bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specifically Sized Hyaluronan (35 kDa) Prevents Ethanol‐Induced Disruption of Epithelial Tight Junctions Through a layilin‐Dependent Mechanism in Caco‐2 Cells
Authors: Bellos Damien A. , Sharma Dhara , McMullen Megan R. , Wat Jeanette , Saikia Paramananda , de la Motte Carol A. , Nagy Laura E. 
Published: June 2019

BackgroundSpecific‐sized species of the carbohydrate hyaluronan elicit a variety of cellular responses mediating tissue integrity and repair, as well as regulating inflammatory responses. Orally provided hyaluronan with an average molecular weight of 35 kDa (HA35) protects mice from short‐term ethanol (EtOH)‐induced liver injury. This protection was associated with maintenance of the colocalization of zonula occludens‐1 (ZO‐1) and occludin at tight junctions in the proximal colon. However, it is not known whether HA35 also protects other regions of the intestine or whether protection is due to a direct and/or indirect interaction of HA35 with the intestinal epithelium.MethodsFemale C57BL/6J mice were fed an EtOH containing diet or pair‐fed control diet (4 days) and treated with or without HA35 via daily gavage during the last 3 days of EtOH feeding. Intestinal morphology and tight junction integrity were assessed. Differentiated Caco‐2 cells were transfected or not with scrambled siRNA or siRNA targeting layilin, a hyaluronan receptor. Caco‐2 cells were treated with or without HA35 prior to challenge with EtOH. Localization of tight junction proteins, fluorescein isothiocyanate (FITC)‐dextran permeability, and transepithelial electrical resistance (TEER) were evaluated.ResultsWhile short‐term EtOH did not result in any apparent changes in the gross morphology of the intestine, colocalization of ZO‐1 and occludin at tight junctions was decreased in the proximal and distal colon. HA35 prevented these effects of EtOH. In differentiated Caco‐2 cells, EtOH decreased the localization of ZO‐1 and occludin at tight junctions and increased permeability of FITC‐dextran. At higher concentrations, EtOH also decreased TEER. Pretreatment with HA35 prevented these changes. When the hyaluronan receptor layilin was knocked down in Caco‐2 cells, HA35 no longer protected cells from EtOH‐induced loss of tight junctions.ConclusionsTaken together, these data indicate that HA35 interacts with layilin on intestinal epithelial cells and maintains intestinal tight junction integrity during short‐term EtOH exposure.
Alcohol Effects on Colon Epithelium are Time‐Dependent
Authors: Bishehsari Faraz , Zhang Lijuan , Voigt Robin M. , Maltby Natalie , Semsarieh Bita , Zorub Eyas , Shaikh Maliha , Wilber Sherry , Armstrong Andrew R. , Mirbagheri Seyed Sina , Preite Nailliw Z. , Song Peter , Stornetta Alessia , Balbo Silvia , Forsyth Christopher B. , Keshavarzian Ali 
Published: June 2019

BackgroundAlcohol intake increases the risk of developing colon cancer. Circadian disruption promotes alcohol's effect on colon carcinogenesis through unknown mechanisms. Alcohol's metabolites induce DNA damage, an early step in carcinogenesis. We assessed the effect of time of alcohol consumption on markers of tissue damage in the colonic epithelium.MethodsMice were treated by alcohol or phosphate‐buffered saline (PBS), at 4‐hour intervals for 3 days, and their colons were analyzed for (i) proliferation (Ki67) and antiapoptosis (Bcl‐2) markers, (ii) DNA damage (γ‐H2AX), and (iii) the major acetaldehyde (AcH)–DNA adduct, N2‐ethylidene‐dG. To model circadian disruption, mice were shifted once weekly for 12 h and then were sacrificed at 4‐hour intervals. Samples of mice with a dysfunctional molecular clock were analyzed. The dynamics of DNA damage repair from AcH treatment as well as role of xeroderma pigmentosum, complementation group A (XPA) in their repair were studied in vitro.ResultsProliferation and survival of colonic epithelium have daily rhythmicity. Alcohol induced colonic epithelium proliferation in a time‐dependent manner, with a stronger effect during the light/rest period. Alcohol‐associated DNA damage also occurred more when alcohol was given at light. Levels of DNA adduct did not vary by time, suggesting rather lower repair efficiency during the light versus dark. XPA gene expression, a key excision repair gene, was time‐dependent, peaking at the beginning of the dark. XPA knockout colon epithelial cells were inefficient in repair of the DNA damage induced by alcohol's metabolite.ConclusionsTime of day of alcohol intake may be an important determinant of colon tissue damage and carcinogenicity.
Reduced sensitivity to ethanol and excessive drinking in a mouse model of neuropathic pain
Authors: Bilbao Ainhoa , Leixner Sarah , Wei Shoupeng , Cantacorps Lídia , Valverde Olga , Spanagel Rainer 
Published: June 2019

AbstractThe co‐occurrence of chronic pain and alcohol use disorders (AUDs) involves complex interactions between genetic and neurophysiological aspects, and the research has reported mixed findings when they both co‐occur. There is also an indication of a gender‐dependent effect; males are more likely to use alcohol to cope with chronic pain problems than females. Recently, a new conceptualization has emerged, proposing that the negative affective component of pain drives and maintains alcohol‐related behaviors. We studied in a longitudinal fashion alterations in alcohol drinking patterns and pain thresholds in a mouse model of chronic neuropathic pain in a sex‐dependent manner. Following partial denervation (spared nerve injury [SNI]), stimulus‐evoked pain responses were measured before chronic alcohol consumption, during drinking, during a deprivation phase, and following an episode of excessive drinking. During the course of alcohol drinking, we observed pronounced sex differences in pain thresholds. Male mice showed a strong increase in pain thresholds, suggesting an analgesic effect induced by alcohol over time, an effect that was not observed in female mice. SNI mice did not differ from sham‐operated controls in baseline alcohol consumption. However, following a deprivation phase and the reintroduction of ethanol, male SNI mice but not female mice showed more pronounced excessive drinking than controls. Finally, we observed decreased central ethanol sensitivity in male SNI mice but not in females. Together with our finding, that ethanol is able to decrease a pain‐induced negative affective memory we come to following conclusion. We propose that a lower sensitivity to the intoxicating effects of alcohol together with the ability of alcohol to reduce the negative affective component of pain may explain the higher co‐occurrence of AUD in male chronic pain patients.
Multiple ventricular bands and the associated trabecula septomarginalis dextra in the right ventricle of the domestic dog (Canis familiaris)
Authors: Cope Lee Anne 
Published: June 2019

AbstractVentricular bands are strand‐like intraventricular structures extending between adjacent papillary muscles; a papillary muscle and the ventricular wall or the interventricular septum and ventricular wall. Examination of the domestic dog right ventricle documented six ventricular band types. Eighty‐five of the 89 examined hearts had at least one right ventricular band. In the current study, the right ventricle of the 85 dog hearts was re‐examined for more than one ventricular band type. Seven patterns of multiple different bands were identified in the 24 dog hearts. The patterns (i.e., combinations) of different ventricular bands were grouped into three categories. Category 1 had five different patterns of bands. Each pattern had two different band types. Category 2 had one combination of three different bands. Category 3 had one combination of four different bands. The presence of right ventricular bands around the trabecula septomarginalis dextra was also documented. All 24 dog hearts with multiple ventricular bands had a trabecula septomarginalis dextra. The main goal of this study was documentation of multiple right ventricular band patterns. A secondary goal was documentation of the combined presence of these bands and a trabecula septomarginalis dextra. In the dog, the ventricular bands and trabecula are both thin, strand‐like intraventricular structures with variable branching patterns before blending into the ventricular wall. The gross similarity of these structures and lack of information on their combined presence could precipitate their misidentification.
Price Deviation Supported by Arbitrage: Evidence from Family Business Groups
Authors: Kim Woojin , Wang Shu‐Feng 
Published: June 2019

AbstractThis paper examines how arbitrage may contribute to, rather than remove, temporary price deviation between two related securities. Based on a unique sample of stock‐for‐stock tender offers by a member firm for another member firm within Korean family business groups, we find that arbitrage opportunity exists in more than three quarters of the sample, which is consistent with Lamont and Thaler (2003). Outside investors’ tendering decisions and institutions’ short‐selling are consistent with exploiting potential arbitrage opportunities, but not large enough to eliminate them. The prices of the two securities tend to diverge leading up to the tender offer, which may be impacted by the controlling families. This deviation, reflected in the exchange ratio of the two securities, is more likely to be sustained when there is more short‐selling during the possible arbitrage period. Our results suggest that arbitrage may support temporary deviations in the relative prices of two related securities under certain circumstances.
Complications related to peri‐operative transoesophageal echocardiography – a one‐year prospective national audit by the Association of Cardiothoracic Anaesthesia and Critical Care
Authors: Ramalingam G. , Choi S.‐W. , Agarwal S. , Kunst G. , Gill R. , Fletcher S. N. , Klein A. A. ,   on behalf of the Association of Cardiothoracic Anaesthesia and Critical Care
Published: June 2019

SummaryPrevious studies on the safety of peri‐operative transoesophageal echocardiography seem to suggest a low rate of associated morbidity and mortality. That said, there has been a paucity of prospective multicentre studies in this important area of clinical practice. We carried out a one‐year prospective study in 2017, co‐ordinated by the Association of Cardiothoracic Anaesthesia and Critical Care, to determine the rate and severity of complications associated with peri‐operative transoesophageal echocardiography in anaesthetised cardiology and cardiac surgical patients. With the help of clinicians from 28 centres across the UK and Ireland, we recorded the total number of examinations conducted in anaesthetised patients during the study period. All major complications at each centre were prospectively reported and recorded. Of the 22,314 examinations, there were 17 patients diagnosed with a major complication which caused either palatal injury or gastro‐oesophageal disruption. This corresponds to an incidence of 0.08% (95%CI 0.05–0.13%) or approximately 1:1300 examinations. There were seven deaths reported during the study period which were directly attributed to these complications, corresponding to an incidence of 0.03% (95%CI 0.01–0.07%) or approximately 1:3000. These figures are higher than previously reported and suggest a high probability of death following the development of a complication (~40%). Most complications occurred in patients without known risk factors for transoesophageal echocardiography associated gastro‐oesophageal injury. We suggest clinicians and departments review their procedural guidelines, especially in relation to probe insertion techniques, together with the information communicated to patients when the risks and benefits of such examinations are discussed.
Robust inference for the stepped wedge design
Authors: Hughes James P. , Heagerty Patrick J. , Xia Fan , Ren Yuqi 
Published: June 2019

AbstractStepped wedge designed trials are a type of cluster‐randomized study in which the intervention is introduced to each cluster in a random order over time. This design is often used to assess the effect of a new intervention as it is rolled out across a series of clinics or communities. Based on a permutation argument, we derive a closed‐form expression for an estimate of the intervention effect, along with its standard error, for a stepped wedge design trial. We show that these estimates are robust to misspecification of both the mean and covariance structure of the underlying data‐generating mechanism, thereby providing a robust approach to inference for the intervention effect in stepped wedge designs. We use simulations to evaluate the type 1 error and power of the proposed estimate and to compare the performance of the proposed estimate to the optimal estimate when the correct model specification is known. The limitations, possible extensions, and open problems regarding the method are discussed.
SIRT3 deacetylase activity confers chemoresistance in AML via regulation of mitochondrial oxidative phosphorylation
Authors: Ma Jiao , Liu Bin , Yu Dan , Zuo Yong , Cai Rong , Yang Jianmin , Cheng Jinke 
Published: June 2019

SummaryAcute myeloid leukaemia (AML) cells possess metabolism profiles, such as higher rates of oxidative phosphorylation and dependence on fatty acid oxidation for survival, and are dependent on the sophisticated regulation of reactive oxygen species (ROS) generation for survival, drug resistance and stemness maintenance. We found that sensitivity of primary AML cells to cytarabine correlated with SOD2 acetylation and the ability of the drug to induce mitochondrial ROS. The SOD2 deacetylase, SIRT3, protected AML cells from chemotherapy as shown by inhibited apoptosis via inhibited drug‐induced production of mitochondrial ROS. SIRT3 significantly decreased nicotinamide adenine dinucleotide phosphate (NADP)/reduced NADP ratio and increased reduced glutathione/oxidized glutathione ratio. Furthermore, SIRT3 enhanced oxidative phosphorylation (OxPhos) in AML cells under both basic and cytarabine‐treated conditions. A xenograft mouse model showed that SIRT3 overexpressing AML cells and patient‐derived xenograft mice bearing high SIRT3 deacetylase activity were more resistant to chemotherapy in vivo. SIRT3 inhibitor displayed synergy with cytarabine to ablate AML cells in vitro and in mouse models. Taken together, our study showed that SIRT3 is capable of reprograming mitochondrial metabolism towards OxPhos and downregulating ROS generation, which contribute to the chemoresistance of AML cells. SIRT3 can be utilized as a potential therapeutic target to improve the anti‐leukaemic efficacy of standard chemotherapeutic agents for AML.
Inhibitors of class I histone deacetylases attenuate thioacetamide‐induced liver fibrosis in mice by suppressing hepatic type 2 inflammation
Authors: Loh Zhixuan , Fitzsimmons Rebecca L. , Reid Robert C. , Ramnath Divya , Clouston Andrew , Gupta Praveer K. , Irvine Katharine M. , Powell Elizabeth E. , Schroder Kate , Stow Jennifer L. , Sweet Matthew J. , Fairlie David P. , Iyer Abishek 
Published: June 2019

Background and PurposeChronic liver diseases feature excessive collagen and matrix protein deposition or crosslinking that characterises fibrosis, leads to scar tissue, and disrupts liver functions. There is no effective treatment. This study investigated whether treatment with selective histone deacetylase (HDAC) inhibitors might specifically reduce type 2 inflammation in the injured liver, thereby attenuating fibrogenesis in mice.Experimental ApproachThioacetamide (TAA) was used to induce hepatic inflammation, fibrosis, and liver damage in female C57BL/6 mice, similar to the clinical features of chronic human liver disease. We used eight inhibitors of different human HDAC enzymes to probe histological (IHC and TUNEL), biochemical and immunological changes (flow cytometry, qPCR, Legendplex, and ELISA) in pathology, fibrosis, hepatic immune cell flux, and inflammatory cytokine expression.Key ResultsInhibitors of class I, but not class II, HDAC enzymes potently suppressed chronic hepatic inflammation and fibrosis in mice, attenuating accumulation and activation of IL‐33‐dependent, but not IL‐25‐dependent, group 2 innate lymphoid cells (ILC2) and inhibiting type 2 inflammation that drives hepatic stellate cells to secrete excessive collagen and matrix proteins.Conclusions and ImplicationsThe results show that potent and selective inhibitors of class I only HDAC enzymes profoundly inhibit hepatocyte death and type 2 inflammation to prevent TAA‐induced liver fibrosis in mice. The specific HDAC enzymes identified here may be key promoters of inflammation in chronic liver fibrosis.
Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T‐cell leukemia/lymphoma
Authors: Morichika Kazuho , Karube Kennosuke , Kayo Hirona , Uchino Shuta , Nishi Yukiko , Nakachi Sawako , Okamoto Shiki , Morishima Satoko , Ohshiro Kazuiku , Nakazato Iwao , Fukushima Takuya , Masuzaki Hiroaki 
Published: June 2019

AbstractAdult T‐cell leukemia/lymphoma (ATLL) is a mature T‐cell neoplasm, and is divided into 2 indolent (smoldering and chronic) and 2 aggressive (acute and lymphoma) clinical subtypes. Based on previous integrated molecular analyses suggesting the importance of the JAK‐STAT pathway in ATLL, we attempted to clarify the clinicopathological significance of this pathway. Clinical and morphological findings were reviewed in 116 cases with ATLL. The nuclear localizations of phosphorylated STAT3 (pSTAT3), pSTAT5, and pSTAT6 were analyzed by immunohistochemistry. Targeted sequencing was undertaken on the portion of STAT3 encoding the Src homology 2 domain. Expression of pSTAT3 was observed in 43% (50/116) of ATLL cases, whereas pSTAT5 and pSTAT6 were largely undetected. Cases with the lymphoma type showed significantly less frequent pSTAT3 expression (8/45, 18%) than those with the other subtypes (41/66, 62%; P < .001). STAT3 mutations were detected in 36% (10/28) and 19% (12/64) of cases with the smoldering and aggressive types of ATLL, respectively. The correlation between STAT3 mutation and pSTAT3 expression was not significant (P = .07). Both univariate and multivariate analysis revealed that pSTAT3 expression was significantly associated with better overall survival and progression‐free survival in the smoldering type of ATLL, whereas STAT3 mutation was not related to a line of clinical outcome. Collectively, our data show that only the lymphoma type showed a low prevalence of tumor cells positive for pSTAT3 expression, and raises the possibility that pSTAT3 expression is a novel biomarker to predict better prognosis in the smoldering type of ATLL.
Agreement among equine veterinarians and between equine veterinarians and inertial sensor system during clinical examination of hindlimb lameness in horses
Authors: Leelamankong P. , Estrada R. , Mählmann K. , Rungsri P. , Lischer C. 
Published: June 2019

SummaryBackgroundHindlimb lameness evaluation is known to be challenging. Experience is essential for the ability of equine veterinarians to detect lameness. Nevertheless, even an experienced veterinarian is still subject to bias. Objective lameness detecting methods have been established to aid veterinarians.Objectives1) To estimate the effect of experience on the interobserver agreement and the agreement between a body‐mounted inertial sensor system (BMISS) and veterinarians on detecting hindlimb lameness, and 2) to estimate the agreement between the BMISS and highly experienced veterinarians on change in lameness after diagnostic analgesia.Study designCross‐sectional study.MethodsTwenty‐six horses with hindlimb lameness were evaluated in clinical conditions by clinicians and simultaneously measured by the BMISS. Videos of their lameness examination were recorded and shown to 13 veterinarians from three groups of varying experience for evaluation. The interobserver agreement and the agreement between veterinarians and the BMISS were calculated.ResultsInterobserver agreement from all three groups was recorded as ‘fair’. The strength of agreement between veterinarians and BMISS was ‘fair’ for the highly experienced group, ‘slight to fair’ for the moderately experienced group and ‘slight’ in the inexperienced group. The BMISS and the highly experienced veterinarians declared a ‘strong’ agreement in assigning an improvement in lameness after diagnostic analgesia.Main limitationsLameness evaluation through video viewing might be more challenging for some evaluators than live situations.ConclusionsGiven the task of evaluating videos of horses trotting in a straight line, the more experienced veterinarians did not show more reliability than those with less experience. Due to 1) the moderate agreement between the BMISS and clinicians (highly experienced and moderately experienced) in the live clinical evaluation in determining hindlimb lameness, and 2) the strong association between the BMISS and highly experienced veterinarians in determining improvement of lameness after anaesthesia, therefore the use of the BMISS as a supporting tool for veterinarians is encouraged.
Evaluation of antitumor effects of aspirin and LGK974 drugs on cellular signaling pathways, cell cycle and apoptosis in colorectal cancer cell lines compared to oxaliplatin drug
Authors: Bagheri Malihe , Tabatabae Far Mohamad Amin , Mirzaei Hamed , Ghasemi Faezeh 
Published: June 2019

AbstractColorectal cancer (CRC) is one of the most common gastrointestinal malignancies. Despite recent advances in the treatment for CRC, resistance to chemotherapy drugs and recurrence of the tumor are among the main problems for treatment in this cancer. The MTT assay was performed to assess the cytotoxic effects of drugs on CRC cell lines (SW742 and SW480) and normal colon cells. Three‐dimensional culture (spheroid) was also used to evaluate the effect of drugs on tumor cell masses. The rate of expression of genes was also evaluated using Real‐Time PCR. The analysis of the results demonstrated that aspirin and LGK974 have cytotoxic effects on CRC cell lines, and in the IC50 dose, they disintegrate the cancerous cell masses. These drugs reduce the invasion and increase apoptosis in SW742 and SW480 cell lines. A decrease in the expression of WNT, AXIN, TCF and APC genes and an increase in the expression of β‐catenin gene in the WNT signaling pathway were revealed. The genes involved in the MAPK signaling pathway such as ERK, JNK, KRAS and MEK showed a decrease in expression and a increase in expression of RAF gene. In the apoptotic pathway, increased expression of BAX and decreased expression of BCL‐2 were reported. Also, decreased expression of P53, cyclin D1 and COX‐2 was observed. This study demonstrates that aspirin and LGK974 could be effective in inhibiting the signaling pathways of WNT and MAPK, arresting cell cycle and inducing apoptosis in CRC cell lines.