bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral bovine lactoferrin protects bone microarchitecture in ovariectomized mice
Authors: Malet Arnaud , Blais Anne , Beaupied Hélène , Takashi Mikogami , Martin‐Rouas Christine , Tomé Daniel 
Published: June 2021

Estrogen deficiency and aging lead to a decrease of bone mineral density (BMD). Injected bovine lactoferrin (bLF) was suspected to improve bone status at physiological doses. The aim of this study was to evaluate the effects of oral bLF on quality of bone tissue in ovariectomized mice.Three‐month‐old female C3H mice were either ovariectomized or sham‐operated and fed for 6 months with the control diet (AIN‐93M) or diets including bLF (1, 5, 10 or 20 g/kg diet). Since BMD analysis does not take into account morphological alteration of bone architecture after ovariectomy, we analyzed microarchitectural parameters of bone tissue. Femurs of the mice were imaged by a Skyscan 1072 µCT with pixel size of 4 µm which may separately analyze trabecular and cortical bone. Volume, number, thickness and diameter of pores were measured at femur mid‐diaphysis.The results showed that oral bLF improved dose‐dependently BMD and femoral failure load, which are correlated to alterations of trabecular and cortical micro‐architecture. bLF inhibited the increase of cortical porosity induced by the ovariectomy. However bLF did not change significantly trabecular bone microarchitecture.In conclusion, oral bLF supplementation could display a beneficial effect on postmenopausal bone loss by modulating microarchitectural parameters of cortical bone which is strongly correlated to femoral failure load.
Dietary Factors related to Insulin Resistance in Overweight Mexican Pregnant Women
Authors: Perez Marcela , De Haene Jessica , Casanueva Esther , Parra Adalberto , Havel Peter , King Janet 
Published: June 2021

Insulin resistance (IR) increases during late pregnancy enhancing the risk of impaired glucose intolerance (IGT) or gestational diabetes mellitus (GDM). Overweight and obese women are at risk for IGT or GDM. Diet is used to treat of GDM, but the relationship between maternal diet and IR in pregnancy is not clear. Objective: To identify dietary factors that influence IR and post glucose load insulin sensitivity (IS) in overweight/obese Mexican women during mid and late gestation.MethodsThirty‐seven overweight Mexican women (BMI: 28.7+4.2) were studied. Nutrition counseling was given at baseline (20 wks gestation). Dietary intakes were estimated from three 24‐hr recalls done between 21 and 28 wk gestation. A 100g oral glucose tolerance test (OGTT) was performed at 28wk. The Homeostasis Model Assessment (HOMA‐IR), the Matsuda/DeFronzo Insulin Sensitivity Index and the insulin area under the curve (AUC) were determined.ResultsDietary polyunsaturated fat (PUFA) intake explained 12% of the variability in HOMA‐IR at 28 wk (p<0.05), and the % energy from protein explained 12% of the variability in the insulin AUC (0.05); none of the dietary variables were related to IS.ConclusionIn this population, HOMA‐IR declined by 4% for each gram of PUFAs consumed per 1000 kcals/day suggesting that pregnant women at risk for IR and GDM should be encouraged to increase their PUFA intake. Partially supported by UC Mexus
Ethanol increases histone H3‐K4 methylation and decreases histone H3‐K9 acetylation in conjunction with increased p16 gene expression in the normal colonic epithelial cells
Authors: Jang Hyeran , Barlev Nickolai A. , Ausman Lynne M. , Mason Joel B. , Moyer Mary P. , Choi Sang‐Woon 
Published: June 2021

The objective of this study was to determine whether disturbances in one‐carbon metabolism could modify p16 gene expression through histone modifications. NCM460, human colonic epithelial cells, were incubated in media 1) deficient in folate, methionine and choline, 2) with 100μM Adox (adenosine‐2', 3′‐dialdehyde, an S‐adenosylhomocysteine hydrolase inhibitor), and 3) with 100mM ethanol, which inhibits methionine synthesis and reduces methyl group availability. Histone methylation at histone H3 lysine 4 (H3‐K4) and acetylation at lysine 9 (H3‐K9), both known to be increased in active genes, were measured by Western blotting and p16 gene expression by RT‐PCR. Ethanol increased H3‐K4 trimethylation (p=0.005) and decreased H3‐K9 acetylation (p<0.0001) in a time‐dependent fashion. These changes in histone modifications were paralleled with increased p16 expression (p=0.003). Adox decreased H3‐K9 acetylation time‐dependently (p=0.004) without any change in p16 expression. Folate/methionine/choline deficiency didn't produce any changes in this in vitro culture model. This study demonstrates that in this normal colonic cell line, ethanol, which inhibits one‐carbon metabolism, alters H3‐K4 trimethylation and H3‐K9 acetylation in conjunction with an increase in p16 expression.Grant Funding SourceNIH R21 AA016681
Whole grain consumption does not slow diabetic progression in GK rats
Authors: Youn Moonyeon , Csallany A. Saari , Gallaher Daniel D. 
Published: June 2021

Whole grain consumption is inversely associated with risk of type II diabetes epidemiologically. The aim of this study was to study the effect of whole grain consumption on diabetic control and progression in an animal model of type II diabetes, the Goto‐Kakisaki (GK) rat. GK rats were fed either a whole grain‐free control diet or a whole grain‐containing diet for 5 months. Whole grain diets contained 65% whole grain flours of either wheat, barley, oat, or corn. After two months, fasting plasma glucose concentration was significantly lower with the wheat, barley, or oat diets compared to the control diet. However, glycated hemoglobin was significantly greater in the wheat group compared to other groups. At 5 months, whole grain diets did not improve glycemic control. Fasting plasma insulin and C‐Peptide levels were decreased from month 2 to month 5 indicating diabetic progression. Insulin resistance, determined by the homeostasis model assessment, was not significantly different among groups at either 2 or 5 months. However, there was a trend for improvement of insulin resistance with the barley and oat diets at 2 months (P=0.06). There were no significant differences in the total pancreatic β‐cell mass among groups. These results offer little support for improvement of diabetic control and delayed progression with consumption of whole grains. (Supported by the General Mills Bell Inst. of Health and Nutrition)Grant Funding SourceGeneral Mills Bell Inst. of Health and Nutrition
The effects of portabella mushrooms on bone mineral density and body composition in mice without and with collagen induced arthritis.
Authors: Traore Djibril , Petersorn Sandra , Lim Yin , Alexander Heather , Sharp Dean , Clarke Stephen , Lucas Edralin , Smith Brenda , Kuvibidila Solo 
Published: June 2021

Certain exotic mushrooms contain beta‐glucan that has been shown to modulate immunity and provide health benefits. However, little information is available on the health benefits of portabella mushrooms (PM). The objective of the study was to assess the effects of PM on indices of nutritional status in mice without and with collagen‐induced arthritis (CIA). Eight‐week old, DBA female mice were fed either the AIN76 (baseline) diet or the same diet fortified with 5% lyophilized PM (20/group) for 6 weeks. To induce CIA, 50% of mice received 100 ug bovine collagen type II intradermally followed by 50 ug LPS 20 days later. Lean and fat mass, bone mineral density, and various organ weights were assessed by standard techniques 10 days after LPS injection. Between 90‐100% of mice that received collagen developed mild‐moderate paw swelling. In PM and baseline fed mice, CIA reduced body weight and thymus weights by 13%‐47%, doubled spleen weights, and increased relative weights of heart, liver, and kidney by 20‐24.5% for PM and 22‐28% for baseline diet (p <0.05). Non‐CIA and CIA mice fed PM diet had higher percent of body fat (32.6% & 25.8%) than those fed baseline diet (25% & 21.9%) (p <0.05). Compared to baseline diet, PM attenuated thymus atrophy (13% vs 47%) and loss of lean mass (10% vs 17%) after CIA induction (p<0.05). PM slightly (4‐5%) increased bone mineral content but not bone mineral density in CIA and non‐CIA mice. Data suggest that PM increase the percent of body fat which may attenuate muscle protein loss and minimize thymus atrophy hence T cell numbers in rheumatoid arthritis. Supp.: Grant # 580790706 (Mushroom Council/USDA/NutriCore) and funds from Oklahoma State University.Grant Funding SourceThe Mushroom Council/USDA
Effects of prebiotic Quercetin on proliferation and beta‐catenin expression in colon cancer cell lines
Authors: Marzo Florencio , Alfaro Maria , Jauregui Patricia , Benito Ivan , Santidrian Santiago , Urdaneta Elena 
Published: June 2021

Colon cancer incidence is increased in the occidental countries, prevention is very important to reduce the incidence of this disease. Functional foods could play a modulating function on colon cancer development. The aim of our study was to study the cellular and molecular effects of quercetin on the proliferation of human HT‐29 colon cells.HT‐29 cells were obtained from the European Collection of Cell Culture (EACC) and cultured in Dulbecco's modified Eagle's medium supplemented. At 80% confluence, cells were plated in 96‐well plates at 4x104cells/well and then were incubated in serum‐free medium in the presence or absence of various concentrations of quercetin (50µM‐ 125µM) during 72h. Cell proliferation was measured by MTT assay. â‐Catenin plays an important role in the Wnt signaling pathway. The expression of â‐catenin in cells treated was analysed by western blott.Quercetin inhibited the proliferation of HT‐29 cells, being the cells treated with quercetin presented a significant decrease (p<0.001) in growth cells compared with control group. â‐catenin expression in the cells treated with quercetin during 48h is lower compared with cells treated during 24h and control group. This data suggests that quercetin shown beneficial effects related to cell proliferation, showing an inhibitory effect.This work was supported by Spanish Education and Science Ministry (AGL2006‐10296).
Secondary effects of 'Duffy Antigen Receptor for Chemokines' (DARC) blockade on inflammation and hemostasis
Authors: Singbartl Kai , Schmolke Mirco , Bishop Jeffrey , Zarbock Alexander 
Published: June 2021

IntroductionUnlike typical chemokine receptors, DARC is presented on red blood and endothelial cells but not on leukocytes. We have previously shown that DARC‐deficient mice (DARC‐/‐) display protection from LPS‐induced kidney injury and lower serum CXC‐chemokine levels. The latter one implies changes in CXC chemokine receptor 2 (CXCR2) expression on neutrophils (PMN). Here, we sought to compare CXCR‐2 homeostasis and its biological effects in wild‐type (WT) and DARC‐/‐ mice.ResultsBefore LPS stimulation, DARC‐/‐ showed 3x higher CXCR2 expression on PMN than WT (*). Afterwards, DARC‐/‐ revealed greater CXCR2 down‐regulation than WT (*), suggesting desensitization of PMN in DARC‐/‐. Compared to WT, DARC‐/‐ showed impaired PMN recruitment in the lung and full protection from ALI (*). Adoptive transfer of PMN proved that these effects were solely due to PMN from DARC‐/‐. DARC‐/‐ revealed prolonged bleeding time and decreased TEG amplitude (*), suggesting impaired platelet‐platelet or platelet‐PMN interactions. Conclusions : Alteration in serum CXC‐chemokine levels and subsequent changes in CXCR2 homeostasis appear to have profound anti‐inflammatory and anti‐hemostatic effects.
Regulation of Cell Adhesion by the Physical Properties of Fibrin(ogen) Substrates
Authors: Yermolenko Ivan , Fuhrmann Alexander , Podolnikova Nataly , Magonov Sergei , Ros Robert , Ugarova Tatiana 
Published: June 2021

The physical properties of substrates are crucial to the regulation of cell adhesion through integrin‐mediated signaling. The matrices formed of fibrin(ogen) represent the natural substrates whose variable rigidity may control adhesion of blood cells. Binding of fibrinogen to the surface of fibrin gel prevents firm adhesion of leukocytes and platelets creating the anti‐adhesive layer. Also, fibrinogen immobilized on surfaces at high density supports weak adhesion whereas at low density it is highly adhesive. To understand the mechanism underlying differential cell adhesion, we have characterized the structural and physical properties of surfaces prepared by deposition of different concentrations of fibrinogen using atomic force microscopy and force spectroscopy. Fibrinogen deposited at high density results in the multilayered material characterized by low rupture forces. In contrast, immobilization of fibrinogen at low density produces a single layer in which molecules are directly attached to the solid surface resulting in higher rupture forces. Consistent with their distinct physical properties, low, but not high density fibrinogen induces strong intracellular signaling and cell spreading. The data suggest that multilayered fibrinogen prevents cell adhesion by modifying the physical properties of surfaces which results in reduced force generation and insufficient signaling.HL63199
B cells compartement in centenarian offspring and old people
Authors: Bulati Matteo , Colonna‐Romano Giuseppina , Vitello Salvatore , Pellicanò Mariavaleria , Vasto Sonya , Candore Giuseppina , Caruso Calogero 
Published: June 2021

Immunosenescence is considered a major contributory factor to the increased frequency of morbidity and mortality among elderly. Immunosenescence studies focus mainly on T cells, although B cells are affected too. In our studies we analyzed B cells in two classes of individuals: old people (O), (age range 70‐85 years) and centenarian offspring (CA). Our data showed difference in number of B cells from O and CA. B cells were analyzed according to the expression of sIgD and CD27. B cells were classified as follows: IgD+CD27−(naïve),IgD+CD27+(unswitched‐memory),IgD−CD27+ (switched ‐memory) and IgD−CD27−(double negative, DN). As expected, in both cohorts we observed a marked decreased of B cell count although within the B cell population, CA do not behave as O subjects. Indeed, in CA , naïve B cells are more abundant whereas DN B cells don't show the typical increase that we have previously demonstrated in healthy elderly donors. So, B cells of the CA seem to be more similar to that of young respect to the old one. B cell subsets changes could represent a hallmark of immunosenescence and could be used as a biomarker of human life span, potentially useful for the evaluation of anti‐ageing treatment.This work was supported by grants from the Italian Ministry of Education, University and Research (MIUR, ex 40%)
Asbestos bodies in lung tissue are associated with pathologic features and patient outcome for epithelial but not non‐epithelial mesothelioma treated by extrapleural pneumonectomy
Authors: Richards William G , Godleski John , Katler Marshall , Mueller Jordan , Sugarbaker David 
Published: June 2021

We examined patient survival and pathologic tumor features in relation to asbestos body (AB) counts in lung tissue from patients with malignant pleural mesothelioma (MPM).Lung tissue was digested with Clorox® by standard methods. AB counts were made using phase contrast light microscopy. Kaplan‐Meier estimates of overall survival were compared using logrank tests for dichotomized AB count in WHO epithelial (E) and non‐epithelial (NE) MPM subgroups. Association of AB count with reported pathological features was assessed using Fisher's Exact test.From 1988 to 2005, 365 E (72% male; median age 57) and 194 NE patients (90% male; median age 60) were treated. Of these, 234 (64%) E and 142 (73%) NE had AB evaluation. Median AB count for E was 265/g (wet weight) vs. 1084/g for NE and 20/g control AB count. Among E patients, 105 with AB≤200/g had 27‐mo. median survial vs 17.1 mo. for 129 with >200 AB/g (p=0.0003). By contrast, survival for 32 NE with AB≤200/g (9.5 mo.) did not differ from 109 NE with >200 AB/g (12.7 mo.;p=0.58). AB counts above median were significantly associated with involvement of lung parenchema (p=0.0055) and intralobar fissure (p=0.0176) for E but not NE. No relation of AB to diaphragm, pericardium or chest wall involvement was evident.We conclude that AB has prognostic significance in MPM and that E and NE represent distinct disease entities.Supported by the International Mesothelioma Program
Anti‐inflammatory benefits of an antibiotic via modulation of neutrophil and macrophage function: The example of tulathromycin
Authors: Fischer Carrie Dawn , Beatty Jennifer K , Morck Douglas W , Lucas Merlin J , Robb Edward J , Buret Andre G 
Published: June 2021

The pathogenesis of bacterial‐induced inflammatory diseases is due, in part, to the host immune response. The ability of an antibiotic to modulate immune cell function during infection may confer anti‐inflammatory benefits. Tulathromycin (TUL), an antibacterial agent for bovine respiratory disease, is a novel model for investigating immuno‐modulating effects of antibiotics. Studies have shown that TUL exerts pro‐apoptotic effects in bovine neutrophils (PMN). Nuclear factor‐¿B (NF¿B), a transcription factor implicated in the onset of inflammation, is known to inhibit apoptosis. The effects of TUL on macrophage function are unclear.AimsTo investigate the mechanisms of TUL‐induced PMN apoptosis and to determine the effects of TUL on bovine macrophage (MØ) function.ResultsELISA revealed TUL‐induced PMN apoptosis is caspase‐3 and ‐8 dependent. Western blotting showed TUL reduces phosphorylation of NF¿B inhibitor, I¿B, in zymosan‐stimulated PMN. Light microscopy suggested TUL stimulates phagocytosis of apoptotic PMN in MØ. ELISA and Greiss reaction showed TUL reduced secreted levels of pro‐inflammatory interleukin‐8 and nitric oxide in E. coli lipopolysaccharide‐challenged MØ.ConclusionModulation of PMN and MØ function by TUL is associated with inhibition of NF¿B signaling. These findings illustrate novel mechanisms through which an antibiotic may deliver anti‐inflammatory benefits.
HIV protease inhibitors induce ER stress and apoptosis in human endothelial cells
Authors: Sun Lixin , Wu Xudong , Cao Risheng , Zha Weibin , Pecora Beth S , Gurley Emily C , Studer Elaine , Hylemon Phillip B. , Pandak William M. , Zhang Luyong , Hu Yiqiao , Wang Guangji , Zhou Huiping 
Published: June 2021

Endothelial dysfunction/injury represents a key step in the early stage of atherogenesis. Recent studies have shown that HIV protease inhibitors (PIs) induce endothelial dysfunction, but the underlying molecular mechanism remains unclear. Our previous studies have shown that HIV PI‐induced ER stress and activation of the unfolded protein response (UPR) represents an important cellular mechanism by which HIV PIs disrupt lipid metabolism and induce inflammation in hepatocytes and macrophages. The aim of this study was to determine if HIV PIs also induce ER stress and apoptosis in human endothelial cells.MethodsHuman umbilical vein endothelial cells (HUVECs) were treated with individual HIV PIs for various time periods. The mRNA and protein levels of ER stress responsive genes were measured by real‐time RT‐PCR and Western blot analysis, respectively. The apoptosis was detected by fluorescence microscopy using Annexin V‐FITC/propidium iodide. The protein levels of TNF‐α, IL‐6, and MCP‐1 were determined by ELISA.ResultsBoth lopinavir and ritonavir dose‐dependently activated the UPR, increased IL‐6 and MCP‐1 expression, and induced apoptosis in HUVECs. But amprenavir had no significant effect.ConclusionsHIV PI‐induced ER stress response and activation of the UPR may represent a critical molecular mechanism underlying HIV PI‐associated endothelial dysfunction and atherogenesis.
Cleavage of glycogen synthase kinase‐3beta by matrix metalloproteinase‐2 enhances its kinase activity
Authors: Kandasamy Arulmozhi D , Schulz Richard 
Published: June 2021

Matrix metalloproteinase (MMP)‐2 is localized to the sarcomere of cardiomyocytes and contributes to myocardial ischemia‐reperfusion injury by degrading sarcomeric and cytoskeletal proteins. Oxidative stress mediates its damaging effects through activation of MMP‐2 within the cardiomyocyte and subsequent proteolysis of susceptible intracellular targets. Glycogen synthase kinase (GSK)‐3β is involved in growth, death & metabolism and susceptible to proteolytic cleavage. We determined whether GSK‐3β is a proteolytic substrate of MMP‐2 and how this cleavage affects its kinase activity.Incubation of MMP‐2 and GSK‐3β resulted in a time‐ and concentration‐dependant cleavage of GSK‐3β with significant increase in GSK‐3β kinase activity. Dephosphorylation of GSK‐3β with λ‐phosphatase prevented MMP‐2 mediated augmented kinase activity. H2O2 treated H9c2 cardiomyoblasts showed increased levels and activity of MMP‐2 accompanied by significant reduction in GSK‐3β protein levels and increased kinase activity.The data indicate that GSK‐3β is a target of MMP‐2 and that its cleavage by MMP‐2 enhances GSK‐3β kinase activity. GSK‐3β dephosphorylation studies suggest that MMP‐2 may cleave off the inhibitory serine‐9 residue. This MMP‐2 mediated augmentation of GSK‐3β kinase activity may contribute to cardiac dysfunction as a result of myocardial oxidative stress injury. This work was supported by CIHR.
Decreased Ovalbumin‐induced Airway Inflammation in Mice Deficient in the Sensory Neuronal Ion Channel TRPA1
Authors: Caceres Ana Isabel , Brackmann Marian , Bessac Bret F , Cohn Lauren , Jordt Sven Eric 
Published: June 2021

The airways are densely innervated by peripheral sensory neurons. Activation of chemosensory C‐fibers by chemical irritants triggers defensive reflexes such as cough and sneezing, and initiates airway constriction and glandular fluid secretion. Local neuronal release of pro‐inflammatory peptides promotes edema formation and vascular leakage. We recently identified TRPA1 as the chemosensory receptor for noxious oxidants and electrophiles in the airways.Chemosensory neurons are activated or sensitized during chronic inflammatory states and may be involved in the initiation and maintenance of airway conditions such as asthma and chronic obstructive pulmonary disease (COPD). Inflammatory mediators, including prostaglandins, bradykinin, histamine, reactive oxygen species and lipid peroxidation products activate or sensitize TRPA1 and other sensory ion channels such as TRPV1, the capsaicin receptor.We asked whether absence of TRPA1 or TRPV1 would affect the inflammatory process in the ovalbumin (OVA) mouse model of allergic airway inflammation. OVA‐challenged TRPA1‐deficient mice showed dramatically diminished eosinophil infiltration in the airways. Multiplex analysis of bronchoalveolar lavage fluid showed a reduction in levels of Th2‐derived cytokines and chemokines.We conclude that neuronal TRPA1 channels are essential for establishment of OVA‐dependent airway inflammation in mice.