bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Thioredoxin‐interacting Protein in Diabetic Myocardial Ischemia‐Reperfusion Injury
Authors: Ye Xiaodong , Cai Yin , Zhang Dengwen , Wang Sheng , Liu Danyong , Irwin Michael Garnet , Xia Zhengyuan 
Published: April 2020

BackgroundMyocardial ischemia‐reperfusion injury is a major threat to human health, causing great cardiac morbidity and mortality worldwide. Yet, it’s even more severe among diabetic patients. Thioredoxin‐interacting protein (TXNIP), a critical regulator with its inhibitory effect against antioxidation, is a novel target during myocardial ischemia‐reperfusion injury. TXNIP is also found to be highly expressed in hyperglycemic conditions, but its role in diabetic myocardial ischemia‐reperfusion injury is unclear. The current research aimed to study the role of TXNIP in myocardial ischemia‐reperfusion injury in diabetes mellitus.MethodsDiabetes was induced by streptozotocin injection via tail vein (65mg/kg) in Sprague‐Dawley rats. In vivo model of myocardial ischemia‐reperfusion injury was established as 30 minutes occlusion of the left anterior descending coronary artery and then 2 hours of reperfusion. In vitro hypoxia/re‐oxygenation (H/R) model was established as 6 hours of hypoxia and 12 hours of re‐oxygenation of H9C2 cells. Also, glucose was added to the medium at a concentration of 33 mmol/L to mimic the condition of diabetes. TXNIP small interference RNA (siRNA) was introduced to knock down the expression of TXNIP.ResultsThe expression of TXNIP significantly increased in the diabetic rat group, together with much greater infarct size and higher release of CK‐MB after myocardial ischemia‐reperfusion injury, compared to non‐diabetic group. In vitro study showed that TXNIP expression was significantly higher in high glucose (HG) group with greater cell injury and much higher LDH release after H/R treatment, compared to normal glucose (NG) group. However, TXNIP knock‐down via siRNA could alleviate this cellular injury with lower LDH release and higher cell viability. The expression of cleaved caspase‐3 significantly decreased even after H/R treatment in the TXNIP knock‐down group. Also, down‐regulation of NF‐kB and less phosphorylation of IkBα were detected after H/R in the TXNIP knock‐down group. Further study found higher conversion of LC3II from LC3I and lower expression of p62, indicating the activation of autophagy via TXNIP knock‐down. Finally, quantitative polymerase chain reaction test revealed significantly lower gene expression of TNF‐α and IL‐6.ConclusionTXNIP is highly expressed in diabetes after myocardial ischemia‐reperfusion injury. TXNIP knock‐down can alleviate myocardial ischemia‐reperfusion injury, possibly via activating autophagy and also via inhibiting inflammation. It is reasonable to believe that TXNIP would be a potential target for the treatment of diabetic myocardial ischemia‐reperfusion injury.Support or Funding InformationSupported by RGC (17118619) and NSFC (81970247)
H2S Photosystems in the Treatment of Glioblastoma
Authors: Esposito Emanuela , Campolo Michela , Paterniti Irene , Lanza Marika , Filippone Alessia , Casili Giovanna , Conoci Sabrina , Cuzzocrea Salvatore 
Published: April 2020

Glioblastoma multiforme (GBM) is the most frequent and deadly primary malignant central nervous system (CNS) tumour in adults. GBM is usually treated through the reduction of tumour mass and cerebral decompression, together with radiotherapy and chemotherapy, which improve the quality of life of the subject and prolong its survival. Treatment remains challenging, as GBM inevitably re‐emerges despite surgical debulking, radiotherapy and chemotherapy. Therefore, the discovery of effective therapy for GBM is an area of interest. Photothermal therapy (PTT) is a newly developed and encouraging therapeutic strategy, in treating cancer. Gold nanorods (AuNRs) are ideal nanomaterials for PTT applications both in vitro and in vivo. There is a reasonable body of evidence suggesting that endogenous H2S production is important for the growth and proliferation of colon and ovarian cancer. A limited number of studies are available in CNS cancer. Photoresponsive systems that delivers H2S on demand were used to treat glioblastoma to design and generate compounds based on photo‐thermal release of H2S that act as anti‐cancer therapy for glioblastoma. AuNRDs were prepared by a modified procedure based on the seed assisted method. These systems were tailored with a thiolate spacer appendages to permit the covalently link to the AuNRDs surface. The dual H2S photoactive‐systems were characterized by electronic microscopy methods, optical absorption, and emission techniques. Photocontrolled H2S‐based therapies were tested on GBM cell lines U87, A172, U138, LN‐18, T98G, U118‐MG. Measurement of H2S relase, Cell Cycle Analysis, Comet assay, determination of intracellular ROS, and apoptotic pathways were performed. Moreover, xenograft and orthotopic model were used to demonstrated the effect of dual H2S photoactive‐systems on tumour volume and weight, neoangiogenesis, tissue invasion. Animals were also subjected to magnetic resonance imaging. Photocontrolled H2S‐based therapies could emerge as new unconventional treatment modalities that complement better‐known photodynamic and photothermal therapies. Nanosystems carrying chemotherapeutic drugs or as mediators of alternative therapies offer several advantages over the standard dosing forms in the treatment of GBM.Support or Funding Informationno funding
Exercise Decreases Estrogen Receptor β and Inflammatory Cytokines in the Mesenteric Fat of an Endometriosis Rat Model
Authors: Del Mar Méndez-Casillas María , Cruz Myrella L. , Velazquez-Cruz Johnathan , Chompre Gladys , Appleyard Caroline B. 
Published: April 2020

Endometriosis, a gynecological disorder, is characterized by increased levels of the estrogen receptor β (ERβ) in endometrial tissue. Estrogen receptors (ER) are also present in visceral fat and dysregulation of their function is known to correlate with increased white adipose tissue. Preliminary data in our lab found increased mesenteric fat and serum leptin levels in endometriosis animals, which are decreased by exercise. In rodents, morphology of the mesenteric fat can be regulated by exercise, however it is still unclear what role exercise plays in this change and how it might impact inflammatory conditions such as endometriosis.HypothesisVoluntary exercise can decrease endometriosis through modulation of ER in the mesenteric fat and a decrease in inflammatory cytokines.MethodsEndometriosis (ENDO) was induced in female Sprague Dawley rats by the implantation of uterine tissue next to the intestinal mesentery while control group (SHAM) received only sutures. The exercised endometriosis group (ENDO‐Ex) had access to a running wheel before and after surgery. After sixty days, rats were sacrificed and mesenteric fat was collected for measurement of ERβ, ERα, interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6) by RT‐PCR. After fixation and staining with hematoxylin & eosin micro‐sections of mesenteric fat were analyzed to ascertain adipocyte morphology and their number and size.ResultsThe Endo animals had significantly higher amounts of mesenteric fat in contrast with the SHAM (p<0.05) and the ENDO‐Ex animals (p<0.01; n=9–10/group). The serum leptin hormone levels were significantly decreased in ENDO‐Ex animals when compared with the SHAM (p<0.001) and ENDO (p<0.001) animals. Across all groups a significant correlation was found between percentage of fat/body weight and ER‐β (p=0.011; n=12). Increased mesenteric fat also correlated with increased levels of IL‐1β (p=0.024) and IL‐6 (p=0.030) in the endometriosis animals (n=4/group). ENDO‐Ex animals developed less endometriotic lesions and these were smaller in size. Exercise significantly decreased ERβ levels (p=0.045) and IL‐1β (p=0.008, n=4/group) compared with ENDO. No significant differences were found in ERα levels between groups.ConclusionOur results demonstrate that exercise can reverse the increased levels of mesenteric fat, ERβ and inflammatory cytokines found in an animal model of endometriosis.Support or Funding InformationP20GM103475‐16, R15AT009915 & R25GM096955
Features of Stable Plaque Phenotype Are Increased by Macrophage Specific Insulin‐Like Growth Factor 1
Authors: Snarski Patricia , Danchuk Svitlana , Sukhanov Sergiy , Yoshida Tadashi , Higashi Yusuke , Shai Shaw-Yung , Chandrasekar Bysani , Delafontaine Patrice 
Published: April 2020

Insulin‐like growth factor I (IGF‐1) reduces atherosclerosis in Apoe‐null mice and promotes stable plaque phenotype. We reported that deficiency for macrophage (MF)‐specific IGF‐1 receptor upregulated matrix metalloproteinases (MMPs) and promoted atherogenesis. To test whether MF‐specific IGF‐1 will suppress MMPs, decrease atherosclerosis, and change plaque stability, we generated Apoe‐null mice with IGF‐1 overexpression driven by MF‐specific promoter (scavenger receptor A) (SRA12 and SRA17 mice). IGF‐1 level was increased in peritoneal MF isolated from SRA12 (21±4% increase) and from SRA17 mice (52±9% increase) compared to control Apoe‐null mice (both P<0.05). SRA12 and SRA17 mice were fed with a high fat diet for 12 weeks. MF‐specific IGF‐1 overexpression significantly decreased atherosclerotic burden (SRA12, 23±3% decrease, n=20, and SRA17, 28±6% decrease, n=16, vs. control, n=29, en face analysis) and increased plaque collagen levels (11.1±6%, SRA12 and 66.5±11%, n=11, SRA17, Trichrome). Atherosclerotic plaques in both SRA12 and SRA17 mice had reduced necrotic cores suggesting elevated plaque stability. Increased levels of plaque collagen in SRA17 mice correlated with a significant decrease of MMP1, MMP2, MMP8, MMP12, MMP13, and MMP14 protein levels in peritoneal MF (immunoblotting, 30–72% decrease vs. control). To assess monocyte recruitment into the plaque, macrophage‐cleavable fluorescent red beads were injected (IV). Plaques in both SRA12 and SRA17 mice have reduced number of red beads compared to Apoe‐null mice (77±2% decrease, p=0.027, 74±3% decrease, p=0.0592, respectively) suggesting decreased monocyte recruitment. Cutlured human THP‐1 MFs were incubated with IGF‐1 (0, 20, 100ng/mL) for 48 hrs. IGF‐1 (20ng/ml) decreased expression of MMP8 (34±13% decrease, P<0.05) and MMP14 protein (35±17% decrease, P<0.05) (ELISA). To demonstrate that downregulation of MMPs was mediated via IGF1R‐dependent mechanism, we used Picropodophyllin (PPP), a specific IGF1R inhibitor. MF pre‐treatment with PPP (1ug/ml, 2hrs) abolished IGF‐1‐induced MMP8 downregulation in MF. In summary, we show that IGF‐1 reduced MMPs in vitro and MF IGF‐1 decreased MMPs, upregulated collagen and suppressed atherosclerotic burden in vivo. We identified the novel MMP‐dependent mechanism potentially mediating MF IGF‐1 atheroprotective effect by increasing features of stable plaque phenotype.Support or Funding InformationNIH/NHLBI 2R01HL070241‐13A1
Effect of a Medical Device containing Xyloglucan and Pea Protein on a Murine Model of Atopical Dermatitis.
Authors: Campolo Michela , Paterniti Irene , Casili Giovanna , Filippone Alessia , lanza Marika , Ardizzone Alessio , Cuzzocrea Salvatore , Esposito Emanuela 
Published: April 2020

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin, characterized by intense itching and dry skin. The etiology of AD is complex and has not been fully clarified, involving genetic susceptibility, immunological dysfunction, epidermal barrier and environmental factors. Xyloglucan (XG) and pea protein (PP) are two compounds of natural origin characterized respectively by a physical barrier creation that protects mucosal tissues reducing inflammation. The aim of the present study was to evaluate the potential beneficial effects of XG + PP in a mouse models of AD and S. aureus infection‐ associated AD.Mice were topically treated with 200 μl of 0.5% oxazolone on the dorsal skin three times a week for AD induction. Mice received XG and PP by topical administration, 1 hour before oxazolone treatment. In experiment of S. aureus infection‐ associated AD, to induce superficial superinfection of the skin, mice were also treated with 5 μl of 108 of a culture of S. aureus for 2 weeks; mice superinfected received XG and PP by topical administration 1 hour before oxazolone + S. aureus. Following 4 weeks, the skin was removed for histological and biochemical analysis. Our results clearly demonstrated the protective barrier effect of XG and PP characterized by a reduction in histological tissue changes induced‐AD, mastocyte degranulation and tight junction permeability in the skin following oxazolone treatment. Moreover, XG+PP was able to reduce filaggrin expression, a hallmark of AD. Our data also support the effectiveness of XG+PP to reduce the damage by superinfection post AD induced by s. aureus. In conclusion, the medical device containing XG and PP could be considered an ideal approach for the treatment of AD.
Long‐term gastrointestinal motility disruption in a mouse Gulf War Illness model treated with palmitoylethanolamide
Authors: Hernandez-Rivera Siomara , Grubišić Vladimir , Fried David , Isufi Kenny , Gulbransen Brian D 
Published: April 2020

Gulf War Illness (GWI) is a chronic disorder characterized by a spectrum of six symptoms that include gastrointestinal (GI) disorders. Exposure to the anti‐nerve gas drug pyridostigmine bromide (PB) is linked with the development of GWI, but the exact mechanisms remain unclear. Our prior data show that PB exposure contributes to long‐lasting pathophysiology by driving enteric neuroinflammation, promoting immunosuppression, and altering physiological function of the colon. Here, we tested the hypothesis that palmitoylethanolamide (PEA), an endogenous anti‐inflammatory mediator, is sufficient to reduce the detrimental effects of PB in the gut and brain of mice. We tested the effects of PB in vivo by exposing male and female mice to 90 μg/mL PB for 7 days and assessing gut function using in vivo and ex vivo tests of colonic motility and barrier function for 5 months. After 2 months of treatment mice were treated with 0.07 mg/mL of PEA. Immune responses were studied using multiplex cytokine and chemokine arrays in the gut and brain. Male, but not female, mice exposed to PB gained less weight during exposure of PEA (4%, p<0.05). Regardless of sex, exposure to PEA cause a decrease in fecal pellet output (male 66.5%, p<0.01; female 66.1%, p<0.05) and fecal fluid content (male 29.3%, p<0.01; female 23.7%, p<0.05). The combination of PB and PEA treatment altered neuromuscular control and slowed colonic bead expulsion (577.7%, p<0.001) in male mice, but only PB treatment caused slower expulsion in females (777.7%, p<0.001). Colonic permeability was not altered in male mice, but females treated with PEA trended towards increased permeability (39.1%, p=0.0534). Exposure to PEA caused major shifts in the expression of pro‐inflammatory cytokines and chemokines in the colon and brain. Interestingly, immune disruption was still evident in the colon and brain of male and female animals at 2 months following exposure to PEA. Our results show that PEA alters the functional anatomy of the colon and promotes immune disruption in a sex dependent manner and provides no tangible benefit for neuroimmune disruptions driven by PB.Support or Funding InformationDepartment of Defense (DOD) W81XWH1610631
Neuronal Deletion of Ghrelin Receptor Attenuates Aging‐Associated Insulin Resistance and Cognitive Decline
Authors: Wu Chia-Shan , Ji Pengfei , Liu Yan , Sun Yuxiang 
Published: April 2020

The aging process is characterized by a progressive decline of metabolic functions, insulin resistance, and cognitive impairment. We and others have reported that Growth Hormone Secretagogue Receptor (GHS‐R) plays a crucial role in metabolic regulation. GHS‐R is an endogenous G‐protein coupled receptor for the gut hormone ghrelin, and ghrelin signals the hypothalamus to increase feeding, decrease energy expenditure and reduce fat utilization. We previously reported that global GHS‐R deletion leads to a healthier metabolic profile compared to WT littermates in aging mice. We showed that ablation of GHS‐R ameliorates age‐associated metabolic impairments, reducing body weight/adiposity and improving insulin sensitivity during aging. Furthermore, we found that suppression of GHS‐R in neurons almost completely prevents diet‐induced obesity in mice (Syn1‐cre;Ghsrf/f), likely through increasing energy expenditure. Here, we further assessed metabolic and memory functions of 18–20 months‐old Syn1‐cre;Ghsrf/f and littermate Ghsrf/f control mice. Similar to young mice, old Syn1‐cre;Ghsrf/f mice showed reduced body weight and adiposity. Consistently, old Syn1‐cre;Ghsrf/f mice are more insulin sensitive than littermate controls. Interestingly, old Syn1‐cre;Ghsrf/f mice spent significantly more time exploring the novel object than the familiar object compared to controls in the novel object recognition test, at both 2 hours and 24 hours after training. These data suggest that old Syn1‐cre;Ghsrf/f mice retained short‐term and long‐term memory better than their littermate controls. In addition, old Syn1‐cre;Ghsrf/f mice exhibited significantly increased freezing behavior in both contextual and conditioned auditory stimulus tests in fear conditioning assay, indicating that old Syn1‐cre;Ghsrf/f mice retained better hippocampal‐dependent and amygdala‐dependent memory function compared to littermate controls. Overall, our data suggest that pan‐neuronal deletion of GHS‐R attenuates aging‐associated obesity, insulin resistance and memory impairment. The metabolic benefits derived from suppression of GHS‐R resemble the effects of calorie restriction, the most recognized strategy for increasing health span in multiple organisms. GHS‐R may provide a novel molecular target for improving metabolic fitness and cognitive function during aging.Support or Funding InformationWe gratefully acknowledges the support of NIH R56DK118334 (YS), NIA R01AG064869 (YS), and NIA R21AG061726 (CW).
Is the Bloom taxonomy level of student‐generated exam‐style questions predictive of exam performance?
Authors: Wisinski Jaclyn , Yu Alder 
Published: April 2020

Bloom’s taxonomy provides a learning framework distinguishing low cognitive level recall and understanding from more advanced levels of application and analysis. As undergraduate level instructors, we push students to advance in cognition as they progress though a bachelor’s degree. Rote memorization and savvy test taking strategies allow many students to be successful through the first semesters of college. However, advanced learning practice must be developed to facilitate student success. Though instructors make many study strategy suggestions based on empirical evidence, many students end up “figuring it out for themselves”. Student study strategies, such as completing instructor‐provided practice questions and making/using flashcards may enhance performance, but fail to engage students in identifying what the most important concepts are and how those concepts might be tested. To encourage students to actively participate in the learning process, Genetics (BIO306) and Cell Biology (BIO315) students were asked to write question related to the lecture material several times throughout the semester. BIO306 and BIO315 instructors score student‐written questions based on Bloom’s taxonomy, with the hypothesis that students who write higher cognitive level questions will perform better on exams. End of semester course evaluations assess the students’ perception of the question writing as a study technique. Unexpectedly, the cognitive level of student‐submitted questions did not correlate with exam scores. In the next phase of the project, BIO315 and BIO306 instructors will provide students with some information about Bloom’s taxonomy and levels of cognition prior to students’ submission of questions. It is hypothesized that this intervention will encourage students to submit higher cognitive level questions in an effort to improve study skill and exam performance. This self‐quizzing strategy is being developed for 300‐level biology courses, but the results have the potential to apply to many other disciplines at other levels of education.Support or Funding InformationUniversity of Wisconsin ‐ LaCrosse Faculty Development Scholarship of Teaching and Learning (SoTL) grant 2019
Nucleosome sliding, histone modifications, and the epigenetic regulation of the Simian Virus 40 life cycle
Authors: Milavetz Barry , Rowbotham Kincaid , Haugen Jacob , Diaz Alexandra Rios , Balakrishnan Lata 
Published: April 2020

We have recently shown that at late times in an SV40 infection a nucleosome containing modified histones is positioned over the enhancer region consistent with repression of early transcription and activation of late transcription. However, this nucleosome appears to slide toward the late region during virion formation consistent with a role in the activation of early transcription and repression of late transcription in a subsequent infection. Because the transcription factor SP1 plays a major role in regulating SV40 early and late transcription and its binding should be sensitive to nucleosome positioning, we measured the ability of HIS‐tagged SP1 to bind to various forms of SV40 chromatin in vitro and compared this to the presence of SP1 in SV40 chromatin derived in vivo. We found that HIS‐tagged SP1 bound well to chromatin from virions and very poorly to other forms of SV40 chromatin in vitro, while cellular SP1 was associated with minichromosomes isolated from infected cells and was not found in chromatin from virions. In order to determine whether the location of nucleosomes and associated histone modifications plays a role in the activation and continuation of early transcription during the initiation of an infection, we have mapped the location of RNAPII and nucleosomes containing a number of histone modifications in chromatin from virions and minichromosomes isolated 30 minutes and 2 hours post‐infection using ChIP‐Seq. During the first two hours of infection we found that RNAPII first associates with the miRNA site in the SV40 genome (at 30 minutes post‐infection) and then shifts to the early regulatory region around the enhancer (2 hours post‐infection). We next compared the location of RNAPII at the two time points to the location of nucleosomes carrying one of nine different specific histone modifications in the chromatin from virions, and minichromosomes isolated at these times. Chromatin from virions was used because it is the substrate for the activation of transcription, while chromatin from the minichromosomes would indicate any changes occurring as a consequence of transcriptional activation or extension. Based upon this rationale, we identified acetylated H3 as the most likely histone modification in SV40 predicting subsequent binding by RNAPII. We also identified acetylated H4 and the shifting of nucleosomes away from the RNAPII binding site as changes which result from activation of transcription. Together these results indicate that positioned nucleosomes carrying certain histone modifications may control accessibility of transcription factors and also serve as marks for either the binding of RNAPII during initiation of transcription or subsequent re‐initiation during active transcription.Support or Funding InformationNIH 1R03AI127969‐01NIH 1R03AI142011‐01