bluuebunny/crossref_metadata_2025_split huggingface dataset:
CC and CXC chemokines play key roles in the development of polyomaviruses related pathological conditions
Authors: Mohammadi Mohammad Hassan , Kariminik Ashraf 
Published: June 2021

AbstractIt has been reported that polyomaviruses are the microbes which can be a cause of several human pathological conditions including cancers, nephropathy, progressive multifocal leukoencephalopathy and gynaecological disease. Although investigators proposed some mechanisms used by the viruses to induce the disorders, the roles played by chemokines in the pathogenesis of polyomaviruses infections are yet to be clarified. This review article investigated recent studies regarding the roles played by chemokines in the pathogenesis of the polyomaviruses infections. The research in the literature revealed that CXC chemokines, including CXCL1, CXCL5, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12 and CXCL16, significantly participate in the pathogenesis of polyomaviruses. CC chemokines, such as CCL2, CCL5 and CCL20 also participate in the induction of the pathological conditions. Therefore, it appears that CXC chemokines may be considered as the strategic factors involved in the pathogenesis of polyomaviruses.
Aerobic exercise promotes the functions of brown adipose tissue in obese mice via a mechanism involving COX2 in the VEGF signaling pathway
Authors: Fu Pengyu , Zhu Rongxin , Jia Jie , Hu Yang , Wu Chengjun , Cieszczyk Pawel , Holmberg Hans-Christer , Gong Lijing 
Published: June 2021

Abstract
Background
High-fat diet (HFD)-induced obesity causes immune cells to infiltrate adipose tissue, leading to chronic inflammation and metabolic syndrome. Brown adipose tissue (BAT) can dissipate the energy produced by lipid oxidation as heat, thereby counteracting obesity. Aerobic exercise activates BAT, but the specific underlying mechanism is still unclear.

Methods
Male C57BL/6 J mice were divided into a normal diet control group (NC group) and HFD group (H group). After becoming obese, the animals in the H group were subdivided into a control group (HC group) and an exercise group (HE group, with treadmill training). After 4 weeks, the mRNA profile of BAT was determined, and then differentially expressed key genes and pathways were verified in vitro.

Results
Relative to the NC group, the genes upregulated in the HC group coded mainly for proteins involved in immune system progression and inflammatory and immune responses, while the downregulated genes regulated lipid metabolism and oxidation–reduction. Relative to the HC group, the genes upregulated in the HE group coded for glycolipid metabolism, while those that were downregulated were involved in cell death and apoptosis. VEGF and other signaling pathways were enhanced by aerobic exercise. Interaction analysis revealed that the gene encoding cyclooxygenase 2 (COX2) of the VEGF signaling pathway is central to this process, which was verified by a sympathetic activator (isoprenaline hydrochloride) and COX2 inhibitor (NS-398).

Conclusions
In mice with HFD-induced obesity, four weeks of aerobic exercise elevated BAT mass and increased the expression of genes related to glycolipid metabolism and anti-inflammatory processes. Several pathways are involved, with COX2 in the VEGF signaling pathway playing a key role.
ANLN promotes carcinogenesis in oral cancer by regulating the PI3K/mTOR signaling pathway
Authors: Wang Bing , Zhang Xiao-li , Li Chen-xi , Liu Ning-ning , Hu Min , Gong Zhong-cheng 
Published: June 2021

Abstract
Background
Oral cancer is a malignant disease that threatenshuman life and greatly reducespatientquality of life. ANLN was reported to promote the progression of cancer. This study aims to investigate the role of ANLNin oral cancer and the underlying molecular mechanism.

Methods
ANLN expression was downregulated by RNAi technology. The effect of ANLN on cell behaviors, including proliferation, cell cycle progression, invasion, and apoptosis, was detected. Western blotting analysis was used to explore the mechanism by whichANLN functions in oral cancer.

Results
Data from TCGA database showed that ANLN was expressed at significantly higher levels in tumor tissues thanin normal control tissues. Patients with higher ANLN expression exhibitedshorter survivaltimes. ANLN was alsoabundantly expressedin the cancer cell lines CAL27 and HN30. When ANLN was knocked down in CAL27 and HN30 cells, cell proliferation and colony formation weredecreased. The cell invasion ability was also inhibited. However, the cell apoptosis rate was increased. In addition, the levels of critical members of the PI3K signaling pathway, includingPI3K, mTOR, Akt, and PDK-1, were significantlyreducedafter ANLN was knocked down in CAL27 cells.

Conclusions
ANLN contributes to oral cancerprogressionand affects activation ofthe PI3K/mTOR signaling pathway. This study providesa new potential targetfor drug development and treatment in oral cancer.
Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer
Authors: Turtle Louise , Bhalla Neeraj , Willett Andrew , Biggar Robert , Leadbetter Jonathan , Georgiou Georgios , Wilson James M. , Vivekanandan Sindu , Hawkins Maria A. , Brada Michael , Fenwick John D. 
Published: June 2021

AbstractBackgroundWe have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC).Materials and methodsBaseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MDHeart). Reductions in MDHeartachievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (VHeart-50-Gy) and left atrial wall volume receiving ≥ 63 Gy (VLAwall-63-Gy).ResultsFollowing re-optimization, mean MDHeart, VHeart-50-Gyand VLAwall-63-Gyvalues fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MDHeartis expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including VHeart-50-Gyand VLAwall-63-Gy, providing some insurance against survival being more strongly related to these measures than to MDHeart. The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MDHeartwas 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MDHeartvalues exceeded the median value in a published series, the average MDHeartreduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MDHeartvalues.ConclusionsCardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MDHeartled to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MDHeartlevels, for whom larger reductions in heart doses can be achieved.
Electroacupuncture reduces cold stress-induced pain through microglial inactivation and transient receptor potential V1 in mice
Authors: Liao Hsien-Yin , Lin Yi-Wen 
Published: June 2021

Abstract
Background
The treatment, and efficacy thereof, is considered to be inadequate with specificity to alleviation of Fibromyalgia and its associated pain. Fibromyalgia patients suffer from chronic and persistent widespread pain and generalized tenderness. Transient receptor potential V1 (TRPV1), which is reported as a Ca2+ permeable ion channel that can be activated by inflammation, is reported to be involved in the development of fibromyalgia pain.

Methods
The current study explored the TRPV1 channel functions as a noxious sensory input in mice cold stress model. It remains unknown whether electroacupuncture (EA) attenuates fibromyalgia pain or affects the TRPV1 pathway.

Results
We show that cold stress increases mechanical and thermal pain (day 7: mechanical: 1.69 ± 0.41 g; thermal: 4.68 ± 0.56 s), and that EA and Trpv1 deletion counter this increase. EA and Trpv1 deletion reduced the cold stress-induced increase in inflammatory mediators and TRPV1-related molecules in the hypothalamus, periaqueductal gray (PAG), and cerebellum of mice.

Conclusions
Our results imply that EA has an analgesic effect associated with TRPV1 downregulation. We provide novel evidence that these inflammatory mediators can modulate the TRPV1 signaling pathway and suggest new potential therapeutic targets for fibromyalgia pain.
Optimization of protocols for pre-embedding immunogold electron microscopy of neurons in cell cultures and brains
Authors: Tao-Cheng Jung-Hwa , Crocker Virginia , Moreira Sandra Lara , Azzam Rita 
Published: June 2021

AbstractImmunogold labeling allows localization of proteins at the electron microscopy (EM) level of resolution, and quantification of signals. The present paper summarizes methodological issues and experiences gained from studies on the distribution of synaptic and other neuron-specific proteins in cell cultures and brain tissues via a pre-embedding method. An optimal protocol includes careful determination of a fixation condition for any particular antibody, a well-planned tissue processing procedure, and a strict evaluation of the credibility of the labeling. Here, tips and caveats on different steps of the sample preparation protocol are illustrated with examples. A good starting condition for EM-compatible fixation and permeabilization is 4% paraformaldehyde in PBS for 30 min at room temperature, followed by 30 min incubation with 0.1% saponin. An optimal condition can then be readjusted for each particular antibody. Each lot of the secondary antibody (conjugated with a 1.4 nm small gold particle) needs to be evaluated against known standards for labeling efficiency. Silver enhancement is required to make the small gold visible, and quality of the silver-enhanced signals can be affected by subsequent steps of osmium tetroxide treatment, uranyl acetate en bloc staining, and by detergent or ethanol used to clean the diamond knife for cutting thin sections. Most importantly, verification of signals requires understanding of the protein of interest in order to validate for correct localization of antibodies at expected epitopes on particular organelles, and quantification of signals needs to take into consideration the penetration gradient of reagents and clumping of secondary antibodies.
Exosomal circ-BRWD1 contributes to osteoarthritis development through the modulation of miR-1277/TRAF6 axis
Authors: Guo Zhenye , Wang Huan , Zhao Feng , Liu Min , Wang Feida , Kang Mingming , He Weifu , Lv Zhi 
Published: June 2021

Abstract
Background
Circular RNAs (circRNAs) can act as vital players in osteoarthritis (OA). However, the roles of circRNAs in OA remain obscure. Herein, we explored the roles of exosomal circRNA bromodomain and WD repeat domain containing 1(circ-BRWD1) in OA pathology.

Methods
In vitro model of OA was constructed by treating CHON-001 cells with interleukin-1β (IL-1β). Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used for circ-BRWD1, BRWD, miR-1277, and TNF receptor-associated factor 6 (TRAF6) levels. RNase R assay was conducted for the feature of circ-BRWD1. Transmission electron microscopy (TEM) was employed to analyze the morphology of exosomes. Western blot assay was performed for protein levels. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis, and 5-Ethynyl-2′-deoxyuridine (EDU) assay were adopted for cell viability, apoptosis, and proliferation, respectively. Enzyme-linked immunosorbent assay (ELISA) was carried out for the concentrations of interleukin-6 (IL-6) and interleukin-8 (IL-8). Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to analyze the interaction between miR-1277 and circ-BRWD1 or TRAF6.

Results
Circ-BRWD1 was increased in OA cartilage tissues, IL-1β-treated CHON-001 cells, and the exosomes derived from IL-1β-treated CHON-001 cells. Exosome treatment elevated circ-BRWD1 level, while exosome blocker reduced circ-BRWD1 level in IL-1β-treated CHON-001 cells. Silencing of circ-BRWD1 promoted cell viability and proliferation and repressed apoptosis, inflammation, and extracellular matrix (ECM) degradation in IL-1β-stimulated CHON-001 cells. For mechanism analysis, circ-BRWD1 could serve as the sponge for miR-1277 to positively regulate TRAF6 expression. Moreover, miR-1277 inhibition ameliorated the effects of circ-BRWD1 knockdown on IL-1β-mediated CHON-001 cell damage. Additionally, miR-1277 overexpression relieved IL-1β-induced CHON-001 cell injury, while TRAF6 elevation restored the impact.

Conclusion
Exosomal circ-BRWD1 promoted IL-1β-induced CHON-001 cell progression by regulating miR-1277/TRAF6 axis.
Expression of IL-23 in gilt endometrium and oviduct after insemination with seminal plasma, spermatozoa or semen extender
Authors: Svensson Anna , Jiwakanon Jatesada , Fossum Caroline , Dalin Anne-Marie 
Published: June 2021

Abstract
Objective
Insemination with spermatozoa, seminal plasma and extender, cause a rapid inflammatory response in pig endometrium, characterized by an influx of neutrophils into the uterus. The transient inflammatory response to semen involves cytokine induction. Potential functions for Interleukin-23 (IL-23) in the inflammatory response to different insemination treatments were examined by studying mRNA expression and immunostaining in gilt oviduct and endometrium 35–40 h after insemination. Insemination was performed with seminal plasma (SP), spermatozoa (SPZ) without SP in the extender Beltsville thawing solution (BTS), or BTS alone. In control gilts an insemination catheter was inserted without anything being inseminated.

Results
Results showed that IL-23 mRNA was expressed in oviduct and endometrium after insemination regardless of treatment. There was an approximate two- to fourfold increase in expression of IL-23 mRNA in catheter-insertion control compared with SPZ, SP and BTS treatment groups. IL-23 immunolabelling was detected in a small number of separate cells and in the sub-epithelial connective tissue of the endometrium, the endosalpinx of isthmus and infundibulum.

Conclusion
In conclusion, insemination with SP, SPZ in BTS, and BTS alone decreased the expression of IL-23 mRNA in the endometrium compared to catheter-insertion control, indicating a possible role for IL-23 in the inflammatory response after insemination in gilts.
A ribonucleoprotein transfection strategy for CRISPR/Cas9‐mediated gene editing and single cell cloning in rainbow trout cells
Authors: Zoppo Marina , Okoniewski Nicole , Pantelyushin Stanislav , vom Berg Johannes , Schirmer Kristin 
Published: June 2021

Abstract
Background
The advent of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology marked the beginning of a new era in the field of molecular biology, allowing the efficient and precise creation of targeted mutations in the genome of every living cell. Since its discovery, different gene editing approaches based on the CRISPR/Cas9 technology have been widely established in mammalian cell lines, while limited knowledge is available on genetic manipulation in fish cell lines. In this work, we developed a strategy to CRISPR/Cas9 gene edit rainbow trout (Oncorhynchus mykiss) cell lines and to generate single cell clone-derived knock-out cell lines, focusing on the phase I biotransformation enzyme encoding gene, cyp1a1, and on the intestinal cell line, RTgutGC, as example.

Results
Ribonucleoprotein (RNP) complexes, consisting of the Cas9 protein and a fluorescently labeled crRNA/tracrRNA duplex targeting the cyp1a1 gene, were delivered via electroporation. A T7 endonuclease I (T7EI) assay was performed on flow cytometry enriched transfected cells in order to detect CRISPR-mediated targeted mutations in the cyp1a1 locus, revealing an overall gene editing efficiency of 39%. Sanger sequencing coupled with bioinformatic analysis led to the detection of multiple insertions and deletions of variable lengths in the cyp1a1 region directed by CRISPR/Cas9 machinery. Clonal isolation based on the use of cloning cylinders was applied, allowing to overcome the genetic heterogeneity created by the CRISPR/Cas9 gene editing. Using this method, two monoclonal CRISPR edited rainbow trout cell lines were established for the first time. Sequencing analysis of the mutant clones confirmed the disruption of the cyp1a1 gene open reading frame through the insertion of 101 or 1 base pair, respectively.

Conclusions
The designed RNP-based CRISPR/Cas9 approach, starting from overcoming limitations of transfection to achieving a clonal cell line, sets the stage for exploiting permanent gene editing in rainbow trout, and potentially other fish cells, for unprecedented exploration of gene function.
The effect of short term peripheral parenteral nutrition on treatment outcomes and mortality in critically ill pediatric canine patients
Authors: Flores Dueñas Cesar Augusto , Gaxiola Camacho Soila Maribel , Montaño Gómez Martin Francisco , Villa Angulo Rafael , Enríquez Verdugo Idalia , Rentería Evangelista Tomás , Pérez Corrales José Ascención , Rodríguez Gaxiola Miguel Ángel 
Published: June 2021

AbstractBackgroundPeripheral parenteral nutrition (PPN) is increasingly considered as an alternative to central parenteral nutrition (CPN) given the higher cost and more frequent clinical complications associated with the latter. However, the assessment of potential risks and benefits of PPN in critically ill pediatric canine patients has not been extensively performed. In this study, we aimed to explore the effect of short-term, hypocaloric PPN on weight loss, length of hospital stay, the incidence of complications, adverse effects, and mortality in critically ill pediatric canine patients.ResultsBetween August 2015 and August 2018, a total of 59 critically ill pediatric canine patients aged from 1 to 6 months admitted at the Veterinary Sciences Research Institute of the Autonomous University of Baja California were included in this non-randomized clinical trial. Canine pediatric patients were initially allocated to 3 groups: 11 in group 1 receiving parenteral nutrition (PN) supplementation equivalent to 40% of the resting energy requirement (RER), 12 in group 2 receiving supplementation of 50% of the RER, and 36 in group 3 receiving no PN supplementation. After establishing that there was no significant difference between 40 and 50% of PN supplementation, these groups were not separated for downstream analysis.Similar lengths of hospital stays were noted among study subjects who received PN supplementation and those who did not (4.3 ± 1.5 vs. 5.0 ± 1.5, days,p = 0.097). No metabolic-, sepsis- or phlebitis-related complications were observed in any animal in the PPN supplemented group. Higher mortality (19.4% vs. 0%,p = 0.036), and a greater percentage of weight loss (9.24% vs. 0%,p <  0.001) were observed in patients who received no supplementation.ConclusionEven though short-term, hypocaloric PPN did not reduce the length of hospital stay, it was associated with lower mortality and resulted in mitigation of weight loss. In contrast to previous studies evaluating central and peripheral parenteral nutrition protocols, we observed a lower frequency of metabolic, septic, and phlebitis complications using a 40–50% parenteral nutrition treatment. The parenteral nutrition therapeutic intervention used in our study may reduce PN-related adverse effects and promote a favorable disease outcome in critically ill canine patients. Larger studies will be needed to confirm these observations.
On the information leakage quantification of camera fingerprint estimates
Authors: Fernández-Menduiña Samuel , Pérez-González Fernando 
Published: June 2021

AbstractCamera fingerprints based on sensor PhotoResponse Non-Uniformity (PRNU) have gained broad popularity in forensic applications due to their ability to univocally identify the camera that captured a certain image. The fingerprint of a given sensor is extracted through some estimation method that requires a few images known to be taken with such sensor. In this paper, we show that the fingerprints extracted in this way leak a considerable amount of information from those images used in the estimation, thus constituting a potential threat to privacy. We propose to quantify the leakage via two measures: one based on the Mutual Information, and another based on the output of a membership inference test. Experiments with practical fingerprint estimators on a real-world image dataset confirm the validity of our measures and highlight the seriousness of the leakage and the importance of implementing techniques to mitigate it. Some of these techniques are presented and briefly discussed.
Finite-/fixed-time synchronization of delayed Clifford-valued recurrent neural networks
Authors: Boonsatit N. , Rajchakit G. , Sriraman R. , Lim C. P. , Agarwal P. 
Published: June 2021

AbstractThis paper investigates the problem of finite-/fixed-time synchronization for Clifford-valued recurrent neural networks with time-varying delays. The considered Clifford-valued drive and response system models are firstly decomposed into real-valued drive and response system models in order to overcome the difficulty of the noncommutativity of the multiplication of Clifford numbers. Then, suitable time-delayed feedback controllers are devised to investigate the synchronization problem in finite-/fixed-time of error system. On the basis of new Lyapunov–Krasovskii functional and new computational techniques, finite-/fixed-time synchronization criteria are formulated for the corresponding real-valued drive and response system models. Two numerical examples demonstrate the effectiveness of the theoretical results.
The formation mechanism of acute dissection of blood blister-like aneurysm and its implication of endovascular treatment
Authors: Ye Zhongyin , Lv Xianli 
Published: June 2021

Abstract
Background
Acute mural dissection of the anterior wall of the internal carotid artery which may contribute to the development of blood blister-like aneurysms (BBLAs) was postulated, and stenting or flow diversion treatment across the soi-disant aneurysm was reported in this study.

Methods
From December 2016 to December 2018, 8 patients presenting with subarachnoid hemorrhage (SAH) due to BBLA were subjected to endovascular treatment with stent-assisted coiling. Clinical outcomes were evaluated using a clinical outcome score scale.

Results
Based on angiograms, pathologic change involving the supraclinoid segments of the internal carotid artery (ICA) adjacent to BBLA was found in all patients. This pathologic change meant a focal dissection of the supraclinoid segment of the ICA which constituted the pathogenesis of BBLAs. Closed-cell, open-cell, and braided stents were used in 1, 1, and 6 patients, respectively. Complete obliteration was achieved following endovascular treatment among all 8 patients harboring BBLA. One re-bleeding successive to a closed-cell stent across the aneurysmal neck was observed. Follow-up angiograms revealed stable complete exclusion of all BBLAs from the parent vessel at 3 to 8 months. All patients had a favorable clinical outcome score of 0–1.

Conclusions
Acute dissection of a focal point of the intracranial vessels underlies the development of BBLAs. Open-cell and braided-cell stent-assisted coiling may constitute appropriate treatment due to good apposition against the vascular walls. Adjunctive coils may facilitate immediate complete occlusion of BBLAs.