bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of cytokine activated NFkB and STAT1 pathways in impairment of insulin secretion by cachectic solid Ehrlich carcinoma‐bearing mice. (LB762)
Authors: Violato Natalia , Bosqueiro José Roberto 
Published: June 2021

The establishment of systemic inflammation seems to play a pivotal role in cancer cachexia progression, mainly by cytokine presence. However, there are no studies assessing the mechanisms responsible for the alterations in insulin secretion in cancer cachexia or correlating these alterations with inflammation in islet. Considering the importance of insulin secretion to metabolic homeostasis control, to identify mechanisms involved in this process in cachexia became important. Thus, in this study we propose to investigate the effects of the high cytokine levels present in cachectic syndrome in pancreatic islets function using solid Ehrlich carcinoma‐bearing mice and the participation of important inflammatory pathways, notably apoptotic pathways, searching for evidence that could indicate the involvement of islet inflammation in the diminished insulin secretion capacity exhibited by these animals. For that, pancreatic islets isolated from Swiss mice (CTL) and tumor‐bearing mice (SET) with 14 days of tumor inoculation were analyzed to evaluate the expression of proteins belonging to NFκB and STAT1 pathways. We analyzed proteins of IKK complex, JAK 1 and 2, STAT1, PUMA, FAS, c‐Myc, BAX, caspase 3 and 9, PDX‐1, and Bcl‐2. The results showed an increase in the expression of the pro‐apoptotic proteins BAX, c‐Myc, FAS, PUMA, caspase 3 and caspase 9. By the other hand, cachetic animals showed decreased expression of the anti‐apoptotic proteins Bcl‐2 and PDX‐1 indicating a possible increase of pancreatic islets apoptosis. These finds are very important in this scenario and will help us to clarify the mechanisms involved in diminished insulin secretion in cancer cachetic animals.Grant Funding Source: FAPESP
PI3K signaling pathway in leptin receptor expressing cells is not required for endotoxemia‐induced hypophagia (LB764)
Authors: Borges Beatriz , Garcia‐Galiano David , Elias Lucila , Elias Carol 
Published: June 2021

Hypophagia and increased energy expenditure under inflammatory conditions, such as that observed after bacterial lipopolysaccharide (LPS) administration, are associated with leptin secretion and stimulation of JAK2‐STAT3 signaling in the CNS. Anorexic effect of leptin also depends on the activation of PI3K signaling pathway. However, the role of PI3K in the endotoxemia‐induced anorexia remains an open question. To investigate if PI3K in leptin receptor expressing cells has a role in the hypophagia and body weight (BW) loss induced by acute endotoxin treatment, mice expressing Cre‐recombinase driven by Lepr promoter were crossed with mice with loxP‐modified p110α allele (Pi3kca gene) and were treated with LPS (100ug/Kg, ip) (1 LPS). Since long term exposure to endotoxin induces desensitization of hypophagia and an inability of leptin to phosphorylate STAT3, we also tested PI3K role in feeding and BW gain in mice submitted to repeated LPS injections (6 LPS). Single LPS, but not 6 LPS control mice (p110α fl/fl), showed reduced food intake (1 LPS: 1.67 ± 0.18g, 6 LPS: 3.07 ± 0.34g), compared with saline injection (3.83 ± 0.25g). Acute LPS also reduced BW (‐0.97 ± 0.19g), compared with 6 LPS (0.49 ± 0.16g) and saline groups (0.31 ± 0.12g). The hypophagia and BW loss induced by 1 LPS were similar in p110α fl/fl‐LepR cre/cre mice; (1.72 ± 0.28g; ‐0.91 ± 0.14g BW), with no changes in 6 LPS (3.47 ± 0.12g; 0.92 ± 0.09g BW) and saline groups (3.25 ± 0.22g; 0.47 ± 0.18g BW). The data suggest that PI3K in leptin receptor expressing cells is not required for acute LPS induced anorexia and has no effect on food intake and BW gain during long term endotoxemia.Grant Funding Source: Supported by FAPESP and NIH: HD61539; HD 69702
Low salt intake during pregnancy alters glucose metabolism and DNA methylation in the offspring (LB765)
Authors: Siqueira Flavia , Oliveira Ivone , Furukawa Luzia , Heimann Joel 
Published: June 2021

Maternal nutritional alterations during pregnancy are associated with metabolic disorders and the period of pregnancy in which these alterations influence adult offspring remains uncertain. Epigenetic changes are proposed to underlie these disorders. Methods: Twelve‐week‐old female Wistar rats were fed a low‐salt (LS) or normal‐salt (NS) diet during gestation or LS during the first (LS10) or second (LS20) half of gestation. Body weight, blood glucose, insulin (ITT) and glucose (GTT) tolerance tests, HOMA‐IR, gene expression and DNA methylation were mapped in the male offspring. Birth weight was lower in LS20 and LS rats compared with NS and LS10 rats. HOMA‐IR was higher in 12‐week‐old LS compared with NS rats and in 20‐week‐old LS10 compared with NS rats. Serum insulin was higher in 20‐week‐old LS10 rats compared with NS rats. The GTT indicated glucose intolerance only in 12‐ and 20‐week‐old LS rats. Methylation of the Insr, Igf1, Igf1r, Ins1 and Ins2 genes in liver of neonates and in liver, white adipose tissue and muscle in 20‐week‐old offspring were influenced by low‐salt intake during pregnancy. In conclusion low‐salt diet in the second half of pregnancy can result in low birth weights in the offspring. Glucose intolerance observed in adult offspring occurred only if low salt intake was given throughout pregnancy. However, insulin resistance in response to low salt intake during pregnancy is related to the time at which this insult occurs and to the age of the offspring. Alterations in the DNA methylation of Igf1 were observed to be correlated with low birth weight in response to low salt feeding during pregnancy.Grant Funding Source: Supported by FAPESP and CAPES
Alterations in oral glucose‐stimulated insulin release in neuromedin B receptor knockout mice (LB768)
Authors: Paula Gabriela , Souza Luana , Magalhães Carolina , Bressane Nina , Maravalhas Rebecca , Oliveira Karen , Pazos‐Moura Carmen 
Published: June 2021

Neuromedin B (NB) is a bombesin‐like peptide found in gastrointestinal tube and pancreas, among other tissues. It has been proposed that NB has a role in insulin secretion, either by a direct effect in pancreatic cells or acting as modulator of the release of gastrointestinal hormones that are incretins. However the relevance of NB and its receptor to insulin secretion and glucose homeostasis is still unclear. Glucose homeostasis in wild type (WT) and neuromedin B receptor knockout (NBR‐KO) mice was examined by measuring glucose and insulin levels at fasted and after oral glucose load states. Female NBR‐KO exhibited similar fasting basal glucose with a 48.4% lower insulinaemia (p<0.05) and lower HOMA (homeostasis model assessment of insulin resistance) index (50.5% lower, p<0.05). Additionally, they were more tolerant to oral glucose as demonstrated by the 18% lower area under the glucose curve (p<0.05). NBR‐KO mice also showed 45.6% less insulin serum levels than WT mice (p<0.05)15 minutes after an oral glucose load, even though blood glucose rose to similar levels in both groups. Male NBR‐KO mice exhibited a mild phenotype, but they also presented lower insulin serum levels 15 minutes after glucose gavage (26.8% lower, p<0.05). Single injection of NB, one hour previous to the oral glucose administration tended to induce higher serum insulin in WT mice, however the same did not occur in NBR‐KO mice. Collectively, data show that NBR‐KO mice have lower insulin response to oral glucose, together with a better glucose tolerance, suggesting that NB and its receptor are involved in insulin secretion by incretins and also, in insulin sensitivity.Grant Funding Source: Supported by: FAPERJ, CAPES and CNPq
Acute hypoxia induces short term potentiation of mid‐cervical interneuron discharge (LB786)
Authors: Sandhu Milap , Baekey David , Guimond Lauren , Lee Kun‐Ze , Maling Nick , Sanchez Justin , Reier Paul , Fuller David 
Published: June 2021

The distribution of respiratory neural drive to phrenic motoneurons appears to be primarily monosynaptic during quiet breathing. Anatomical studies, however, indicate a population of cervical interneurons which is synaptically coupled to the phrenic motor pool. We hypothesize that these cells may be part of the neural substrate which drives plasticity in the phrenic motor system. In this study we used a multi‐electrode array approach to characterize the bursting patterns of cervical interneurons (C3/4) during and following a 4 min period of respiratory stimulation with hypoxia (arterial partial pressure of oxygen ~ 40 mmHg). A total of 95 neurons were recorded from 15 anesthetized, paralyzed, vagotomized and mechanically ventilated adult rats. Interneurons were classified as either phasic (n=13) or tonic (n=82) based on bursting patterns relative to the inspiratory cycle. Based on the hypoxic response, tonic bursting interneurons were classified as 1) excited (n=38), 2) inhibited (n=36), 3) insensitive (n=6) or 4) recruited (n=2). Following hypoxia, 43% of interneurons showed short term potentiation of activity that was manifest by a progressive increase in discharge rate after the acute hypoxic response and a gradual decrease in discharge on termination of hypoxia. Non‐linear regression analyses showed a strong relationship between the baseline firing rate and magnitude of short term potentiation in both the hypoxia‐excited and hypoxia‐inhibited interneurons (P<0.001). In other words, interneurons with a low firing rate during baseline were more likely to show persistent changes in bursting following hypoxia. Our results indicate that hypoxia‐induced plasticity is not limited to phrenic motoneurons but can also be expressed in cervical interneurons.Grant Funding Source: Supported by Craig H. Neilsen (MS) and NIH 1R01NS080180‐01A1 (DF)
A new method for instantaneous quantification of leg muscle fatigue during cycle ergometry (LB797)
Authors: Coelho Ana , Cannon Daniel , Cao Robert , Ferguson Carrie , Casaburi Richard , Porszasz Janos , Rossiter Harry 
Published: June 2021

Quantifying skeletal muscle fatigue (MF) during whole‐body exercise is confounded by the power‐velocity relationship. We reasoned that the relationship between isokinetic power and electromyography (EMG) would be linear, allowing MF to be quantified by deviation from this line. Using a rapid switch from standard (hyperbolic) to isokinetic cycling, we hypothesized that the EMG‐power relationship is: 1) linear and velocity dependent; 2) reproducible; and 3) sufficiently precise to quantify leg MF during exercise. Ten subjects (4 healthy and 6 COPD, GOLD 2/3, 29‐86 yr) repeated 5 s of isokinetic cycling at 50, 70 and 100 rpm from low to maximum effort, to determine baseline right‐leg EMG (of 5 muscles) and power (from crank torque and velocity). The patients also completed incremental exercise to the limit of tolerance, terminated with a maximal 5 s isokinetic effort to quantify MF. The EMG‐power relationship was linear (r² = 0.96±0.03), velocity dependent (p < .01) and reproducible (p > .05; ANCOVA). Mean precision (SEE) was 14±6 W. In COPD, isokinetic power was reduced from 167±64 W to 93±52 W at the limit of tolerance (p < .05) with MF contributing between 8 W and 50 W of the total. Establishing an individual’s isokinetic EMG‐power relationship is a reliable addition to a cardiopulmonary exercise test. EMG, combined with instantaneous hyperbolic‐to‐isokinetic switching ergometry, can quantify leg MF during exercise.Grant Funding Source: Supported by the Pulmonary Education and Research Foundation
The ultrastructural study of suburothelial unmyelinated nerve profile in women with urinary stress incontinence. (LB80)
Authors: Abtahi Bahareh , Venner Kerrie , Groves Mike , Digesu Alex , Elneil Sohier 
Published: June 2021

Objective: The ultrastructure of the nerve profile in women with urinary stress incontinence (USI), who are supposed to have a normal bladder function, is still unknown.Methods: Bladder biopsy were obtained from 11 patients with USI (Age: 55±13 yrs ) and 4 patients ( Age : 58 ±17 yrs) diagnosed with detrusor overactivity /overactive bladder (DO/OAB). Axonal contents of unmyelinated nerve bundles and schwann cells within the suburothelium were studied using electron microscope.Results: A total of 175 and 63 axons were counted in USI and OAB/DO groups. The mean number of axons/nerve bundle was higher in USI patients in comparison to OAB/DO patients (4.11 vs. 3.15). 4 out of 63 axons (6.35%) in OAB/DO and 3 out of 175 axons (1.71%) in the USI group did not contain small vesicles. The mean number of axons/ nerve bundle without large dense‐cored vesicles in OAB/DO and USI groups was similar (0.55).Degenerated axons were interestingly observed in both groups of patients. However, the mean number of the degenerated axons/nerve bundle was nearly twice in OAB/DO group in comparison (figure 1) to the USI group (figure 2) (0.55 vs. 0.31).Degenerated axons with empty appearance were observed in both groups. These changes were observed in 2 out of 63 axons in patients with OAB/DO and 4 out of 175 in USI patients. The regenerated axonal profile was higher in the USI group (7% vs. 3%). Activated schwann cells were observed in both groups of patients (OAB/DO: 30% vs.USI: 45%). The mean short diameter of the nerve bundle was higher in OAB/DO group in comparison to the USI group (3.41 µm vs 1.54 µm).Conclusion: This study showed ultrastructural changes and nerve degeneration in patients with USI, which has hitherto not been reported.
The profile of axons

OAB/DO patients (n=4)
USI patients (n=11)

Number of biopsies
4
11

Total number of nerve bundle counted
20
53

Total number of axons counted
63
175

Mean number of axons in a nerve bundle
3.15
4.11

Mean number of vesicles per axon
21.03
15.98

Mean number of large dense‐cored vesicles per axon
1.29
1.24

Mean number of number of mitochondria per axon
0.6
0.7
Running wheel activity is reduced in rat pregnancy (LB801)
Authors: Welshhans Elizabeth , Clarizio Katharine , Murphy Robert , O'Hagan Kathleen 
Published: June 2021

Rats provided with cage running wheels engage in daily spontaneous exercise, and this model is used to study the impact of exercise on maternal and fetal outcomes in normal and compromised pregnancies. We hypothesized that exercise volume would decrease during gestation. Cage running wheel revolutions were electronically recorded 24/7 in 5 rats before and through 21 days of gestation. Values are expressed as mean (SD). Pre‐gestation, rats completed 503(262) bouts at 17(3)s per bout at average velocity of 51(21) m/min, accumulating 6.5(2.9) km and 135(75) min per day of exercise, with >90% during lights off. Pregnancy decreased exercise distance [‐63(24)% P<0.02] the first day post breeding via a decrease in total bouts [‐69(15)% P<0.02]. Advancing gestation further suppressed exercise volume with distance and time decreased by 91(7)% at day 14 and 98(3)% by day 21, due to decreased number of bouts [‐93(5%)][all P<0.02]. After day 14 gestation, time and distance per bout also decreased (P<0.01) with a smaller contribution from reduced velocity. Spontaneous exercise volume abruptly decreases during the first week of gestation due to reduction in bout frequency and is minimal during the final week of gestation. The >50% reduction in exercise volume during early pregnancy suggests initiation of an energy conservation strategy.Grant Funding Source: Supported by Midwestern University
Dietary nitrate increases maximal knee extensor speed and power in healthy men and women (LB820)
Authors: Coggan Andrew , Leibowitz Joshua , Kadkhodayan Ana , Farmer Marsha , Anderson Spearie Catherine , Thomas Deepak , Ramamurthy Sujata , Peterson Linda 
Published: June 2021

Nitric oxide (NO) has been demonstrated to enhance the maximal shortening velocity and maximal power of rodent muscle. Dietary nitrate (NO3‐) intake has been demonstrated to increase NO bioavailability in humans. We therefore hypothesized that acute dietary NO3‐ intake (in the form of a concentrated beetroot juice (BRJ) supplement) would improve muscle speed and power in humans. To test this hypothesis, healthy men and women (n=8; age=34±9 y) were studied using a randomized, double‐blind, placebo‐controlled crossover design. After an overnight fast, subjects ingested 140 mL of BRJ either containing or devoid of 11.2 mmol of NO3‐. After 2 h, knee extensor speed and power were assessed using a Biodex 4 isokinetic dynamometer. Breath NO levels were also measured periodically using a Niox Mino analyzer as a biomarker of whole‐body NO production. No significant changes in breath NO were observed in the placebo trial, whereas breath NO rose by 66±25% (P<0.05) after dietary NO3‐ intake. This was accompanied by a 5±2% (P<0.05) increase in muscle torque (force) production at the highest angular velocity tested (i.e., 6.28 rad/s). Calculated maximal knee extensor power therefore tended to be greater (i.e., 7.81±0.84 vs. 7.36±0.74 W/kg; P=0.08) and occurred at a higher angular velocity (i.e., 7.00±0.36 vs. 6.31±0.26 rad/s; P<0.05) after dietary NO3 intake. We conclude that acute dietary NO3‐ intake increases whole‐body NO production and muscle speed and power in healthy men and women. This improvement in muscle function may be of relevance in both athletic and clinical populations.Grant Funding Source: Supported by Washington University Mentors in Medicine, Barnes‐Jewish Hospital Foundation, and ICTS UL1 TR000448
A simplified model of valveless pumping in avian lungs (LB824)
Authors: Harvey Emily , Ben‐Tal Alona 
Published: June 2021

Birds have a remarkable respiratory system in which air flows unidirectionally through rigid lungs. This unique structure enables birds to utilize oxygen at a much higher rate than is possible in mammals, and allows them to cope with much lower atmospheric pressure and oxygen levels. However, the dynamics leading to this unidirectional flow are poorly understood. We construct a phenomenological one‐dimensional model of flow in a closed loop with a single pumping source. The complex anatomical structure of the avian respiratory system is represented in our model using varying compliances and resistances to flow. This leads to a simplified model of air flow in avian lungs. Using our model, we investigate conditions under which unidirectional flow is generated, and demonstrate that the anatomically determined parameters are important in determining the direction and magnitude of a net flow. We then incorporate the effect of a second pumping source, in order to represent both the caudal and cranial air sacs.Grant Funding Source: NIH grant R01 NS069220
Association of myelin oligodendrocyte glycoprotein with vitamin D inhibited Experimental autoimmune encephalomyelitis development (LB826)
Authors: Chiuso‐Minicucci Fernanda , Ishikawa Larissa , Mimura Luiza , Silva Thais , Zorzella‐Pezavento Sofia , França Thais , Marques Camila , Ikoma Maura , Okoshi Marina , Sartori Alexandrina 
Published: June 2021

Experimental autoimmune encephalomyelitis (EAE) is a murine model of multiple sclerosis (MS). Current MS treatment consists in general suppression of immune response which increases susceptibility to infections. Considering the immunomodulatory properties and tolerogenic effects of active vitamin D, this study aimed to evaluate the therapeutic effect of myelin oligodendrocyte glycoprotein (MOG) associated with vitamin D in EAE development. Female C57BL/6 mice were submitted to EAE induction by immunization with MOG emulsified with Complete Freund Adjuvant plus Mycobacterium tuberculosis. Two intraperitoneal doses of Bordetella pertussis toxin were also injected. One day after immunization, mice were treated with 0,1mug of vitamin D every other day during 15 days (on days 1, 3, 5, 7, 9, 11, 13 and 15). MOG (150mug) was co‐administered on days 3 and 11. The administration of vitamin D or MOG alone determined significant reduction in EAE incidence and in clinical scores. When MOG was associated with vitamin D the animals (n=12) did not develop clinical disease. In this group there was also a decreased production of IL‐17 and IL‐6 by spleen and CNS mononuclear inﬁltrating cells stimulated with MOG, in comparison to the EAE control. In addition, this treatment inhibited dendritic cells (CD11c+MHC‐II+CD86+) maturation in the spleen. In conclusion, the association of MOG with vitamin D was able to control EAE development.Grant Funding Source: FAPESP
Assessment of Ethanol Induction of Breast Cancer Metastasis: the Involvement of ErbB2 and Endoplasmic Reticulum (ER) Stress (LB833)
Authors: Pan Daniel , Xu Mei , Luo Jia 
Published: June 2021

Ethanol consumption is a risk factor for the development of breast cancer and a possible promoter of breast cancer metastasis. However, the mechanisms of oncogenic action are still unknown. Previous studies have shown that breast cancer cells over‐expressing ErbB2 have been more susceptible to ethanol‐induced invasion and migration and that ER stress also promotes tumor metastasis. The objective of this study is to determine whether ethanol exposure may activate ErbB2 and induce ER stress in breast cancer cells. In this study, we test this hypothesis by examining the effect of ethanol on the activation of ErbB2 and eIF2α/PKR. The enhanced phosphorylation of eIF2α and PKR are considered indicators of ER stress. MCF7 human breast cancer cells were treated with or without ethanol for 20 days. The results indicated that phosphorylated ErbB2 was increased by a factor of 1.4 in cells treated with 0.1% ethanol and by a factor of 1.2 for cells treated with 0.2% ethanol when compared to the untreated control. Also, phosphorylated eIF2α was shown to have a 1.3 and 1.2 fold increase in 0.1% and 0.2% ethanol, respectively, while phospho‐PKR was shown to have a 1.7 and 1.5 fold increase for 0.1% and 0.2% ethanol, respectively. These findings suggest that ethanol can activate ErbB2 and induce ER stress in breast cancer cells, which may result in increased metastasis. This study was supported by NIH grant (AA017226).Grant Funding Source: Supported by NIH grant (AA017226)
Expression changes of histone deacetylases in dexamethasone‐induced neurotoxicity in human neuroblastoma SH‐SY5Y cells (LB849)
Authors: Lee Gyuhwi , Park Yoon Jung 
Published: June 2021

Chronic stress induces an abnormal increase in glucocorticoids level, which is related with neurodegenerative conditions and mood disorders. Histone deacetylase(HDAC) inhibitors have been suggested to have a promising therapeutic potential for those conditions. However, it is not clear whether HDAC is directly involved in the reverse of glucocorticoid‐mediated stress. We investigated changes of HDAC expression in response to treatment of dexamethasone(Dex), a synthetic glucocorticoid in human neuroblastoma SH‐SY5Y cells. Dex treatment affects cell viability even with 1uM. The stress induction was confirmed with stress‐response genes in neurons such as norepinephrine transporter and monoamine oxidase‐A, which increased in 4.2 and 5.1 folds, respectively. Various HDAC mRNA levels were profiled upon Dex treatment. While expression of HDAC1, 6, and 8 were not changed, HDAC4 and HDAC9 were significantly overexpressed in 1.8 and 2.1 folds, respectively. The direct changes of specific HDACs in reponse to Dex‐induced stress might suggest a potential mechanism by which chronic stress leads to neurodegenerative conditions.Grant Funding Source: supported by Korean NRF ( 22A20130012143)