bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pattern of offering ritual fluids (agüitas) to infants and toddlers in the Guatemalan highlands in metropolitan Quetzaltenango
Authors: Doak Colleen M , van der Staare Robine , van Beukoms Ilse , Campos Maiza , Vossenaar Marieke , Solomons Noel W 
Published: June 2021

BackgroundIn many cultures, simple herbal infusions, thin gruels or sweetened water (‘agüitas’ in Guatemalan parlance) are given to infants and toddlers.ObjectiveTo examine the prevalence and timing of introduction of agüitas during early life in a low‐income population of metropolitan Quetzaltenango.Methods452 responses about ever introduction of agüitas through ages 5 to 23 mo were analyzed using logistic regression to explore relationships between growth (stunting) and morbidity (diarrheal and respiratory infection) and timing of first consuming agüitas.ResultsFor 452 dyads, 354 (78%) were agüitas‐users, independent of sex or ethnicity. Of those given agüitas, half were introduced within the first 2 mo. These subjects were 1.6 times more likely to be stunted (CI=1.0, 2.5) after adjusting for ethnicity. Early introduction of agüitas was strongly associated with more reported instances of diarrhea (OR=3.4; CI=2.1, 5.4) and respiratory infections OR=2.5 (CI=1.6,4.0), irrespective of ethnicity.ConclusionThe high prevalence and early introduction of agüitas are consistent with other findings showing agüitas to be deeply rooted in the culture of infant rearing. Understanding these associations requires an in‐depth understanding of the meaning and use of agüitas.Funded by the Nestlé Foundation and Sight and Life, Switzerland
Loss of maternal atrial natriuretic peptide programs cardiac and renal gene expression: role of GATA4 and Npr‐1 in the fetal programming of cardiovascular health and disease
Authors: Armstrong David WJ , Tse M Yat , Wong Philip G , Pang Stephen C 
Published: June 2021

ObjectiveTo determine the effect of loss of maternal atrial natriuretic peptide (ANP) on cardiac hypertrophy (CH) and salt‐sensitivity in offspring.MethodsWe obtained heterozygous offspring from ANP wild‐type (+/+) and knockout (−/−) dams (ANP+/−WTand ANP+/−KO offspring). Gene expression was measured using real‐time PCR.ResultsMaternal ANP had no effect on litter size or offspring growth. At 9‐weeks of age, ANP+/−KO had significantly higher left ventricular (LV) mass compared to ANP+/−WT. Left ventricular mRNA levels of ANP (a marker hypertrophy) and the pro‐hypertrophic factors GATA4 and P300 were significantly higher in ANP+/−KOmice. There was no significant difference in the hypertrophic response to daily injections of isoproterenol (ISO) between ANP+/−WT and ANP+/−KO, although CH remained significantly higher in ANP+/−KO. In the kidney of ANP+/−KO, we observed significantly higher mRNA levels of natriuretic peptide receptor 1 (Npr1), as well as P300 and Ets‐1, which are known to cooperatively stimulate Npr1 transcription. To determine the effect of elevated Npr1 on salt‐sensitivity, we treated offspring with a high salt diet for 5 weeks. Salt‐induced CH was only evident in ANP+/−WT and not ANP+/−KO mice.ConclusionsMaternal ANP programs the structure and function of the cardio‐renal axis, and the loss of maternal ANP prevents salt‐sensitive CH in offspring, possibly via elevated renal Npr1.Grant Funding Source: Heart and Stroke Foundation of Ontario
Gut microbiota modulates metabolic and nutrient sensing signaling pathways in obesity
Authors: Duca Frank , Sakar Yassine , Covasa Mihai 
Published: June 2021

Accumulating evidence shows a complex interaction between gut microbiota, weight gain and energy regulation. However, the mechanisms by which this interaction occurs to influence satiety and food intake leading to body weight changes in animals prone for obesity (OP) are not well known. Therefore, in these studies, we first examined changes in lipogenic and adipogenic markers, as well as intestinal nutrient signaling components (GPCRs) in OP and obese‐resistant (OR) rats. Next, we examined whether the metabolic and intestinal “phenotypical signatures” present in OP and OR rats are transferable, by inoculating germ free animals with fecal microbiota obtained from OP (OP/GF) and OR (OR/GF) donor rats. After 8wks of high‐fat feeding, we found that OP/GF animals gained more weight, and had increased adiposity and 24hr food intake compared to OR/GF. Alterations in lipogenesis and adipogenesis, as well as intestinal nutrient receptor signaling molecules characteristic of the OP phenotype were recapitulated in the germ free animals that received microbiota from the OP rat. These results demonstrate the ability of the gut microbiota to modulate host metabolism, by altering both intestinal nutrient sensing and energy‐storing signaling pathway information, and ultimately contributing to the obese state.Grant Funding Source : INRA
Black Raspberry Powder Inhibits IL‐8‐Mediated Angiogenesis in Human Intestinal Microvascular Endothelial Cells Role of; MAPK, Bcl2, Akt and COX‐2
Authors: Link Benjamin , Medda Rituparna , Nie Linghui , Schmidt Jamie , Jovanovic Nebosja , Otterson Mary F , Rafiee Parvaneh 
Published: June 2021

BACKGROUNDAngiogenesis, the growth of new blood vessels, plays an important role in gastrointestinal chronic inflammation and cancer. Previously we have shown that interleukin 8 (IL‐8) exerts a potent angiogenic effect on human intestinal microvascular endothelial cells (HIMEC). Black raspberry (BRP) is a dietary product and an effective chemopreventive agent in animal models of malignancy, undergoing evaluation for the treatment of inflammatory bowel disease (IBD). However, the effect of BRP on HIMEC is not well defined. We investigated the antiangiogenic effect of BRP on IL‐8 activated HIMEC.METHODSHIMECs were treated with IL‐8 and BRP (5–50 μg/ml). Effect of BRP on survival/apoptosis, proliferation, transmigration, stress fiber and tube formation in IL‐8 activated cells were examined. The intracellular signaling molecules; MAPKs, Akt, Bcl2, Bax, NFκB and COX‐2 were assessed with or without BRP by Real‐time, Western blot and Immunofluorescence microscopy.RESULTSBRP inhibited IL‐8‐induced in vitro tube formation, cell migration, proliferation and stress fiber formation. IL‐8 enhanced Bcl2, Akt, COX‐2 expression and ERK1/2 and JNK activation. BRP down regulates Bcl2, Akt, ERK1/2, JNK, and COX‐2 expression and enhanced Bax expression in HIMEC.CONCLUSIONSTaken together, BRP possesses antiangiogenic properties, which warrants further investigation as adjuvant treatment of IBD and cancer.
Accumulation and biochemical effects of microcystin‐LR on Patagonian silverside (Odontesthes hatcheri) fed with Microcystis aeruginosa cells
Authors: Luquet Carlos Marcelo , Bieczynski Flavia , Bianchi Virginia Angélica 
Published: June 2021

We studied accumulation and biochemical effects of microcystin‐LR (MC) in the Patagonian silverside Odontesthes hatcheri after dietary administration of the cyanobacteria Microcystis aeruginosa (load~1.3 μg MC / g fish, incorporated in standard fish food). After 12 h, MC content in liver did not differ between fish fed with crushed or intact cells, demonstrating O. hatcheri's capacity to digest cyanobacterial cells and also absorb free MC.In a second experiment, fish received crushed toxic cells, non‐toxic cells or control feed; MC accumulation was monitored for 48 h. Protein phosphatase 1 (PP1), catalase (CAT) and glutathione S transferase (GST) activities and lipid peroxidation (MDA) were measured in liver and intestine. Methanol‐extractable MC was determined by PP1 inhibition assay, total MC (extractable + protein‐bound) was measured by Lemieux oxidation ‐ gas chromatography / mass spectrometry. MC accumulated rapidly up to 22.9 and 9.4 μg MC / g in intestine and liver respectively, followed by a decreasing tendency. Protein‐bound MC represented 65–98 % of total MC in both tissues. CAT and GST activities and MDA were significantly increased by MC in liver, but not in intestine. We conclude O. hatcheri is able to digest cyanobacteria, accumulating MC mostly bound to proteins. This could have implications for aquaculture and trophic chain toxic transference.Grants: CONICET PIP 0282, ANPCYT PICT 00214
Integrin‐β1 participates in the spreading, adhesion, and migration of human adipose tissue‐derived stem cells
Authors: Bai Xiaowen , Yan Yasheng , Bosnjak Zeljko 
Published: June 2021

Transplantation of human adipose tissue‐derived stem cells (hASCs) is a promising treatment for cardiac regeneration following myocardial infarction. However, the reported improvements in cardiac function have been generally modest partly due to low engraftment of injected stem cells in ischemic hearts. In addition, the mechanisms underlying engraftment and migration of stem cells remain unknown. Thus, the aim of study is to investigate the roles of integrin‐β1 in the engraftment and migration of hASCs using an in vitro cell culture model. Lentivirus‐mediated short hairpin RNA was used to knockdown integrin‐β1 in hASCs. The expression of integrin‐β1 and cytoskeletal F‐actin in hASCs were analyzed by immunofluorescence staining. Cell adhesion assay was performed by counting adherent cell number 3 hours after seeding. Cell migration ability was examined using a Chemotaxis Cell Migration kit. The results show that inactivation of integrin‐β1 resulted in 1) poor cell spreading and few membrane protrusions; 2) disorganized F‐actin fibers in hASCs; and 3) decreased adhesion efficiency and migration potential of hASCs (p<0.05, n=3). Together, integrin‐β1 participates in the engraftment and migration of hASCs. The finding may guide the design of novel therapies that can increase stem cell‐mediated myocardial regeneration efficiency by increasing the ability of hASCs to engraft and persist in ischemic hearts.Supported in part by P01GM066730, R01HL034708 (ZJB) from the NIH, Bethesda, MD.
Pronounced and persistent inflammatory response induced through Polymicrobial sepsis is exacerbated by second insult by Pseudomonas aeruginosa: A “Two‐Hit” model of sepsis
Authors: Figueiredo Maria José , Celes Mara , Nascimento Daniele , Dias Priscila , Cunha Fernando Q. , Filho José C. A. , Rossi Marcos A. 
Published: June 2021

This study analysed the morphological changes and inflammatory response on cecum and lung of animals undergoing sepsis induced by cecal ligation and puncture (CLP) followed by pneumonia. Male balb/c mice were subjected to sham or moderated septic injury (MSI) induced by CLP, 24 and 48 hours after CLP the cecum was collected and submitted to morphological evaluation. Three days post‐CLP, surviving mice were subjected to a second hit (SH) with P. aeruginosa, 24 and 48 hours after pneumonia induction the morphology of cecum/lung were evaluated. The MSI‐cecum presented increased foci of necrotic cells, spreading of neutrophils near the punctures site and outside of the gut wall, 24 and 48 hours after CLP. However, 24 and 48 hours after SH this inflammatory response was not as pronounced as earlier. After SH, the morphology of lung showed an increased amount of polymorphonuclear cells associated to fibrin deposition. In addition, a significant increased mortality after the SH was observed when compared to animals submitted to CLP or pneumonia alone.CLP induces severe neutrophil infiltration characterizing hyperinflammatory response and the SH (that mimics a clinical scenario of secondary infection) aggravated the sepsis. New studies are essential to better understand of the hyperinflammatory response during sepsis given the continued impact of sepsis and the risks of secondary infection on morbidity and mortality.
Role of interleukin‐33 in sepsis‐induced myocardial dysfunction
Authors: Choe Yoonmi , Kao Raymond , Xenocostas Anargyros , Martin Claudio M , Rui Tao 
Published: June 2021

The disruption of myocardial extracellular matrix (ECM) protein has been implicated in myocardial dysfunction during sepsis. However, the underlying mechanism(s) are not clear. Interleukin‐ 33 (IL‐33) is a cytokine which can regulate collagen synthesis in various cardiac pathologies. The purpose of the present study is to test whether IL‐33 contributes to the sepsis‐induced myocardial dysfunction through regulation of matrix metalloprotease‐9 (MMP‐ 9).MethodsIn vivo, feces‐induced peritonitis (FIP) in mice and in vitro LPS treatments to isolated cardiomyocytes were used in the study.ResultsIn mice with FIP, myocardial IL‐33 and MMP‐9 expression were increased and myocardial contractility was decreased. Myocardial function in mice with FIP was improved when the mice were treated with soluble ST2 (sST2), a decoy receptor of IL‐33. The in vitro, expression of IL‐33 and MMP‐9 in cardiomyocytes treated with LPS was increased. Addition of sST2 prevented the increase in MMP‐9 expression in LPS treated myocytes.ConclusionOur results indicate IL‐33 plays an important role in mediating sepsis‐induced myocardial dysfunction by regulation of myocyte MMP‐9 expression. (Supported by the Department of National Defense, Canadian Forces Medical Group)
Tie‐2‐Cre‐mediated Inactivation of Lipid phosphate phosphatase (Lpp)‐3 Results in Vascular Defects
Authors: Chatterjee Ishita , Wary Kishore K 
Published: June 2021

RationaleMouse embryos with null Lpp3 alleles die as early as E6.5days as they fail to form chorio‐allantoic placenta and yolk‐sac blood vessels. Thus, in vivo function of Lpp3 gene during later stages of embryonic development is not known.GoalTo examine tissue specific function of Lpp3, we generated Lpp3flox/flox mice. To delete Lpp3 in endothelial cell (ECs), we crossed Lpp3flox/flox mice with Tie‐2‐Cre transgenic line.ResultsIn contrast to the conventional Lpp3 deletion, Tie‐2‐Cre mediated Lpp3 deletion in ECs did not affect normal vasculogenesis; however, this led to impaired angiogenesis and late embryonic lethal phenotype. Microscopic analyses revealed reduced fibronectin and VE‐cadherin expression, and increased apoptosis in CD31‐positive vascular structures. Transmission electron microscopy confirmed the presence of apoptotic ECs in mutants. Accordingly, Lpp3 null cells showed increase in p53 and p21 levels, with concomitant decrease in cell proliferation as illustrated by reduced 6‐Bromodeoxyuridine incorporation. In vitro, LPP3 knockdown decreased transendothelial electrical resistance, interestingly re‐expression of β‐catenin cDNA into LPP3 depleted ECs partially restored the effect of loss of LPP3.ConclusionThese results define a critical role of LPP3 in angiogenesis, vascular development and control of apoptotic pathway.Support: NIH R01HL07935, UIC CCTS UL1RR029879.
Characterization of SERT I172M sensitivity to SSRI metabolites
Authors: Thompson Brent , Denny Ashley D , Ye Wen Rui 
Published: June 2021

Altered activity of the serotonin transporter (SERT) has been hypothesized to contribute to the etiology of major depression, anxiety, obsessive‐compulsive disorder, and autism. SERTs are thought to be the primary target for selective serotonin reuptake inhibitor (SSRI)‐class antidepressants, as well as many tricyclic antidepressants (TCA's) used to treat these disorders. Previously, we generated mice expressing a SERT variant (SERT I172M) that displays a dramatic loss of SERT affinity for cocaine, several SSRI's and TCA's, without impacting serotonin (5‐HT) transport (Thompson B.J., et al., 2011). Ex vivo forebrain synaptosomal 5‐HT transport assays with mice carrying the I172M substitution reveal an ~1,000 fold shift in citalopram potency, ~150 fold shift in venlafaxine potency, ~ 60 fold shift in sertraline potency and an ~10 fold shift in fluoxetine potency. Here we demonstrate that citalopram's metabolite, desmethylcitalopram, maintains an ~1000 fold shift in potency for SERT I172M, while the metabolites of venlafaxine, sertraline and fluoxetine display much smaller shifts in potency (~40 fold shift for desvenlafaxine, <2 fold shift for desmethysertraline and <2 fold shift for norfluoxetine). These results highlight the importance of considering the actions of drug metabolites. Ongoing studies are examining the effects chronic SSRIs have on gene expression and behavior.Grant Funding Source : UTHSCSA Faculty Startup Funds
Chronic fluoxetine treatment is associated with persistent desensitization of the 5HT2A receptor and decreased cocaine‐primed reinstatement in rhesus monkeys
Authors: Sawyer Eileen K , Howell Leonard L 
Published: June 2021

Previously, we showed that chronic selective serotonin reuptake inhibitor (SSRI) treatment resulted in a significant suppression of cocaine‐primed reinstatement that persisted after 6 weeks of washout. The therapeutic effects of selective serotonin reuptake inhibitors (SSRIs) for depression are believed to rely on neuroadaptive changes in the serotonin system that emerge during chronic treatment, but these effects have not been evaluated in the context of cocaine use. Therefore, we examined the effects of chronic fluoxetine treatment (10 mg/kg/day, p.o.) in rhesus macaques trained to self administer cocaine and evaluated pre‐and post‐synaptic receptor level and function using positron emission tomography and concurrent in vivo microdialysis and prolactin response. A significant increase in serotonin 2A receptor binding potential was observed, which persisted following a 6‐week washout period. Serotonin transporter binding potential and serotonin release in response to fenfluramine (3.0 mg/kg, i.v.) were not affected, while prolactin release was significantly blunted. Furthermore, cocaine‐induced increases in dopamine and cocaine‐primed reinstatement were also significantly blunted following fluoxetine treatment and washout. Together, these results suggest that chronic fluoxetine treatment is associated with a persistent change in 5HT2A receptor function which may contribute to suppressed cocaine‐primed reinstatement.This research was supported by NIH grants DA10344 (LLH), DA000517 (LLH), T‐32 DA015040 (support for EKS), and RR00065 (YNPRC).
Complement‐derived anaphylatoxin, C5a‐mediated signaling pathway is a novel pharmacological target for IVIG‐regulated humoral immunotherapy in Alzheimer's Disease
Authors: Vempati Prashant , Gong Bing , Zhao Wei , Wang Jun , Devi Lakshmi A , Pasinetti Giulio M 
Published: June 2021

Human intravenous immunoglobulin (IVIG) has been found to benefit patients with Alzheimer's disease (AD) and other neurodegenerative diseases. According to a common hypothesis, IVIG contains naturally occurring auto antibodies that block the toxic effects of β‐amyloid (Aβ) and promote brain Aβ clearance. However, with the discrepancy between Aβ pathology in postmortem AD brains and the severity of clinical dementia in the elderly, the beneficial effects of IVIG may extend beyond Aβ clearance. We hypothesized that elevated brain levels of complement C5‐derived C5a anaphylatoxins play a crucial role in the regulation of signaling pathways related to learning and memory functions, which contribute to successful aging, and that human intravenous immunoglobulin may have beneficial effects on cognitive function in age‐related dementia by modulating C5a expression in the brain. Our studies show that the levels of C5a are decreased in C57BL6 mice (24–28 month old), and that reduced brain C5a content is correlated with a decline in cognitive function. Most importantly, four weeks of treatment with IVIG in TG2576 mice significantly increased the level of C5a in the brain and improved synaptic plasticity. Given the high safety of IVIG in clinical practice over the past decade and the lack of effective AD therapy, our study would provide novel mechanisms in AD treatment for the elderly.Supported by unrestricted grant to GMP
Cognitive and motor effects of endurance related compound AICAR: from muscle to brain
Authors: Kobilo Tali , van Praag Henriette 
Published: June 2021

Neurogenesis occurs in the hippocampus, a crucial structure for cognition. Running increases neurogenesis and improves memory. The mechanisms underlying these benefits remain undefined. Transcriptional factors regulating muscle fiber metabolic genes were identified. AMPK is important for mitochondria function and exercise physiology. The agonist AICAR enhanced endurance. The possibility that peripheral triggers, such as skeletal muscle activation as a result of exercise or pharmacological agents, underlies cognitive effects of exercise, has not been explored.Mice were injected with AICAR for 7 or 14 days. Two weeks later mice were trained in water maze, open field and rotarod. In young mice 7 days of AICAR increased spatial memory, cell survival and percentage of new neurons in the hippocampus. The effects of AICAR were clearly dependent on the duration of administration. In aged mice, 14 days of injections improved motor abilities and cognition, correlated with findings that AMPK activity declines with aging in skeletal muscle. Microarray analysis revealed effects on metabolic processes and muscle composition. Thus, we show that endurance related compounds confer CNS benefits.
Decrease in Hepatic TNF‐alpha and increase in DNA yield defines hepatoprotection of stem‐bark aqueous extract of Sclerocarya Birrea in ethanol‐induced liver injury in Wistar rats
Authors: Alawa Judith Nkiruka , Ahmadu Sadiya , Kwanashie Helen , Akpulu Peter , Ellah Ezekiel 
Published: June 2021

Modulation of the toxicity of tumor necrosis factor‐alpha (TNF‐α) is important in treatment of alcoholic liver damage as it depletes oxygen in hepatocytes leading to damage of biomolecules (DNA) and apoptosis. Sclerocarya birrea (SB) has shown hepatoprotection in ethanol‐induced liver damage. This study investigates whether the stem‐bark aqueous extract of SB will modulate the expression of hepatic TNF‐α thereby preventing oxidative DNA damage in rats exposed to ethanol. Male Wistar rats were exposed to 40% (v/v) ethanol and/or two doses of SB (15 mg/kg or 30 mg/kg) or distilled water for four weeks by gastric gavage. Liver homogenates and tissue were analyzed for TNF‐α, DNA yield and histopathology. Serum was analyzed for antioxidants (superoxide dismutase and reduced glutathione) and liver function enzymes (alanine and aspartate aminotransferases). Ethanol induced hepatotoxicity with marked increase in hepatic TNF‐α and liver function enzymes while antioxidants and DNA yield decreased. Treatment with SB modulated hepatic damage by decreasing levels of TNF‐α, liver function enzymes and increasing antioxidants. Histopathological examination showed that SB attenuated degenerative changes in hepatocytes and liver parenchyma. Results demonstrate that SB modulates TNF‐α expression and induces antioxidant activity thereby preventing oxidative DNA damage and liver injury.Grant Funding Source: Ahmadu Bello University Research Grant