bluuebunny/crossref_metadata_2025_split huggingface dataset:
Food Sources of Total Energy, Total Sugars and Added Sugars Among Infants, Toddlers and Preschoolers Living in Mexico: Findings from the 2012 Mexican National Health and Nutrition Survey
Authors: Deming Denise , Afeiche Myriam , Reidy Kathleen , Eldridge Alison , Villalpando‐Carrión Salvador 
Published: November 2023

Excessive usual energy intakes (total energy intake > 1.5SD above the estimated average energy requirement) have been reported for Mexican infants (14%), toddlers (33%), and preschoolers (14%). The consumption of energy dense, nutrient‐poor foods and beverages already begins in infancy and increases rapidly through age 3 years. To further understand the dietary intakes of young Mexican children, the food sources of total energy and sugars were examined, using data from a nationally representative sample of children ages 0–47.9 months (m) (n=2057) from the 2012 Mexican National Health and Nutrition Survey (ENSANUT 2012). Dietary intake data from a single, proxy‐reported 24‐hour dietary recall for each child was assessed in infants 0–11 months (m) (n=411), toddlers 12–23m (n=538) and preschoolers 24–47m (n=1108). Per capita percentage contributions to intakes of total energy (TE), total sugars (TS), and added sugars (AS) were calculated for 1) major food groups (milks, grains, fruits, vegetables, meat/proteins, mixed dishes, sweets and sugar‐sweetened beverages (SSB)) and 2) specific foods and beverages. Overall, trends in major food group sources of TE and TS from ages 0–47m showed a decrease in the contribution of milks (from ~96 to 13%) and an increase in the contribution of sweets and SSB (from ~2 to 26%). Sweets and SSB contributed more than half of the AS intake during infancy (~54–66%) and increased to more than two thirds of AS intake among toddlers and preschoolers (~66–70%). Overall, the leading sources of TE and TS among infants were breast milk, infant formula, and also cow's milk in ages 6–11m; the top sources of AS were cookies, yogurt, sugar‐sweetened tea/coffee, fruit flavored drinks, and ice cream. Compared to infants, the diets of toddlers and preschoolers were more diverse. The major sources of TE were cow's milk, tortillas, soups, stews, egg dishes (mixed dishes), and sweetened breads. Cow's milk, fresh fruit, sugar‐sweetened tea/coffee and carbonated sodas were major contributors of TS. Overall, three to four of the top five food sources of AS were sweets and SSB contributing ~38% of total intake of AS for toddlers and ~30% for preschoolers. Yogurt and cow's milk were also among the top sources of AS, but unlike sweets and SBB, these foods provide key nutrients for young children and are major food sources of calcium and vitamin D in Mexican toddlers and preschoolers. These findings provide important insights into the consumption patterns of sweets and SSB and the key dietary sources contributing to intakes of energy and sugars. Understanding the dietary sources of energy and nutrients is critical in influencing the development of early dietary patterns and improving the diets and long term health of young Mexican children.Support or Funding InformationFunded by Nestlé Research Center, Lausanne, Switzerland.
Snacking Starts Early and Is Prevalent Among Infants, Toddlers and Preschoolers in Mexico
Authors: Deming Denise , Afeiche Myriam , Reidy Kathleen , Eldridge Alison , Villalpando‐Carrión Salvador 
Published: November 2023

The aim of this study was to examine snacking patterns among young children living in Mexico. We used data from the 2012 Mexican National Health and Nutrition Survey (ENSANUT 2012) to assess the snacking prevalence, energy intake from snacks and common snacks foods consumed among infants, toddlers and preschoolers (n=2057). Dietary intake interviews (24‐hour recalls) were conducted with parents or caregivers of infants ages 6–11 months (m) (n=229), toddlers 12–23m (n=538) and preschoolers 24–47m (n=1108). Snacking was defined as eating outside of meals (excluding infant feedings), and was self‐reported by parents or caregivers. Most children >11m were snacking on a given day (~82–85%) and consumed snacks more frequently before and after lunch (~55–65%) than before breakfast and after dinner (~20–30%). Snacks contributed ~15% of total energy intake among infants ages 6–11m and ~22% among both toddlers and preschoolers, who consumed ~2 snacks/day (2.2±0.1, and 1.8±0.1, respectively). Energy intake from snacks among consumers increased with age and by the age of 2 years, children consumed on average 392±21 kcals from snacks in a day and about 150–200 kcals per snack occasion. Cookies, salty snacks, fruits, yogurt and cow's milk ranked in the top five most frequently consumed foods during snacking among infants. Fruit, cow's milk, cookies, candy, and salty snacks were the most frequently consumed snacks by toddlers and preschoolers. These findings show that snacking patterns begin in infancy and snacks foods contribute a large percentage to the total caloric intake of young Mexican children and that the quality of some foods consumed as snacks could be improved. Since food preferences and dietary patterns start early in life it is critical to acknowledge the importance of snacking patterns among young Mexican children and the implications for long term health.Support or Funding InformationFunded by Nestlé Research Center, Lausanne, Switzerland
Endothelial Follistatin‐like 1 Regulates The Maturation of The Pulmonary Vasculature by Modulating BMP/Smad Signaling
Authors: Tania Navessa Padma , Maarsingh Harm , Bos Sophie T , Mattiotti Andrea , Prakash Stuti , Timens Wim , Schmidt Martina , van den Hoff Maurice , Gosens Reinoud 
Published: November 2023

Pulmonary arterial hypertension (PAH) is a progressive disease that is characterized by vascular remodeling and sustained vasoconstriction which consequently lead to high blood pressure in the pulmonary vasculature and right ventricle remodeling. Altered bone morphogenetic protein (BMP) signaling has been implicated in the pathogenesis of PAH as well as in pulmonary vascular maturation. The endogenous BMP antagonist follistatin‐like 1 (Fstl1) is highly expressed in pulmonary vascular endothelium of the developing lung in mice, suggesting a role in pulmonary vessel formation. In this study, the role of Fstl1 in the maturation of the pulmonary vasculature was investigated using Tie2‐cre mediated endothelial‐specific Fstl1 knockout mice. To this end, Fstl1fl/fl mice were bred with Fstl1WT/KO Tie2‐cre mice to generate Fstl1KO/fl Tie2‐cre mice and control littermates Fstl1WT/fl Tie2‐cre, Fstl1KO/fl, and Fstl1WT/fl. Heart and lung tissue was collected from pups at 1 and 3 weeks after birth. The percentage of actin‐positive small vessels per total number of vessels was determined. The expression level of Fstl1 and BMP/Smad‐regulated genes was determined in total RNA isolated from lungs using qPCR. Activation of BMP signaling was investigated using western blot. In wildtype mice, the mRNA expression of Fstl1 was higher in lung tissue at 1 week than 3 weeks (p<0.005). In line with the idea that Fstl1 is a BMP inhibitor, BMP signaling was more active at 3 weeks than 1 week, reflected by the higher level of pSmad1/5/8 at 3 weeks than 1 week. Moreover, the mRNA levels of the BMP/Smad‐regulated genes JAG1 (p<0.05) and endothelin‐1 (p<0.005) were increased at 3 weeks compared to 1 week after birth. Endothelial‐specific deletion of Fstl1 was postnatally lethal, approx. 70% of Fstl KO/fl Tie2‐cre mice died at 3 weeks after birth. Though most were found dead, some were found in respiratory distress prior to dying. In these mice, Fstl1 mRNA expression was reduced (p<0.01) compared to wildtype mice at 1 week. Endothelial deletion of Fstl1 resulted in activation of Smad1/5/8 signaling and increased BMP/Smad‐regulated gene expression of JAG1 (p<0.05), endoglin (p<0.05), and endothelin‐1 (p<0.05) at 1 week. At 3 weeks, JAG1 was reduced (p<0.01) whereas endoglin and endothelin‐1 were unchanged. Furthermore, the percentage of actin‐positive small pulmonary vessels was increased at 3 weeks old of Fstl1KO/fl Tie2‐cre mice compare to wildtype (p<0.005) whereas it was unaltered at 1 week. Loss of endothelial Fstl1 induces activation of BMP‐mediated gene expression and microvasculature remodeling, which presumably due to alteration in endothelin‐1 expression.Support or Funding InformationThis study was supported by a grant from the Netherlands Lung Foundation (grant number: 3.2.12.083)
Nucleoside reverse transcriptase inhibitors attenuate angiogenesis and lymphangiogenesis by impairing receptor tyrosine kinases signaling in endothelial cells.
Authors: Song Lin , Zhu Xiaolong , Qiu Cong , Qin Lingfeng , Chow Samson A , Yu Luyang 
Published: November 2023

The successful roll‐out of antiretroviral therapy (ART) makes clinical challenges now confronting HIV‐positive patients shift significantly from acquired immunodeficiency syndromes (AIDS) to chronic noncommunicable diseases, especially cardiovascular defects. Previous reports indicated that antiretroviral therapy exacerbated arteriosclerosis by inducing dysfunction of aortic endothelial cells, while HIV‐protease inhibitor administration was associated with regression of Kaposi sarcoma by impairing tumor angiogenesis. However, the role of ART in regular blood vessel growth is unknown. In the present study, we used an integral component of ART, nucleoside reverse transcriptase inhibitors (NRTIs), to investigate their effects on major microvascular function including angiogenesis and lymphangiogenesis. Here we demonstrated that pharmaceutical dose of NRTIs (AZT, TDF and 3TC) can inhibit angiogenesis and lymphangiogenesis both in vivo and in vitro via affecting the migration but not proliferation of endothelial cells. Correspondingly, NRTIs treatment attenuated VEGFR2 and FGFR1 signaling, classical angiogenic pathways, in vascular endothelial cells and VEGFR3 signaling, classical lymphangiogenic pathway, in lymphatic endothelial cells, both in the intensity and sensitivity. However, NRTIs had little effect on endothelial Notch1 pathway, the other kind of membrane receptor signaling. Taken together, it implied a special role of NRTIs in regulating receptor tyrosine kinase (RTK) in endothelial cells. In regard to the inhibitory mechanisms targeting the RTK pathways, a special capability of AZT was observed for blocking glycosylation of these RTKs. On the other hand, both TDF and 3TC significantly restrained RTKs endocytosis into early endosome while do not affect their internalization. Furthermore, NRTI induced excessive mitoROS resulted from endothelial mitochondrial dysfunction. Reciprocally, MnSOD, mitoROS scavenger, rescued both defects of RTK signaling and angiogenic or lymphangiogenic function in microvascular endothelial cells treated with NRTIs. Therefore, we conclude that NRTIs negatively regulate angiogenesis and lymphangiogenesis by inducing vicious mitoROS generation, and subsequently impairing RTK signaling in endothelial cells.Support or Funding InformationNational Natural Science Foundation of China (Grant No. 81270357, 81422005 and 31470057), Zhejiang Provincial Natural Science Foundation of China (Grant No. LR14H020002)
Central Role for Intestinal Epithelial IL‐10R1 Signaling in Barrier Restitution
Authors: Lanis Jordi M. , Alexeev Erica E. , Kao Daniel J. , Kitzenberg David A. , Schwisow Kayla D. , Kominsky Douglas J. , Colgan Sean P. 
Published: November 2023

IL‐10 is a potent anti‐inflammatory cytokine that inhibits the production of numerous pro‐inflammatory mediators in a number of cell types. Studies in animal models and in humans have demonstrated a critical role of IL‐10 signaling in a broad range of chronic inflammatory conditions, including inflammatory bowel disease. Our recent studies identified a prominent role for intestinal epithelial cell (IEC) IL‐10 signaling in inflammatory resolution during colitis. At present, little is known about how IL‐10 signaling interfaces with epithelial function in health and during inflammation. Based on our previous studies implicating enhanced restitution of epithelial monolayers in response to IL‐10, we hypothesized that IL‐10 signaling in IECs influences epithelial barrier maintenance and healing. Initial studies in IEC cell lines revealed that lentiviral‐mediated knockdown of IL‐10R1 resulted in significant defects in the formation of epithelial barrier function, measured by transepithelial resistance and paracellular flux assays (p<0.01). Studies in vivo using conditional IEC IL‐10R1 knockout mice identified a baseline defect in barrier function as evidenced by increased FITC‐dextran permeability with concomitant increases associated with ongoing inflammation (e.g. DSS colitis). Ongoing studies to identify regulatory mechanisms of IEC IL‐10R1 revealed a prominent role of the aryl hydrocarbon receptor (AHR) in induction of IL‐10R1 during inflammation. Parallel studies in AHR knockdown cell lines revealed barrier defects similar to the loss of IL‐10R1. We next utilized a scratch wound assay to define epithelial restitution and the role of this AHR‐IL‐10R1 axis. Induction of IL‐10R1 via the AHR ligand FICZ significantly increased IL‐10‐dependent wound healing. This response was abolished in cells lacking either IL‐10R1 or AHR. Together, these results provide compelling evidence on the importance of IL‐10 signaling in intestinal epithelial barrier function and restitution following injury.Support or Funding InformationThis work was supported by NIH grants DK099452, DK095491, DK50189, and by the Crohn's and Colitis Foundation of America.
Intestinal Epithelial Cell Expression of CD47 Facilitates Proliferation, Neutrophil Transmigration, and Wound Healing in vivo
Authors: Reed Michelle , Luissint Anny‐Claude , Nusrat Asma , Parkos Charles A 
Published: November 2023

The cell membrane glycoprotein CD47 is a ubiquitously expressed ‘self’ antigen that is known to facilitate a wide variety of interactions involving hematopoietic cells depending on the cell type and context. Specifically, CD47 has been reported to regulate the induction of apoptosis, leukocyte transmigration, and non‐classical recognition/phagocytosis of cells by macrophages. Despite mounting evidence on CD47 function in leukocytes, comparatively little is known about the function of CD47 expression by non‐hematopoietic cells. Previous studies suggest that epithelial expression of CD47 is important for rapid neutrophil transepithelial migration in response to chemotactic agent sin vitro, yet the function of epithelial expressed CD47 has not been explored in vivo.In this study, we utilized both epithelial‐targeted (Villin‐CreCD47f/f) and tamoxifen‐inducible epithelial‐targeted (Villin‐Cre‐ERT2CD47f/f) CD47‐deficient transgenic mice to assess the function of CD47 in the intestinal epithelium in vivo, under steady‐state conditions and during intestinal inflammation, respectively. While gross intestinal mucosal architecture and barrier integrity of Villin‐Cre CD47f/fmice was not altered under steady state conditions in vivo, CD47‐deficient crypt epithelial cells displayed decreased proliferation, as evidenced by reduced EdU uptake. Similarly, acute loss of intestinal epithelial CD47 expression in Villin‐Cre‐ERT2 CD47f/fmice produced no increase in intestinal permeability or symptoms of colitis at one month post‐tamoxifen treatment. Consistent with our previous in vitro findings of delayed neutrophil transmigration upon antibody‐mediated blockade of epithelial CD47, induced loss of intestinal epithelial CD47 expression in Villin‐Cre‐ERT2 CD47f/fmice impaired neutrophil recruitment into the intestinal lumen in response to the chemokine KC in vivo. Finally, in keeping with diminished epithelial proliferation and neutrophil infiltration observed in epithelial‐targeted CD47 deficient mice, both Villin‐Cre CD47f/fmice and tamoxifen‐treated Villin‐Cre‐ERT2 CD47f/f mice displayed increased disease activity and mucosal damage in an injury induced (DSS) model of chronic colitis.These findings provide novel insights into the function ofCD47 expression by non‐hematopoietic cells that involves maintenance of normal epithelial cell proliferation and turnover, while enabling rapid recruitment of neutrophils under inflammatory conditions. Furthermore, given the current appreciation of CD47 as a non‐classical regulator of “don't eat me” signals such that cells deficient in CD47 are cleared by splenic macrophages, our observations that mice harboring epithelial‐targeted CD47 deficiency are healthy indicate that additional regulatory mechanisms mediate CD47 function.Support or Funding InformationThis work was funded by the National Institutes of Health grant R01DK079392.
Cortactin is Required to Maintain Intestinal Epithelial Barrier Homeostasis
Authors: Citalán‐Madrid Alí Francisco , García‐Ponce Alexander , Vargas‐Robles Hilda , Betanzos Abigail , Nava Porfirio , Rottner Klemens , Menningen Rudolf , Schnoor Michael 
Published: November 2023

A stable intestinal epithelium is the basis for healthy intestines. Epithelial dysfunction causes increased intestinal permeability and bacterial translocation that may eventually cause an aberrant immune response as seen in chronic inflammatory diseases of the intestines such as ulcerative colitis (UC) and Crohn disease (CD). The actin cytoskeleton regulates epithelial barrier integrity through tight junction and adherens junction molecules, but the role of actin regulators such as cortactin (CTTN) is not well understood. Analyzing CTTN‐KO mice, we found that these animals have increased basal intestinal permeability similar to what has been demonstrated in the vasculature. Furthermore, CTTN‐KO mice were more susceptible to DSS‐induced experimental colitis with animals dying already after 5 days of DSS treatment. Histopathological analysis of CTTN‐KO colons revealed differences in the intestinal epithelial structure such as hypoplasia, edema, hemorrhage and infiltration already under basal conditions which it worsened after experimental colitis. Immunofluorescence staining of colon tissues of mice demonstrated a reduced expression and localization at junctions of ZO‐1 and E‐cadherin and intestinal epithelial crypt disassembly. Using a stable CTTN‐depleted Caco‐2 cell line, we confirmed epithelial dysfunction including reduced transepithelial electrical resistance, increased paracellular flux of 4 kDa FITC‐dextran and weaker cortical actin rings. This was accompanied by a decreased expression and internalization of ZO‐1, occludin, claudin‐1 and E‐cadherin; while claudin‐4 and b‐catenin remained unchanged. Interestingly, expression of the pore‐forming claudin‐2 was increased and neutrophils transmigrated more rapidly. While CTTN depletion did not cause increased apoptosis, we observed increased proliferation and stress fiber formation that may be responsible for the observed barrier dysfunction. Importantly, CTTN localized at cell contacts in colon biopsies of healthy individuals, whereas in IBD patients we observed strong translocation of CTTN into the cytosol and loss of colocalization with actin and ZO‐1. Our data imply that CTTN controls intestinal barrier integrity by controlling actin cytoskeleton and intercellular junction functionality causing epithelial dysfunction as seen in IBD.Support or Funding InformationThis work was supported by grants and a Ph.D stipend from the Mexican Council for Science and Technology (333396 to AFCM & 179895 to MS and a special fund PNPC.2013‐2014)
Nebulized delivery of the MAPKAP kinase 2 peptide inhibitor MMI‐0100 protects against ischemia‐induced systolic dysfunction
Authors: Brown David , Cooley Brian , Quintana Megan , Landers Cynthia , Willis Monte S 
Published: November 2023

Acute myocardial infarction (AMI) results in systolic dysfunction, myocarditis and fibrotic remodeling, which causes irreversible pathological remodeling of the heart. Associated cell death and inflammation cause cytokine release, which activates the p38 MAPK signaling pathway to propagate damaging signals via MAPKAP kinase 2 (MK2). Previously we showed that intraperitoneal injection of a cell permeable peptide inhibitor of MK2, MMI‐0100, protects against fibrosis, apoptosis and systolic dysfunction in a mouse model of AMI, left‐anterior descending coronary artery (LAD) ligation. Here we tested a new route of administration of MMI‐0100: inhalation of nebulized peptide. When given within 30 minutes of AMI and daily for 2 weeks thereafter, both inhaled and injected MMI‐0100 improved cardiac function as measured by conscious echocardiography. Limited fibrosis was observed after two weeks by Massons trichrome staining, suggesting that MMI‐0100 protects the heart prior to the formation of significant fibrosis. These results support a nebulized route of administration of MMI‐0100 can protect the myocardium from ischemic damage.Support or Funding InformationThis work was supported by the National Institutes of Health (R01HL104129 to M.W.), a Fellowship from the Jefferson‐Pilot Corporation (to M.W.), and the Leducq Foundation (to M.W.).
The Role of the Duffy Antigen Receptor for Chemokines in Metabolic Disease
Authors: Benson Tyler Wendorf , Chatterjee Tapan , Joseph Joel , Popoola Orishebawo , Crowe Matthew , Yiew Nicole , Unruh Dusten , Weintraub Daniel , Pillai Ajay , Williams Jo , Mintz James , Stansfield Brian , Stepp David , Brittain Julia , Bogdanov Vladimir , Weintraub Neal 
Published: November 2023

Inflammation in adipose tissues contributes to obesity‐related insulin resistance and metabolic disease, a problem with greater prevalence in African, Asian, and Hispanic populations. The Duffy Antigen Receptor for Chemokines (DARC) is a promiscuous non‐signaling receptor expressed primarily on erythrocytes and classically thought to modulate inflammation by binding chemokines such as MCP‐1 to buffer tissue inflammation and act as a chemokine reservoir. DARC allele variants protect against malaria and are prevalent in African, Asian, and Hispanic populations. We hypothesized that genetic deletion of DARC would augment adipose tissue inflammation and glucose intolerance in the setting of diet‐induced obesity.Eight week‐old male Wild Type (WT) and DARC−/− mice (C57BL/6 background) were maintained either on chow diet or switched to high fat diet (HFD, 60% calories from fat) for up to 24 weeks. Thereafter, metabolic phenotyping was performed, mice were subsequently euthanized, and tissues and blood were collected for analysis. Bone marrow (BM) transplants were performed by irradiating eight week old WT mice and injecting BM harvested from either DARC−/− (to eliminate BM‐derived DARC) or WT mice (control).Food intake, energy expenditure and locomotion were similar between WT and DARC−/− mice, leading to equivalent body‐weight gain and adipose tissue mass. Compared to WT mice, HFD‐fed DARC−/− mice exhibited lower plasma levels of the DARC‐bound cytokines MCP‐1, CCL11 and CXCL5, but higher adipose tissue MCP‐1 mRNA expression, more adipose tissue macrophages, and significantly larger adipocytes in the visceral adipose depots, implying enhanced adipose tissue inflammation. In addition, glucose tolerance and insulin sensitivity were significantly impaired in DARC−/− mice compared to WT mice on HFD. CD DARC−/− mice did not display increased adipose inflammation; however, they were less sensitive to insulin, exhibited larger subcutaneous adipocytes, and had higher levels of leptin mRNA and AKT phosphorylation (SER473) upon insulin stimulation when compared to WT mice. Mice reconstituted with DARC −/− BM and fed a HFD did not exhibit glucose intolerance or insulin resistance compared to mice with WT BM. Notably, we detected high levels of DARC mRNA in subcutaneous and visceral (but not brown) fat depots, and DARC protein immunoreactivity was detected in subcutaneous fat from WT but not DARC −/− mice.We conclude that loss of DARC enhances HFD‐induced adipose tissue inflammation and metabolic disease. However, the mechanism appears to be independent of its expression on erythrocytes and its classic role as a chemokine buffer‐sink. We report for the first time that DARC is expressed on adipocytes, where it may regulate insulin signaling.