bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural killer cell maturation is blocked by mTOR inhibition in C57Bl/6 mice
Authors: Clinthorne Jonathan F , Gardner Elizabeth M
Published: June 2021

Recent work established a pathway by which the energy sensitive kinase mammalian target of rapamycin (mTOR) regulates T cell biology, and this pathway is directly influenced by energy intake. Energy restriction (ER) is a dietary intervention shown to increase lifespan and reduce the incidence of tumors in rodents. The objective of this study was to examine the role of mTOR in NK cell metabolism and biology, based on the observation that ER results in fewer mature NK cells. NK cells from 40% ER mice exhibited mTOR inhibition directly ex vivo, and reduced expression of the transcription factors Eomes and T‐bet, which are required for NK cell maturation. Consequences of mTOR inhibition on NK cell biology was examined in vitro and revealed IL‐12 + IL‐18 induced NK cell maturation and function was impaired following rapamycin treatment. mTOR inhibition reduced upregulation of metabolic transporters, and repressed expression of NK cell maturation markers. Concurrently, mTOR inhibition in NK cells blocked upregulation of transcription factors Eomes and T‐bet following stimulation. Mature NK cells play a critical role in killing tumor cells and here we show NK cell maturation is linked to metabolic signaling through mTOR. Thus, manipulation of energy intake or energy sensitive pathways directly influences NK cell maturation, which has significant implications during the immune response to cancers or viral infections.

Grant Funding Source: R01AG034949
Sodium Claims or Health Focused Messages Help Consumers to Identify Sodium Levels in Foods Better than the Nutrition Facts Table
Authors: Schermel Alyssa , L'Abbé Mary R.
Published: June 2021

The aim of this study was to determine whether consumers can properly classify sodium levels (low, moderate, or high) based on the Nutrition Facts table (NFt) alone and whether sodium focused messages influence these judgements. Participants from a national online consumer panel (n=3,437) were randomly assigned to 1 of 5 treatment conditions on mock cheese products. Treatment group 1 was shown a Nutrition Facts table (NFt) with typical levels of sodium and groups 2 to 5 were shown a NFt with a 25% reduction. Groups 3 to 5 were shown various additional sodium focused messages. Groups 1 and 2 made similar classification judgements, regardless of whether or not the product was higher or reduced in sodium. By comparison, groups 3 and 4 who were shown a “reduced sodium” claim in addition to the NFt classified products as lower in sodium (P<0.05). This effect was even greater when consumers were shown a one‐page sodium advisory message (P<0.05). These results indicate that Canadian consumers generally have a poor understanding of what constitutes low, moderate, or high amounts of sodium based on information from the NFt only. Sodium focused messages significantly improve consumer judgements. Funding Source: Dairy Farmers of Canada
Sound advice or biased reporting? Breakfast as a strategy to reduce or prevent obesity or weight gain
Authors: Brown Andrew W , Brown Michelle M Bohan , Allison David B
Published: June 2021

Eating breakfast to control weight is a strategy presumed true without sufficient supporting evidence. We investigated whether biased reporting in primary literature exaggerates the protective effect of breakfast against obesity. From 92 identified studies of breakfast and obesity (all observational), ORs were calculated and meta‐analyzed from 88 study groups in 57 publications representing 30 countries. The resulting p‐value of p<10−42 demonstrates gratuitous repetition of the breakfast‐obesity presumption. No publication bias was detected. Analysis of 88 of the 92 studies’ abstracts revealed that authors biased the reporting of their own findings: breakfast‐obesity associations were more likely to be mentioned in abstracts’ conclusions if results were pro‐breakfast, compared to associations that showed mixed, negative, or no relationships (65% vs. 39%, p=0.0492); and causal language was used in 26% of abstracts that mentioned breakfast and weight in the conclusions. Citing of others’ work was also biased: 67% of relevant citations of one breakfast RCT were overly positive toward breakfast (2% overly negative), while 48% of relevant citations of a case‐series paper inappropriately used associative or causal language. In conclusion, there is evidence of biases in the breakfast literature that misleadingly exaggerate the strength of the evidence for a presumed protective effect against obesity.

Grant Funding Source: NIDDK P30DK056336 and NIDDK T32DK62710–01A1
Sodium alginate addition to chocolate milk reduces appetite and glycemic responses in healthy young men
Authors: El Khoury Dalia , Goff H. Douglas , Berengut Shari , Yavorska Nataliya , Kubant Ruslan , Anderson G. Harvey
Published: June 2021

Sodium alginate reduced appetite and glycemia, when consumed in water‐based drinks. But, its effects when added to usual beverages were not reported. Because chocolate milk (CM) is criticized for its elevated glycemic property, we hypothesized that alginate additions to CM promote satiety and attenuate glycemia. In a randomized crossover design, 24 men (22.9±0.4 years; 22.5±0.3 kg/m2) were provided isovolumetric preloads (325 ml) of CM, 1.25% alginate CM, 2.5% alginate CM or 2.5% alginate solution. All treatments were standardized for lactose and sucrose content and provided 120 min prior to an ad libitum pizza meal. Pizza intake and total caloric intake were not different among treatments. Glucose, insulin and appetite were measured at baseline and at intervals pre‐ and post‐meal. Pre‐meal appetite was attenuated dose‐dependently by alginate; CM with 2.5% alginate resulted in the lowest appetite (P<0.0001). Glucose area under the curve was reduced by 36% after 2.5% alginate CM compared to CM (P=0.004), with no differences with 1.25% alginate CM and 2.5% alginate solution. Yet, glucose peaks at 30 min were lower after 2.5% alginate CM compared to 1.25% alginate CM and CM (P<0.0001). Insulin peaks at 30 min were also lower after 2.5% alginate CM relative to CM (P<0.0001). In conclusion, 2.5% alginate in CM exerted an additive effect on satiety, and improved glycemia in a synergistic manner while reducing insulin demand.

Supported by Natural Sciences and Engineering Research Council of Canada‐Collaborative Research and Development Garant, Dairy Farmers of Ontario and Kraft Canada Inc.
α(1,3)‐Fucosylated Glycans on Myeloid Cells Regulate IL‐17‐ Dependent Granulopoiesis
Authors: Mackey Lantz C. , Rose Jason M , Weiss Jacob R. , Homeister Jonathon W.
Published: June 2021

Mice deficient in α(1,3)‐fucosyltransferases (FUT) 4 and 7 (DKO) lack selectin ligand activity and selectin‐dependent leukocyte trafficking. They have an 18‐fold increase in circulating neutrophils, an increased prevalence of Th17 cells, and elevated plasma concentrations of IL‐17 and G‐CSF. We sought to determine the FUT‐dependent mechanisms responsible for the enhanced IL‐17 production and neutrophilia in DKO mice. Flow cytometry was used to assess IL‐17 production by natural killer Tcells (NKT) and γδTcells in WT, C57BL/6c‐fms‐CRE.Loxp.FUT7tg (CRE)(myeloid‐specific trafficking deficiency), DKO, and DKOc‐fms‐ FUT7tg (DKOtg) (myeloid‐specific restoration of selectin‐dependent trafficking) mice. Mononuclear splenocytes were stimulated for IL‐17 production with PMA/Ionomycin with brefeldin A, and analyzed for IL‐17. DKO mice had a 23‐fold increase in NKTcells, 24‐fold increase in γδTcells, and 18‐fold more neutrophils compared to WT. CRE mice had a 20‐fold increase in NKTcells, 19‐fold increase in γδTcells, and 15‐fold more neutrophils compared to WT mice. DKOtg mice had WT numbers of IL‐17‐producing cells and neutrophils. These results suggest that the myeloid cell trafficking deficiency in DKO and CRE mice alters steady‐state granulopoiesis resulting in a pronounced neutrophilia, and elevated plasma concentrations of IL‐17 and G‐CSF. Supported by RO1‐HL090823 and T32‐ HL069768
Wnt signaling in liver homeostasis and regeneration
Authors: Yang Jing , Wiiliams Bart , Monga Satdarshan P
Published: June 2021

β‐catenin plays a critical role in liver homeostasis and during liver regeneration (LR). Numerous pathways can activate β‐catenin, the primary one being Wnt signaling. In this study we investigated the source of Wnts and to what extent β‐catenin signaling in liver is Wnt‐dependent. LRP5/6 are the co‐receptors for Wnts. We generated hepatocyte specific LRP5/6 double knockout mice (KO1) where Wnt‐signaling was abolished while Wnt‐independent signaling can still activate β‐catenin, and compared KO1 with hepatocyte specific β‐catenin knockout mice (KO2). We found that KO1 phenocopied KO2 in defective hepatic zonation and delay in LR. β‐catenin activation was impaired after partial hepatectomy (PH) in KO1 due to the lack of Wnt‐signaling. Given the importance of Wnt‐signaling in LR, we further investigated the source of Wnts. Evenness interrupted (Evi) regulates Wnt secretion. We generated hepatocyte specific Evi knockout mice (KO3), which lack the ability of hepatocytes to secrete Wnts. KO3 had normal hepatic zonation and initiation of LR; however, KO3 had sustained proliferation after PH at 72 & 96h. In WT, we found an induction of Wnt5a along with an increase in ROR2, an inhibitor of β‐catenin signaling, which is absent in KO3. Our study suggests that Wnt‐signaling is the major determinant controlling β‐ catenin activation in liver. Further, hepatocytes are not the source of canonical Wnts that activate β‐catenin, but rather produce noncanonical Wnt5a that terminates β‐catenin signaling during late LR.
Hypoxia‐inducible factor‐1α activation in hepatocytes promotes liver regeneration after acetaminophen overdose
Authors: Copple Bryan Lloyd , Luyendyk James P
Published: June 2021

Acetaminophen (APAP)‐induced liver injury is a leading cause of drug‐induced liver injury. Global hypoxia‐inducible factor‐1α (HIF‐1α) deficiency transiently reduced APAP‐induced liver injury in mice. The cellular source of HIF‐1α that promotes APAP‐induced liver injury is not known. We tested the hypothesis that activation of HIF‐1α in hepatocytes promotes APAP‐induced liver injury. Hepatocyte‐specific HIF‐1α‐deficient mice (HIF‐1αflox/flox/Albumin‐Cre mice) and control mice (HIF‐1αflox/flox mice) were treated with APAP (300 mg/kg, ip) and both liver injury and regeneration assessed 24 hours later. In contrast to global HIF‐1α deficiency, hepatocyte HIF‐1α deficiency did not reduce liver injury. Rather, liver injury was modestly increased in hepatocytes‐pecific HIF‐1α‐deficient mice treatment. Moreover, hepatic cyclin D1 mRNA levels and the number of PCNA‐positive hepatocytes was substantially reduced in hepatocyte specific‐HIF‐1α‐deficient mice 24 hours after APAP administration, implicating HIF‐1α as a promoter of liver regeneration after APAP overdose. Collectively, the results indicate that activation of HIF‐1α in hepatocytes protects the liver after APAP exposure by promoting liver regeneration.
Growth of poor rural Chinese children fed meat as a daily complementary food from 6–18 months of age
Authors: Hambidge K Michael , Sheng Xiaoyang , Westcott Jamie , Sun Qian‐Qian , Hu Yang‐Qi , Liu Jin‐Rong , Liu Shan‐Shan , Zhang Jie , Ma Jin‐Qiu , Geng Shan‐Shan , Krebs Nancy F
Published: June 2021

Objective

To determine the efficacy of a daily intake of meat as a complementary food from 6–18 mo on linear growth in a poor rural Chinese population.

Methods

The project was an unmasked RCT with cluster design in which 60 rural villages were randomly assigned to three groups. The daily interventions were 50g pork (M), equi‐caloric micronutrient‐fortified cereal‐based supplement (FC), and local non‐fortified rice supplement (UC) respectively. Anthropometry was performed at 6 and 18 mo.

Results

1465 subjects were enrolled at 6 mo of age (511M; 465 FC; 489 UC). At 18 mo old, 1317 subjects completed follow up (462 M; 436 FC; 419 UC). After adjustment for baseline values and mother's education levels, between M and FC, estimated Δ linear growth over 12 mo was 0.399 cm (95% CI: 0.163–0.636 cm, P=0.001), and LAZ was 0.137 (95% CI: 0.053–0.221, P=0.001) by pairwise comparisons. Mean (SD) LAZ, WAZ, & WLZ are given in table.

Conclusion

Meat was associated with a significantly higher linear growth rate. However treatment group differences were small. Mean LAZ was low at 6 mo and declined further by 18 mo in all groups.

Support: Thrasher Research Foundation; Sci & Tech Commission of Shanghai Municipality; Shanghai Key Lab of Ped Gastroenter & Nutr; Nat'l Natural Sci Foundation of China.
Niacin (vitamin B3, nicotinic acid) Decreases VLDLA‐polipoprotein B Secretion and Reduces Hepatic and Blood Lipid Concentrations: Roles of Niacin Metabolism and Autophagy Degradation
Authors: Guo Liang , Tuyama Ana , Butkinaree Chutikarn , Chung Kellie , O'Donnell Michael D. , Montenont Emilie , Fisher Edward A.
Published: June 2021

Niacin therapy, used either alone or in combination with another agent to reduced the risk of coronary heart disease, is effective in raising and lowering, respectively, HDL‐c and apoB/VLDL triglyceride (TG) levels in dyslipidemia. To further understand if part of the mechanism is by reducing the secretion of apoB‐containing lipoproteins through autophagy, we did a series of niacin studies in isolated primary hepatocytes or in intact mice. Metabolic labeling and pulse‐chase results showed niacin increased intracellular apoB degradation by 30%, and decreased apoB/VLDL TG secretions by 40%. These effects were lost in autophagy‐deficient cells. Mice fed with diet containing 3% niacin had 40% increases in plasma HDL‐c. Feeding high fat diet (HFD) with niacin lowered LDL‐c by 50%. Niacin was able to suppress postprandial plasma triglyceride by 30%. Niacin reduced hepatic triglyceride and cholesterol concentrations by 40% and 50%, respectively, in mice fed with HFD. These data suggest niacin decreases hepatic lipid concentrations, apoB/VLDL secretion, and modifies plasma cholesterol levels. Some of the effects required niacin metabolism and autophagy degradation. Supported by grants from the NIH (HL58541) and Merck & Co., Inc.

Grant Funding Source: NIH (HL58541) and Merck & Co., Inc.
Comparison of Genomic Profiling, Cytogenetics, and Histology in Adult and Pediatric Cases of Medulloblastoma
Authors: Schober Ralf , Holland Heidrun , Ahnert Peter , Fritzsch Dominik , Xu Li‐Xin , Krupp Wolfgang , Meixensberger Jürgen
Published: June 2021

The current WHO‐classification of medulloblastoma comprises four subgroups but has been extended by recent molecular genetic findings, differentiating the adult WNT related type, the adult sonic hedgehog related type, and two pediatric types that are incompletely defined yet. We present four cases with a comparison of clinical, neuropathological, cytogenetic, and genetic data on the basis of genome wide SNP array typing of both blood and tumor cells. Both adult cases, compatible with two recently reported subtypes (WNT, SHH) and the pediatric cases exhibited several novel findings. These included constitutional de novo losses 5q21.1, 15q11.2, 17q21.31, 19p12, (pediatric medulloblastoma), 9p21.1, 19p12, 19q13.3, 21q11.2 (adult medulloblastoma) and gains 16p11.1–16p11.2, 18p11.32, Yq11.223‐Yq11.23 (pediatric medullobl.), Xp22.31 (adult medullobl.), possibly representing inherited causal events for tumor formation. Furthermore, we show evidence for somatic segmental uniparental disomy in regions 1p36, 6q16.3, 6q24.1, 14q21.2, 17p13.3 and 17q22. Histological observations, such as desmoplasia in one adult case and undifferentiated large cells in one pediatric case corresponded to reported data. Other observed features of differentiation such as Homer‐Wright rosettes, however, have to be further analyzed and correlated in molecularly defined medulloblastoma subgroup cases
Exploring two different gross anatomy laboratory experiences: The perspective of the repeating first year medical student
Authors: Fillmore Erin , Seifert Mark F. , Helfenbein Robert J.
Published: June 2021

This qualitative case study examines the perceptions and experiences of medical students who repeated gross anatomy at Indiana University School of Medicine—Indianapolis under two different formats of instruction. In the fall of 2010, the students experienced the anatomy laboratory as an open laboratory. In the fall of 2011, the course implemented peer teaching in the laboratory and the repeating students experienced this new format of instruction. This study sought to better understand student perspectives regarding the learning processes experienced in these two different laboratory formats and the implications for curriculum and pedagogy in medical education. Four major themes were identified from data analysis: the loss and reclaiming of confidence; the intensification of accountability towards fellow students and future patients; the struggle for, and equalization of power; and the metamorphosis of anatomy as parts into anatomy as body. Results highlight the complex, multifaceted learning experience medical students have while dissecting, and in particular, while teaching their peers. Participants’ experiences encompassed the intellectual, yet transcended it. Exploring these results within the context of curriculum and pedagogy in medical education brings to the forefront important perspectives on the educational, intrapersonal, and interpersonal dynamics present in the laboratory.

Grant Funding Source: N/A
Autologous subcutaneous adipose tissue transplant in diet induced obese rats.
Authors: Torres‐Villalobos Gonzalo Manuel , Hamdan‐Pérez Nashla , Torres Nimbe , Ordaz‐Nava Guillermo , Moran‐Ramos Sofia , Noriega Lilia , Bravo‐Reyna Carlos , Torre‐Villalvazo Ivan , Hiriart Marcia , Medina‐Santillan Roberto
Published: June 2021

Obesity is a complex disease

Objective

Evaluate autologous subcutaneous adipose tissue (SAT) functionality as a therapeutic measure for obesity and its comorbidities.

Methods

We feed Wistar rats with a high‐carbohydrate (HC) or a high animal fat (HF) diet for 90 days. Glucose and triglyceride (TG) concentrations were evaluated each 30 days, oral glucose tolerance test (OGGT) at days 0, 90 and 180. On day 90 surgical procedures were performed randomly on all rats: 1) Sham (S) control, 2) autologous SAT transplant to visceral adipose tissue (T), 3) extraction (E) of SAT.

Results

On day 180 OGGT showed lower insulin concentrations on T group with HF diet (p =0.002) in comparison to S, as well as a smaller increase in groups T and E on both diets (p=0.004) compared to S. The group with less weight gain was T with both diets. At day 180 TG concentrations were lower in groups E and T of both diets compared to group S. We measured cholesterol and TG in hepatic tissue, it was higher in S and E groups compared with T on HF diet (p=0.008). Rats that underwent autologous SAT transplantation showed a better response during OGGT and a smaller increase in weight compared to S group.

Conclusion

Autologous SAT transplantation to visceral compartment might be a useful clinical measure to improve carbohydrate metabolism and weight control.
Femoral Bone Marrow Adiposity in Men with Motor Complete Spinal Cord Injury
Authors: Gorgey Ashraf S , Adler Robert A , Khalil Refka , Gater David R
Published: June 2021

Obesity and osteoporosis are hallmark adaptations following spinal cord injury (SCI). Bone marrow (BM) mesenchymal cells can be differentiated to become osteoblasts or adipocytes. The major objective of the work is to quantify yellow marrow and cortical bone cross‐sectional areas (CSA) of the femur in individuals with SCI compared to healthy able‐bodied (AB) controls. Eight individuals with motor complete SCI as well as 6 age matched healthy AB controls underwent MRI of both thighs to measure BM adiposity (BMA) and cortical geometry. Cortical bone CSA adjusted to total sub‐perisoteal bone CSA was 1.5–2 × lower in men with SCI compared to AB‐controls across the femoral length (P =0.003). Yellow BMA CSA was 2–3 × greater in men with SCI compared to AB‐controls (P < 0.0001). BMA CSA was twice greater in the distal 1/3 compared to the proximal 2/3 in both groups. Negative association was noted between the yellow BMA CSA and cortical bone CSAs in men with SCI and positive association in AB‐controls. Yellow BMA was negatively associated with skeletal muscle CSA (P < 0.05) in men with SCI. After SCI, cortical bone CSA becomes thinner and associated with greater accumulation of yellow marrow as measured by BMA. BMA is linked to several of the adaptations that men with SCI encounter, including changes in bone geometry as well as increased fat mass. Loading may reciprocally influence the relationships between BMA and cortical bone CSA.
The influence of heroin withdrawal and relapse on pituitary ACTH, beta‐EP cells and serum cortisol level in rats
Authors: Liang Wen‐mei , Li Yi‐xin
Published: June 2021

To investigate the effect of heroin withdrawal and relapse on the morphology and function of pituitary ACTH, β‐EP cells and the serum cortisol level and to further explore the possible mechanism. 63 adult male SD rats were randomly divided into normal control group (NCG), saline control group (SCG), and experiment group(EG). The rats in EG group were sub‐divided into heroin withdrawal group (HWG), methadone detoxication group (MDG), and heroin relapse group (HRG). The pituitary of rats was excised soon after the serum was obtained via heart puncture. The morphology of pituitary ACTH, β‐EP cells was observed by using immunohistochemical SABC method, image analysis, and transmission electron microscopy (TEM). RIA was used to detect the serum cortisol level. The immunostaining intensity of ACTH cells in HWG and HRG was higher and β‐EP cells was lower when compared with NCG and SCG. TEM showed that vacuolation, dilatation of endoplasmic reticulum, secretory granules decreased, smaller irregular nucleus, and the increased perinuclear space occurred in the ACTH cells in HWG and HRG. The results of RIA showed that the level of serum cortisol in each group of EG was significantly increased as compared with NCG (P<0.05). The results suggest that the pituitary‐adrenal axis is activated and the secretion of endogenous opioid peptides is inhibited during heroin withdrawal and relapse period.
Oral administration of cholic acid modulates the gut microbiota and epithelial proliferation
Authors: Ishizuka Satoshi , Takatsuki Manami , Shiwaku Maiko , Hagio Masahito , Yoshitsugu Reika , Kikuchi Keidai , Fujii Nobuyuki , Joe Ga‐Hyun , Shimizu Hidehisa , Hara Hiroshi , Fukiya Satoru , Yokota Atsushi
Published: June 2021

Bile acid (BA) increases in feces under consumption of high‐fat and high‐sucrose diet and some BAs, such as deoxycholic acid (DCA), have strong antibiotic activity. We evaluated bile acid metabolism, serum biochemical parameters, epithelial proliferation, as well as cecal microbiota in response to oral administration of cholic acid (CA) in rats. WKAH/HkmSlc rats (3‐ week‐old, male) were divided into two dietary groups, such as control group fed an AIN‐93 based diet or CA (0.2g/kg diet)‐ containing diet for 10 days. Some of the rats were irradiated with gamma‐rays (0.65 Gy/min, 60Co) at the end of the dietary intervention. We measured BA concentration in the sera, bile, and feces in an unirradiated condition by using UPLC/ESI‐MS. In CA–fed rats, a large amount of DCA and CA are found in the sera and taurocholic acid was also detected in the feces. Cecal microbita were determined with 16S rRNA clone library method. In the gut microbiota, population of Firmicutes was beyond 90% in the CA‐fed rats. There was a significant increase in epithelial proliferation assessed by bromodeoxyuridine‐incorporation in CA‐fed rats even after exposure to gamma‐rays. These results indicate that BA is a factor regulating the gut microbiota as well as epithelial proliferation. This work is supported by Regional Innovation Strategy Support Program of the MEXT, The Japanese Government.
Method for the Preparation of Gram Quantities of Highly Purified Bowman Birk Inhibitor from Glycine max
Authors: Tulk Barry Michael , Mekel Marlene , Wu Jennifer , Schasteen Charles
Published: June 2021

Bowman Birk Inhibitor (BBI) is a trypsin/chymotrypsin inhibitor originally prepared from soybean extract that has been implicated as a potential treatment for certain forms of cancer and neuromuscular disease. At present, BBI is not commercially available in a form suitable for this purpose. In this paper, we describe a scalable method that has been used to prepare highly purified BBI in gram quantities. A BBI enriched soy processing stream was used as starting material for purification. The stream was adjusted to pH 3.0, clarified by centrifugation at 4000×g for 10 min, and then applied to a 21.6 × 5 cm column of SP Sepharose Fast Flow resin (GE Healthcare) at 50 ml/min. After washing unbound material away, BBI was eluted with 75 mM Na Citrate, pH 3.0 buffer, concentrated using tangential flow filtration (10 kDa MWCO membrane), then diafiltered to remove buffer salts. Final purification was achieved using Triton X114 detergent to remove endotoxin. This procedure produced approximately 3.6 gms of >;95% pure BBI (as estimated by SDS‐PAGE) with a specific activity of 1687 chymotrypsin inhibition units/gram of protein.
Methacrylate polymer nanoparticle loaded with ZnPc as a promising anticancer drug delivery system
Authors: Barros Susan S , Gomes Anderson J
Published: June 2021

This study aimed to investigate the effect of a established cancer drugs such as Zinc Phthalocyanine (ZnPc) and it encapsulation into a matrix of ethyl acrylate copolymer, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups (EUDRAGIT® RL 100). ZnPc a well‐known photosensitizer used in photodynamic therapy (PDT), was selected in these experiments due to its high affinity for tumor targets and efficiency due to singlet oxygen photogeneration. These new drug delivery systems (ZnPc‐NP) was designed to protect the drugs from environmental, to promote a sustained drug delivery profile and also be tracked by the emission of fluorescence probe. Size and entrapment efficiency were evaluated at different preparation protocols. ZnPc‐NP showed an entrapment efficient of 17.6% (2.5g of polymer) using a emulsification–evaporation method. Size measurements were compared with the empty nanoparticles, which showed values of 273± 50 nm, nanoparticles loaded with ZnPc showed values of 146.0± 72 nm. Empty particles zeta potential presented +38.0 ZnPc‐NP. Parameters analyzed in this study demonstrate new promise drug delivery systems, supporting future in vitro tests. Supported by CNPq, CAPES, FAPDF, FINATEC and DPP‐UnB.
Phospholipid remodeling as a target for antifungal drug development against Candida albicans
Authors: Algahmi Amal M , Ayyash Mariam K , Oelkers Peter
Published: June 2021

In healthy individuals, Candida yeast species are found within the mouth and gastrointestinal tract. However, these species, particularly C. albicans, are the 4th most common cause of bloodstream infections, with an estimated mortality rate upwards of 25%. Treatment often involves two classes of anti‐fungals, one of which compromises plasma membrane integrity, establishing the membrane as a target for drug development. Limiting phospholipid remodeling may thus enhance the effect of these drugs. To test our hypothesis we created a homozygous deletion strain of a putative lysophospholipid acyltransferase (LPLAT) gene in C. albicans, designated 1881. Preliminary results indicate the 1881 double deletion‐mutation strains show mild resistance to a polyene antibiotic and two azoles. C. elegans is currently being used as a host to assess the virulence of 1881 deletion strains in an assay monitoring nematode survival after C. albicans exposure. We also hypothesize that phosphodiacylglycerol acyltransferases (PDGAT) work in conjunction with LPLATs in phospholipid remodeling. A putative PDGAT gene (designated 6018) in C. albicans is a homolog to the S. cerevisiae LRO1 gene. Generating S. cerevisiae and C. albicans deletion strains of their respective PDGAT genes, and characterizing virulence and phospholipid remodeling of these strains is our goal. Office of Sponsored Research, University of Michigan – Deaborn.
Discovery of selective inhibitors of fibroblast growth factor receptor 1 kinase with potent anti‐human lung carcinoma activity
Authors: Liang Guang , Wang Yi , Zhou Huiping , Li Xiaokun
Published: June 2021

The fibroblast growth factor receptor (FGFR) tyrosine kinases represent promising therapeutic targets in a number of cancers. In this study, we developed two potent and selective inhibitors of FGFR1, which we named A114 and A117. We demonstrated that the inhibitors potently inhibit the FGFR1 kinase activity in a non‐ATP competitive manner through caliper mobility shift assay. The docking simulation of indicated compound with FGFR1 protein reveals that the 4‐substituted groups of phenyl ring may occupy the hydrophobic front region, which is consisted of hinge residues (Ile 651, Lys 655, Val 664, Met 667 and Tyr 677). Furthermore, we proved that the inhibitors potently inhibit the growth of numerous FGFR‐dependent cancer cell lines via inactivating the phosphorylation of FGFR1, leading to a decrease in phosphorylation of Akt and ERK signaling. The inhibitory effect in both the FGFR and MAPK signaling pathway finally leads to the decrease in cell viability, cell cycle arrest, and apoptosis in non‐small cell lung cancer H460 cells both in vitro and in vivo. Together, these results suggest the anti‐cancer potential of novel curcumin analogs for the prevention and treatment of FGFR‐depending cancers.

The work was supported by grants from the National Natural Science Foundation of China (81173083 & 21102106).
Regulation of Akt/AMPK/mTOR signaling by grape polyphenols in triple negative breast cancer
Authors: Rivera‐Rivera Amilcar , Castillo‐Pichardo Linnette , Dharmawardhane Suranganie
Published: June 2021

Triple negative breast cancers (TNBC) overexpress epidermal growth factor receptors (EGFR); however, TNBCs are often resistant to EGFR inhibitors. Targeting the Akt/mammalian target of rapamycin (mTOR) pathway in combination with anti‐EGFRs is a viable strategy for TNBC therapy. We reported that a combined diet of grape polyphenols (Resveratrol, Quercetin and Catechin (RQC)), at equimolar concentrations, inhibits mammary tumor growth and metastasis in nude mice. Moreover, RQC chemosensitized TNBC tumors to the anti‐EGFR therapeutic gefitinib, via inhibition of the Akt/mTOR pathway. The current objective is to determine the effective concentrations, and individual and combined contributions of RQC to the mTOR pathway. MDA‐MB‐231 TNBC cells were treated with RQC at 1, 3, 5, 9 and 15 μM individually and in combination. Western blots were performed to detect the activation (phosphorylation) of AMP kinase (AMPK), an endogenous inhibitor of mTOR, Akt, and the mTOR downstream effector p70S6K. RQC at 5 μM each and quercetin at 15 μM were most effective at inhibition of Akt and p70S6K and activation of AMPK. MDA‐MB‐231 cells with AMPK knockdowns are being analyzed to determine the relative contribution of Akt inhibition and AMPK activation to the effects of RQC on mTOR pathway. These data implicate RQC as a dietary non‐toxic alternative to potentiate current TNBC therapy. Funding: DoD/BCRP W81XWH‐07–1‐0330 to SD.
Don't starve your body! A service‐learning experience for a Biochemistry course
Authors: Benitez Benedetta Sampoli
Published: June 2021

Service learning is a wonderful opportunity for students to apply their knowledge and skills to the service of the community. In the sciences, experiential learning has been largely relegated to laboratories. However, an established body of research proved that service learning in the college years has a positive effect on the students’ outcomes, while increasing civic engagement and citizenship. In particular, the research suggests that when science students are exposed to service learning, they develop a deeper understanding of how science is connected to local and global issues. We devised a service‐learning component for our Biochemistry capstone course. This project will take place during the Spring 2013 semester. Partnering with students in an advanced Health Psychology class, Biochemistry students will prepare a booklet on Anorexia Nervosa (AN) detailing the chemical and psychological aspects of this disease. They will then present the material to local high school students to raise awareness about this eating disorder, and will distribute copies of the booklet they created. Finally, the students will organize a day‐long workshop open to the entire community to raise awareness about AN and eating disorders in general. The final implementation of this project will be discussed.
Impact evaluation of the Nutritional Support Program (PAL by its Spanish acronym) on food diversity and consumption of iron‐rich or iron‐fortified foods in 6–23 month‐old children
Authors: Ramirez Maria Jose , de Cossio Teresa González , Unar Mishel , Rodriguez Sonia , Rivera Juan
Published: June 2021

Micronutrient deficiencies in the first two years of life have adverse developmental and health effects. Part of the cause is complementary feeding (CF) of low nutritional quality. In order to prevent malnutrition in the most vulnerable individuals, the Mexican state has implemented the Nutritional Support Program, which is directed towards small communities with fewer services and includes conditional distribution of food or monetary transfers and education. The impact of PAL was evaluated in minimum dietary diversity and consumption of iron‐rich or iron‐fortified foods indicators. A longitudinal sample of 168 communities was analyzed using the double‐difference method with fixed effects at the community level. Baseline values for children aged 6–23 months of (n=664 children, 591 households) were compared with values for children aged 6–23 months who live in the same communities after 18 months from the start of the intervention (n=478 children, 368 households). PAL, in its ‘provisions without education’ modality, increased the prevalence of consumption of iron‐rich foods by 31 percentage points (PP), (p<0.01) and by 25 PP (p<0.01) for minimum dietary diversity in children aged 6–23 months when compared to the control group. Social programs based on conditioned provision of foods that are fortified with iron and multiple micronutrients contribute to improving CF practices. Funding for the study was obtained from the Mexican Secretariat of Social Development.
The Effect of High Added Sugar Intake on Micronutrient Intakes During Pregnancy
Authors: Forbes Laura , Babwick Stephanie , Zeng Grace , Graham Jocelyn , Gilbert Anne , Bell Rhonda , The APrON Team
Published: June 2021

High added sugar intake in pregnancy increases risk of excess gestational weight gain, gestational diabetes and preeclampsia. These effects may be due to low diet quality observed with higher sugar intakes. This study described micronutrient intakes in pregnant women with varying intakes of added sugar. Pregnant women (n = 489; < 27 wks gestation) completed a validated FFQ to assess dietary intake in the 12 months prior to pregnancy. Percent energy from added sugars was assessed using an expanded sugar database. Women were classified as having Low (0–14.9 % kcal; n=423), Medium (15.0–24.9 % kcal; n=60), or High (>;25.0 % kcal; n=6 ) added sugar intakes. Linear regression was used to assess the effect added sugar intake on micronutrients. Women with higher added sugar intakes consumed fewer total kcal (Low: 1860 ± 560 kcal/d; Medium: 1740 ± 550 kcal/d; High: 1290 ± 480 kcal/d; p= 0.02) but were similar in demographic characteristics. Women in Medium and High groups had lower vitamin E, potassium and sodium intakes compared to Low (p<0.05). After adjusting for total kcal, vitamin E intake remained significantly lower in Medium and High groups (p<0.05 Median ± SE: Low: 8.5 ± 0.11mg/d; Medium: 6.7 ± 0.24mg/d; High: 4.9 ± 0.55mg/d). High intake of added sugars during pregnancy may be associated with lower micronutrient intakes, however, further studies of women with a wider variety of sugar intakes is warranted.
Mutivariate Analysis of Factors Affecting Skipping Breakfast in Korean Middle School Students
Authors: Chang Kyung Ja , Jang Myung ju
Published: June 2021

The purpose of this study was to investigate factors affecting skipping breakfast for nutrition education related to skipping breakfast in Korean middle school students. The subjects were 618 middle school students (7th grade 223, 8th grade 201, 9th grade 194) in Bucheon, Gyeonggi Province, Korea. A cross‐sectional survey was conducted using a questionnaire and data were analyzed with SPSS 12.0 program. As the results from logistic regression, the factors significantly associated with skipping breakfast were attitude of parents toward skipping breakfast (p<0.001), awareness about importance of breakfast (p<0.001), necessity of breakfast for health (p<0.001) and concentration on class (p<0.05). As for the attitude of parents toward breakfast skipping, the students had more breakfast as their parents forced them to have breakfast. The students had more breakfast as they knew importance of breakfast or necessity of breakfast for health. Also the students had more breakfast as they knew that they concentrated their attention less on class when they skipped breakfast. There were no significant association between skipping breakfast and wake‐up hour, socio‐demographic factors including gender, education levels and economic status of parents. Therefore, nutrition education about breakfast should be provided toward their parents as well as Korean middle school students.
Comparison of the sialic acid components of mature human milk in three countries
Authors: Burgher Anita M. , Li Xi , Ramirez‐Mayans Jaime A. , Ontijo‐Barrios Ericka M. , Sablan Benjamin , Wali Yassar , Van Alstine Leslie , Pramuk Kathryn
Published: June 2021

The objective of this study was to evaluate the relationship between the total sialic acid, 3′‐sialyllactose (3SL), 6′‐sialyllactose (6SL), and free sialic acid (SA) of mature human milk and stage of lactation in mothers from the Philippines, Oman and Mexico.

Milk samples were obtained from 176 healthy mothers from Mexico, Oman and the Philippines. who were exclusively breast feeding infants (1–4 months old). Anion exchange chromatography with pulsed amperometric detection (HPAEC‐PAD) was used to quantify 3SL, 6SL, and free SA in all human milk samples. Total SA was quantified after an acid hydrolysis sample treatment. Method validations were conducted to confirm the precision and accuracy for all analytes.

Results

Total SA, Free SA and SA from 3′‐sialyllactose and 6′‐sialyllactose in human milk (Mean, mg/L)

Lactation Stage
28–30 days
31–60 days
61–90 days
91–115 days
All samples

Total Sialic Acid
866
619
484
359
525

SA from 6′SL
226
135
97
51
108

SA from 3′SL
60
59
55
48
55

Free SA
7
9
11
11
10

Other SA
573
417
322
249
354

Conclusions

The predominant trend demonstrated using an Analysis of Covariance with Lactation Stage in days as the covariate showed that for all measures except the Free Sialic Acid, there is a statistically significant decrease in the amount of Sialic Acid in human milk as Lactation Stage increases (p‐values < 0.0001).

This research was funded by Pfizer Nutrition.
Development and in vitro characterization of a novel prenatal multi‐micronutrient powder incorporating differentially microencapsulated calcium carbonate and ferrous fumarate to overcome intra‐intestinal calcium‐iron interactions
Authors: Baxter Jo‐Anna , Roth Daniel , Aimone Ashley , Martinuzzi Frank , Bassani Diego , Zlotkin Stanley
Published: June 2021

To overcome calcium(Ca)‐iron(Fe) interactions in a prenatal multi‐micronutrient supplement for low‐income settings, we developed a Ca‐Fe‐folic acid (FA) powder for home fortification incorporating enteric coatings sensitive to low pH (for gastric Fe release) and high pH (for mid‐duodenal Ca release). Ca carbonate and ferrous fumarate granules were generated by wet granulation. A fluid‐bed coating process was used to apply subcoat to the Ca granules to improve sphericity and to apply a pH‐sensitive enteric coat. Fe granules were encapsulated with a time‐dependent coating, including FA in the matrix. Fe and Ca dissolution profiles were assessed during sequential exposure to acidic (pH 1.2, 120 min) and basic (pH 5.8, 100 min) media using a modified USP methodology. At pH 1.2, Ca release was 15% after 120 min; Fe release was 90% and 100% at 20 and 35 min, respectively. After 100 min at pH 5.8, 85% of total Ca was released. These dissolution profiles indicated that the differential release of Ca and Fe was achieved within targeted acid‐base environments. Clinical testing to document fractional Ca absorption during pregnancy is underway. Research support was provided by the Saving Lives at Birth partners.

Grant Funding Source: Saving Lives at Birth
Megalo types of α‐1,6‐glucosaccharide enhance absorption of quercetin glycosides in rats
Authors: Shinoki Aki , Lang Weeranuch , Mori Haruhide , Kimura Atsuo , Ishizuka Satoshi , Hara Hiroshi
Published: June 2021

We investigated the effects of linear α‐1,6‐glucosaccharides on the absorption of quercetin glycosides in rats. The quercetin glycoside mixture (Q3Gn) and quercetin‐3‐O‐glucoside (Q3G) were used in situ and in vivo study, respectively. Q3Gn was composed of Q3G with one or up to seven d‐glucose adducts. Some linear α‐1,6‐glucosaccharides were enzymatically prepared, and separated into a megalo‐isomaltosaccharide‐containing fraction [M‐IM, average degree of polymerization (DP) =8.4–11.0] and an oligo‐isomaltosaccharide‐containing fraction (O‐IM, average DP=3.3–3.6). M‐IM enhanced absorption of the flavonoid glycosides in the in situ study using small intestinal segment of anesthetized rats. Both α‐1,6‐glucosaccharides increased Q3G concentration in the supernatants of the intestinal contents, and such effect was greater in M‐IM. An in vitro study revealed that the M‐IM was effective for Q3G solubilization. Postprandial plasma level of quercetin‐conjugates was significantly higher in the rats fed M‐IM diet for 14 days than in those fed an α‐1,6‐glucosaccharides‐free diet. In conclusion, M‐IM promotes the absorption rate of Q3G and may contribute to health promotion by Q3G. This work was supported by the Programme for Promotion of Basic and Applied Researches for Innovations in Bio‐oriented Industry.
Development of a sensitive, high‐throughput UPLC‐MS/MS method for detecting both native flavonoid compounds from Vitaflavan grape seed extract and their gut microbial metabolites
Authors: Goodrich Katheryn , Neilson Andrew
Published: June 2021

Flavonoids found in Vitaflavan grape seed extract and their gut microbial metabolites are of interest due to the possible health benefits they may provide. While there are numerous examples of chromatographic methods to measure both groups of compounds separately, there is limited methodology to evaluate them together in one analysis. This increases analysis time and required resources, and decreases data throughput. A single UPLC‐MS/MS method was developed to measure both native monomers and procyanidins as well as predominant microbial metabolites simultaneously. The UPLC‐MS/MS method developed was able to baseline resolve 38 standard peaks within 10.0 min using an ACQUITY UPLC HSS T3 column (2.1 mm × 100 mm, 1.8μm particle size) and a mobile phase gradient containing 0.1% formic acid in water and 0.1% formic acid in acetonitrile. MS was run in negative ESI with capillary voltage of −4.25 kV. Compounds measured included native GSE monomers (catechin, epicatechin, epicatechin gallate, epigallocatechin, and epigallocatechin gallate), native GSE procyanidins (dimers B1, B2, B5, and B2‐gallate, trimers C1 and T2, tetramer cinnamtannin A2, pentamers, and hexamers), as well as predominant colonic microbial metabolites including phenylacetic acids, phenylpropionic acids, and hydroxybenzoic acids. Values for the lower limit of detection were in the range of 0.0006–0.02 ng/mL for monomers and procyanidins and 0.0002–0.02 ng/mL for microbial metabolites, while values for the lower limit of quantitation were in the range of 0.0008–0.06 ng/mL for monomers and procyanidins and 0.0008–0.2 ng/mL for microbial metabolites. This method can be used for complex polyphenol and metabolite analyses in biological samples in a single chromatographic run. This method will facilitate future research to discover when, where, and to what scale these polyphenols are metabolized in the colon.
EPA and DHA do not exert equivalent effects on B lymphocyte plasma membrane organization: Implications for developing biomarkers of fish oil for targeting B cell immunity
Authors: Teague Heather , Gurzell Eric , Rockett Benjamin Drew , Fenton Jenifer , Shaikh Saame Raza
Published: June 2021

We have established that fish oil, enriched in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can regulate the function of B cells. Specifically, we reported that fish oil exerts immunomodulatory effects on B cell antigen presentation and lipopolysaccharide induced activation. We have also discovered that the functional changes in response to fish oil are accompanied by a disruption in the clustering of signaling lipid microdomains known as lipid rafts, a potential biomarker for B cell activity. Therefore, we first determined the dose of fish oil that serves to disrupt B cell lipid rafts. Administration of fish oil at the human equivalent of 4 grams and above per day (currently used pharmacologically) disrupted raft clustering, which correlated with changes in function. We then determined which fatty acid in fish oil was responsible for disrupting rafts by feeding mice diets enriched either in EPA or DHA. B cells isolated from mice consuming the DHA‐enriched but not the EPA‐enriched diet had diminished raft clustering. Supporting studies in cell culture and in liposomes revealed the same effect. Altogether, our data suggest that DHA is more potent than EPA in disrupting the B cell plasma membrane, which has implications for biomarker development and ultimately the design of fish oil formulations for targeting B cell function.

Grant Funding Source: NIH R15AT006122 (to S.R.S.) and NIH R03CA162427 (to J.F.)
Human Airway Epithelial Secretions Inhibit the Formation of Pseudomonas aeruginosa Biofilms
Authors: Sorum Alexander W , Zank Allison M , Bankers‐Fulbright Jennifer L
Published: June 2021

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that rarely causes respiratory disease except in individuals with specific risk factors, such as cystic fibrosis (CF). The ability of P. aeruginosa to readily form biofilms in vivo is associated with airway colonization in susceptible individuals. Thus, we hypothesized that non‐CF airway epithelial cells secrete one or more compounds that inhibit P. aeruginosa biofilm formation. To test this, we modified and optimized a static biofilm assay and tested the ability of apical Calu‐3 cell secretions to inhibit biofilm formation by the P. aeruginosa strain, PA14. PA14 formed robust biofilms after 18–24 hours, and biofilm formation was significantly inhibited in the presence of Calu‐3 secretions. Preliminary experiments using secretions from a Calu‐3 cell line not expressing the CF transmembrane regulator (CFTR) suggest that CF‐like secretions do not inhibit PA14 biofilm formation. Thus, normal airway epithelial cells, but not CF‐like epithelial cells, appear to secrete one or more compounds that inhibit P. aeruginosa biofilm formation.

This project was funded by the Augsburg College Undergraduate Research and Graduate Opportunities (URGO) Office, the Augsburg Sundquist Scholars Program, the Augsburg McNair Scholars Program, and the Augsburg Department of Biology.