bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL‐8 inhibits bortezomib‐induced apoptosis in ovarian cancer cells (1010.2)
Authors: Phyo Sai , Singha Bipradeb , Gatla Himavanth , Vancurova Ivana 
Published: June 2021

Proteasome inhibition is a promising therapeutic strategy in a number of human cancers, including ovarian cancer, one of the most lethal human cancers. Bortezomib (BZ) is the first FDA approved proteasome inhibitor that has a remarkable anti‐tumor activity in many hematological malignancies. In solid tumors, BZ has been less effective; however, the underlying mechanisms are not fully understood. The rationale behind BZ development and use was its inhibition of NFκB activity and resulting suppression of NFκB‐dependent pro‐inflammatory and anti‐apoptotic genes. However, recent studies from our laboratory demonstrated that while BZ decreases expressions of most NFκB‐regulated genes, it actually increases expression of the pro‐inflammatory and pro‐angiogenic chemokine, IL‐8, in ovarian cancer cells. The goal of this study was to investigate whether the BZ‐increased IL‐8 expression regulates survival of ovarian cancer cells. Here, we show that suppression of IL‐8 levels by siRNA significantly induces apoptosis in BZ‐treated ovarian cancer SKOV3 cells. Our results indicate that the BZ‐increased IL‐8 expression represents one of the mechanisms responsible for the decreased BZ effectiveness in ovarian cancer, and suggest that a new combination therapy targeting the IL‐8 expression might enhance BZ effectiveness in ovarian cancer treatment.Grant Funding Source: Supported by NIH grants AI085497 and CA173452 to I.V.
Antagonism of the prostaglandin E2 EP1 receptor in MDCK cells increases growth through activation of Akt and the epidermal growth factor receptor (1012.6)
Authors: Taub Mary , Mathivanan Paremala , Parker Robert , Rudra Trina , Ariff Mohamad 
Published: June 2021

Prostaglandin E2 (PGE2) plays a number of roles in the kidney that are mediated by 4 classes of E‐prostanoid (EP) receptors, including EP2 and EP4, which activate adenylate cyclase (AC), EP3 that inhibits AC, and EP1, that activates Phospholipase C. Each of these receptors contributes to a number of renal diseases. Here, the role of EP1, EP2 and EP4 in mediating the effects of PGE2 on MDCK cell growth is examined. The results indicate that EP2 and EP4 contribute to the growth stimulatory effect of PGE2, unlike EP1, which is growth inhibitory. Indeed, the EP1 antagonists ONO‐8711 and SC51089 increase, rather than inhibit MDCK cell growth. Growth stimulatory effects of ONO‐8711 and SC51089 were observed in the absence of exogenous PGE2. This latter effect was prevented by the cyclooxygenase inhibitor ibuprofen, indicating that EP1 mediated growth inhibition was dependent upon endogenous PGE2. Evidence was obtained that EP1 activation results in the inhibition of Akt signaling, including the observation that 1) ONO‐8711 and SC51089 increase Akt phosphorylation, and 2) MK2206, an Akt inhibitor, prevents the increased growth caused by EP1 antagonists. In addition, evidence was obtained for the involvement of the EGF Receptor (EGFR), including the observation that 1) SC51089 increases the phosphorylation of the EGF Receptor (EGFR), and 2) the EGFR kinase inhibitor AG1478 prevents the growth stimulatory effects of ONO‐8711 and SC51089. These latter results support the hypothesis that EP1 receptor activation also affects signaling via the EGFR. Thus, EP1 receptor pharmacology may prevent aberrant growth associated with a number of renal diseases.Grant Funding Source: NIH
Insulin‐like growth factor I regulation of FOXO1 in gonadotropes (1012.7)
Authors: Skarra Danalea , Thackray Varykina 
Published: June 2021

The transcription factor FOXO1 is important for several aspects of reproductive function, including endometrial decidualization, ovarian follicular maturation, and spermatogenesis. We have previously reported that in pituitary gonadotropes FOXO1 functions as a repressor of both luteinizing hormone beta (Lhb) and follicle stimulating hormone beta (Fshb) transcription, which are critical for reproduction. Insulin‐like growth factor I (IGFI) is a negative regulator of FOXO1 transcriptional activity. Given that FOXO1 can repress Lhb and Fshb transcription and that IGFI stimulation of gonadotrope cells enhances Lhb and Fshb synthesis, we investigated how IGFI regulates FOXO1 activity in gonadotropes in the current study. In LβT2 gonadotrope cells, we determined by western analyses that IGFI induced Ser256 FOXO1 phosphorylation, causing FOXO1 inhibition and cytoplasmic localization as identified by immunofluorescence microscopy. In addition, inhibition of components of the IGFI signaling pathway, such as PI3K or AKT, blocked IGFI‐induced phosphorylation of FOXO1. As the in vivo gonadotrope hormone milieu includes GnRH along with IGFI, we next investigated the effect of GnRH on FOXO1 phosphorylation and subcellular localization. Stimulation of LβT2 cells with GnRH alone induced moderate cytoplasmic localization of FOXO1, although GnRH did not induce phosphorylation of FOXO1 Ser256. Moreover, the GnRH‐induced shuttling of FOXO1 to the cytoplasm was not blocked by inhibition of PI3K activity. We are currently investigating the effects of IGFI and GnRH co‐treatment.Grant Funding Source: Supported by NIH Grants T32 HD007203 and F32 HD074414 to DVS; R01 HD067448 and U54 HD012303 to VGT.
Soluble IP4 limits NK cell effector functions by controlling PI3K signaling (1013.1)
Authors: Sauer Karsten , Park Eugene , Siegemund Sabine , French Anthony , Wahle Joseph , Sternberg Luise , Rigaud Stephanie , Jonsson Helena , Yokoyama Wayne 
Published: June 2021

NK cells are important for cancer immunosurveillance, bone marrow allograft rejection, fighting infections and reproduction. Overcoming their limited efficacy in cancer immunotherapies requires a better understanding of the mechanisms limiting NK cell effector functions. NK cells recognize and kill pathogen‐infected or tumor cells through NK cell receptors (NKR). Two second‐messenger downstream pathways are required for NK cell maturation and function: PIP3‐generation by PI3K, and generation of DAG and IP3 by PLCγ. IP3 has a key signaling role by mobilizing Calcium, but can also be converted into soluble inositol(1,3,4,5)tetrakisphosphate (IP4). IP4 can act as a soluble analog of the PI3K lipid‐product phosphatidylinositol(3,4,5)trisphosphate (PIP3) and control PIP3‐mediated signaling protein membrane recruitment and activation in thymocytes and granulocytes. Here, we show published and unpublished data which suggest that IP4 limits NKR induced IFNγ secretion, granule exocytosis and target‐cell clearance, in part by inhibiting the PIP3 effector‐kinase Akt in NK cells. This identifies IP4 as an important novel regulator of NK cell function, and expands our understanding of the therapeutically important mechanisms dampening NK cell responses. Our results further suggest that PI3K regulation by soluble IP4 is a broadly important signaling paradigm.Grant Funding Source: Supported by NIH grants AI070845, GM088647, AI089805 & Leukemia & Lymphoma Society Award 1440‐11
A mixed‐methods approach to construct program‐impact pathways and highlight the role of an agricultural and market development program in supporting household food security and dietary diversity among smallholder farmers in Guatemala (1014.9)
Authors: López Cintrón Julio , Peterson Ross , Torres Pablo , Wuth Alicia , Dong Faye , Engeseth Nicki , Greene Jennifer , Helferich William , Andrade Juan 
Published: June 2021

There is a critical need to understand what agricultural interventions are most effective in supporting food security, a determinant of nutrition security. We constructed and linked impact pathways based on a mixed‐methods approach to highlight the role of WFP’s Purchase for Progress (P4P), a program that promotes agricultural productivity and connects smallholder farmers to markets, in supporting food security (FS) and dietary diversity (DD). Socioeconomic variables and FS and DD were measured and associated in 271 P4P and 101 control households using a cross‐sectional design in Guatemala. The Most Significant Change, a qualitative methodology, was applied to a subset sample (46 P4P; 11 control) to explain relationship of P4P core tenets and measured variables. Each pathway factor was laid out along the hypothesized PIP using as blueprints P4P’s program theory and current conceptual frameworks linking agriculture, FS and nutrition. Factor inclusion was supported by evidence from three sources: our study, P4P’s monitoring and evaluation, and current literature. A six‐step process integrated information: data weighting, entry, preparation, analysis, interpretation and final integration. P4P promotes household FS and DD among smallholder farmers by enabling four PIPs: income, agricultural productivity via crop diversification and production practices, market access, and empowerment strategies. PIP research illustrates the role of P4P activities in underpinning nutrition security, specifically by supporting FS and DD among smallholder farmers in Guatemala.Grant Funding Source: Supported by: Ayre international research fellowship (JRL), Hatch (JEA), USDA‐ISE (WGH, NJE, & JEA)
Neonatal survival appears unaffected by timing in the start of breast‐feeding in rural Bangladesh (1015.5)
Authors: Klemm Rolf , Wu Lee , Christian Parul , Shamim Abu Ahmed , Shaikh Saijuddin , Ali Hasmot , Mehra Sucheta , Labrique Alain , Schulze Kerry , West Keith 
Published: June 2021

Breast‐feeding initiation in the first hour of life in Nepal and within the first day of life in India has been associated with reduced neonatal mortality. We assessed the association between breast‐feeding initiation time and neonatal mortality in prospective data collected during a cluster‐randomized, controlled trial of antenatal multiple micronutrient vs. iron‐folic acid supplementation in a typical rural area of northern Bangladesh.Time of breast‐feeding initiation was obtained during home visits at birth, at one month of age, or during verbal autopsies for infants who died before 1‐month of age. Multivariate binomial regression analysis was used to estimate the association between neonatal mortality and breast‐feeding initiation time (<1 h, 1‐23 h, 蠅24 h) among 26,374 breast‐fed singleton newborns surviving to 48 hr.We found that 26.8%, 63.0%, and 8.7% of newborns were first breast‐fed at <1 h, 1‐23 h, and > 24 h, respectively. Neonatal mortality was not higher among newborns initiating breast feeding at 1‐23 h (RR=0.86; 95%CI: 0.69‐1.08) or 蠅24 h (RR=1.1; 95%CI: 0.84‐1.68) compared with early (<1 h) initiators in unadjusted analysis; nor between infants initiating breast feeding 蠅24 h (RR=1.32; 95%CI: 0.96, 1.80) compared with those initiating at <24 h. Adjusting individually or collectively for low birth weight, preterm birth and/or living standards index did not change the results.Initiating breast‐feeding within 1 hr, as recommended by WHO, or within 24 h, was not associated with improved neonatal survival in this rural Bangladesh context. Explanatory factors are being explored.
Breast milk correlates of immune protection against early infancy Cryptosporidium infection in a rural Tanzanian cohort (1015.6)
Authors: Pedersen Sarah , Wilkinson Amanda , Andreasen Aura , Kinung'hi Safari , Warhurst David , Urassa Mark , Mkwashapi Denna , Todd Jim , Changalucha John , McDermid Joann 
Published: June 2021

Breast milk (BM) offers an important immunological bridge from mothers to infants; but BM immunology is incompletely understood. We aimed to determine how BM cytokines and immunoglobulins (Ig) were associated with infant Cryptosporidium infection in a prospective cohort of 108 mother (39% HIV+)/infant pairs. BM and maternal serum was analyzed at month 1, 2, 3, and 6 postpartum. Greater BM IgA, IgM, IgG1, IgG2, IgG3 and IgG4 levels were consistently associated with lower odds of infant Cryptosporidium infection, but the trend was not significant. Absolute BM cytokine levels did not differ by maternal Cryptosporidium or HIV infection, and BM and serum cytokines were uncorrelated. The BM cytokine score was determined by categorizing BM cytokines (tertiles) and calculating individual scores for the equation: IFNγ + IL2 + IL6 + IL13 ‐ TNFα. Infant Cryptosporidium infection was associated with the BM cytokine score at each time point (OR=0.57; p=0.034), adjusting for breastfeeding practice and maternal Cryptosporidium infection. These results suggest BM cytokines are associated with early infant Cryptosporidium infection independent of current maternal Cryptosporidium infection or breastfeeding practices.Grant Funding Source: Supported in part by National Science Foundation IGERT
The value of swabbing sore nipples during lactation (1016.1)
Authors: Hartmann Peter , Rowan Marnie , Chia Elisa , Fairclough Kyle , Menon Lalitha , Ashton Elizabeth , Kent Jacqueline 
Published: June 2021

This study aimed to provide insight into nipple pain in breastfeeding mothers focusing on the microbiology, treatments and subsequent outcomes. For a 6‐month period, data were retrieved from the lactation consultant records of 489 clients of the Breast Feeding Centre of WA. Nipple pain was identified in 36% of the clients. Nipple swabs were collected from 46% of the clients with nipple pain when infection was clinically suspected as the cause. The rate of detected infection was 61%. Staphylococcus species were present in 90% of the positive cultures. Other infective organisms detected were a variant of the Streptococcus species, Acinetobacter baumannii, Pseudomonas stutzeri and Candida. Targeted treatment was provided for 77% of the mothers who were positive. Antibiotic choice included flucloxacillin alone or with a combination of other antimicrobials or antifungals, cephalexin, or cephalosporin, depending on the sensitivity of the organism grown from the swab to antibiotics. Fluconazole was prescribed when candida was detected. The treatment resulted in the nipple pain resolving or resolved in 71% of cases. We conclude that swabbing painful nipples during lactation can provide successful, targeted treatment.Grant Funding Source: Supported by Medela, AG
Distribution of retinol, carotenoids and tocopherols in serum lipoproteins in lactating women: a longitudinal study (1017.10)
Authors: Torres Alexandre , Machado Michele , Silva Danubia , Nunes Juliana , Kamp Fernanda 
Published: June 2021

We aimed to investigate the distribution of retinol, carotenoids and tocopherols in serum lipoprotein fractions, and to investigate associations with dietary intake in a longitudinal observational study with Brazilian lactating women. Lactating adults (n=15) were followed from between the weeks 2 to 4 (t1) through to weeks 12 and 14 (t2) postpartum. Dietary intake was assessed through dietary records and a quantitative food frequency questionnaire. Dietary data were analyzed by the Multiple Source Method internet tool (https://msm.dife.de/). Serum vitamins were analyzed by reversed phase HPLC‐DAD‐FL. Levels of carotenoids in serum were comparable to those reported for Brazilian lactating women in other studies. Alpha‐tocoferol, alpha‐carotene, beta‐carotene and lycopene were primarily parted in LDL/VLDL fraction and lutein and zeaxanthin were primarily in HDL fraction. In contrast, retinol was equally distributed between the LDL/VLDL and the HDL/RBP fractions. Both total and HDL‐fraction lutein/zeaxanthin were positively correlated (Pearson) with dietary intake (p< 0.007 and p< 0.005, respectively). Our results indicate that retinol, carotenoids and tocopherols are differently distributed in serum lipoproteins, suggesting that selective mechanisms can account for serum transport of these components in lactating women, with potential consequences to mechanisms of transference into breast milk.Grant Funding Source: Supported by FAPERJ, CNPq, CAPES (Brazil)
Breastfeeding during late pregnancy did not affect infant breast milk consumption and growth (1017.2)
Authors: Pareja Rossina , Marquis Grace , Penny Mary 
Published: June 2021

Objective: The one thousand days window is the most important period when maternal nutrition demands and infant feeding practices affect infant development. We explored if the practice of breastfeeding until the third trimester of pregnancy affects birth outcomes and infant breast milk (BM) consumption and growth. Methods: Between 2009 and 2013, a cohort of 162 pregnant women was followed from the third trimester of pregnancy through 6 months postpartum in a peri‐urban community in Lima, Peru. The cohort included two groups: group 1 (cases) consisted of pregnant women who reported that they continued to breastfeed their child during the third trimester of pregnancy; group 2 (controls) consisted of pregnant women who had not breastfed during their pregnancy or if they did, it was only in the first trimester. The cohort was visited pre‐ and postpartum when toddler and infant 24‐h BM consumption and anthropometry were measured, respectively. Results: We compared 81 case‐control pairs. Of the 49 cases who accepted a prenatal visit, around 60% of the toddlers had 0 g of BM intake during 24 h, even though an average of 4 breastfeeds was observed. No significant difference was found between cases and controls regarding birth weight, birth length, and BM consumption at the 1st, 3rd, and 6th month postpartum (all p>0.10). Conclusion: There was no effect of the practice of breastfeeding until the third trimester of pregnancy on birth outcomes and infant BM consumption or growth during the first six months of life.Grant Funding Source: Supported by Canadian Institutes of Health Research
Body composition of breastfed infants ő a comparison of bioelectrical impedance spectroscopy and ultrasound assessment (1017.3)
Authors: Geddes Donna , Gridneva Zoya , Hepworth Anna , Tat Lai Ching , Hartmann Peter 
Published: June 2021

An accurate non‐invasive methodology to measure infant body composition is required to identify infants at risk of obesity. This study compared bioelectrical impedance spectroscopy (BIS) and ultrasound (US) methods and assessed effect of milk intake on BIS. Percentage Fat Mass (%FM) of 5 and 9 month old healthy, term infants was determined with BIS pre and post a breastfeed using software default calculations. Milk intake was measured by the test‐weigh method. Skin and subcutaneous fat thickness was measured at the tricipital and subscapular sites with US and the measurements were used to predict %FM. Milk intake (mL) was (median [IQR] 64.5 [43.3, 87.0]). Post and pre feed BIS measurements were not significantly different (p=0.29), regardless of milk intake. US %FM predictions (median [IQR] 25.5 [21.8, 28.8]) were consistent with reference values for infant body composition. BIS %FM measurements (median [IQR] 16.7 [14.5,19.4]) were significantly lower than US %FM (p<0.001). Milk intake did not significantly affect BIS readings. Preliminary results indicate that US is an acceptable non‐invasive method for predicting %FM and BIS consistently underestimates %FM.Grant Funding Source: Medela AG
Breastfeeding support increases breastfeeding duration among middle‐ to high‐income women (1017.6)
Authors: Clark Alena , Baker Susan , McGirr Kathryn , Harris Mary , Davalos Deana 
Published: June 2021

The objective of the Omega Smart Baby Project was to determine if supplementing pregnant/breastfeeding mothers with DHA would improve infants’ neuropsychological development. One hundred and fifteen women with singleton pregnancies were given either a placebo or DHA supplement of 300 mg a day during the third trimester and first three months of the infant’s life. A breastfeeding peer support program including prenatal visits, hospital and home visits and phone calls throughout the infants’ first year of life was provided with anticipatory breastfeeding guidance to increase breastfeeding duration rates of study participants to then establish the link between DHA and neuropsychological development. Factors that were associated with a significant increase (p<.05) in breastfeeding duration included marital status, mother’s ethnicity, mother’s medical history and delivery type. At three months, 84% of mothers were breastfeeding, 74% at six months and 56% at twelve months; all higher than the current national and Colorado averages. Results indicate that having consistent breastfeeding support during the infant’s first year of life may increase duration rates.Grant Funding Source: Supported by USDA NRI
Effect of dairy foods vs. calcium and vitamin‐D supplements on bone metabolism: use of 41Ca tracer (1018.12)
Authors: Demmer Elieke , Gertz Erik , Rogers Tara , Hillgonds Darren , Garrod Marge , Van Loan Marta 
Published: June 2021

Effect of dairy foods vs calcium & vitamin‐D supplements on bone metabolism: Use of 41Ca tracer E Demmer1, ER Gertz2, T Rogers1, D Hillgonds3, M Garrod2, MD Van Loan2 1. Graduate Group in Nutritional Biology, University of California Davis, Davis, CA 2. USDA/ARS Western Human Nutrition Research Center, Davis, CA 3. Lawrence Livermore National Laboratory, Livermore, CA Calcium(Ca) & vitamin D (D) are essential for bone health but other dietary components may also be important. Dairy products provide a rich supply of Mg, P, K, and protein, all important to bone health. We examined the effect of 4 servings/d milk & yogurt compared to equal intakes of Ca & D from supplements on bone metabolism. Twelve healthy postmenopausal women, who were low‐moderate dairy consumers, completed a randomized crossover trial with two 6 wk interventions separated by a 6 wk washout period. Six months prior to intervention women were dosed with 41Ca to label the skeleton. 24‐hr urine samples were analyzed for 41Ca/40Ca using accelerator mass spectrometry. Both interventions resulted in a significant decline (p < 0.0001) of Ca lost from the skeleton. Reduced resorption for supplement (p=0.0034) and dairy (p= 0.0002) groups was confirmed by CTx. Formation (BAP) significantly increased (p=0.032) in the dairy group only. Ca intake for the dairy group was significantly less (‐120mg/d) than that consumed by supplements, this difference can be attributed to other dietary Ca sources, e.g. increased vegetable and grain intake in the supplement group. Our results suggest that the nutrient‐rich composition of milk and yogurt may be more effective in maintaining bone health in healthy postmenopausal women compared to Ca and D supplements alone.Funding: Dairy Research Institute, California Dairy Council, USDA‐ARS‐Western Human Nutrition Research CenterGrant Funding Source: Dairy Research Institute, California Dairy Council, USDA‐ARS‐Western Human Nutrition Research Center