bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of cayenne pepper on hepatic gene expression involved in lipid metabolism in DSS treated rats fed an atherogenic diet (647.20)
Authors: Bloem Kyrié , Hong Mee Young 
Published: June 2021

Cardiovascular disease is the number one cause of morbidity and mortality in America. It is critical to understand the benefits of supplementing the diet with functional foods that may help in reducing risk factors for developing the disease. We have previously shown that a cayenne pepper diet improves the lipid profile in atherogenic diet fed rats and decreased C‐reactive protein level. The goal of this study is to determine the underlying mechanism of cayenne pepper on alteration of lipid profile and inflammation in DSS treated rats fed an atherogenic diet by analysis of hepatic gene expression using quantitative real time PCR. Forty male weanling (21 days old) Sprague‐Dawley rats were divided evenly into four groups (10/group, total N=40) in a 2 (diet) x 2 (treatment) factorial design using an atherogenic diet with or without cayenne pepper (2.9%) for 30 days, and with or without 3% Dextran sodium sulfate (DSS) inflammation inducing agent for 24 hours. Cayenne pepper‐fed rats had significantly down regulated fatty acid synthase (P=0.042), HMG CoA reductase (P=0.047), SREBP1 (P=0.045), SREBP2 (P=0.043), and RelA (P=0.035). Transcription of LDL‐receptor was significantly lower (P=0.017) in the cayenne pepper‐fed rats not treated with DSS. These findings demonstrate the use of cayenne pepper to beneficially augment gene expression of genes involved in lipid metabolism and inflammation and reduce the risk factors for CVD.Supported by SDSU UGP and NUTR 302L class.
The effect of defecate function in constipation by a 8‐week supplementation of Prunus mume fruit extract: a randomized double‐blind, placebo‐controlled trial (647.30)
Authors: Jung Eun Soo , Ha Ki Chan , Choi Eun Kyung , Jung Su Young , Na Ju Ryun , Lee Dong Wook , Kim Young Gon , Kim Sun Oh , Chae Soo Wan 
Published: June 2021

In our previous study, Prunus Mume Fruit Extract (PMFE) has laxative effects in animal model induced constipation by a low‐fibre diet. The purpose of this study was to investigate whether supplementation with PMFE could improve defecate function in human subjects with constipation.We conducted a double‐blind, randomized, placebo‐controlled trial. Patients consumed PMFE (7.2 g) or a placebo before consumption of a meal every morning and evening for 8 weeks. The effects of PMFE on colon transit time (CTT) and defecation function by questionnaire were evaluated in 28 patients and compared with the placebo group (n=29).Among CTT, no significant differences in right CTT, left CTT were observed between the two groups. However, a significant decrease rectosigmoid CTT and total CTT was observed in the PMFE group. Moreover, PMFE decreased abdominal pain during defecation and significant and increase refreshing feeling after evacuation compared with compared with the placebo group at the end of the study. No adverse effects were reported in any of the patients.Based on the results of this study, PMFE supplementation improved defecate function in human subjects with constipation. 2
Cardiac compensation for lack of trabeculae in ErbB2‐deficient zebrafish (648.3)
Authors: Fleming Nicole , Samsa Leigh Ann , Liu Jiandong 
Published: June 2021

Congenital heart disease (CHD) is one of the major causes of birth defects among infants in the United States. CHD can be characterized by malformations during heart development. Initially, the heart is a smooth, linear tube of cardiomyocytes lined with specialized endothelial cells. Following cardiac looping, the heart chambers undergo dramatic changes in chamber topology, most notably the formation of luminal, muscular protrusions called trabeculae. While altered trabeculation leads to severe cardiac defects, complete failure to form trabeculae results in embryonic lethality in human, mouse, chick, and zebrafish due to cardiovascular failure. We hypothesize that cardiac trabeculation is critical for cardiac function in the developing heart. Due to their external fertilization and genetic tractability, we use the zebrafish embryo to observe trabeculation. Zebrafish cardiac trabeculation requires both genetic and non‐genetic mediators: requiring input from the Neuregulin/ErbB2 signaling pathway and hemodynamic forces, respectively. To understand the cellular mechanism of progressive cardiac dysfunction in the absence of trabeculae, we inhibited ErbB2 signaling in the zebrafish model. Preliminary data indicates increased compact myocardial thickness (2.09 ± 0.19 μm in DMSO treated fish vs. 3.96 ± 0.35 μm in ErbB2‐inhibitor treated fish; p <0.05) and sarcomere length (1.30 ± 0.15 μm in DMSO treated fish vs. 1.92 ± 0.18 μm in ErbB2‐inhibitor treated fish; p <0.001), a phenotype reminiscent of pressure overload‐stimulated cardiac hypertrophy. This compensatory mechanism suggests that trabeculae may play a role in optimizing chamber topology for efficient cardiac function.Grant Funding Source: Supported by: Initiative for Maximizing Student Diversity (IMSD): 5R25GM055336 and BBSP
Clinical evaluation of heart failure: agreement among tests (648.4)
Authors: Pandey Amit , Penny William , Bhargava Valmik , Lai N. Chin , Hammond H. Kirk 
Published: June 2021

Congestive heart failure (CHF) is the most common cause of nonelective hospitalization of subjects over the age of 65 in the US. CHF clinical status is evaluated by ejection fraction (EF), symptoms, and exercise tolerance. Although difficult to apply clinically, a gold standard of left ventricular (LV) function is the rate of LV pressure development (+dP/dt). We tested the hypothesis that EF, symptoms, and exercise treadmill test (ETT) duration would correlate with each other and with +dP/dt. Subjects with symptomatic CHF (62 ± 2 yo; EF 30 ± 2%; n = 27) underwent measurement of EF, symptoms (Kansas City Cardiomyopathy Questionnaire Score, KCCQS), ETT duration, and +dP/dt (via cardiac catheterization). EF and +dP/dt were measured before and during dobutamine infusion. Results were compared using Pearson’s correlation analysis. Overall, tests correlated poorly. The only significant correlations were between KCCQS and +dP/dt. KCCQS correlated with both basal +dP/dt (r = ‐0.47, p = 0.021) and stimulated +dP/dt (r = ‐0.63, p < 0.001). KCCQS and stimulated +dP/dt were correlated regardless of ischemic (r = ‐0.69, p = 0.026) or non‐ischemic etiology (r = ‐0.56, p = 0.038).Conclusion: EF, ETT, and symptoms are not correlated in CHF patients. Using +dP/dt as a gold standard, EF and ETT do not correlate as well with LV function as symptoms do. EF and ETT may be less effective measures of LV function than commonly believed.Grant Funding Source: Supported by National Institutes of Health grants (P01 HL66941, HL088426, HL081741, and HL107200)
Gene network analysis of liver allografts preserved with machine perfusion (649.10)
Authors: Paranjpe Shirish , Fontes Paulo , Vodovotz Yoram , Michalopoulos George 
Published: June 2021

Machine perfusion (MP) with a cell‐free oxygen carrier solution (CFOCS) was compared to cold static preservation (CSP) in a porcine model. Methods: Two groups of 6 animals underwent liver transplantation after 9 hours of cold ischemia time. Clinical and laboratorial data was obtained in additional to serial histological and electron microscopy analysis. Affymetrix gene‐arrays were performed on liver tissues from both groups. A cytokine profile was obtained from liver tissues and perfusate with Luminex. Additional metabolomics analysis (Metabolon) was performed. Results: The MP group had 100% survival and the CSP group had 33% survival. A significant (p<0.004) benefit of MP was detected after 16 different variables were analyzed. Over‐expression of genes associated with general metabolic functions, anti‐inflammatory, regenerative and protective mechanisms against free radicals were observed in the MP group. Genes associated with hepatic system development and cellular proliferation were significantly up‐regulated in the MP group. Genes associated with critical metabolic networks were significantly down regulated in the CSP group compared to MP livers. The lipid metabolic pathway was up regulated in the CSP group. Signaling pathways that are critical for liver growth (NF‐kB, PI3K/AT, ErbB) were significantly up‐regulated in MP liver samples when compared to CSP group. INF‐α, IL‐1β, IL‐1RA, IL‐4, IL‐10, IL‐12p40, IL‐18 and TNF‐α showed significant differences between the groups in liver tissues analyzed during preservation. Ingenuity® pathway analysis of functional groups revealed that genes associated with liver damage were significantly down regulated in the MP group. The CSP group showed significant up‐regulation of genes associated with liver pathology when compared to the MP group. Conclusions: MP with a CFOCS up‐regulated a regenerative and prosurvival response when compared to CSP.Grant Funding Source: NIH GrantNo.CA35373,CA103958 & Rangos Fund for Enhancement of Researchin Pathology.
T3 receptor‐beta agonists GC‐1 (Sobetirome) and KB2115 (Eprotirome) stimulate hepatocyte proliferation in mice (649.5)
Authors: Feliciano Tamara , Monga Satdarshan 
Published: June 2021

T3 hormone is known to be a strong inducer of hepatocyte proliferation in rats and mice. Recent work has shown that the molecular mechanism for this may be Protein Kinase A‐dependent activation of the β‐Catenin signaling pathway. This finding has shed light on the potential therapeutic use of thyroid hormone in select cases of liver failure. However, systemic side effects of T3 may preclude its clinical use. GC‐1 and KB2115 are T3 hormone analogs that bind selectively to the T3 hormone β‐receptor and do not seem to produce the undesirable cardiovascular effects. We investigate whether GC‐1 and KB2115 are able to induce proliferation in mouse hepatocytes. Nine C57/BL6 2‐month old male mice received eight daily intraperitoneal injections with GC‐1, KB2115, or DMSO (control) at 0.3mg/Kg body weight. Livers from mice injected with GC‐1 and KB2115 showed increased levels of Cyclin D‐1 on Western Blot compared with controls. We also saw an increase in Beta‐Catenin, Cyclin D‐1, and Ki‐67 by immunohistochemistry, without significant difference in serum biochemistry. This suggests that selective thyromimetics are likely activating β‐Catenin signaling pathway in a similar manner to T3 hormone, and with further study may prove useful as an adjunct therapeutic option in select cases of liver failure.Grant Funding Source: 1RO1DK62277 to SPM
Necrotizing enterocolitis leads to increased intestinal permeability mediated through differential expression of tight junction proteins (650.7)
Authors: Ravisankar Srikanth Sankar , Tatum Rodney , Garg Parvesh , Shekhawat Prem , Chen Yan‐Hua 
Published: June 2021

Necrotizing enterocolitis (NEC) is a devastating disease with a prevalence of 7% in premature neonates weighing <1500 grams and an estimated death rate of 20‐30%. The precise etiology remains unknown and it is believed to be caused by a disturbance in the delicate balance of multiple pathophysiological factors. In this study, 4‐day old C57BL/6 mice pups were fed 50 µl of 33% Esbilac formula every 3 hours, asphyxiated twice daily (100% N2 for 60 sec) followed by cold stress at 4°C for 10 min to induce NEC and study the tight junction (TJ) proteins. Dam‐fed pups from the same litter served as controls. Histopathology results revealed successful induction of NEC up to grade 2, where sloughing of the epithelial cells at the tips of the villi with mild villous necrosis was seen. Western blot showed decreased expression of claudin‐1 and an increased expression of claudin‐7 in the NEC intestines compared to control pups. The TJ permeability assay was performed by injecting biotin tracer into the lumen of the small intestine of both control and NEC pups. Biotin tracer diffused easily through the intercellular space of intestinal epithelial cells in NEC mice, suggesting loss of integrity of the TJ barrier function. We conclude that there is disruption of TJs mediated through differential regulation of TJ proteins in our NEC mouse model.Grant Funding Source: NIH
Matching the mechanical properties of the brain: histological performance of soft elastomeric wires designed for use in neural interface devices (651.15)
Authors: Kolarcik Christi , Hanner Jenna , Snyder Noah , Du Zhanhong , Sapp Shawn , Luebben Silvia , Cui X. 
Published: June 2021

A number of factors contribute to the failure of microelectrodes implanted into the central nervous system and designed for therapeutic purposes. We hypothesized that more closely matching the mechanical properties of the microelectrode to those of the brain in combination with biomolecule coatings would promote a lower inflammatory response and less scar tissue encapsulation. In vitro cell culture studies were used to evaluate novel elastomeric wires with Young’s modulus lower than 1 MPa; the L1 protein coating was compared to laminin‐coated and uncoated microelectrodes. In vivo work included characterization of the tissue response associated with microelectrode implantation into the subthalamic nucleus of rats (n = 4/group) at acute and chronic time points. Commercial tungsten microelectrodes with Young’s modulus of 411,000 MPa were used as a standard (stiff control). The in vitro results indicate that soft wires had greater neuronal but less astrocyte and microglial attachment than stiff wires. Additional benefits were noted with the L1 protein coating. In vivo histological assessment indicates the superior performance of soft wires with the L1 protein coating: increased neuronal density (NF200 staining), decreased microglial presence (Iba1 staining), decreased astrocyte activation (GFAP staining) and decreased neuronal cell death (NeuN/Caspase‐3 colocalization) when compared to control stiff wires either with or without L1 coating and to soft wires without L1. This work contributes to evidence supporting the use of soft microelectrodes and the L1 protein coating.Grant Funding Source: Supported by DARPA Contract W31P4Q‐11‐C‐0134.
Double‐edged effect of early reperfusion on arrhythmias and death after transient coronary artery occlusion in the rat (652.16)
Authors: Liao Kate , Hong Daphne , Chen Kuen‐Bao , Kuo Eva , Lai Ted 
Published: June 2021

Reperfusion of blood supply following a sustained period of ischemia can be injurious to the heart. Here, we monitored cardiac reperfusion in rats subjected to 10 min of wide‐area coronary artery occlusion (CAO) by injecting them with the Evans blue dye, a visible inert tracer. The rats were then divided into three groups depending on their rate of reperfusion. Group 1 consisted of rats that showed no signs of early reperfusion within the 10 min period of ischemia, and these rats demonstrated a moderate rate of sudden cardiac death within the ischemic period. Group 2 included rats that showed early signs of reperfusion, and these rats demonstrated a higher rate of cardiac death than those in Group 1. Rats in Group 3 had poor ligation such that they sustained partial reperfusion almost immediately post‐CAO, yet surprisingly, this group demonstrated highest rate of cardiac death during the ischemic period. In contrast to mortality during the ischemic period, rats that survived the first 10 min of ischemia then received ligation‐removal and thus full‐blown reperfusion. Interestingly, surviving rats from Group 3 now has best chance of continued survival post‐reperfusion, whereas rats from Group 2 had poor survival rate and no rats from Group 1 survived reperfusion. To better understand the pre‐conditioning effect of early reperfusion on full‐reperfusion‐mediated sudden cardiac death, we challenged rats to 5 min of small‐area CAO. This model produced 100% survival rate during the ischemic period, and therefore all rats survived to receive full‐reperfusion. In this model, rats from Group 1 demonstrated highest rate of sudden cardiac death after full‐reperfusion, whereas rats from Group 2 demonstrated higher rate of survival and all rats from Group 3 survived reperfusion. Taken together, early reperfusion of blood supply may induce sudden death of the ischemic heart, but if the heart survived this earlier attack, it becomes more resistant to full‐reperfusion‐mediated sudden cardiac death.Grant Funding Source: Supported by the National Science Council of Taiwan
Mortality in patients in providing emergency medical care at a pre‐hospital stage (652.18)
Authors: Dubitsky A. , Karp L. 
Published: June 2021

Introduction. Providing of emergency medical care to the patients in the pre‐hospital phase has a great importance in medicine.Material. The analysis was made of the calls of Astana city ambulance teams to patients who have been pronounced dead in the presence of doctors from 2006 to 2012. In total, 1002 cases were registered.Results. By nosology the patients were distributed as follows: acute coronary pathology (69.7%), strokes (12.7%), pulmonary arterial thromboembolism (6.0%), asthma status (2.8%), infectious‐toxic shock (2.2%) and other diseases (6.6%). In 137 cases, the pain was assessed as “very severe”, in 88 ‐ as “severe”. Acute cardiovascular insufficiency of 2nd and 3rd degree according to Killip was observed in 132 patients.115 patients had baseline sinus tachycardia, other arrhythmias were in 19 patients.60 patients were observed with a violation of A‐V conduction (1st degree A‐V block ‐ 39 cases, 2nd degree A‐V block of Mobits II type ‐ 4 cases and 3rd degree A‐V block ‐ 17 cases). Myocardial infarction was localized in anterior wall in 141 patient and in 87 patients ‐ in the rear wall. Right ventricular myocardial infarction was in 3 patients. Pathologic Q wave on the electrocardiograms was formed in 139 patients.The rise of ST interval above contour line for more than 5 mm was observed in 186 patients.16 patients were detected with the prolongation of QT interval above normal, calculated by Bazett formula.
Enhanced oxidative stress/DAPK3/Akt/ERK signaling accounts for estrogen exacerbation of cardiac dysfunction caused by ethanol in male rats (652.20)
Authors: El‐Mas Mahmoud , Abdel‐Rahman Abdel 
Published: June 2021

We have previously shown that acute ethanol reduces blood pressure (BP) and cardiac output in female, but not in male, rats. Because these effects of ethanol were estrogen (E2)‐dependent, we investigated whether E2 treatment of male rats uncovers a hypotensive effect for ethanol, and whether left ventricular (LV) dysfunction, due to oxidative damage, contributes to the ethanol‐E2 hemodynamic interaction. The effect of ethanol (0.5, 1 or 1.5 g/kg; i.v.) on BP, LV function, and oxidative stress markers in male rats treated with E2 (1 μg/kg i.v.) or the vehicle were investigated. While ethanol had no effect on BP in vehicle‐treated rats, it caused dose‐related falls in BP in E2‐pretreated rats. This was associated with (i) compromised myocardial function as suggested by the reductions in LV developed pressure (LVDP), end diastolic pressure (LVEDP), and rate of rise in LV pressure (LV dP/dtmax), and (ii) oxidative damage as evidenced by the increases in LV generation of reactive oxygen species, protein expression of the malondialdehyde adducts, and phosphorylated death‐associated protein kinase‐3 (DAPK3), Akt, and ERK1/2. Together, E2 propagates LV dysfunction and hypotension in response to ethanol in male rats via facilitation of the myocardial oxidative stress/lipid peroxidation/DAPK3/Akt/ERK1/2 cascade. Because E2 was administered acutely, its effects are likely to involve rapid nongenomic mechanisms. Grant Funding Source: Supported by NIAAA [2R01 AA014441‐07].
The effect of ethanol on loperamide‐induced tolerance (653.15)
Authors: Khan Fayez , Stevens David , Scoggins Krista , Akbarali Hamid , Dewey William 
Published: June 2021

We have reported that the mechanism for the production of morphine tolerance differs in the brain and ileum. In more recent studies we have shown that ethanol reversed morphine antinociceptive tolerance in a dose dependent manner. Therefore we investigated the ability of ethanol to reverse the tolerance produced by chronic exposure to Loperamide, a peripherally selective μ‐opioid receptor agonist that inhibits gastrointestinal motility. Gastrointestinal transit was measured by intragastric gavage of a charcoal meal. In vehicle treated mice, the leading edge of charcoal after 30 min transits 74 ± 6 % (n=6) of the length of the ileum. When Loperamide (0.1‐10 mg/kg) was administered subcutaneously 15 minutes before charcoal meal gavage, it significantly and dose‐dependently inhibited gastrointestinal transit. Loperamide (30 mg/kg) given acutely inhibited intestinal transit by 75%. When this dose was administered subcutaneously twice daily for two days and again at 15 minutes before oral injection of the charcoal meal the inhibitory effect on gastrointestinal transit was reduced to 46% (n=6) inhibition; suggesting that tolerance to loperamide occurred. When Loperamide (30 mg/kg) was chronically administered subcutaneous twice daily for two days and on the third day, ethanol (1g/kg) was injected intraperitoneally 30 minutes before a loperamide (30 mg/kg) challenge dose, the inhibition was 47% (n=6) indicating that ethanol did not reverse the tolerance produced by loperamide. These data suggest that ethanol reverses opioid tolerance to central efffects but not to their effects on the ileum.Grant Funding Source: Supported by NIH DA024009 and ASPET SURF Award (FK)
Effect of HIV‐1 Tat on enteric neuropathogenesis (653.6)
Authors: Ngwainmbi Joy , De Dipanjana , El‐Hage Nazira , Fitting Sylvia , Dewey William , Hauser Kurt , Akbarali Hamid 
Published: June 2021

The gastrointestinal (GI) tract is a major target and reservoir of the HIV virus. Acute and chronic HIV infection induces a higher level of CD4 T cell depletion in the GI tract compared to peripheral blood and affects motility and digestion. Since the enteric nervous system regulates these processes, it may be a potential target of HIV infection. The majority of HIV effects are not achieved by lytic propagation of the virus but by viral proteins. HIV‐1 Tat, a regulatory protein between 86 to 101 amino acids is released by infected cells and together with other HIV proteins has been shown to modulate neuronal function in the central nervous system. However little is known about its effects on the GI tract. In this study, we examined the effects of Tat on single isolated enteric neurons and in isolated ileum tissue. At the cellular level, in whole cell patch clamp experiments, Tat increased enteric neuronal excitability both in Tat treated (n=20) and in ileum neurons isolated from mice expressing the tat gene (n=9) by a significant increase in number of action potentials evoked, decrease in rheobase (from 20pA to 10pA) and threshold potential (from ‐13.2mV to ‐16.1 mV). This increase was mediated by a leftward shift of the sodium channel activation curve (‐ 10mV decrease in V0.5 of activation) thereby increasing the steady state availability of sodium channels. Tat selectively increased the mRNA and protein expression of Nav1.7 and Nav1.8 isoforms of the sodium channel. In isolated ileum tissues, Tat elicited an inflammatory response which was observed by an up regulation of pro‐inflammatory cytokines and increased GI motility thereby contributing to the HIV mediated GI dysmotilities observed in HIV patientsGrant Funding Source: Supported by the National Institute of Health grants DK046367 and DA024009 and the VCU‐IMSD 541332