bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of β‐catenin transactivation by IFNγ is regulated by Akt1 and 14.3.3z (650.1)
Authors: Candelario Aurora , Nava‐Dominguez Porfirio , Kamekura Ryuta , Laur Oskar , Parkos Charles , Nusrat Asma 
Published: June 2021

The proinflammatory cytokine IFNg influences intestinal epithelial cell (IEC) homeostasis in a biphasic manner by acutely stimulating proliferation that is followed by sustained inhibition of proliferation despite continued mucosal injury. B‐catenin activation has been classically associated with increased IEC proliferation. However, we have observed that IFNg inhibits IEC proliferation despite sustained activation of Akt/B‐catenin signaling. Here we show that inhibition of Akt/B‐catenin‐mediated cell proliferation by IFNg requires the formation of a protein complex containing phosphorylated B‐catenin 552 (pB‐cat552) and 14.3.3Z. We identify Akt1 as a bimodal switch that promotes or inhibits B‐catenin transcriptional activity in response to IFNg stimulation. We demonstrate that IFNg initially induces B‐catenin transactivation through Akt‐dependent c‐terminal phosphorylation of B‐catenin to promote its association with 14.3.3Z. Augmented B‐catenin transactivation leads to increased Akt1 protein and active Akt1 accumulates in the nucleus where it phosphorylates 14.3.3Z to induce relocalization of 14.3.3Z/B‐catenin from the nucleus thereby inhibiting B‐catenin transactivation and IEC proliferation. These results outline an unexpected dual function of Akt1 that suppresses IEC proliferation during intestinal inflammation.Grant Funding Source: Supported by NIH (CP and AN) and Conacyt (PN) grants.
Hypergravity delocalizes thyrotropin receptor (650.3)
Authors: Lazzarini Andrea , Albi Elisabetta , Floridi Antonio , Lazzarini Remo , Loreti Elisabetta , Ferri Ivana , Curcio Francesco , Ambesi‐Impiombato Francesco 
Published: June 2021

Thyrotropin receptor (TSHR) is a a heterodimer G protein‐coupled receptor constituted by an α extracellular subunit (53 kDa) interacting with thyrotropin (TSH) and a broad β transmembrane and intracellular subunit (30‐42 kDa) held together by disulphide bridges. TSHR are localized in the basolateral membrane rich in lipid rafts, microdomains with high level of cholesterol and sphingolipids, that provide a platform for the assembly of signaling complexes after TSH‐TSHR interaction. This interaction was perturbed in hypogravity during parabolic flights and longer missions in Space on board the ISS. In the present work the influence of complex mechanical effects of hypergravity on TSHR, cholesterol and sphingolipid in thyroid gland in vivo was investigated. Seven mice were maintained in hypergravity in a 2g centrifuge. Our results show that hypergravity up‐regulated 65% TSHR. TSH treatment did not cause significant changes in the thyroid gland of the control mice and induced about 50% reduction of the α subunit TSHR of 2g animal. TSH‐stimulated cAMP production was similar in control and 2g samples, indicating that even if TSHR is up‐regulated in hypergravity, the loss of its α subunit that binds TSH was responsible for the lack of the expected increased response to hormonal stimulation. Immunofluorescence analysis of TSHR demonstrated that in control samples the receptor was present on the surface of thyrocytes that surrounded follicles with a precise location, whereas in 2g samples the fluorescent signal was higher and spread over the entire surface of thyrocytes. The UFLC‐MS/MS study on lipid fraction of thyroid tissue showed that sphingomyelin and ceramide species remained unchanged whereas cholesterol was reduced 49% in 2g in comparison with control samples. We thus suggest that gravity, by inducing a significant loss of cholesterol, perturbed lipid rafts modifying TSH‐TSHR interaction.Grant Funding Source: Agenzia Spaziale Italiana
The anti‐oxidant, anti‐inflammatory and antinociceptive activities of the methanol leaf extract of Moringa oleifera in some laboratory animals (657.19)
Authors: Adedapo Adeolu , Falayi Olufunke , Oyagbemi Ademola 
Published: June 2021

Moringa oleifera is an annual herbal shrub which has been used in traditional medicine in Nigeria to treat some disease conditions. This study evaluated the methanol leaf extract (MLE) of the plant for pharmacological activities in rats and mice to validate its folkloric use in Nigeria.MLE was prepared by dissolving ground plant materials (200g) in methanol for 48 h, filtered, dried and thereafter used for pharmacological investigations. Standard phytochemical methods were used to test for the presence of phytoactive compounds in the plant. Anti‐oxidant activities of the plant were assessed using ABTS, DPPH, FRAP and total phenolics test. The anti‐inflammatory activities were conducted using carrageenan and histamine‐induced tests while antinociceptive activities were carried out using writhes and formalin licking tests.Acute toxicity test showed that no animals died at the doses even at 1600mg/kg dose. The extract at 50, 100 and 200mg/kg body weight caused a significant reduction in the anti‐inflammatory and analgesic activities though not in the same magnitude as indomethacin, the reference drug used in this study. In the case of anti‐oxidant activities, the extract at 20mg caused 86.0% ABTS inhibitory activity; 49.0% DPPH inhibitory activity; 82.7µmol/L ascorbic acid equivalent for FRAP and 17.2µmol/L gallic acid equivalent for total phenolics.The results from this study may have validated the traditional basis for the use of Moringa oleifera as medicinal agent. The pharmacological activities noted in this study may be attributed to the presence of flavonoids and other phenolics contained in this plant.
Sphingosine 1‐phosphate induces anti‐inflammatory M2 polarization through IL‐4 signaling in macrophages (662.14)
Authors: Park Soo‐Jin , Lee Kyoung‐Pil , Kang Saeromi , Im Dong‐Soon 
Published: June 2021

Phenotypes of macrophages, classic pro‐inflammatory M1 and alternative anti‐inflammatory M2, could influence many disease states like atherosclerosis. Lipopolysaccharide (LPS)‐activated macrophages increase pro‐inflammatory cytokine secretion. Such LPS‐induced‐M1 phenotype expression was suppressed by sphingosine 1‐phosphate (S1P), an anti‐atherogenic lipid mediator in HDL. Previously, suppression of NF‐κB activity through S1P1 was suggested as a key mechanism for the suppression of M1 phenotype (Hughes et al. Circ Res. 2008; 102: 950‐958). In the present study, we addressed how S1P induces M2 macrophage polarization in mouse macrophages and found that S1P induced anti‐inflammatory M2 polarization through IL‐4 secretion and its signaling. S1P induced not only induction and secretion of IL‐4 but also induction of their receptors, IL‐4Rα and IL‐2Rγ. In addition, down‐stream signaling such as phosphorylation of stat‐6, induction of SOCS1, and suppression of SOCS3 expression was also observed in response to S1P. Furthermore, S1P‐induced activation of ERK and inhibition of p38 MAPK and JNK were found to be key signaling for IL‐4 induction. Present data suggest that anti‐atherogenic effect of S1P in HDL may be mediated through IL‐4 secretion and its phenotype switching from M1 to M2 anti‐inflammatory macrophages.Grant Funding Source: This research was supported by Basic Science Research Program through the NRF (2011‐0021158)
N‐cadherin adherens junctions in rat cerebral artery are mechano‐sensitive (664.9)
Authors: Sun zhe , Li Zhaohui , Li Min , Hill Michael , Meininger Gerald 
Published: June 2021

N‐cadherins physically link apposing vascular smooth muscle cells (VSMC) via formation of adherens junctions (AJ) that are coupled to the actin cytoskeleton. In isolated rat mid‐cerebral artery, immunofluorescence studies revealed that the density of N‐cadherin‐AJs increased when lumen pressure was raised from 50 to 110 mmHg, suggesting that the N‐cadherin AJs are mechanosensitive and respond to changes of lumen pressure. In addition, the N‐cadherin‐AJs were observed to align along the cell membrane in pattern of strings when pressure increased from 50 to 90 mmHg. Atomic force microscopy (AFM) with N‐cadherin‐coated microbead (10 μm) tipped probes was employed to examine the response of N‐cadherin adhesion sites to pulling force in VSMC. AFM pulling of the N‐cadherin adhesion (~1 nN) induced an opposing force‐generating contractile response from the VSMC. Transfection of freshly isolated VSMC with N‐cadherin‐GFP was used to study clustering of N‐cadherin to the microbead adhesion site. Upon contact with cell membrane, the N‐cadherin‐coated microbead induced progressive clustering of N‐cadherin‐GFP. Furthermore, there was additional recruitment of N‐cadherin to the microbead when AFM pulling force was applied and the bead was pulled back toward the cell surface by the VSMC. Collectively, these results support a functional role of N‐cadherin AJs as mechano‐sensitive sites in the small resistance arteries. (1P01HL095486 to G.A.M.)Grant Funding Source: Supported by NIH 1P01HL095486 to G.A.M.
Purine metabolism in diving and non‐diving mammals (667.4)
Authors: Lopez‐Cruz Roberto , Barjau Perez‐Milicua Myrna , Crocker Daniel , Gaxiola‐Robles Ramon , Vazquez‐Medina Jose , Zenteno‐Savin Tania 
Published: June 2021

When tissues are deprived of blood (ischemia) there is a progressive reduction of oxygen (hypoxia). Tissue function can be maintained until oxygen and ATP stores are depleted. During breath‐hold diving, blood flow to most tissues is decreased and blood is directed preferentially to the central nervous system. Diving mammals (seals and dolphins) routinely dive as part of their natural history. The hypothesis of this study is that diving mammals have a refined purine salvage system to avoid loss of nucleotides and to maximize ATP recycling during ischemia/reperfusion associated to diving. The goal of this study is to analyze the activities of purine nuceoside phosphorylase (PNP), xanthine oxidase (XO) and hypoxanthine‐guanine phosphorybosil transferase (HGPRT), key enzymes involved in the purine salvage pathway in marine mammals adapted to tolerate repeated cycles of ischemia/reperfusion associated with diving (bottlenose dolphin, northern elephant seal, river otter) and compare with those from non‐diving mammals (human, pig). PNP, XO and HGPRT activities were analyzed by spectrophotometry, purine nucleotide metabolite concentrations was analyzed by HPLC. No clear relationship in circulating PNP or XO activity could be established between diving and non‐diving mammals. Intraerythrocyte PNP activity in bottlenose dolphins could be related to a release of purine nucleotides from the liver. The plasma PNP and XO activities observed in river otters may be due to their precarious energetic balance. Low erythrocyte PNP activity and elevated plasma XO activity in northern elephant seal could be due to fasting and/or sleep‐ and dive‐associated apneas.Grant Funding Source: Supported by CONACYT
Microfluidic device and assay for mimicking the leukocyte‐endothelium interactions in vivo (669.4)
Authors: Lamberti Giuseppina , Prabhakarpandian Balabhaskar , Smith Ashley , Pant Kapil , Wang Bin , Kiani Mohammad 
Published: June 2021

There is no in vitro model that allows investigation of the entire leukocyte adhesion cascade. In this study we present a novel microvasculature network based microfluidic device (MFD) that enables a single assay to study the entire cascade.Our modified Geographic Information System (GIS) approach was used to digitize the microvascular networks and generate the MFD using soft‐lithography based microfabrication. The MFD consisted of vascular channels seeded with endothelial cells, in communication with the tissue compartment filled with chemoattractant (fMLP) via a 3µm porous barrier. Leukocytes were flowed on activated endothelial cells under physiologic flow conditions.Leukocytes rolling, adhesion and migration was imaged as a function of time and position in the MFD and compared with in vivo data from mouse cremaster muscle. Our findings indicate that in MFD rolling and adhesion patterns are in agreement with the in vivo data, with 50% of adhered leukocytes migrating from the vascular channels into the tissue compartment after 120min. Furthermore, we blocked the individual steps treating endothelial cells with E‐selectin and ICAM‐1antibody and leukocytes with wortmanin, showing that we can respectively reduce rolling to ~20%, adhesion to ~50%, and migration to ~18% of their original values. In conclusion, this device more realistically mimics geometric and physiologic characteristics of an in vivo microvascular network for studying the entire leukocyte cascade during inflammation.Grant Funding Source: Supported by NIH
Upregulation of pro‐inflammatory cytokine receptors in forebrain subfornical organ and hypothalamic paraventricular nucleus in rats with heart failure (686.23)
Authors: Wei Shun‐Guang , Zhang Zhi‐Hua , Yu Yang , Weiss Robert , Felder Robert 
Published: June 2021

The pro‐inflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β play an important role in regulating sympathetic drive and neuroendocrine activation in heart failure (HF). Previous studies in normal rats have demonstrated that receptors for TNF‐α and IL‐1β are abundant in the subfornical organ (SFO) but only sparsely expressed in the hypothalamic paraventricular nucleus (PVN). In HF rats, TNF‐α and IL‐1β increase in the circulation and in cardiovascular autonomic regions of the brain. Pro‐inflammatory cytokines can upregulate their own receptors, but the question of whether TNF‐α and IL‐1β receptors increase in SFO or PVN in HF has not been addressed. We examined TNF‐α and IL‐1β receptor (IL‐1RAcP component) expression in SFO and PVN in adult male Srague‐Dawley rats 4‐5 weeks after myocardial infarction or sham operation (Sham), using immunofluorescent staining and real‐time PCR analysis. Fluorescent intensity for TNF‐α and IL‐1β receptors was significantly (*p<0.05, n=6) greater in both SFO and PVN in the HF rats, compared with Sham rats. Similarly, the mRNA levels of TNF‐α and IL‐1β receptors in SFO and PVN were significantly (n=5) higher in HF compared with Sham rats. These data indicate that upregulation of TNF‐α and IL‐1β receptors contributes to the inflammatory state driving sympathetic and neuroendocrine activity in these key cardiovascular autonomic regions of the brain in HF.Grant Funding Source: Supportd by NIH R01HL073986
Adipose dysfunction with aging is associated with resistance artery endothelial dysfunction and impaired angiogenic capacity (688.3)
Authors: Hazra Sugata , Henson Grant , Bramwell R , Reihl Kelly , Donato Anthony , Lesniewski Lisa 
Published: June 2021

Although tissue dysfunction is reported in aging, effects of aging on adipose tissue per se are not well studied. To address this, we assessed metabolic homeostasis, adipose tissue structure‐function and adipose artery endothelial function from young (6 mo) and old (29 mo) male B6D2F1 mice. Fasted blood glucose was not different with age but plasma insulin, homeostatic model assessment (HOMA‐) of insulin resistance (IR), and beta cell function (‐B) were increased by 84%, 54%, 57% respectively (P<0.05) in old mice. Old mice also were glucose intolerant (P<0.05), concomitant with increased plasma free fatty acids (P<0.05) and liver triglycerides (P<0.05). Despite no difference in body mass, epididymal white adipose tissue (eWAT) mass was 40% lower in old mice. There was ~60% reduction in mean adipocyte area (p<0.01), 7‐fold increase in fibrosis (p<0.01) and ~50% reduction in vascular density (p<0.01) in old eWAT. There also was a 2‐fold reduction in in vitro eWAT angiogenesis and a ~25% reduction in endothelium dependent dilation to acetylcholine in eWAT arteries (p<0.01) from old mice, without a reduction in endothelium independent dilation. Thus, aging results in metabolic dysfunction associated with increased circulating and ectopic lipids, altered adipose tissue morphology and reduced vascular density, concomitant with impaired angiogenic potential and endothelial dysfunction in adipose arteries.Grant Funding Source: Supported by R21 AG033755, K01 AG033196, R01 AG040297
Beneficial effect of Oryeongsan in diabetic nephrosclerosis (701.2)
Authors: Yoon Jung Joo , Lee Yun Jung , Lee So Min , Kim Mi Kyeong , Kang Dae Gill , Lee Ho Sub 
Published: June 2021

Beneficial effect of Oryeongsan in diabetic nephrosclerosisJung Joo Yoon1,2, Yun Jung Lee1,2, So Min Lee 1,2, Mi Kyeong Kim1,2, Dae Gill Kang1,2*, Ho Sub Lee1,2*1College of Oriental Medicine and Professional Graduate School of Oriental Medicine, 2Hanbang Body‐fluid Research Center, Wonkwang University, Shinyong‐dong, Iksan, Jeonbuk, 570‐749, KoreaMesangial fibrosis and expansion are caused by extracellular matrix accumulation leading to diabetic nephrosclerosis. Oryeongsan, traditional herbal formula, is widely used for the treatment of nephrosis, dropsy, and uremia. In this study, the anti‐fibrotic effect of Oryeongsan was investigated in db/db mice.Db/db mice were treated with 100 mg/kg Oryeongsan daily for 8 weeks. In Oryeongsan treated db/db mice, plasma glucose/insulin, glucose tolerance, and HOMA‐IR index were significantly improved compared with untreated db/db mice, respectively. Immunohistological analysis revealed that glomerular type IV collagen and TGF‐β1 expression was decreased by Oryeongsan. Oryeongsan was also markedly reduced the ratio of mesangial matrix/glomerular area. In addition, protein expression levels of TGF‐β1, Smad‐2/‐4, type IV collagen, CTGF and TIMP were significantly decreased by Oryeongsan, whereas, Smad‐7 and MT1‐MMP were increased in the renal cortex. Smad‐2/‐4 activation in nucleus was also markedly decreased by Oryeongsan.Therefore, this study suggests that Oryeongsan suppresses mesangial fibrosis through the inhibition of type IV collagen and TGF‐β1/Smads action. Hence, Oryeongsan may be a new therapeutic option for the treatment of diabetic nephrosclerosis.
The effect of light load resistance exercise and whey protein supplementation on muscle protein synthesis and amino‐acid transporters in elderly (702.7)
Authors: Agergaard Jakob , Bülow Jacob , Kildevang Jensen Jacob , Reitelseder Søren , Schjerling Peter , Drummond Micah J. , Kjær Michael , Holm Lars 
Published: June 2021

In this study we tested how light load resistance exercise (LL RE) affects skeletal muscle protein synthesis (FSR) and amino‐acid transporter (AAT) protein expression as a way to counteract anabolic resistance and age related loss of muscle mass. Untrained healthy men (age: +65 yrs) were subjected to 13 hours supine rest. After 2½ hours of rest, unilateral LL RE was conducted: 10 times 36 reps of knee‐extensions at 15% 1RM. Hereafter, the subjects were randomized to oral intake of Placebo (4g maltodextrin/hour) (n=10), Pro‐C (4g whey protein/hour) (n=10) or Pro‐2 (28g whey protein at 0 hours and 12g whey protein at 7 hours post exercise) (n=10). Quadriceps muscle biopsies were taken at 0, 3, 7 and 10 hours post exercise from both resting and exercised leg. Myofibrillar‐FSR and membrane protein expression of select AATs were analyzed from the biopsies. LL RE increased myofibrillar‐FSR compared to the resting leg in all groups. An increase in AAT protein expression was only observed when LL RE was followed by whey protein intake. Specifically, Pro‐C increased LAT1, PAT1 and a tendency towards increased SNAT2 protein expression, Pro‐2 only increased PAT1 protein expression. We conclude that myofibrillar‐FSR increased in response to LL RE, irrespective of feeding in older adults. AAT protein expression only increased when LL RE was combined with whey protein intake.Grant Funding Source: Arla Foods Ingredients Group P/S, Viby J, Denmark
Investigating oxidative modification of anti‐oxidant enzymes and protein carbonylation as mechanisms of cigarette smoke‐induced cardiac stem cell damage (732.6)
Authors: Sumanasekera Wasana , Dao Halle , Gyamfi Felix , Shultz Kadi , Le Uyen , Rokosh Gregg 
Published: June 2021

Rationale and Objective: Cigarette smoking is a major health crisis across the globe resulting in many diseases including cardiovascular injuries. This study mainly focused on delineating mechanisms of CS induced cardiac stem cell (CSC) damage, which was observed earlier by our research group. We hypothesized that cigarette smoke induced reactive oxygen intermediates modify anti oxidant enzymes and proteins present in CSC via carbonylation leading to CSC damage, which can be attenuated by ascorbate treatment. Methods: C‐kit positive CSCs have been used as the experimental model. Following treatment of CSCs with cigarette smoke extract (CSE) for 24 hours, CSE induced oxidative modification of CSC proteins, total glutathione level, catalase activity, inhibition of super oxide dismutase (SOD) activity and ascorbate mediated prevention were assessed. The employed methods were; oxi‐ELISA, oxi‐blot / SDS polyacrylamide electrophoresis followed by western blotting, catalase, SOD activity, and total glutathione detection assays. Results: CSE induced oxidative modification / carbonylation of CSC proteins, inhibition of SOD activity, and alleviation of inhibition by ascorbate was observed. CSE caused increase in both catalase activity and total glutathione level in CSCs, which are indicative of oxidative stress. Ascorbate treatment decreased catalase activity indicating squelching of free radicals. Ascorbate increased total glutathione level in CSCs. Conclusions: Oxidative stress induced modulation of CSC proteins and antioxidant enzyme activity is the main mechanism for CSE induced attenuation of CSC function. Ascorbate served as a preventative measure. Implications: As CS attenuates CSC functions, it is crucial to find a way to optimize CSCs prior to transplant. Ascorbate pre‐conditioning serves as a promising target.Grant Funding Source: Supportyed by Sullivan University Faculty Development Grant
Comparison of lipoplasty technique effects on the cellular fate potential of adipose derived stem cells (732.7)
Authors: Belogorodsky Dimitry , Genoese Angela , Debo Matthew , Murphy Daniel , Chmielewski Sarah , Cho Ellen , Adams Christopher , D'Angelo Marina 
Published: June 2021

Clinical use of stem cells provide undeniable advantages as they can substitute for injured cells, tissues, and even organs in the human body. Adult adipose‐derived stem cells (ADSCs), have vast potential for clinical medicine because they can easily be harvested from a patient and provide an autologous transplant option. Data gathered in our lab has shown that harvesting ADSCs using water‐jet assisted liposuction (BodyJet) with laser‐assisted lipoplasty (SmartLipo) techniques produces a high yield of viable stem cells. These isolated cells can be plated in monolayer culture and retain their stem cell phenotype. In this study, we test the differentiation abilities of these BodyJet/SmartLipo harvested cells following cryopreservation. Since the clinical use of ADSCs is highly indicated for orthopedic and arthritis applications, we tested the ability of the liposuction‐harvested ADSCs to differentiate along the chondrocyte and osteoblast lineages. In this study, we compare the cryopreserved primary human ADSCs to a normal human, mesenchymal ADSC line, to measure stem cell viability and differentiation following thaw. Utilizing confocal microscopy, real‐time PCR, cell counts, alizarin red and alcian blue staining, the stem cells show promise in their ability to differentiate along the chondrocyte and osteoblast lineages. These data support the clinically‐relevant idea that lipoplasty‐obtained ADSCs will retain multipotency.Grant Funding Source: Supported by Pennsylvania Department of Health