bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mirthful laughter, as adjunct therapy in diabetic care, attenuates catecholamines, inflammatory cytokines, C‐RP, and myocardial infarction occurrence
Authors: Berk Lee S , Tan Linda , Tan Stanley 
Published: June 2021

Objectives: Catecholamines are implicated in causing arrhythmias, hypertension, and MI. Inflammatory cytokines TNF‐α, IFN‐γ and IL‐6 contribute to the acceleration of atherosclerosis. Attenuation of catecholamines and inflammatory cytokines may provide cardiovascular protection. We hypothesized that mirthful laughter, by diminishing catecholamines production, can attenuate inflammatory cytokines, and provide cardiovascular protection.Methods: We divided 20 high risk diabetic patients with hypertension and hyperlipidemia into 2 matched groups and followed them for one year in our Metabolic Syndrome Clinic. The experimental group was asked to view self‐selected humor for 30 minutes daily as an adjunct to standard diabetes (glipizide, TZD, metformin), hypertension (ACE inhibitor or ARB) and hyperlipidemia (statin) therapies. Plasma fractionated catecholamines levels, lipid panel, TNF‐α, IFN‐γ, IL‐6, and CRP were monitored and assayed every 2 months.Results: Patients in the laughter group had lower EP and NEP levels by 2 months, increased HDL cholesterol, decreased TNF‐α, IFN‐γ, IL‐6 and CRP levels by 4 months, and a lower incidence of MI (1/10) than the control group (3/10).Conclusions: Addition of mirthful laughter may be an effective cardiovascular preventive adjunct in diabetes mellitus and metabolic syndrome care. These effects may contribute to lower MI occurrence.
Exercise‐induced alterations and fibre type specific distribution of ARC protein in human skeletal muscle
Authors: Vigna Chris , Bombardier Eric , Tupling A. Russell , Quadrilatero Joe 
Published: June 2021

Apoptosis repressor with caspase recruitment domain (ARC), is an anti‐apoptotic protein expressed highly in cardiac and skeletal muscle. This study characterized the fibre type specific expression pattern of ARC in human skeletal muscle for up to six days following acute isometric knee extension exercise. Eight males (age 19.5 ± 0.6 yrs; mass 81.8 ± 2.9 kg; height 182.3 ± 4.9 cm; mean ± SE) completed 30 min of intermittent (50% duty cycle, 5 sec on – 5 sec off) isometric exercise at 40% of their maximal voluntary contraction. Biopsies were taken from the vastus lateralis before and after exercise and at 1, 2, 3 and 6 days post exercise. Immunohistochemical analysis revealed fibre type specific differences in ARC expression prior to exercise with Type I fibres having ∼22% and 33% higher (p<0.05) protein content relative to Type IIA and IIAX/X fibres, respectively. Immediately post exercise, ARC protein was decreased (p<0.05) by ∼24%, 32% and 26% in Type I, IIA and IIAX/X fibres, respectively. ARC remained depressed in all fibres for up to six days following exercise. Similar results were observed with western blot analysis on whole muscle homogenates. These results suggest the anti‐apoptotic protein, ARC, is differentially expressed in skeletal muscle by fibre type, but equally responsive to exercise.Research supported by NSERC Canada
Enhanced apoptotic propensity in diabetic cardiac interfibrillar mitochondria
Authors: Williamson Courtney L , Dabkowski Erinne R , Hollander John M 
Published: June 2021

Cardiovascular complications, including diabetic cardiomyopathy, are the leading cause of mortality among diabetic patients. Enhanced mitochondrion‐dependent apoptosis is associated with diabetic cardiomyopathy pathogenesis. Two spatially distinct mitochondria populations exist in the cardiac myocyte, interfibrillar mitochondria (IFM), which situate between the contractile apparatus, and subsarcolemmal mitochondria (SSM), which exist beneath the plasma membrane. The goal of this study was to determine the impact of diabetic insult on the apoptotic propensity of spatially distinct mitochondrial populations. Swiss Webster mice were made diabetic by streptozotocin injection and sacrificed following diabetes onset. Our findings indicate that diabetic IFM display a greater propensity for undergoing apoptosis as compared to SSM. Specifically, mitochondrial permeability transition pore time to Vmax was decreased in diabetic IFM as compared to control (P<0.05), with no difference in SSM. Mitochondrial membrane potential was decreased in diabetic IFM as compared to control (P<0.05) with no difference in SSM. Mitochondrial cytochrome C content in IFM was decreased as a result of diabetic insult. These results indicate that cardiac IFM are more susceptible to diabetes‐associated apoptosis, and may be more contributory to the pathogenesis of diabetic cardiomyopathy.(Supported by AHA 0665237B)
Protective effect of curcumin against high glucose‐induced endoplasmic reticulum stress by downregulation of COX‐2 expression in human umbilical vein endothelial cells
Authors: Fan Ying , Meng Xiang‐hong , Chen Wen‐liang , Zhu Li , Shen Yue‐liang , Chen Ying‐ying 
Published: June 2021

OBJECTIVE: The aim of this study is to investigate whether curcumin could protect against high glucose‐induced apoptosis by suppressing endoplasmic reticulum (ER) stress pathway in human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were exposed to low glucose (5.5mmol/L) or high glucose (30mmol/L) for 12~48 h. The expression of ER stress‐related markers (glucose‐regulated protein 78 (GRP78/Bip) and CAAT/enhancer binding protein homologous protein (CHOP)) and cyclooxygenase‐2 (COX‐2) were also evaluated by western blotting analysis. RESULTS: (1) Annexin V‐FITC/PI flow cytometry analysis revealed a time‐dependent increase of apoptotic cells in HUVECs treated with high glucose. Curcumin (10~100 μ mol/L) inhibited the high glucose‐induced apoptosis in a dose‐denpendent manner. (2) High glucose induced a time‐dependent increase in the levels of COX‐2, GRP78 and CHOP proteins expression in HUVECs. (3) Curcumin and NS‐398 (a COX‐2 inhibitor) downregulated high glucose‐induced overexpression of COX‐2 and CHOP expression in HUVECs. CONCLUSION: These data suggest that curcumin can protect the HUVECs against high glucose‐induced apoptosis by downregulation of COX‐2 and inhibition of endoplasmic reticulum stress.(This work was supported by the National Natural Science Foundation of China (No. 30400094))
Effects of BITC on TRAIL Sensitization in Human Pancreatic Adenocarcinomas
Authors: Wicker Christina Ann , Kulkarni‐Datar Kashmira , Srivastava Sanjay K. , Brown Thomas L. 
Published: June 2021

Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95 % mortality rate and an average survival period of 4–6 months after diagnosis. Treatment options for pancreatic cancer are limited. Chemotherapeutic resistance has been associated with mutations within codon 12 of the K‐Ras gene (K‐Ras 12). These mutations are present in over 90 % of all pancreatic adenocarcinomas and leave Ras in a constitutively‐active state leading to continual cellular proliferation.Benzyl isothiocyanate (BITC) is a component of cruciferous vegetable extract, and a reported cell cycle inhibitor. TNF‐related apoptosis inducing ligand (TRAIL) is a novel cytokine, whose receptor is highly expressed on tumor cells but generally absent on normal cells. Thus, TRAIL can preferentially target tumor cells to induce apoptosis while leaving non‐tumor cells relatively unharmed.Our study determined if TRAIL resistance in pancreatic adenocarcinoma with codon 12 K‐Ras mutations can be overcome by first sensitizing the cells using BITC. Western blot analysis revealed activation of early apoptotic pathways but failure to activate later apoptotic pathways resulting in little increase in apoptosis between TRAIL alone and BITC with TRAIL. These results reveal the need to further study alternative survival mechanisms that contribute to chemotherapeutic resistance.
Osteoprotegerin modulation of immunefunction during of the atherosclerotic lesion progression
Authors: Scatena Marta , Rosenfeld Michael 
Published: June 2021

Osteoprotegerin (OPG) is a secreted TNF‐like decoy receptor shown to regulate bone homeostasis. Evidence indicates that serum levels of OPG correlate with the severity of cardiovascular disease. We have shown that in ApoE−/− mice, OPG deficiency worsen the lesion burden, suggesting that OPG is an athero‐protective factor. Recent studies indicate that OPG also plays a role in adaptive immunity. B cells subsets are expanded in OPG−/− mice, and in vivo OPG induces increase of IgM and IgG antibodies titers. Furthermore, DCs isolated from OPG−/− mice were more effective in stimulating T‐cells than WT. Thus, we hypothesize that in ApoE−/− mice OPG stimulates the production of athero‐protective antibodies and dampens the production pro‐atherogenic Th1 cytokines, thus explaining the increased lesion size observed in ApoE−/− mice also lacking OPG. To test this hypothesis we have measured serum levels of total IgG and IgM, and of anti‐ox‐LDL antibodies. We have also measured serum levels for the pro‐atherogeneic IL12 cytokine. We have found that ApoE−/− OPG−/− mice have lower serum levels of IgM and IgG and lower serum levels of the atheroprotective anti‐oxLDL antibodies compared to ApoE−/− OPG+/+. ApoE−/− OPG−/− mice have higher serum levels of IL12 than ApoE−/− OPG+/+. In vitro we found that ApoE−/− OPG−/− DCs and macrophages express more IL12 than ApoE−/− OPG+/+. These results indicate that OPG may modulate key immune factors and cells during the atherosclerosis process. Future studies will be aimed to determine whether OPG in immune cells subsets causatively modulate the atherosclerotic lesion progression.Supported by AHA Grant in Aid #0655677Z
Interactome Networks
Authors: Vidal Marc 
Published: June 2021

For over half a century it has been conjectured that macromolecules form complex networks of functionally interacting components, and that the molecular mechanisms underlying most biological processes correspond to particular steady states adopted by such cellular networks. However, until recently, systems‐level theoretical conjectures remained largely unappreciated, mainly because of lack of supporting experimental data.To generate the information necessary to eventually address how complex cellular networks relate to biology, we initiated, at the scale of the whole proteome, an integrated approach for modeling protein‐protein interaction or “interactome” networks. Our main questions are: How are interactome networks organized at the scale of the whole cell? How can we uncover local and global features underlying this organization, and how are interactome networks modified in human disease, such as cancer?
The Effects of Escalating Quantities of Salvia hispanica L. (Salba) on Postprandial Glycemia and Appetite in Healthy Individuals
Authors: Vuksan Vladimir , Dias Andre , Chiavaroli Laura , Lee Amy 
Published: June 2021

Objective: To assess the effects of escalating quantities of the whole grain Salvia hispanica L. (Salba) on postprandial glycemia and appetite.Methods: Using an acute randomized controlled design, 12 healthy individuals (7M;5F;BMI 22.3±2.8 kg/m2) received either 0, 7, 15 or 24 g of Salba baked into white bread. The control (0g) was repeated twice. All meals contained 50 g of available carbohydrates. Thus, subjects consumed 5 different meals with at least 3 days in between visits. Fingerprick blood samples and ratings of satiety scores on a 100 mm visual analog scale were taken at 0, 15, 30, 45, 60, 90 and 120 minutes post‐consumption.Results: There was a dose‐response reduction of postprandial glycemia with the highest and intermediate quantities of Salba resulting in an IAUC blood glucose reduction of 43% (p=0.0013) and 33% (p=0.0115), respectively. Only the intermediate dose resulted in a significant reduction in combined satiety score, with an average reduction of 47% compared to the two other experimental meals and controls at every time point after 15 minutes.Conclusions: Addition of the whole grain Salba to white bread lowers postprandial glycemia and appetite, and may be potentially cardioprotective. Thus, further research is warranted to assess the effects of Salba on long‐term reduction of cardiovascular risk factors, carbohydrate metabolism and control of body weight.Sponsor: Salba Inc, Toronto
Including rapeseed protein in a high‐fat meal prevents postprandial vascular endothelial dysfunction in rats
Authors: Magné Joëlle , Huneau Jean‐François , Tomé Daniel , Mariotti François 
Published: June 2021

High saturated fat/ high sucrose meals induce oxidative stress associated with vascular endothelial dysfunction, an early hallmark in atherogenesis, but the impact of meal protein on vascular homeostasis remains misunderstood. Here, we investigated the potential of rapeseed protein, an emergent cysteine‐rich protein, to modulate the adverse effects of a high‐fat meal (HFM).In a cross‐over design, 12 healthy rats received 3 isoenergetic HFM (saturated fat: 60%; sucrose: 20%; proteins: 20% of total energy) with the protein source being either total milk protein (C), rapeseed protein (R), or milk protein supplemented with cysteine and arginine up to the same level as in R (AA). Endothelium‐related vascular reactivity, measured as acetylcholine‐induced transient fall in blood pressure, and plasma triglycerides, hydroperoxides and cGMP were measured before and 2, 4 and 6 h after meal.While plasma triglycerides rose similarly in all meals, the decrease in endothelial function after C was attenuated after AA and steadily blunted after R. The postmeal decrease in plasma cGMP was lessened 2h after R, as compared to after meal C. Plasma hydroperoxydes increased after the 3 meals, but were lower 6h after meals AA and R than after C.These results show that rapeseed protein specifically suppresses the acute deleterious effects of HFM on endothelial function, and this may be mediated in part by cysteine and arginine.
Effect of α‐ and γ‐Tocopherols on 4‐Hydroxyestradiol Induced Oxidative Stresses in MCF‐10A Breast Epithelial Cells
Authors: Sung Mi‐Kyung , Lee Eun‐Ju , Oh Seung‐Yeon 
Published: June 2021

Both estrogen and oxidative stress are known risk factors for breast cancer development. Human breast epithelial cells(MCF‐10A) were incubated with 0.1uM 4‐ Hydroxyestradiol (4‐OHE2)with or without 30uM α‐, γ‐tocopherols(α‐T, γ‐T) for 24 to 96hrs. Intracellular ROS, glutathione and MnSOD expression as oxidative stress markers were measured. The level of DNA damage repair‐related protein including p53, PARP‐1, and BRCA1 were also measured. By oxidative stimuli, p53 is phophorylated and PARP‐1 was cleavaged, which leads to DNA repair. PARP‐1 is also essential in regulating BRCA1 in response to DNA damage. Results showed 4‐ OHE2 increased the intracellular ROS level with a down‐regulation of MnSOD protein. A significant negative correlation was found between ROS level and GSH/GSSG ratio. Cleavaged PARP‐1 was increased and BRCA1 and PARP‐1 depletion was observed with ROS accumulation. γ‐T reduced 4‐OHE2‐induced ROS, while increased GSH/GSSG ratio and MnSOD protein. γ‐T also up‐regulated phosphorylated p53 protein. α‐T is shown to up‐regulate BRCA 1 and PARP‐1 protein. In conclusion, 4‐OHE2 increases oxidative stresses which possibly down‐regulate protein related to DNA repair. α‐and γ‐T may prevent 4‐OHE2 induced oxidative stress and DNA damage and thereby retard breast tumor development.This work was supported by the Korea Research Foundation Grant(KRF‐2005‐042‐C00194).
Novel epigenetic mechanisms involved in enhanced inflammatory gene expression in vascular smooth muscle cells derived from diabetic db/db mice and relation to diabetic memory
Authors: Villeneuve Louisa M , Reddy Marpadga A , Lanting Linda L , Wang Mei , Meng Li , Natarajan Rama 
Published: June 2021

Diabetes and associated inflammation are major risk factors for vascular complications despite glycemic control, thus implicating a “diabetic memory”. However, the molecular mechanisms are unclear. We hypothesized that dysregulation of histone H3 lysine trimethylation (H3K9me3), a key repressive epigenetic chromatin mark, may lead to diabetic memory. This was tested in vascular smooth muscle cells (VSMC) derived from insulin resistant type 2 diabetic db/db mice, which exhibit persistent pro‐atherogenic and inflammatory phenotype even in normoglycemic culture. H3K9me3 levels at promoters of key inflammatory genes (ChIP assays) and protein levels of the H3K9me3 methyltransferase Suv39h1 (W. Blot) were significantly decreased in db/db VSMC relative to non‐diabetic control db/+ cells. Furthermore, db/db VSMC were hypersensitive to inflammatory stimuli (TNFα) which induced dramatic reductions in promoter H3K9me3 and occupancies of Suv39h1. Suv39H1 gene silencing in non‐diabetic VSMC increased inflammatory genes, while conversely, Suv39H1 overexpression in db/db VSMC reversed this diabetic phenotype. These novel findings demonstrate protective roles for H3K9me3 and Suv39H1 in the pre‐activated diabetic cells. Aberrant epigenetic histone methylation may be a major mechanism for diabetic memory implicated in chronic inflammation and diabetic complications.Support: NIH, Myrtle Carr Fdn
TLR4‐signaling is required for NOD2 but not NOD1 activation in hepatocytes
Authors: Scott Melanie J , Liao Hong , Billiar Timothy R 
Published: June 2021

NACHT‐LRR receptors (NLRs) are recently identified intracellular pattern recognition receptors. The NLRs NOD1 and NOD2 respond to microbial ligands, e.g. diaminopimelic acid (DAP) and muramyl dipeptide (MDP) respectively. Hepatocytes (HC) are microbial‐responsive cells that express and activate Toll‐like receptors (TLRs). We hypothesized that HC also express and activate NOD1 and NOD2 as part of the initiation and regulation of innate immunity. Protein expression of NOD1 and NOD2 was detected in whole cell lysates of primary isolated HC from C57BL/6 mice. Other HC were treated with LPS (100ng/mL), iE‐DAP (100ng/mL; NOD1 ligand), or MDP (10μg/mL; NOD2‐ligand) for up to 60min before collection of whole cell lysates or nuclear isolation. NOD ligands were endotoxin free as determined by sensitive colorimetric endotoxin assay. MAPK (ERK, JNK, and p38) were activated and NFκB translocated to the nucleus in HC treated with iE‐DAP (NOD1 ligand), to similar levels as with LPS‐stimulation. However there was minimal activation of NFκB with MDP (NOD2 ligand) unless cells were pretreated for 24h with LPS. Activation of NFκB after MDP stimulation (NOD2 ligand) was partially TLR4‐dependent but activation of NFκB with iE‐DAP was similar in isolated WT and TLR4−/− HC. Taken together these data show expression of NOD1/NOD2 in HC, and differential regulation of their activation by TLR4.Work supported by NIH grant R01‐GM‐50441
Development of M cells within the follicle‐associated epithelium of Peyer's Patches depends on expression of TRANCE/RANKL by stromal cells
Authors: Freel Kathryn A , Taylor Rebekah T , Butler Betsy R , Kumar Nachiket , Williams Ifor R 
Published: June 2021

M cells are specialized epithelial cells found in the follicle‐associated epithelium (FAE) covering Peyer's patches (PP). M cells sample small particulate antigens from the intestinal lumen and transport these antigens to intraepithelial pockets found on the basal aspect of M cells. PP from mice lacking B cells (μMT knockout mice) have a marked reduction (over 150‐fold) in the overall number of intestinal M cells, but the specific receptor‐ligand interaction(s) central to promoting normal M cell differentiation within the FAE have not yet been identified. We now report that PP from mice deficient in the TNF superfamily member TRANCE/RANKL (TNFSF11) display a defect in M cell development that is even more pervasive than that of μMT mice. M cells identified by whole mount immunofluorescence microscopy using rhodamine‐conjugated Ulex europaeus lectin (UEA‐1) are essentially absent from PP in the proximal and central portions of the small intestine. Rare UEA‐1+ M cells are present in a few follicles from the most distal PP of TRANCE‐deficient mice, but these M cells don't have the normal radial symmetry of FAE M cells and are instead abnormally clustered near the apex of the dome. The M cell deficiency in the PP of TRANCE‐deficient mice is associated with impaired formation of PP germinal centers and decreased fecal IgA. TRANCE is selectively expressed by subepithelial stromal cells located in the dome area of PP. These findings indicate that local production of TRANCE by PP stromal cells is required for the normal induction and differentiation of M cells within the FAE.Supported by the NIH (DK‐64730, DK‐64399).
High intakes of fructose are associated with alterations in liver fatty acid composition in rats
Authors: Riediger Natalie Diane , Chen Qilin , Abdullah Mohammad , Kroeker Amy , Lanoo Christy‐Anne , Othman Rgia , Xu Zuyuan , Zou Jitao , Azordegan Nazila , Moghadasian Mohammed H 
Published: June 2021

Background: Diets high in fructose may result in abnormalities in glucose and lipid metabolism.Purpose: To investigate the effects of a high‐fructose diet on liver fatty acid composition.Methods: Male Sprague‐Dawley rats were divided into two groups: a control group (n=5) receiving standard chow diet, and treatment group (n=7) receiving a diet containing 10% w/w lard and 60% w/w fructose for 20 weeks. Fatty acid profile of various lipid fractions in the liver of these animals was characterized.Results: Total liver lipids including cholesterol and triacyglycerol (TAG) were significantly higher in the treated group as compared to controls. The livers from treated animals had significantly lower levels of C16:0 and higher levels of C18:1 in the TAG fraction, and lower levels of C18:1c11, C18:2c9, C20:1c11, C20:1c13 along with higher levels of C16:1 and C18:1c9 in the free fatty acid fraction. The levels of C16:0, C18:2c9, C20:1c11, C20:1c13, C20:2c11 and C24:0 were significantly increased in the phosholipid fraction of the treated animals.Conclusions: High intakes of fructose change liver lipid composition and fatty acid profile in rats. TAG and phospholipid fractions seem to be affected more. These changes may lead to alterations in hepatocyte functions including lipid metabolism and may modify cardiovascular risk.
Bone, diet and physical activity in a group of Puerto Rican obese adults.
Authors: Palacios Cristina , Soltero Sandra , Rios Ruth , Beltran Jose Juan 
Published: June 2021

Diet, physical activity and bone mineral content (BMC) and density (BMD) were measured in a group of Puerto Rican obese adults, 21–50 years old. A total of 29 subjects, 23 females and 6 males, participated in this study. Dietary intake was estimated from 3 24‐h diet records and daily physical activity level was measured by the Framingham Physical Activity Index during the same 3 days. BMD was measured by Dual‐Energy X‐Ray Absorptiometry (Hologic). BMI was 40.2±5.9 kg/m2, and 39.9±6.7 kg/m2, in females and males, respectively. Calcium intake was 528±146 mg/d and 624±197 mg/d, magnesium intake was 184.6±65 mg/d and 219±75 mg/d, vitamin K intake was 30±20 mcg/d and 17±6 mcg/d, and physical activity index score was 29±2.6 and 31±3, in females and males, respectively. Total BMC was 2325±389 g and 2856±577 g and BMD was 1.164±0.121 g/cm2 and 1.270±0.139 g/cm2, in females and males, respectively. BMI was significantly correlated to BMC (r=0.45, p<0.05). In this group of young obese adults, dietary intake was not related to BMC or BMD. Calcium, magnesium and vitamin K intakes were much lower than recommended intakes and most subjects had a sedentary lifestyle. A larger study is needed to determine the major determinants of bone in Puerto Ricans.This investigation was supported by the RCMI Clinical Research Infrastructure Initiative (RCRII) Award, 1P20 ‐ RR11126, from NCRR, NIH.