bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of 4‐phenylbutyric acid on the process and development of cerebrum injury in diabetic rats: regulation of endoplasmic reticulum stress inflammatory response
Authors: Wang zhouguang , Zhang Hongyu , Shi Hongxue , Xiao Jian 
Published: June 2021

BackgroundInflammation may contribute to the pathogenesis of diabetic nephropathy (DN) and inflammatory response plays an important role in diabetic cerebrum injury, although the precise regulatory mechanism is still unclear. Recent reports have shown that 4‐phenylbutyric acid (4‐PBA) can suppress endoplasmic reticulum (ER) stress. We therefore hypothesized that 4‐PBA could provide neuroprotection through the suppression of ER stress inflammatory response in DN rats.Methods and ResultsMale SD rats were randomly divided into three groups: a normal control group, a streptozotocin and high fat diet‐induced DN model group, and a DN plus 4‐PBA (1g/kg) treatment group. In diabetic animals, elevated ER stress markers, GRP78, ATF‐4, XBP‐1, CHOP and the expression of p‐eIF, p‐JNK in the cerebral cortex were increased; TNF‐¦Á and IL‐6 levels were increased and NF‐kappaB signal pathway was activated; In cultured hippocampus neurons, high glucose induced a time‐dependent increase of ER stress and inflammatory factor production. In contrast, alleviation of ER stress by 4‐PBA or blockade of JNK activity attenuated inflammatory gene expression induced by high glucose, 4‐PBA also inhibit neuron cell apoptosis in vitro and in vivo.Conclusion4‐PBA exerts a marked neuroprotective effect possibly due to modulating ER stress and related inflammatory response.
Deregulation of the non‐canonical pathway in triple‐negative breast cancer
Authors: Borg Jean‐Paul , Belotti Edwige , Daulat Avais , Lembo Frederique , Bertucci Francois , Charafe‐Jauffret Emmanuelle , Birnbaum Daniel 
Published: June 2021

Planar cell polarity (PCP) is controlled by a non‐canonical Wnt pathway. It organizes the polarization of many epithelial tissues and organs within the plane, and drives cell migration and cell intercalation of non‐epithelial cells such as mesenchymal cells. Loss of function of PCP genes can lead to severe neural tube defects in animal models and human. Little is known about the role of PCP genes in tumor growth and dissemination.A screen led us to identify Vangl2, a PCP receptor, as a molecule overexpressed at the genomic, transcriptomic and protein levels in poor prognosis triple negative breast cancers. Using cultured breast cancer cells, we show that Vangl2 is implicated in tumorigenicity and cell migration, and triggers a non‐canonical Wnt‐JNK pathway. Implication of Vangl2 in tumor growth was confirmed in xenograft assays in nude mice. Through a combinatory two‐hybrid/proteomic approach, we further discovered Vangl2 PDZ partners including Scribble and Dishevelled. Interaction with Scribble, but not Dishevelled, is required for cell migration of cancer cells. Our work reveals a novel implication for PCP proteins in triple negative breast cancer.
Effect of medical advice for diet on diabetes self‐management and glycemic control for Haitian and African Americans with type 2 diabetes
Authors: Dixon Zisca , Exebio Joel C , Vaccaro Joan A , Zarini Gustavo G , Huffman Fatma G 
Published: June 2021

ObjectiveThe purpose was to assess dietary advice with diabetes self‐management and glycemic control by ethnicity.MethodsCross‐sectional analysis of 254 Blacks with type 2 diabetes (Haitian Americans=129; African Americans=125) recruited from Miami‐Dade and Broward Counties, Florida by community outreach. Sociodemographics, anthropometrics and blood samples were collected after informed consent.ResultsDietary advice and behavior dependent on ethnicity. The combined model ethnicity by ‘given advice to follow a diet’ was not significant, so separate logistic regression analyses were conducted for each ethnicity. Haitian Americans given advice ‘to follow a diet’ were more likely to ‘use food groups’ than not [OR=3.27(1.32, 8.00) p=.007]. A one unit increase in diabetes self‐management score decreased the odds ratio point estimate of having less than optimal glycemic control (A1C >; 7.2%) by a factor of 0.94 in African Americans (p=.009).ConclusionsThese results suggest that medical advice for diet plans may not be communicated effectively to some race/ethnicities. Studies of diet management specific to Black ethnicities are recommended. Funding was by an NIH/NIDDK grant.
A Simple, non‐Destructive Method for Bromide Analysis in Plasma for Field Body Composition Studies
Authors: Kehayias Christopher Erkki , Kempf Kari G , Roto Anna V , Kehayias Joseph J 
Published: June 2021

ObjectiveExpansion of extracellular water (ECW) space serves as a measure of muscle loss, cachexia or inflammation. It is used to monitor frailty, depletion of muscle mass, and the efficacy of nutritional interventions. ECW is measured by bromide dilution, where a known amount of NaBr is administered and a plasma (or urine) sample is analyzed, after equilibrium, by instrumental neutron activation analysis (INAA) or high‐performance liquid chromatography (HPLC). The objective of this work is to develop an alternative, automated method of analysis that does not require the complexity of INAA or HPLC.MethodWe tested a non‐destructive energy dispersive X‐ray fluorescent (XRF) device which uses a Cd‐109 radioactive source, a miniature (25 mm2), electronically cooled, high resolution (<150 eV) silicon detector and a microprocessor‐controlled sample‐positioning system to obtain X‐ray spectra from plasma samples. The method requires no sample preparation and preserves 100% of each specimen.ResultsSensitivity: 0.1ug/cc, reproducibility for Br in plasma or urine <0.8%, accuracy <1.0%. Validated against INAA (R2=0.994).ConclusionThe method can be used in the field for repeated measurements. The lack of sample preparation eliminates the opportunity for bromide loss due to filtering. Being non‐destructive, XRF allows for full preservation of the specimen. Support: USDA contr. 51000–071
A systematic review of the effects of sodium reduction on glucose levels
Authors: PATEL SHEENA , COBB PAUL , SAYDAH SHARON , ZHANG XUANPING , DE JESUS JANET , COGSWELL MARY 
Published: June 2021

OBJECTIVEAssess effects of sodium reduction on glucose levels.METHODSWe systematically searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, and Web of Science through July 2012. We initially included randomized and non‐randomized intervention trials comparing ≥2 sodium intake levels and examining ≥1 measure of glucose levels.RESULTSOf 2920 abstracts screened, 37 trials (1402 participants) evaluated the effects of sodium intake on glucose levels. Participants were 10–79 years old, primarily healthy or with hypertension. Metaanalysis of 10 randomized, cross‐over trials with ≥7 day interventions, >;80% follow‐up, and intent‐to‐treat analysis of follow‐up fasting glucose concentrations, showed that fasting glucose did not differ by sodium intake (N=299, mean difference, mmol/L: 0.04; 95% confidence interval −0.07,0.14) and heterogeneity was not significant (I2=0%, P=1.0) in the random effects model. Among these studies, mean excretion for the lowest sodium reduction group ranged from 280–2875 mg/d (weighted mean=713 mg/d) versus 2171–6859 mg/d (weighted mean= 5723 mg/d) for the other group.CONCLUSIONOur meta‐analysis of randomized, cross‐over trials, with fasting glucose and low risk of bias, suggests ≥7 day sodium reduction (weighted mean ‐5010 mg/d) does not affect fasting glucose. Variation in methods precluded meta‐analysis of other glucose measures.
Active transcription factors in the development of the small intestine during early life
Authors: Zhang Man , Liao Yalin , Lönnerdal Bo 
Published: June 2021

Transcription factors (TFs) regulate downstream gene expression individually or cooperatively in different cell types and tissues. Human milk contains growth factors that maintain gastrointestinal mucosal homeostasis. We chose two major growth factors in human milk, TGF‐â (10 ng/ml) and IGF‐1 (30 ng/ml) to study global activation of TFs during early intestinal development in IEC‐6 (crypt cell) and FHs74 cells (fetal intestine). Active transcription factors were detected by Protein‐DNA Array. Among all the active TFs, EGR‐1 expression showed the most substantial up‐(IEC‐6 cell differentiation) and down‐regulation (FHs74 cell proliferation) after stimulation of the two cell lines. For IEC‐6 cells, EGR‐1 is predicted to have binding sites in the promoters of the Axin1 (‐258bp/260bp) and LRP5 (‐84bp/113bp) genes, which are mediators involved in the Wnt signaling pathway. The binding sites were verified by chromatin immunoprecipitation (CHIP) and EMSA. Changes in the Wnt/â‐catenin downstream targets Cyclin D and E‐cadherin further indicate that EGR1 interferes with the Wnt pathway through Axin1 and LRP5. In conclusion, we showed transcription factors regulated by growth factors during small intestinal development. EGR1 was further found to regulate the Wnt pathway through the multiprotein complex, which shows that human milk growth factors are likely to impact small intestinal development considerably.Grant Funding Source: research grant from Mead Johnson Nutrition
Bacterial flora in human milk in health and disease
Authors: Kvist Linda , Schalén Claes 
Published: June 2021

Backgroundthe presence of bacteria in breast milk of lactating women was described more than 30 years ago and it was assumed that the cause was contamination of specimens from the mothers’ skin and infants’ mouths (Gavin & Ostovr 1977). A recent Swedish study showed that many healthy women harbour potential pathogens in their breast milk at similar concentrations to those with mastitis (Kvist et al, 2008). New methods of DNA sequencing of bacteria will revolutionize our understanding of the bacterial content of human milk. New knowledge must either be synthesized with the old or replace it.Aimto provide a synthesis and a comparison of findings from recent empirical research on microbial content of human breast milk in healthy women and women with mastitis in order to clarify present day knowledge.Methoda synthesis of the literature regarding bacterial content of breast milk from healthy women and women with mastitis, published between 1990 and 2010. This resulted in an analysis of milk from 844 healthy women and 624 women with mastitis.Findingsseven articles reported bacterial content in breast milk from healthy women, four reported findings from women with symptoms of mastitis and one study reported on bacterial content of milk from both groups. The isolate most commonly found in women with mastitis was S. epidermis (45.5%) and in healthy women the most common bacterial isolate was CNS (77.4%). S.aureus was reported in 5.1% of women with mastitis.Conclusionsa bacterial flora appears to exist in all breast milk. It is unclear why reports of sterile breast milk occur in the literature from time to time. The results of this synthesis challenge the conventional claim, that S. aureus is the most common cause of lactational mastitis.
Multiplexing of Human Preterm and Term Milk Cytokines
Authors: Groer Maureen Edith , Williams S. Nicole , Kane Bradley Patrick 
Published: June 2021

The first objective was to use an 18‐plex cytokine panel to compare preterm and term colostrum collected at day 1 postpartum. After observing matrix effects, we worked to develop a milk assay matrix for Luminex and MagPix technologies. After matrix development proved satisfactory, we have progressed to a longitudinal study of immunobiology of milk from 100 mothers of Very Low Birth Weight (VLBW) infants.We multiplexed milk whey using bead based methods and performed linear spiking experiments. We used a variety of matrix solutions and these matrices did not give reliable results. When we used serum matrix for controls and standards, and added serum matrix to milk samples, the spiking experiments were successful and showed linearity.Based on our preliminary experiments on preterm and term colostrum and the matrix solution, we designed a plex of 8 cytokines that differed in preterm compared to term colostrum (IL‐4, IL‐6, IL‐8, IL‐10, IP‐10, MIP‐1α, IP‐10, MCP‐1, and TNFα). We are now measuring milk cytokines from 100 mothers of VLBW infants across 6 weeks of the NICU stay. From these data we will describe the trajectory of human milk immunobiology over the first six weeks postpartum.Multiplexing provides excellent screening for important immune molecules. However there are no plexes specifically for milk. We have developed an assay for multiplexing using serum matrix that is sensitive and reliable.Funded by 5R21NR013094–02
Caffeic acid and ferulic acid improves diet induced metabolic syndrome on mice but induces inflammatory process in white adipose tissue
Authors: Bocco Barbara Miranda Leite da Costa , Lorena Fernada Beraldo , Fernandes Gustavo Werpel , Lancelloti Carmem Lucia Penteado , Cysneiros Roberta Monterazzo , Ribeiro Miriam Oliveira 
Published: June 2021

Several studies have been shown that Caffeic Acid (CA) and Ferulic Acid (FA) present antioxidant and anti‐inflammatory properties and improve several abnormalities related to metabolic syndrome. The aim of this study was to analyze the effect of CA and FA combined on diet induced obesity in mice. For that, C57 mice fed with high fat diet (HFD) (40%) received CA plus FA concomitantly for 60 days. Our results showed that the combination of CA (0.9 or 1.8 mg/kg/day) with FA (50 mg/kg/day) reduced body weight gain induced by HFD (8.6±1.8 vs. −4.2±2.0 (CA0.9+FA50) and −3,7±1,9 (CA1.8+FA50); p<0.0001), fasting hyperglycemia (223±40 vs. 181±44 (CA0.9+FA50) and 168±41 (CA1.8+FA50); p<0.05), hypercholesterolemia (134±20 vs. 110±7.3 (CA0.9+FA50) and 104±2.7 (CA1.8+FA50); p<0.05), hypertriglyceridemia (45±4 vs. 40±9 (CA0.9+FA50) and 21.1±9 (CA1.8+FA50); p<0.001). Liver histology showed that CA and FA combined improved the hepatic steatosis induced by high fat diet. On the other hand, significant inflammation was observed in WAT of the mice treated with both acids, with neutrophil and macrophage infiltration. In conclusion, the combination of CA and FA improves the abnormalities observed in metabolic syndrome induced by high fat diet but leads to inflammatory process in white adipose tissue.Supported: CAPES.
Dietary Cod Protein Improves the IGF1‐Akt/PKB Signaling Pathway in Rat Skeletal Muscle during Recovery from Injury
Authors: Dort Junio , Leblanc Nadine , Côté Claude H , Jacques Hélène 
Published: June 2021

This study was designed to assess the mechanisms by which dietary cod protein may facilitate skeletal muscle recovery from injury through analyses of the IGF1‐Akt/PKB signaling pathway. Male Wistar rats were fed isoenergetic diets containing either casein (C), cod protein (CP), or casein supplemented with a mixture of arginine, glycine, taurine and lysine (C+), matching their respective levels as in CP. Muscle injury was induced by bupivacaine injection and downstream IGF1‐Akt/PKB effectors were measured post‐injury. At day 2 post‐injury, C+ upregulated (p=0.0008) whereas CP tended to upregulate phospho‐Akt Thr308 compared with C (p=0.075), suggesting that the myogenic effect of CP is due in part to its high levels of arginine, glycine, taurine and lysine. At day 2 post‐injury, CP reduced the expression of MuRF‐1 by 38% compared with C (p=0.03), supporting a decrease in the ubiquitylation of muscle proteins and their degradation. At day 5 post‐injury, CP tended to increase the muscle IGF‐1 level compared with C (p=0.098); phospho‐Akt Ser473, a phosphorylation required for maximum activation of Akt in addition to phosphorylation at Thr308, was also increased (p<0.0001). These findings suggest that at early time‐points of recovery, CP can reduce muscle protein degradation through modulation of the ubiquitination process and upregulate protein synthesis through enhanced Akt activation.Supported by NSERC
Iron Metabolism in a Rodent Model of Menkes Disease (Brindled Mice)
Authors: Gulec Sukru , Collins James F. 
Published: June 2021

The Menkes copper‐transporting ATPase (Atp7a) is induced in the rodent duodenum during iron deficiency. To understand its role in intestinal iron metabolism, we thus initiated an investigation in Atp7a mutant mice (Brindled). As mutant mice die perinatally of severe copper deficiency, IP copper injections were administered at 7 and 9 days‐of‐age. Mice developed normally thereafter and were similar in size and activity level to wt littermates. Subsequently, mice were deprived of dietary iron for 3 wks and iron and copper homeostasis was studied. Several important observations arose from these analyses, including: 1) mutant mice on control diet were copper deficient and anemic with no changes in iron status; 2) mutant mice on iron‐deficient diet were iron and copper deficient and more significantly anemic; 3) the transcriptional response to iron deficiency in enterocytes was seen only in mutant mice on low Fe diet, suggesting that the HIF2α‐mediated induction of iron and copper homeostasis‐related genes is triggered by iron levels and not hypoxia per se; and 4) Brindled mice had increased hepatic copper levels during iron deprivation, leading to a concomitant increase in serum ferroxidase activity, while no such changes were noted in control or low Fe wt mice. This study has thus revealed novel aspects of the iron‐copper connection and is the first to investigate iron homeostasis in a model of genetic copper deficiency.Grant Funding Source: NIH
Roles of dietary vitamin A in the regulation of hepatic gene expression in response to fasting‐refeeding cycle
Authors: Li Yang , Chen Guoxun 
Published: June 2021

We have shown that vitamin A (VA) status affects the plasma glucose and lipid levels, and hepatic gene expression in rats. Therefore, we hypothesize that dietary VA intake and its hepatic metabolism regulate the expression of genes involved in glucose and lipid metabolism in response to fasting‐refeeding cycle. Male Zucker lean rats were fed with a VA deficient (VAD) or a VA sufficient (VAS) diet for 8 weeks. The VAD or VAS rats were fed ad libitum, fasted for 48 hours (H) or refed a VAD or VAS diet for 6H. The plasma parameters were measured using commercial kits. The hepatic protein and mRNA levels were respectively examined by Western blot and real‐time PCR. The responses of plasma insulin and leptin levels to the feeding cycle were altered in VAD rats compared to VAS ones. The hepatic mRNA levels of Gck, Srebp‐1c, and Fas were reduced after 48H fasting regardless of VA status. The 6H refeeding of a VAS diet induced their mRNA levels in VAD and VAS rats. However, the 6H refeeding of a VAD diet only induced their expression levels in VAS, but not VAD rats. We conclude that dietary VA and its hepatic metabolism contribute to the regulation of plasma hormone levels and hepatic gene expression in rats.Grant Funding Source: American Heart Association
Vitamin A equivalence of spirulina β‐carotene in US men
Authors: Tang Guangwen , Muzhingi Tawanda , Grusak Michael 
Published: June 2021

To evaluate the vitamin A value of spirulina β‐carotene and to assess dose‐related responses, spirulina was grown in a 23 atom% 2H2O cultural solution, harvested, made as capsules, and fed to volunteers. Spirulina β‐carotene showed the highest abundance of enrichment as [2H10] trans β‐carotene. Eight healthy US male subjects (51±6 y) with a mean serum retinol concentration of 1.7 ±0.3 μmole/L and a BMI of 23 ± 3 kg/m2 consumed 5.8 μmole (2.0 mg) of [13C10] retinyl acetate in oil as a reference dose with a standard liquid breakfast containing 13 g of fat (day 1). At day 8, each subject was randomly assigned to consume 4 g or 2 g of spirulina containing 5.1 (2.8 mg) or 2.6 (1.4 mg) μmoles of trans β‐carotene with the same standard breakfast as day 1. Serum samples were collected at various time points over 50 days. Concentrations and enrichments of retinol and β‐carotene in serum samples were determined by using HPLC and GC/MS0.A comparison of the mean area‐under‐the‐curve (AUC) for the total labeled serum retinol response after the 4 g (n=4) or 2 g (n=4) of spirulina, with the AUC of the reference dose of 2.0 mg [13C10]retinyl acetate, did not show differences related to the amount of dose taken. The mean vitamin A equivalence of spirulina β‐carotene to retinol was 2.7 and 2.8 to 1 by weight, for the 4 g or 2 g spirulina doses, respectively. (Funded by the Nestle Foundation).
Fish oil differentially regulates B cell and dendritic cell activation in response to a T‐independent antigen
Authors: Teague Heather , Rockett Benjamin Drew , Harris Mitchel , Shaikh Saame Raza 
Published: June 2021

Fish oil (FO) has clinical utility for regulating immunity. The functional consequences of FO on B cells and dendritic cells (DC) are poorly studied, especially at the animal level. Here we tested the effects of FO, modeling human pharmacological intake, on murine ex vivo B cell and DC activation in response to the T‐independent antigen lipopolysaccharide (LPS). LPS stimulation of B cells increased CD69 surface expression and enhanced secretion of IL‐6, TNFα and IFNγ with FO. In comparison, LPS stimulation of DCs resulted in reduced CD80 surface expression and TNFα secretion with FO, which was associated with decreased phagocytosis of E. coli bioparticles. To reconcile differences between cell types, we measured the formation of plasma membrane lipid microdomains. Although FO promoted an increase in EPA and DHA levels, we discovered differential effects on the ability of B cells and DCs to cluster lipid microdomains. Overall, this study shows FO differentially regulates the activation of B cells and DCs in response to LPS, which may be due to differences in underlying membrane organization. Our data highlight the possibility that FO can be used to exert both immune enhancing and immunosuppressive effects, depending on the cellular target.Grant Funding Source: NIH R15AT006122 (to S.R.S.)
Effect of a new compounds of substituted 5R1, 6H2–1,3,4‐thiadiazine‐2‐amines on the histological pictures in ligation models of experimental acute myocardial infarction and experimental acute pancreatitis in rats.
Authors: Sarapultsev Alexey Petrovich , Chupakhin Oleg Nickolaevich , Sarapultsev Petr Alekseevich , Rantsev Maxim Anatolevich , Medvedeva Svetlana Ur'evna , Danilova Irina Georgievna 
Published: June 2021

Models of experimental acute myocardial infarction (EAMI) and experimental acute pancreatitis (EAP) have been developed to solve this problem. The animals got injection of the compound from the group of substituted 5R1, 6H2–1,3,4‐thiadiazine‐2‐amines, dozed 40 mg/kg. Histological study has been carried out at the 1st, 5st and 7th days. All animal experimental procedures were performed in accordance with the APS's Guiding Principles and in accordance with the Laboratory Practice Regulations of RF.Already during the 1st day of the EAMI no leucopenia was observed and the signs of proliferative inflammation were detected. Later, at the 5th day, the necrosis area got surrounded by demarcation bank, and further on (7th day) had been entirely replaced by granulation tissue. Withal, the application of compound in EAP results in occurrence of proliferative inflammation, prevents lympho‐ and monocytopenia development and cuts down the lethality rate two‐fold.Conduction research enabled to state repeatability of the mechanism of the compounds impact on ischemia‐induced inflammation process, both in case of EAMI and EAP. The compounds modulated the transition of destructive inflammation into proliferative one, thereby preventing spreading of the inflammation process to tissues surrounding the necrotic zone and promoting reparative processes as well.Research Grant 12‐Ì‐34–2064 of Ural Branch of RAS.