bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship among Framingham Heart Score, Nutrients and Food Group Intakes in Korean Adults
Authors: Choi Mi‐Kyeong , Kim Soon‐Kyung , Bae Yun Jung
Published: June 2021

The objective of this study was to investigate the relationship among Framingham Heart Score (FHS), nutrients and food group intakes in Korean adults. A total 310 healthy adult (males; 131, female; 179) aged 30~79 participated in this study. FHS of total subjects was 11.72. The subjects were divided into two groups: low FHS group (FHS<13) (n=150), and high FHS group (FSH>=13) (n=160) according their FHS. The average energy intakes of low and high FHS groups were 1622.53 kcal and 1498.78 kcal, respectively and no significant difference in energy intake was observed between two groups. However, low FHS group consumed significantly higher quantities of fat (p<.0001), vitamin A (p=.0244), vitamin B1 (p=.0186), vitamin B2 (p<.0001), vitamin E (p=.0251), animal calcium (p=.0050), and cholesterol (p<.0001) per 1000 kcal, whereas intake of carbohydrate per 1000 kcal of high FHS group (p=.0013) was significantly higher than that of low FHS group. Also, intake of egg (p=.0024) and milk (p=.0007) in low FHS group were significantly higher than those of high FHS group. Fat, vitamin A, B2, calcium, and cholesterol intake showed significantly negative correlations with FHS adjusted for energy intake. These results suggest that low intakes of micronutrients such as calcium and vitamins may be more related to Framingham Heart Score than high energy and food intakes in Korean adults.
Comparison of dietary intake and clinical characteristics of obese with normal weight subjects
Authors: Jeon Kyeong Jin , Lee Okeui , Kim Min Soo , Han Sung Nim
Published: June 2021

Obesity contributes to increased risk for chronic diseases including diabetes, cardiovascular diseases and certain types of cancer. Prevalence of obesity has been increasing in Korea. We compared characteristics of obese (n=30, 17 males and 13 females) with normal weight subjects (n=16, 8 males and 8 females). Clinical parameters including lipid profiles, FBS, blood pressure, and serum free fatty acid (FFA) were determined. Dietary intake was estimated using food frequency questionnaire (FFQ) and 3‐day dietary record. Exercise pattern and alcohol intake were determined through individual interviews. Average BMI was 28.3 in obese group and 21.2 in normal weight group. Obese group had significantly higher serum levels of total cholesterol, LDL cholesterol, and triglyceride compared with normal weight group. HDL cholesterol level was significantly lower in obese group. There was no significant difference in FBS between two groups. Both systolic and diastolic blood pressures were significantly higher in obese group. Serum FFA level tended to be higher in obese group (p=0.075). Female had significantly higher levels of serum FFA. No significant difference in caloric intake was observed between two groups. Carbohydrate, protein, and fat intakes were not significantly different. Frequency and amount of exercise did not differ between two groups. Obese group consumed significantly more alcohol. Results from this study confirm that excessive weight is associated with disturbance in lipid metabolism. Dietary factors contributing to obesity was not identified, but, excessive alcohol consumption does seem to be an important contributing factor.

Supported by the Korea Research Foundation grant funded by the Korea government (KRF‐2009‐0068320).
Study on relationship between dietary sodium intake and hypertension in Heilongjiang residents
Authors: Liu Shumei , Qin Aiping , Zhang Yaxu
Published: June 2021

To explore the relationship between dietary sodium intake and hypertension and provide scientific evidence on hypertension intervention, we used a subpopulation of 1,254 subjects aged 18–65 years old in Heilongjiang province from an ongoing longitudinal study, China Health and Nutrition Survey. We used a stratified multistage cluster sampling scheme to randomly select two cities and four counties in Heilongjiang province. Experienced physicians collected detailed diet data and measured blood pressures. The prevalence of hypertension increased from 25.0% in 2004 to 28.0% in 2009. Added salt intake decreased slightly from 7.6 g/day to 7.4 g/day; however this was offset by an increased sodium intake from 3.6 d/day to 3.8 g/day. One key change was the significant increase in processed food consumption from 60.5 g/day to 70.4 g/day. The increased prevalence of hypertension is much more rapid and has attained a much higher level in Heilongjiang than in other areas in China. Excessive intakes of sodium and processed foods, particularly pickled vegetables, may attribute to the high prevalence of hypertension.

This study was supported by NIH (R01‐HD30880) and Fogarty International Center, NIH (5D43TW007709).
Body mass index and suboptimal energy or protein intake predict risks of dialysis and mortality in patients with chronic kidney disease (CKD)
Authors: Chen Mei‐En , Hung Chi‐Chih , Hwang Shang‐Jyh , Chen Hung‐Chun , Huang Meng‐Chuan
Published: June 2021

Background

Prognostic roles of BMI or diets for progression in CKD remain unclear.

Aims

We prospectively investigated relationships between BMI and intake of energy/protein and risks of ESRD and mortality in a cohort of CKD patients with stage 3 or less in Taiwan. The median follow‐up time was 27.3 months.

Methods

High dietary protein intake (DPI) was defined as ratio of intake/recommendation ≥110%; low dietary energy intake (DEI) was as the ratio <90%. High DPI and/or low DEI were classified as suboptimal intake.

Results

Upon adjusting for confounders, BMI 24 to 26.9 (RR=0.80), BMI≥27 (RR=0.70) had progressively lower (all p<0.05) risks of renal death or mortality than BMI<24, and suboptimal intake of either DPI or DEI (RR=1.86), suboptimal intake of both DEI and DPI (RR=2.51) showed significantly greater (all p<0.05) risks compared to the optimal counterpart based on Cox's proportional‐hazard models.

Conclusions

Both BMI and intake of energy and protein amount appear to associate with progression of CKD. Nutrition counseling may be needed for CKD patients with respect to optimal management of weight and diet.
Supplementation of amphiregulin improves fatty liver regeneration after partial hepatectomy (PHX): the role of c‐Jun N‐terminal kinase (JNK) and extracellular signal‐regulated kinases (ERK)
Authors: Zhong Zhi , Liu Qinlong , Rehman Hasibur , He Songqing , Shi Yanjun , Krishnasamy Yasodha , Schnellmann Rick G
Published: June 2021

In previous work, we reported that the growth factor, amphiregulin (AR), decreased in steatotic livers after PHX. In this study, we investigated whether supplementation of AR improved regeneration of remnant fatty livers. Mice were fed a high‐fat, high‐fructose diet (HFFr) or a low‐fat, low‐fructose control diet for 2 weeks and then underwent two‐thirds‐PHX. In contrast to the control diet, the HFFr diet caused moderate hepatic steatosis as indicated by Oil‐Red‐O staining (~40%). At 48 h after PHX, liver regeneration was suppressed in fatty livers. Treatment of mice with fatty livers with recombinant human AR (5 μg/mouse, iv immediately after PHX) improved liver regeneration and increased survival from 40 to 100% after PHX. The phosphorylation levels of EGFR, JNK and ERK were lower in fatty than lean remnant livers, and exogenous AR increased EGFR, JNK and ERK phosphorylation in fatty remnant livers. Phospho‐mTOR, phospho‐AKT, phospho‐p70S6 kinase, and phospho‐p38 MAP kinase were not significantly different between lean and fatty remnant livers. Together, these data reveal that fatty livers remain responsive to AR, which stimulates regeneration of fatty livers after PHX, at least in part, by activating EGFR and its downstream JNK and ERK pathways (NIDDK).
Application of a labeled antibody for noninvasive monitoring of transplanted hepatocytes by Near‐Infrared (NIR) imaging
Authors: Stock Peggy , Weber Kristin , Ebensing Sabine , Caysa Henrike , Christ Bruno
Published: June 2021

Technologies for in vivo imaging gain significance to monitor distribution and integration of cells for the use in cell therapies during the regeneration of diseased organs. The aim of the study was to identify NIR dyes for visualization of transplanted hepatocytes in vivo in rats. Wild type and CD26‐deficient hepatocytes and livers from wild type Fisher rats were used. A total of six dyes (DY676, 681, 776, 777, 782, 800 emission range 699–801nm) were analyzed using a multispectral imager. For quantification, the Regions‐of‐Interests (ROI) of defined mixtures of CD26‐positive and negative cells were detected. Results were verified by flow cytometry.

DY676, 776, 777, 782, 800 yielded non‐specific conjugates with undefined cellular components. DY681 linked to the CD26‐antibody specifically detected CD26‐positive hepatocytes. DY681 displayed ROIs of 372, 375, 244, 102 and 9 [average signal] using defined mixtures of 100%, 85%, 50%, 15% and 0% CD26‐positive cells. Flow cytometry confirmed 99%, 78%, 56%, 21% and 0.2% CD26‐positive cells. Wildtype livers treated in situ with DY681‐CD26 antibody displayed positive signals throughout the whole organ.

The DY681‐linked antibody is eligible for the non‐invasive labeling of transplanted hepatocytes. Thus, the hepatic distribution of the cells and repopulation of the liver might be observed, which helps to reduce the amount of animal experiments.
Hepatocyte‐targeted Overexpresssion of Glypican 3 in Mice Suppresses Hepatocyte Proliferation and Hepatomegaly after Phenobarbital Administration
Authors: Lin Chih‐Wen , Liu Bowen , Donthamsetty Shashikiran , Orr Anne , Bowen William C , Kang Liang‐I , Mars Wendy M , Michalopoulos George K
Published: June 2021

Glypican 3 (GPC3) belongs to a family of GPI‐anchored, cell‐surface HSPGs. GPC3 is overexpressed in HCC. Loss‐of‐function mutations of GPC3 result in SGBS by overgrowth of multiple organs. Our previous study showed that in GPC3 transgenic (TG) mice, hepatocyte overexpression of GPC3 suppresses hepatocyte proliferation and liver regeneration and alters gene expression. This study investigates the role of GPC3 in hepatocyte proliferation and liver enlargement induced by phenobarbital (PB). WT and GPC3 TG mice were given 0.1 % PB in drinking water for 10 days. Livers were harvested on 1, 3, 5, and 10 days during PB administration. In WT mice, the liver weight was double as compared to day 0 at day 5. In TG mice, the liver weight was a little larger as compared to day 0 at day 5 (1.3 times). In TG mice, the hepatocyte proliferation by Ki67 positive nuclear staining was significantly suppressed at day 3 compared with WT mice after PB administration. An increase of GPC3 protein levels was observed in TG mice compared with WT mice. Moreover, gene array analysis revealed a series of changes in the gene expression profile in TG mice. After PB administration, a panel of cell cycle related genes are either up‐ or down‐regulated, as confirmed by western blotting. In summary, hepatocyte overexpression of GPC3 suppresses proliferative response not only to liver regeneration but also to xenobiotic chemical mitogens, such as PB.
A 12 Amino Acid Peptide Reduces the Oncogenic Potential of EWS‐FLI1 in Ewing's Sarcoma
Authors: Erkizan Hayriye Verda , Jacobwitz‐Scher Lauren M , Gamble Ellen , Barber‐Rotenberg Julie , Sajwan Kamal , Uren Aykut , Toretsky Jeffrey A
Published: June 2021

Introduction

The EWS‐FLI1 oncogenic fusion protein is derived from a tumor‐specific t(11;22) chromosomal translocation that is uniquely expressed in Ewing's Sarcoma. We hypothesize that peptides interacting with EWS‐FLI1 can modulate protein function and improve therapies for Ewing's Sarcoma patients.

Methods

Phage display peptide screening was performed by using EWS‐FLI1 as the bait.

Results

We identified 27 unique EWS‐FLI1 binding peptides. These Ewing Sarcoma Antagonist peptides (ESAPs) were synthesized with Antennapedia and evaluated in TC32 (Ewing's Sarcoma), and SKNAS (neuroblastoma) cell lines for growth inhibition. We found that the cytotoxicity for ESAP‐1 is the most potent among other peptides. We further explored this peptide's inhibitory effect in Ewing's Sarcoma. We confirmed that ESAP‐1 peptide binds directly to EWS‐FLI1 by ELISA and Surface Plasmon Resonance. This peptide reduced the transcriptional activity of EWS‐FLI1 and interfered the cell cycle by G2M arrest.

Discussion

The ESAP‐1 peptide directly binds to the EWS‐FLI1 and leads to cell death in cells that harbor this fusion protein. This finding provides a novel experimental and potential therapeutic tool for Ewing's Sarcoma. This work is supported by Children's Cancer Foundation, Baltimore, MD
Studies on the function of Ufd3/Doa1 in the distribution of sterol in yeast
Authors: Li Guangtao , Zhao Gang , Lennarz William J
Published: June 2021

Ufd3/Doa1 (mamallian homologue PLAA) was initially identified as a component involved in the UFD (Ubiquitin Fusion Degradation) pathway. The defects in Ufd3/Doa1 null strain were mainly caused by the loss of ubiquitin levels, because overexpression of ubiquitin can rescue the defects. However, it is still not clear how Ufd3/Doa1maintains the ubiquitin. In addition to the effect on the ubiquitin level, Ufd3/Doa1 was also plays critical roles in sorting of ubiquitinated protein into the vascuolar/lysosome lumen via the MVB pathway. Recently we found that the C‐terminus of PLAA not only interacts with reported p97/Cdc48, but OBP9L, an oxylsterol binding protein like protein. We also confirmed that the interaction between the yeast Ufd3/Doa1 and OSH proteins. Furthermore, we found that yeast Ufd3/Doa1 null strain is sensitive to a polyene antifungal, amphitericin B, which associates with the main component of yeast cell membrane, ergosterol. All these results indicate that Ufd3/Doa1 might play important roles on the sterol system.
Hyaluronan synthesis is controlled through protein O‐GlcNAcylation in vascular smooth muscle cells
Authors: passi alberto , Vigetti Davide , Deleonibus Sara , Moretto Paola , Viola Manuela , Karousou Evgenia , De Luca Giancarlo
Published: June 2021

The accumulation of hyaluronan (HA) into vessel wall supports neointima formation and cardiovascular disease progression, here we reported the intracellular regulation of HA synthesis throughout O‐GlcNacylation. The excess of glucose could enter in the hexosamine biosynthetic pathway (HBP) that increases the concentration of the HA precursor UDP‐N‐acetylglucosamine (UDP‐GlcNac) leading to an increase of HA synthesis. In this study, we tested the role the HBP in the regulation of HA biosynthesis in human primary aortic smooth muscle cells. UDP‐GlcNAc can be the donor of GlcNAc for O‐GlcNacylation, a type of cytoplasmic protein O‐glycosylation to ser/thr residues. We found that the inhibition of O‐GlcNacylation strongly reduced HA production whereas treatments that induced protein O‐GlcNacylation increased HA secretion. Gene expression studies revealed that HAS2 mRNA (i.e., the main HA synthesizing enzyme located in the plasma membrane) was the most sensible to O‐GlcNacylation and accumulated after its induction. We found evidences that the transcription regulator YY1 activates HAS2 expression after O‐GlcNacylation. At protein level, experiments with wheat germ agglutinin and recombinant 6myc‐HAS2 revealed that this enzyme was actually O‐GlcNacylated. Further, HAS2 O‐GlcNacylation increased HAS activity in purified microsomes leading to HA accumulation. This work was supported by FAR and Onlus Varesotto‐ITALY.
Conserved charged residues in the extracellular domain of epithelial sodium channel (ENaC) essential for cell‐surface expression
Authors: Hanukoglu Israel , Edelheit Oded , Dascal Nathan , Hanukoglu Aaron
Published: June 2021

Epithelial sodium channels (ENaC) are composed of three subunits whose extracellular domains (ECD) form a funnel that directs ions from the lumen into the pore of ENaC. To examine the roles of conserved charged residues on ECD, we mutated 16 residues in human α‐ENaC to alanine. The modified cRNAs were expressed in Xenopus oocytes together with wild type β‐ and γ‐ENaC. The effect of each mutation was examined on three parameters: amiloride‐sensitive Na+ conductance, Na+‐dependent self‐inhibition of ENaC and oocyte cell surface expression of ENaC (quantitated by confocal imaging of Yellow Fluorescent Protein linked to γ‐ENaC). All 16 mutants showed a strong correlation between ENaC activity and oocyte surface expression. Control mutations to a homologous charged residue (e.g. Asp to Glu) did not significantly affect ENaC activity. Changes in the two parameters, Na+ self‐inhibition and oocyte surface expression level, accounted for the magnitude of reduction in ENaC activity as a result mutation to Ala. These results establish that while some conserved charged residues are part of the structure responsible for Na+ self‐inhibition, most are essential for transport to the oocyte cell‐surface.
Dinoflagellate Bioluminescence: Cloning and Sequence Analysis of Luciferase from Pyrocystis fusiformis
Authors: Ngo Phong D , Haines Donovan C , Loeffler Paul A
Published: June 2021

Pyrocystis fusiformis is a protozoan species, approximately forty micrometers in length, that is closely related to plants and algae. These dinoflagellates are photosynthetic and also utilize a luciferase bioluminescence system. Luciferases are a class of enzymes that are responsible for luminescence by catalyzing the oxidation of a substrate molecule, luciferin, in a reaction that produces light at 475 nm. In an effort to discover the structural biology of the luciferase contained within Pyrocystis fusiformis, long‐term research is focused on cloning the genes that code luciferase and purifying luciferin. Alignments of the sequence of this luciferase with other characterized dinoflagellate luciferase allowed the identification of a catalytic core and related fragments for later studies. Extraction and purification of chromosomal DNA from Pyrocystis fusiformis was performed for the purposes of PCR cloning. Dinoflagellates are thecate, meaning that their cellular membranes are interlaced with polysaccharide deposits that form rigid plates making it incredibly difficult to lyse, short of homogenization. Several DNA extraction methods and combinations were tested in order to determine the most effective protocol for preparation of genomic DNA for PCR.
Novel Regulation of CREB Activation by Reactive Oxygen Species in B Lymphocytes
Authors: Gravis Demetrius , Stick Adam
Published: June 2021

cAMP Responsive Element Binding protein (CREB) is a transcription factor that promotes expression of genes involved in cell growth and survival. Signaling via reactive oxygen species (ROS) has been reported to attenuate CREB activity by phosphorylation of CREB at the inhibitory site serine‐121. However, ROS signaling has also been reported to enhance CREB activity via phosphorylation at the positive regulatory site serine‐133. We investigated the effects of ROS on CREB activity in murine B lymphocyte cells and observed that hydrogen peroxide induced CREB phosphorylation at ser‐133. Menadione, a superoxide inducer, also promoted CREB phosphorylation at ser‐133. In contrast to our prediction, we observed that peroxide did not induce ser‐121 phosphorylation but rather suppressed ser‐121 phosphorylation. Menadione treatment, however, did not exhibit this marked suppression of ser‐121 phosphorylation. ATM, a kinase activated by DNA damage and ROS, has been previously reported to mediate CREB phosphorylation at ser‐121 in other cell types, and we observed a similar role for ATM in B cells. Intriguingly, we also observed that U0126, an inhibitor of the MEK‐ERK pathway, also suppressed ser‐121 phosphorylation of CREB. Our data therefore illustrate novel mechanisms of CREB regulation in B lymphocytes and suggest that different species of ROS can mediate distinct effects on CREB activation.
Efficiency of Gαs‐Coupling is different between Vasoactive Intestinal Peptide Receptor 1 and 2 in T Lymphoblastic Cells
Authors: Van der Steen Travis , Light Naomi , Haring Jodie , Dorsam Sheri , Dorsam Glenn
Published: June 2021

Vasoactive intestinal peptide (VIP) influences cell proliferation in a complex, cell‐context manner. Two G‐protein coupled receptors called, vasoactive intestinal peptide receptors 1 (VPAC1) and VPAC2, bind VIP with a similar affinity and elicits signaling through Gαs. It has been reported that T cell lines that express VPAC1 or VPAC2 show differing effects on chemotaxis. In contrast, wild type CD4 T cells expressing both receptors demonstrated a similar affect on chemotaxis. Consequently, this discrepancy regarding cellular effects of VIP receptor signaling, along with coexpression of both receptors on T cells, has made it difficult to determine the biology of these receptors. We hypothesize that VPAC1 and VPAC2 receptors couple through Gαs and mediate different magnitudes of intracellular cAMP (i[cAMP]). Utilizing two T cell lines that exclusively express VPAC1 (HuT 78) or VPAC2 (Molt 4) as validated by qPCR and immunoblots, we investigated the effects of VIP ligand binding by measuring i[cAMP] and GTP‐Gαs immunoprecipitation (IP). In the presence or absence of serum, Molt 4 cells elicited a greater i[cAMP] response compared to HuT 78 cells. These data were confirmed by IP of the active GTP‐Gαs complex showing a greater exchange for Molt 4 vs. HuT 78 cells. We conclude that VPAC signaling elicits different magnitudes in Gαs signaling and supports distinct receptor function. Funding: (COBRE) 2P20RR015566
Role of guanine‐binding protein inhibitory alpha in activation of the Akt/mTORC1 pathway by growth factors
Authors: Wang Zhanwei , Cruz Rica Dela , Jiang Meisheng , Chu Wen‐Ming
Published: June 2021

The Akt/mTOR pathway is essential for cell growth, migration and survival mediated by growth factors. Although it has been known that growth factor receptors called receptor tyrosine kinases (RTKs) and adaptor proteins including Grb2, Gabs, IRSs as well as FRSs are critical for activation of this pathway, it is still not well understood how these adaptor proteins are activated. We have found that the heterotrimeric guanine‐nucleotide binding protein (G protein) alpha inhibitory (Gia) is critical for mediating this activation. In Gi1a and Gi3a double knockout mouse embryonic fibroblasts (Gia1/3 DKO MEFs), the activation of the Akt/mTORC pathway was largely impaired by epidermal growth factor (EGF), EGF family members, fibroblast growth factors, and low doses of platelet derived growth factor (PDGF). In contrast, Gia1 and Gi3a double deficiency had no profound defect in activation of this pathway by insulin and insulin‐like growth factors. Mechanistic study results indicated that Gia proteins are important for the association of adaptor proteins and PI3K regulatory subunit p85. Further analysis revealed that loss of Gia proteins impaired MEFs migration and proliferation in response to growth factors. In addition, Gia proteins are important for cancer cell growth and migration. Overall, our results suggest that Gia proteins are new players in growth factor signaling and the pathogenesis process of cancer.
Discovery of novel benzoisoquinoline compounds for anti‐coronaviruses
Authors: Lee Shiow‐Ju , Lee Yue‐Zhi , Yang Cheng‐Wei , Chao Yu‐Sheng
Published: June 2021

Human Severe Acute Respiratory Syndrome (SARS) is a disease caused by SARS coronavirus (SARS CoV). The outbreak of SARS in year 2003 had caused worldwide panic and chaos. Although no cases of SARS have been reported since April 2004, the nature of the unpredictable outbreak of SARS CoV is still a potential threat to the global economy and public health. No effective therapy exists for SARS CoV infection, despite tremendous effort invested in finding anti‐SARS CoV drugs, including targeting SARS‐CoV‐specific main protease or viral attachment, entry, and fusion for intervention. Thus, SARS‐CoV or some variant thereof could easily remerge to cause disease. Previously, we reported on the discovery, synthesis and identification of tylophorine compounds as novel, potent inhibitors of TGEV and SARS CoV in vitro with IC50 values at low nanomolar range. Herein, we further explored new classes of novel benzoisoquinoline compounds for anti‐coronaviruses. Their inhibition in cellular effects is similar to that of phenanthroindolizidine tylophorine compounds. These compounds exerted profound anti‐TGEV replication activity and thereby blocked the TGEV‐induced apoptosis and subsequent cytopathic effect in ST cells.
Niacin (Vitamin B3, Nicotinic Acid) Decreases Apolipoprotein B (ApoB) and VLDL Secretion from Mouse Hepatocytes
Authors: Guo Liang (Charles) , Fisher Edward A.
Published: June 2021

Niacin reduces plasma atherogenic apolipoprotein B (apoB)‐containing lipoproteins. To further understand if part of the mechanism of the VLDL‐lowering effect is on secretion of apoB‐containing lipoproteins, we isolated primary hepatocytes from Apobec1−/ − mice, which, like human liver, express apoB100 only. Niacin was well tolerated by hepatocytes showing no hepatotoxicity up to 100 mM. Metabolic labeling and pulse‐chase studies showed that niacin increased intracellular apoB100 degradation by 30%, decreased VLDL secretion from hepatocytes by 40%. These effects were found depend on medium supplementation of nicotinamide, the amide of niacin, which supplies sufficient NAD biosynthesis. The nicotinamide supplementation resulted in a dose‐dependent increase of apoB100 secretion and recovery, suggesting that adequate cellular NAD level is important for maximum VLDL secretion and a critical condition for niacin‐induced apoB100 degradation. Intraperitoneal niacin administration to Apobec1−/− mice caused a 40% decrease in the hepatic VLDL‐triglyceride production rate in vivo. Taken together, these data suggest that niacin decreases apoB100 and VLDL secretion from hepatocytes. The molecular mechanism responsible for these effects of niacin on the assembly and secretion steps of apoB100‐containing lipoprotein is under further investigation. Supported by grants from the NIH (HL58541) and Merck & Co., Inc.
Anthropometric characteristics and predictors of adiposity among preschool children in a multiethnic population
Authors: Ramcharitar‐Bourne Anisa , Nichols Selby , Badrie Neela
Published: June 2021

In this study we evaluated the anthropometric characteristics, as well as, anthropometric predictors of adiposity among preschool children 3–5 years old. Five hundred and ninety‐six preschool children had anthropometry using standard procedures. Percentage body fat was estimated using a foot‐to‐foot bioelectric impedance analyser. Our results indicate that 31.2 % of participants were of African descent, 43.6 % were of East Indian descent and 24% were of Mixed (African‐East Indian) descent. Participants of African descent were significantly taller, heavier, had higher abdominal fat and mid‐upper arm circumference than those of East Indian and Mixed descent. Weight and BMI each explained over 75% of the variance in adiposity among females, while in males weight accounted for only 24% of the variance, while BMI explained 31%. In males, waist circumference, triceps skinfold and biceps skinfold each predicted less than 40% of the variance in adiposity, while in females, it explained over 55% (83.2%, 67.4% and 56% respectively). Our results suggest that there are ethnic differences in anthropometry in this population. They also suggest that weight, BMI and waist circumference are each excellent predictors of adiposity in female preschoolers in this population, while triceps was the best predictor of adiposity in the males.
Prevalence and determinants of iron depletion and anemia among Canadian Inuit
Authors: Jamieson Jennifer A , Weiler Hope , Kuhnlein Harriet , Egeland Grace
Published: June 2021

Accelerated loss of traditional lifestyles may place Inuit at risk of iron depletion, given that anemia has been frequently observed. Study objectives were to determine the prevalence of anemia, storage iron depletion and iron overload; and to identify correlates of iron status in Canadian Inuit adults. In a cross‐sectional survey of 2550 adults, hemoglobin, serum ferritin, soluble transferrin receptor (on a subset), and C‐reactive protein (CRP) were measured on fasting venous blood. Anthropometry, dietary, sociodemographic and health data were collected. Correlates of iron status were assessed with multivariate linear and logistics models. Low prevalence of inadequate iron intake was observed (<10 %). For men with CRP<10 mg/L (n=804) 6.5 % had depleted and 10.3 % had elevated iron stores. For women with CRP<10 mg/L (n=1260) 29.4 % had depleted iron stores. Anemia was present in 16.1 % of men and 21.7 % of women. Iron depletion explained 51 % of anemia cases in women but few cases in men (15 %). Odds ratios for iron depletion were 2.3 (1.2–4.6 95% CI) for food insecure men and 2.1 (1.0–4.1) for men without a household hunter. Among food insecure women, higher n3‐PUFA status was associated with reduced risk of iron depletion (OR=0.84; 0.72–0.98). Iron depletion is a concern for young Canadian Inuit women. Interventions should address food security and traditional food access. Funding: IPY, HC, CIHR, INA, GNHSS, ArcticNet.
Effects of diet type during an exercise and weight loss program on markers of metabolic syndrome in women with elevated uric acid levels
Authors: Kreider R , Oliver JM , Kresta JY , Byrd M , Baetge C , Mardock M , Simbo S , Lockard B , Jung Y , Koozehchian M , Khanna D , Kyul H , Jagim A , Rasmussen C
Published: June 2021

237 women (41±9 yrs, 164±7 cm; 93±17 kg; 35±6 kg/m2) consumed 1,200 kcal/d for 1‐wk and 1,600 kcal/d for 9 wks consisting of 55% CHO, 15% P, and 30% F (HC, n=76) or 7–15% CHO, 55–63% P, and 30% F (HP, n=161) while participating in a 30‐min circuit training program 3 d/wk. Blood samples and DEXA body composition measurements were obtained at 0 & 10 wks and analyzed by MANOVA. Subjects were stratified into groups of less than (LU) and higher than (HU) median uric acid (UA) levels (4.8 mg/dl). UA levels were significantly different between groups (LU 3.8±0.6; HU 5.7±0.9 mg/dl, p=0.001). Diet and training significantly decreased (p<0.003) body weight (−3.6±3.0 kg), fat mass (−2.6±2.8 kg), waist circumference (−2.8±9 %), total CHL (−2.9±13 %), and SBP (−2.1±12 %). Significant interactions were seen in weight loss (HP −3.9±4.2; HC −2.8±3.1 kg, p=0.06), fat loss (HP −3.0±3.0; HC −1.7±2.1 kg, p=0.001), waist circumference (HP −3.6±8; HC −1.3±11 %, p=0.08), and TG (HP −4.7±31; HC −5.0±39 %, p=0.04). Significant diet x UA level x time effects were seen in weight loss (HP/LU −3.2±4.3, HP/HU −4.6±4.1, HC/LU −3.7±3.4, HC/HU −3.9±3.9, p=0.03), fat loss (HP/LU −2.7±3.0, HP/HU −3.3±3.0, HC/LU −2.3±2.2, HC/HU −1.1±2.0, p=0.02), and blood glucose (HP/LU 0.4±19, HP/HU −2.7±12, HC/LU −1.4±9, HC/HU 2.6±11, p=0.08). Results indicate that individuals with higher UA levels may experience greater weight and fat loss following a HP diet during training.
Maternal weight change at three months postpartum and postpartum breastfeeding, diet and physical activity in Mexican women
Authors: López‐Olmedo Nancy Paulina , Hernández‐Cordero Sonia , Neufeld Lynnette , García‐Guerra Armando , Mejía‐Rodríguez Fabiola , Méndez Ignacio
Published: June 2021

Objective

To explore the association of breastfeeding, diet and physical activity with maternal weight change from the first to the third month postpartum.

Material and methods

Secondary data analysis from a randomized trial in women from urban Mexico.. The information was collected in prospective form. The association of postpartum weight change and diet, physical activity and breastfeeding practices changes in the same period was assessed using generalized estimating equations.

Results

The overall prevalence of overweight and obesity was 59.5% at three months postpartum. Women who breastfed her infants exclusively until three months postpartum decreased 4.2 (1.96) kg in comparison with women who never breastfed or stop breastfeeding before three months postpartum (p<0.05).

Discussion

Exclusive breastfeeding can contribute to lose weight in the postpartum period, at least during the first three months. Our finding suggest that exclusive breastfeeding can reduce the prevalence of overweight and obesity in the early postpartum.
Functional improvement and neuroprotection provided by human cerebral endothelial cells intravenouly‐transplanted in focal ischemia rat brain
Authors: Kim Hyung‐Seok , Park Man‐Seok , Lee Min‐Cheol , Lee Jung‐Kil
Published: June 2021

Stable clonal cell line of hCEC, HEN7, has been generated from human fetal telencephalon using a retroviral vector encoding human telomerase reverse transcriptase (hTERT). HEN7 cells were transplanted intravenously in rat brain with photochemically induced focal cerebral ischemia, and the clinical effects for infarct size, edema volume, and clinical outcome were evaluated. FACS analysis showed HEN7 cells express the characteristics of cerebral endothelial cells. Matrigel assay showed HEN7 cells are capable of good tube formation. HEN7 showed positive immunoreactivity for vascular, stem cell, and tight junction proteins. HEN7 transplanted group showed reduced infarct lesion as identified by bioluminescence and X‐gal staining located in the infracted lesion border area. HEN7 transplanted group showed markedly reduced edema volume, MMP‐9 expression, and Caveolin‐1 expression. HEN7 transplanted group showed earlier recovery from the neurological deficit.Intravenously transplanted hCECs selectively migrated and integrated into cerebral ischemic lesion area and accelerate neurological functional recovery. This new hCEC‐based cellular therapy is applicable for clinical trial in ischemic stroke patients.
A Central Role of PTP1B in Hyperinsulinemia‐enhanced IL‐6 Signaling in Vascular Smooth Muscle Cells
Authors: Chang Yingzi
Published: June 2021

Aims

Hyperinsulinemia is associated with increased risk of vascular restenosis after angioplasty, a process that involves an extensive inflammation caused by the procedure, which leads to smooth muscle cell proliferation and migration resulting in neointima thickening. As a major pro‐inflammatory cytokine and an early responder in vascular injury‐induced neointima thickening, interleukin‐6 (IL‐6) induces motogenic effect on vascular smooth muscle cells. Attenuation of vascular injury‐induced neointima thickening was observed by blocking a key component of IL‐6 signaling, STAT3 tyrosine phosphorylation. A non‐receptor protein tyrosine phosphatase, PTP1B, plays a counter‐regulatory role in injury‐induced neointima formation by inhibiting platelet‐derived growth factor (PDGF)‐induced smooth muscle cell migration and proliferation. However, the role of IL‐6 in association of hyperinsulinemia with increased risk of vascular restenosis, and the involvement of PTP1B in this process have never been studied.

Methods and results

Using subcultured smooth muscle cells isolated from rat aorta, we found that: 1) chronic insulin treatment potentiated IL‐6‐induced smooth muscle cell migration (P<0.05) and STAT3 tyrosine phosphorylation (P<0.01); 2) chronic insulin dose‐dependently suppressed the baseline expression of endogenous PTP1B (P<0.05); 3) overexpressing wild‐type PTP1B significantly attenuated whereas C215S‐PTP1B enhanced IL‐6‐induced STAT3 phsophorylation and smooth muscle cell migration.

Conclusion

Abovementioned results suggest that inhibition of baseline expression of PTP1B and subsequent potentiation of IL‐6‐stimulated vascular smooth muscle migration may serve as a potential mechanism for increased risk of vascular restenosis after angioplasty in patients with insulin resistance.
Characterization of RecQL4 biochemical and cellular functions
Authors: Rossi Marie L , Croteau Deborah L , Bohr Vilhelm A
Published: June 2021

Three members of the evolutionarily conserved RecQ helicase family important for genome maintenance are linked with human segmental premature aging and cancer: BLM, WRN, and RecQL4. In recent studies, purified human RecQL4 displayed weak helicase activity compared to a strong strand annealing activity, which was only revealed when excess of single stranded DNA was used to trap the released strand. We detect novel ATPase‐driven and strand annealing‐independent RecQL4 unwinding activity on forked duplexes in the absence of excess ssDNA. Additionally, we extend the characterization of human RecQL4 activities to other DNA substrates. We also show that RecQL4's ATPase and unwinding activities are abolished by mutation of the conserved lysine within the helicase domain. Together our results indicate that RecQL4 shares the biochemical activities of the other RecQ helicases. However, unlike the other RecQ helicases, RecQL4 has been reported in both the nucleus and cytoplasm. Recently, using confocal microscopy and fractionated cell extracts, we observed RecQL4 in mitochondria. Therefore, studies have been initiated to investigate interactions between RecQL4 and mitochondrial proteins. This research was supported by funds from the Intramural Research Program of the National Institutes of Health, National Institute on Aging.
Actaea racemosa (black cohosh) hydroethanolic extract alters LPS‐induced expression of pro‐ and anti‐inflammatory factors in the cervix of ovariectomized mice
Authors: Diggins Nicole , McCoy JoeAnn , Hou Guichuan , Okunji Chris , Jesmin Subrina , Mowa Chishimba N
Published: June 2021

Cervical remodeling (CR) and parturition are essentially inflammatory‐like responses, implying that normal and abnormal factors that either induce or diminish inflammatory conditions, could potentially lead to obstetrical complications, such as prolonged labor (diminished inflammation) or preterm labor (heightened inflammation). Plant extracts with proven anti‐inflammatory activity, such as Actaea racemosa L. (black cohosh)(Fam. Ranunculaceae) could potentially be used to attenuate preterm labor in high‐risk women. Here, we test the effectiveness of the hydroethanolic extracts of A. racemosa to attenuate LPS‐induced expression of pro‐ and anti‐inflammatory factors in the cervix using ovariectomized mice, real‐time PCR and Western blot analysis. Our preliminary data show that A racemosa attenuates LPS‐induced expression of IL‐6 in the cervices of mice (x1 fold, > x4 fold for 0.1mg and 0.3/3mg IP, respectively, compared to positive control) in a dose‐dependent manner; whereas IL‐10 increased at 0.1mg (x1 fold), and decreased at subsequent doses (0.3/3mg, IP, >x1 fold), respectively. We conclude that expression of LPS‐induced pro‐inflammatory factors is blocked by A. racemosa (IP), whereas the extent of anti‐inflammatory factor expression is inversely proportional to the degree that A racemosa attenuates pro‐inflammatory factors in the cervix of ovariectomized mice.
The degree of expressed inconvertible damages of neurons and phagocytic activity of microglia of different parts of rats' cerebrum brain during prolonged inhalation by the vapour of flying narcotically affecting substances (FNAS)
Authors: Manekenova Kengegul , Suleymanov B. , Omarov T. , Dosmambetova Z. , Smailova G.
Published: June 2021

Morphometric research of quantity exponents occurrence of inconvertible damages of neurons (contracted neurons and cell‐shadows) was carried out: in the cortex of large hemispheres, in the thalamic areas, in the hippocampus and in the trunk of cerebrum, and also cells of Purkinye in the cortex of cerebellum, at daily inhalation by the glue vapour “Moment” and petrol vapour, during 30 days. Morphometric exponents of contracted neurons and cell‐shadows have demonstrated different expressed degree of cytotoxic reactions in the investigated perts of the cerebrum. It was established, that more sensitive to the cytotoxic effects of glue vapour “Moment” is the neurons of the cortex of large hemispheres and cells of Purkinye of cerebellum cortex, but to the cytotoxic effects of petrol vapour – neurons of thalamic areas of the cerebrum.

It was revealed that toxic affection by the glue vapour is associated by large phagocytic activity of microglia in the area of thalamic zones, and affection by the petrol vapour – more expressed phagocytic activity of microglia cells in the cortex of large hemispheres, in the result of investigation of number of satellite cells on 1 neuron and neuronophagocytic nodules on 30 day of daily inhalations by the glue vapour “Moment” and petrol vapour.
Restoration of Nephrotoxic Serum Induced Injury by PGE2 in Nephrotoxic Serum Nephritis in Mice and Glomerular Cells
Authors: Kvirkvelia Nino , Mcmenamin Maggie , Chaudhary Kapil , Madaio Michael P.
Published: June 2021

We postulated that PGE2, which exhibits multiple, tissue dependent regulatory functions to control immune‐mediated inflammation, tissue repair and fibrosis, has the potential to improve the course of ongoing nephritis. Therefore, the therapeutic potential and protective effect of exogenous PGE2 on established NTN in mice was evaluated along with its' cytoprotective effect on murine endothelial cells (GEC) and podocytes (POD). Initially, mice were injected with nephrotoxic serum (NTS), followed by PGE2 administration 5μg/g/d, started either on day 1, 2 or 3 after NTS dosing. Mice injected with PGE2 were protected, with normalization of BUN, Upr and histology. Protection was most beneficial with dosing at day 1, although later treatment was effective. Further, the capacity of PGE2 to limit injury of cultured cells was evaluated. Thus, POD and GEC were pretreated with PGE2, 1‐5μg/ml for 2–4h, and afterwards, NTS 5–10% was added for additional 7–12 h and apoptosis assessed by FACS. PGE2 reduced NTS induced apoptosis of cultured POD and GEC up to 30%. Furthermore, when POD and GEC were subjected to NTS, and then treated with PGE2 (1–5μg/ml), cell numbers were increased (25–55%) in a dose dependent fashion, indicating that PGE2 promoted cell regeneration after NTS induced injury. PGE2 also limited NTS induced GEC upregulation of CD47, an integrin associated protein; its' ligation in many cases leads to inhibition of cell proliferation and cell death. Altogether, the results indicate that PGE2 is candidate to further investigate its therapeutic potential to improve cellular recovery and improved function during the course of glomerulonephritis.

The work was supported by NI‐HDDK 081140‐02.
Angiopoietin‐1 but not angiopoietin‐2 promotes neutrophil viability: Role of interleukin‐8 and platelet‐activating factor
Authors: Dumas Elizabeth , Martel Catherine , Neagoe Paul‐Eduard , Bonnefoy Arnaud , Sirois Martin G.
Published: June 2021

We reported that the angiopoietins (Ang1 and Ang2) induce platelet activating factor (PAF) synthesis from endothelial cells and neutrophils. Since PAF can promote neutrophil viability, we addressed whether Ang1 and/or Ang2 could modulate neutrophil survival. Viability was assessed by flow cytometry using apoptotic and necrotic markers. Basal neutrophil viability from 0 to 24 hours post‐isolation decreased from 98% to ≈50%. Treatment with pro‐survival mediators such as interleukin‐8 (IL‐8; 25 nM) and PAF (100 nM) increased neutrophil viability by 22 and 35% (raising it from 56 to 69 and 76%) respectively. Treatment with Ang1 (0.001– 10 nM) increased neutrophil viability by up to 40%, while Ang2 had no effect. Combination of IL‐8 or PAF with Ang1 (10 nM) further increased neutrophil viability by 44 and 67% respectively. We also observed that Ang1, but not Ang2, can promote IL‐8 release and that a pretreatment of the neutrophils with blocking anti‐IL‐8 antibodies inhibited the pro‐survival effect of IL‐8 and Ang1 by 82 and 66% respectively. Pretreatment with a PAF receptor antagonist did abrogate PAF pro‐survival activity, without affecting Ang1‐induced neutrophil viability. Our data are the first one to report Ang1 pro‐survival activity on neutrophils, which is mainly driven through IL‐8 release. This work was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Quebec.
VEGF Induces Vascular Leakage, Edema and Cervical Epithelial Growth in Mice Cervix
Authors: Donnelly Siobhan , Estes Jordan , Jesmin Subrina , Rhyne Scott , Mowa Chishimba
Published: June 2021

Cervical remodeling (CR) is characterized by pronounced vascular alterations and cellular growth, such as increase in vascular leakage, white blood cell (WBC) tissue infiltration and cervical epithelial growth. However, factors that underlie these changes are not completely known. Here, we build on our previous data and investigate in depth the specific effects of vascular endothelial growth factor (VEGF), the best characterized angiogenic factor, on vascular leakage, edema, and cervical epithelial growth. Ovariectomized mice were treated with recombinant VEGF protein to determine the optimal dosage (vehicle, 50ng, 200ng and 400ng/mouse twice daily for 4 days, IP and intra‐vaginal alternately) and cervical tissues were harvested and analyzed using scanning electron microscope (SEM), immunohistochemistry (Anti‐BrdU) and tissue hydration techniques. Mice used for cervical epithelial growth studies were also administered BrdU. VEGF was found to induce pronounced cervical epithelial growth and WBC infiltration and moderately increased edema in a dose‐dependent manner. These results demonstrate that VEGF is a potent regulatory factor of multiple processes of CR.
Angiotensin‐(1–7) Induced Modulation of NPY Release from the Mesenteric Arterial Bed of the Rat
Authors: Murray Jessica Maria , Yang Chun Lian , Macarthur Heather , Westfall Thomas C.
Published: June 2021

Ang‐(1–7) produces a significant decreasein the nerve stimulation (NS)‐induced release of both NE andNPY as well as perfusion pressure of the perfused mesentericarterial bed of the rat. This effect is greater in mesenteric beds obtained from Spontaneously Hypertensive Rats (SHR) compared to normotensive control. Two hypotheses were examined; 1. The Ang‐(1–7) induced inhibition of sympatheticneurotransmission is mediated at least in part by prostacyclin(PGI2) and 2. Ang‐(1–7) elicits greater effects in mesenteric beds of SHR because there is decreased Ang‐(1–7) present in the mesenteric artery and plasma of SHR. Experiments were carried out using mesenteric beds and plasmaobtained from 10–12 week old SHR and Wistar‐Kyoto (WKY) rats. The effect of Ang‐(1–7) on the NS‐evokedrelease of NPY was determined before and after the administrationof the COX inhibitor Indomethacin (to prevent PGI2 synthesis) and the PGI2 receptor blocker CAY 10441. A reversal in the attenuation of perfusion pressure by Ang‐(1–7) was observed in the presence of Indomethacin and CAY10441. The attenuation of NPY release by Ang‐(1‐7) also appears to be reversed by Indomethacin and CAY10441. Additionally, plasma and tissue concentration of Ang‐(1–7) were significantly lower in SHR, while those of Ang II were significantly higher. (Supported by HL60260 and NIGMS008306)
Interactions of peroxisome proliferator‐activated receptor alpha (PPARá) and adenosine receptors (AR) in angiogenesis
Authors: Rizvi Yasmeen Q , Oyekan Adebayo
Published: June 2021

Hypoxia (HYP) stimulates angiogenesis (ANG) by promoting expression of many pro‐angiogenic genes, including AR. The role of PPARα in ANG is controversial. A2BR‐induced activation is known to reduce PPARα‐mediated activity but the effect of PPARα activation on A2BR is unknown. Here, we tested that PPARα attenuates adenosine(AD)‐mediated HYP –induced ANG. Using zebrafish embryo, ANG was measured by counting intersegmental vessel (ISV) and dorsal longitudinal anastomotic vessels (DLAV). Under normoxic condition, WY‐14643 (WY, 10 μM), a PPARα agonist, increased ISV (P<0.01) at 28 hpf but NECA (10 μM), a non selective AR agonist showed no effect. Combined exposure of WY 10 or 100 μM or NECA (10μM) decreased ISV at 28 hpf (p<0.01). However, WY (10 μM) +NECA increased DLAV (P<0.001), whereas, WY (100 μM)+NECA decreased DLAV (P<0.05) at 48 hpf. HYP alone increased ANG (72±19%) at 48 hpf. WY(10 μM) showed no effect on ISV but increased DLAV (P<0.05). At 28 hpf WY (10 μM)+NECA decreased ISV (P<0.001). Our data show that activation of PPARα and AR individually promote HYP‐induced ANG, but combined activation inhibits AD‐mediated HYP‐induced ANG.