on the mechanisms of phase retention. Their retention mechanism is based on hydrogen bonding and electrostatic interactions. The results show a significant recovery rate for the three drugs, selectivity, and low cost. The method has successfully reduced the amount of tested pharmaceuticals with recoveries >87% at pH 4.
Vocal Hygiene Education Program Reduces Surgical Interventions for Benign Vocal Fold Lesions: A Randomized Controlled Trial
Authors: Hosoya Makoto , Kobayashi Rika , Ishii Toyota , Senarita Masamitsu , Kuroda Hiroyuki , Misawa Hayato , Tanaka Fujinobu , Takiguchi Tetsuya , Tashiro Masatsugu , Masuda Sawako , Hashimoto Sho , Goto Fumiyuki , Minami Shujiro , Yamamoto Nobuko , Nagai Ryoto , Sayama Akiko , Wakabayashi Takeshi , Toshikuni Keitaro , Ueha Rumi , Fujimaki Yoko , Takazawa Mihiro , Sekimoto Sotaro , Itoh Kenji , Nito Takaharu , Kada Akiko , Tsunoda Koichi 
Published: August 2018

Objectives/HypothesisVocal fold polyps and nodules are common benign laryngeal lesions. Currently, the Japanese health insurance system covers surgical interventions. However, the establishment of more cost‐effective conservative methods is required, because healthcare costs are viewed as a major concern, and the government and taxpayers are demanding more economical, effective treatments. In this situation, more suitable vocal hygiene education may be important for the success of cost‐effective conservative treatment. In this study, we developed a novel reinforced vocal hygiene education program and compared the results of this program with those of previous methods of teaching vocal hygiene.Study DesignMulticenter randomized controlled trial.MethodsPatients who visited a National Hospital Organization (NHO) hospital for the surgical indication of hoarseness were included in the study. Before undergoing surgery, 200 patients with benign vocal fold lesions (vocal fold polyps/nodules) were enrolled and randomly allocated to the NHO‐style vocal hygiene educational program (intervention group) or control education program (control group). Two months after enrollment, the patients in both groups underwent laryngeal fiberscopic examinations to determine whether the benign lesions had resolved or whether surgery was indicated for the vocal fold polyps/nodules.ResultsAfter 2 months, in the intervention group, the proportion of lesion resolution (61.3%) was significantly greater than that in the control group (26.3%) (P < .001, Fisher exact test).ConclusionsOur results clearly indicate that the quality and features of the education program could affect the outcome of the intervention. We found that a reinforced vocal hygiene education program increased the rate of the resolution of benign vocal fold polyps and nodules in a multicenter randomized clinical trial.Level of Evidence1b Laryngoscope, 2593–2599, 2018