bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery, characterization, and structural determination of a novel UDP‐2,3‐diacylglucosamine hydrolase
Authors: Metzger Louis Eugene , Lee John K. , Stroud Robert M. , Raetz Christian R. H.
Published: June 2021

Gram‐negative bacteria possess an asymmetric outer membrane in which the inner leaflet is composed primarily of phospholipids, while the outer leaflet contains mainly lipopolysaccharide (LPS). LPS forms a structural barrier that protects Gram‐negative bacteria from antibiotics and other environmental stressors. LPS is anchored to the outer membrane by Lipid A, a unique glucosamine‐based saccharolipid. Lipid A biosynthesis is required for viability and pathogenesis. While most lipid A biosynthetic genes are present in a single copy, one gene, lpxH, encoding a membrane‐associated specific UDP‐diacylglucosamine hydrolase, is absent in ~30% of Gram‐negative bacteria. We hypothesized that a transformational analogue of lpxH must exist in these organisms. We identified this gene, designated lpxI, in Caulobacter crescentus, and confirmed its ability to cover for a deficiency of lpxH in Eschserichia coli. LpxI lacks homology to any other known enzyme. We over‐expressed LpxI, purified it, and obtained protein crystals. We solved the x‐ray crystal structure of this peripheral membrane enzyme to a resolution of 2.7 angstroms using a single‐wavelength anomalous dispersion (SAD) dataset collected on Se‐Met derivatized protein. The structural data reveal two domains, each having a novel fold. Unexpectedly, “apo” LpxI co‐purified and co‐crystallized in a 1:1 stoichiometric ratio with its product, lipid X. These data provide an interesting example of lipid‐protein interaction, and set the stage for additional structural and mechanistic work. Support was provided by NIH grant GM5150 to C.R.H.R., Specialized Center grant of the Protein Structure Initiative U54 GM074929‐01 to R.M.S., and NSF GRF grant 2005029353 to L.E.M.
Pasteurella multocida toxin activates mTORC1 and induces cell spreading in Swiss 3T3 cells
Authors: Oubrahim Hammou , Wilson Brenda , Chock P. Boon
Published: June 2021

Pasteurella multocida toxin (PMT), a potent mitogen known to activate via G protein dependent pathway, phospholipase Cβ1, Jak‐Stat, and Rho kinase pathways. The mechanism of these activation processes is not well established. Here, we show that with serum‐starved Swiss 3T3 cells, PMT induces protein synthesis, monitored by 35S‐methionine incorporation, ATP synthesis as monitored by the luciferase assay method, and cell spreading. This study reveal that the mechanism of PMT‐induced protein synthesis proceeds, in part, via a Gαq‐dependent activation of mTORC1, monitored by the phosphorylation of ribosomal S6 protein and the inhibitory effect of rapamycin, a mTORC1 specific inhibitor. The results for 35S‐methionine incorporation obtained with 3T3 cells in the presence of rapamycin and with Gαq/11 knocked out MEF cells indicate that, in addition to mTORC1, PMT also activates a rapamycin and Gαq/11‐insensitive protein synthesis pathway. Based on our data on PMT induced cells spreading and 35S‐methionine incorporation, a mechanistic scheme was proposed. This finding reveals that PMT could exert some of its biological effect via the mTOR signaling pathway, known to play an essential role in cell growth control and in human tumorigenesis.
Methotrexate encapsulated in PLGA microparticles conjugates with biotin as drug delivery system for cancer cells from domestic animals
Authors: Gomes Anderson J , Oliveira Naiara A , Alves Talita JS , Rocha Marta ST , Azevedo Ricardo B
Published: June 2021

Methotrexate (MTX) encapsulated in poly(lactic/glycolic acid) (PLGA) microparticles (MTX‐MP) can be a useful tool for intra‐tumor administration showing several benefits in minimizing systemic toxicities of MTX and improve its efficiency in vivo. MTX‐MP conjugated with biotin (with fluorescent probe) was prepared by solvent evaporation technique with drug encapsulation efficiency of 90 %. Particle size and external morphology showed that the particles are spherical in shape with 353 ± 30 nm diameter (MTX‐MP) using scanning electron microscopy (SEM) and dynamic light scattering (DLS). MTX‐MP revealed a tendency of aggregation with zeta potential −12.9 mV. Fluorescence spectra showed that biotin binding effectively on the MP‐MTX. The ability of the MPs to deliver the loaded MTX was tested on the primary cancer cell culture of the mammary gland obtained from female dog. Cell toxicity was evaluated in a concentration of 1x10−7 and 1x10−4M using a cell viability measurement (MTT). These tests showed MP‐MTX was efficient in release of MTX conducing to 66% of cell death after 24 hours and 90% after 48 hours. The results suggest that polymeric MPs are efficient drug delivery systems and can be used for administration of MTX directly to the cell target. Supported by CNPq and CAPES.
ERK3‐MK5 regulates interstitial fibrosis during pressure‐overload hypertrophy
Authors: Dingar Dharmendra D , Gillis Marc‐Antoine , Shi Yanfen , Tardif Jean‐Claude , Gaestel Matthias , Allen Bruce G
Published: June 2021

Cardiac hypertrophy occurs when the myocyte is continuously exposed to increased external stimuli such as stretch, hemodynamic overload and/or an increase in neurohormonal factors. MK5 was originally identified as p38 regulated and activated kinase and the physiological role of MK5 remains unknown. Therefore, we studied the effect of transverse aortic constriction (TAC)‐induced pressure overload hypertrophy in mice heterozygous for a functional knockout of MK5 (MK5+/−) and their wild‐type (MK5+/+) littermates. Following 2‐wk of TAC, heart weight/body weight ratios were significantly (p<0.01, n=6–9) and similarly increased in both MK5+/− and MK5+/+ hearts. Transthoracic echocardiography revealed TAC reduced diastolic function in MK5+/+, but not in MK5+/− hearts. Less collagen deposition, assessed by Masson trichrome staining, was observed in MK5+/− hearts following both 2‐ and 3‐wks of TAC. Furthermore, TAC‐induced increases in collagen alpha1 type1 mRNA levels was significantly lower at both 2 (p<0.001 vs MK5+/+, n=6–9) and 3 (p<0.01 vs MK5+/+, n=8) wks of TAC. Immunoprecipitation of MK5 resulted in co‐immunoprecipitation of ERK3 but not ERK4 or p38α in control, sham‐operated and TAC hearts. These data suggest that MK5 associates with and is regulated by ERK3 but not ERK4 or p38α in heart. Furthermore, ERK3‐MK5 signaling may play a key role in reactive fibrosis during pressure overload hypertrophy.
Vitamin D dose response study in Canadian infants: 25‐hydroxy‐vitamin D status during a 20 week intervention
Authors: Gallo Sina , Vanstone Catherine A , Comeau Kathryn , Agellon Sherry , Rodd Celia , Sharma Atul , Weiler Hope A
Published: June 2021

The Canadian Paediatric Society (CPS) recommends breastfed infants receive vitamin D supplementation (400 to 800 IU/d) in support of optimal plasma 25‐hydroxy vitamin D (25(OH)D), defined as 75 nM. The objective of this study was to establish a dosage of vitamin D that would support optimal status in 97% of young infants. Healthy term born infants from Montreal (32 girls, 46 boys) were randomized to 400, 800 or 1200 IU vitamin D3 daily from age 4 wk and plasma 25(OH)D (RIA, Diasorin Inc.) measured at baseline, 4, 8 and 20 wk (NCT00381914; clinicaltrials.gov). Blinded treatments were re‐coded. Repeated measures ANOVA (by ITT) accounting for within‐subject serial correlations demonstrated season of birth, weight, time, treatment and treatment‐time interaction as significant (p<0.01) predictors of 25(OH)D. Table 1 shows estimated means by time and treatment. Mean 25(OH)D concentrations were higher over time (p<0.01) in dose regimen A vs. other treatments. Using 25(OH)D categories, overall 32% were above 75 nM after the 20 wk intervention. These results suggest that daily dosages of vitamin D from 400 to 1200 IU support a mean 25(OH)D concentration above that associated with deficiency, but the majority do not reach optimal status by 20 wk of supplementation.

Estimated mean 25(OH)D ± SE (nM) [% reaching 75 nM].

Time points
Treatments

A (n=25)
B (n=25)
C (n=28)

Baseline
47.8 ± 3.7 [0.0]
42.8 ± 3.7 [0.0]
41.7 ± 3.8 [4.0]

4 wk
63.4 ± 2.8† [28.6]
44.3 ± 2.8‡ [0.0]
40.8 ± 2.8‡ [0.0]

8 wk
57.6 ± 2.4 [5.3]
47.1 ± 2.3‡ [0.0]
51.7 ± 2.2 [8.7]

20 wk
84.0 ± 5.3† [38.9]
76.7 ± 5.3† [23.5]
77.0 ± 4.6† [33.3]

p<0.05 vs treatment‐specific baseline,

p<0.05 vs treatment A at same time.

Grant Funding Source: Canadian Institutes of Health Research
Differential modulation of biomarkers of Metabolic Syndrome (MetS) in C57BL/6J mice by isomers of tocopherol
Authors: Sundaresan Sinju , Mills Nathaniel , Prasad Chandan , Juma Shanil , Vijayagopal Parakat , Imrhan Victorine
Published: June 2021

Antioxidant activities of tocopherols are well documented. However, it has become evident they also exhibit other biologic activities. We investigated the effects of alpha (α) and gamma (γ) tocopherol on biomarkers of MetS in mice including, adipocyte peroxisome proliferator activated receptor (PPAR‐γ), uncoupling protein (UCP), fatty acid binding protein 4 (fabp4), CD36, hepatic PPAR α, and acyl CoA oxidase (ACO) expressions. C57BL/6J mice (n=75) were divided into 5 groups and placed on five different dietary regimens as follows. Groups 1 and 5 (control): low‐fat (LF) and high‐fat (HF) diets for 25 weeks, respectively; groups 2–4: HF diet for 15 weeks followed by 10 weeks on HF supplemented with αT, γT, αT + γT, respectively. Animals were sacrificed at the end of 25 weeks. α‐T and αT + γT significantly reduced weight gain and improved insulin sensitivity indices. Protein and mRNA expressions of adipocyte PPAR‐γ, UCP, fabp 4, CD36, hepatic PPAR α, and ACO were significantly increased with α‐T and αT + γT but not γT alone. ACO and fatty acid synthetase expressions in treatment groups were not different from HF controls. αT alone and in combination with γT led to modulation of biomarkers of MetS in mice. The study for the first time demonstrates the ability of αT to function as dual PPAR agonist in modulating biomarkers of MetS in vivo.

Supported by grants from Texas Department of Agriculture, Human Nutrition Fund
Altered nutrient status in alcohol‐exposed pregnant women
Authors: Uriu‐Adams Janet Y. , Gross Heidrun B. , Chambers Christina D. , Green Kerri , Ensunsa Jodi L. , Le Anh , Yevtushok Lyubov , Wertelecki Wladimir , Keen Carl L.
Published: June 2021

This ongoing collaborative study investigates the nutrient and oxidative stress status of alcohol‐exposed Ukrainian pregnant women and whether micronutrient supplementation with and without choline, a nutrient critical for brain development, will reduce Fetal Alcohol Spectrum Disorders in the offspring. Analysis to date of maternal baseline plasma samples shows that alcohol‐exposed women (N=49) had lower Zn and Cu concentrations, and Total Radical‐trapping Antioxidant Potential (TRAP) vs. controls (N=40). There were no differences in Fe, ferritin, Mg, Ca, or ceruloplasmin activity. Methyl‐donor nutrients (choline, betaine, DMG, folate, Vit B12, and homocysteine), Vit A, E and select carotenoids, and oxidative stress (TBARS, protein carbonyls) and inflammation (hsCRP) indices were similar. Absolute oz. of alcohol/drinking day during the 2 wks prior to interview was associated with higher Vit A and ferritin, and lower Vit B12. The low Zn, Cu and Vit B12 in ethanol‐exposed women may contribute to adverse fetal development. It has been reported that alcohol increases body Fe stores, which can lead to oxidative stress. In our study, alcohol intake was associated with increased ferritin in pregnant women, which, when coupled with lower TRAP, may increase oxidative stress‐induced teratogenesis. These data will be updated as sample size requirements are met.

Supported by NIAAA‐U01‐AA014835‐05 and HD01743.
Evidence of in vivo Immune Modulation with Vitamin D3 and Calcium Supplementation in Multiple Sclerosis
Authors: Kimball Samantha M , Vieth Reinhold , Bar‐Or Amit , Gagne Donald , Dosch Hans Michael , Cheung Roy , O'Connor Paul G , Burton Jodie
Published: June 2021

We have recently established that high‐dose oral vitamin D3 is safe in MS with apparent clinical benefit. Our objective was to characterize the immunological profile in patients receiving pharmacological doses of vitamin D3 with calcium. A prospective controlled 52‐week trial matched MS patients for demographic and disease characteristics, with randomization to treatment and control groups. Treatment patients received escalating doses of vitamin D3 (4,000–40,000 IU/d) with calcium (1,200mg/d) for one year, and control patients none. PBMC proliferation in response to antigenic stimulation was measured and T cell stimulation (TCS) scores calculated. PBMC proliferation was markedly reduced in treatment patients after one year (WSRT p<0.002) and unchanged in controls. TCS dropped significantly in treatment patients (p=0.0023), but not in controls. The proportion of patients with a TCS below the pre‐determined positive threshold was greater in treatment patients (p=0.0318). There were no differences detected between groups for other inflammatory markers. Patients with MS receiving high dose vitamin D3 with calcium supplementation had significantly reduced PBMC proliferative responses to self‐antigen. Such effects may explain clinical improvement seen in treatment patients.

Funding was provided by Direct MS and the Multiple Sclerosis Society of Canada.
Can dietary treatment without iron supplementation correct mild iron deficiency anemia in young Beninese adolescent girls?
Authors: Alaofè Halimatou , Zee John , Dossa Romain , O'Brien Huguette Turgeon
Published: June 2021

The impact of a 4‐weeks nutrition education program combined with an increase in the content and bioavailability of dietary iron for 22 weeks was studied in 34 intervention boarding‐school girls who suffered from mild iron deficiency anemia. Thirty‐four anemic adolescent girls from another boarding‐school not exposed to the dietary program, served as control. There were no significant differences between the two groups for iron and vitamin C intakes at baseline. Within the intervention group, dietary iron increased from baseline (18.2 ± 5.0 mg) to mid (21.6 ± 5.4 mg) and post‐intervention (23.2 ± 4.5 mg) indicating a significant time effect interaction. In the control group, dietary iron intakes decreased from baseline (17.0 ± 3.6 mg) to mid‐intervention (15.6 ± 6.8mg) but increased at the end of the study (18.3 ± 5.9 mg), although the interaction time effect was not significant. A significant group‐by‐time interaction was observed between the two groups for dietary iron. Similar results were observed for all other nutrients including absorbable iron. A significant reduction in the prevalence of anemia (68%) and iron‐deficiency anemia (74%) was observed in the intervention group compared to the control group (15 and 44% respectively). A multi‐dietary strategy aiming to improve iron intakes and bioavailability without iron supplementation reduced iron deficiency anemia in these young Beninese adolescent girls.
Arterial tissue culture medium accelerates anthocyanin degradation and polymeric formation in extracts from chokeberry, bilberry and elderberry
Authors: Bell David Robert , Nalliah Ruth E , Cressman Scott J , Swartz Andrew J , Moon Haley
Published: June 2021

We examined whether anthocyanin degradation and polymeric formation in extracts from chokeberry (Ch), bilberry (B) and elderberry (E) occurs in tissue culture media as reported for extracts in salt solutions used for arterial vasoreactivity studies. Extract solutions at 0.8 or 0.08 mg/ml were made in sterile HEPES buffered DMEM and stored at 37°C in or out of an O2/CO2 tissue culture incubator. Samples were measured for monomeric anthocyanin concentration and polymeric color formation over 72 hours. Monomeric anthocyanin concentration in medium diminished over time (Ch = 50%, E = 28%, B = 4% of 0.8 mg/ml remaining at 24 hrs). CO2 accelerated monomeric degradation in all extracts (Ch = 0%, E = 10%, B = 2% of 0.8 mg/ml remaining at 24 hrs). Degradation of extracts at 0.08 mg/ml was generally greater. In all cases an increase in anthocyanin polymeric formation paralleled the rate of monomer degradation. Thus tissue culture medium transforms monomeric anthocyanins into anthocyanin polymers or addition products at rates dependent on the individual anthocyanin composition and medium conditions. This transformation must be taken into account in interpreting studies that examine effects of anthocyanins in cell culture systems and raises the possibility that anthocyanin polymers may play a role in in vivo biological effects of these extracts. (Support: The Ferne and Audry Hammel Fund of Huntington University, Huntington, IN)
Effects of epigallocatechin gallate on regulatory T cell number and function in obese versus lean volunteers
Authors: Yun Jung‐Mi , Jialal Ishwarlal
Published: June 2021

Obesity is associated with increased inflammation. Regulatory T cells (Tregs) are essential negative regulators of inflammation. Animal models of obesity are associated with decreased Tregs. Dietary modulation of Tregs could be used as a therapeutic strategy to control inflammation. Epigallocatechin gallate (EGCG) is a potent anti‐inflammatory agent and is suggested to have a role as a preventive agent in obesity, diabetes, and cardiovascular disease. The role of EGCG in modulation of Tregs has however not been studied. Thus, the aim of this study was to determine the effect of EGCG on Tregs number and function in obese and lean human subjects in vitro, and to delineate its specific regulation mechanisms. Tregs were isolated from normal and obese subjects and cultured in the absence or presence of EGCG (20 μM) for 24 h. Foxp3 +Tregs were enumerated using flow cytometry. Histone deacetylases (HDACs) expression and NF‐κBp65 activity were measured by ELISA and western blots. Obese subjects had lower Tregs and IL‐10 production than lean subjects. EGCG significantly enhanced Foxp3 expressing‐Tregs number and IL‐10 production ex vivo (p<0.05). Also, EGCG decreased NF‐κB activity and increased HDACs activity and HDAC 2 expression in Tregs (p<0.05) in both groups. Thus, EGCG enhances Tregs function and number by suppressing NF‐κB signaling pathway via epigenetic changes.
Dietary sitosterol, stigmasterol, and stigmastanol stearate esters elicit similar responses on hepatic and plasma lipids and cholesterol absorption in Syrian hamsters
Authors: Ash Mark M , Hang Jiliang , Dussault Patrick H , Carr Timothy P
Published: June 2021

Plant sterol/stanol esters (PSE) have been shown to decrease the atherosclerotic risk factor LDL cholesterol (LDL‐C). However, the significance of the individual sterol species has not been studied. To investigate the sterol contribution, stigmasterol (Sg), sitosterol (Si), and stigmastanol (Sn) stearate esters were synthesized and administered to male Syrian hamsters fed an atherosclerotic diet (high cholesterol, high saturated fat); an atherosclerotic diet without PSEs served as the control (Cn). There were no significant differences in the plasma HDL or non‐HDL cholesterol concentrations. Cholesterol absorption was equivalent among the diets: Cn 61.6±10.4%, Sn 59.9±8.8%, Sg 63.0±6.6%, and Si 66.2±10.3%. Liver esterified cholesterol, triglyceride, and phospholipid concentrations were similar. The sitosterol and stigmastanol diets significantly reduced the free cholesterol concentration in the liver in comparison to the control and stigmasterol: Cn 4.7±0.3 and Sg 4.5±0.2 vs. Sn 4.2±0.3 and Si 4.2±0.3 μmol/g of liver (P<0.05). Our findings indicate only minor unique cholesterol‐lowering properties of the individual sterol species studied.

Grant Funding Source: USDA‐NRI competitive grant no. 2007‐35200‐18298
Dietary calcium affects the differentiation potential of mesenchymal stem cells
Authors: Mahajan Avanika , Alexander Lindsey S. , Seabolt Brynn S. , Odle Jack , Loboa Elizabeth G. , Stahl Chad H.
Published: June 2021

Mesenchymal stem cells (MSC) provide the cells responsible for bone formation, but can also adopt an adipocytic lineage. The balance between osteogenic versus adipocytic differentiation of MSC is of critical importance to bone health. The impact of Ca nutrition on MSC activity was assessed by examining the effect of the Ca status of the MSC and the Ca status of homologous sera, under both proliferative and adipogenic culture conditions. MSC were isolated from 6, 19d old pigs that had been fed either a Ca adequate (Ca+) or deficient (Ca−) milk‐replacer for 18d. Sera were pooled samples from days 6, 12, and 18 of the feeding trial. Cells were cultured for 6d prior to analysis. Under proliferative culture conditions, Ca− sera reduced MSC proliferation and Ca+ MSC had greater expression of osteocalcin and Runx2 mRNA. Under adipogenic culture conditions, MSC cultured in Ca− sera had greater Oil Red O staining and Ca+ MSC also had greater Oil Red O staining than did there Ca− counterparts. Ca− MSC cultured with Ca− sera under adipogenic conditions had 2 fold greater expression of PPARG2 mRNA than any other treatment group. Concentrations of calcitropic hormones were not different between Ca+ and Ca− sera, but we identified 22 differentially expressed proteins in these sera. The results indicate that neonatal Ca restriction may have long‐term effects on bone integrity via programming of MSC.
Melissa officinalis essential oil reduces plasma triglyceride levels by downregulating SREBP‐1c expression and the epigenetic modifications on SREBP‐1c target genes
Authors: Jun Hee‐Jin , Kim Jin Young , Cho Sung‐Yun , Jeun Jungae , Lee Sung‐Joon
Published: June 2021

We investigated hypolipidemic mechanism of Melissa officinalis essential oil (MOEO). The major compound in MOEO was geranial (65%, w/w), quantified with GC/MS. After 2‐week feeding (0.0125 mg MOEO/mouse/day), plasma triglyceride levels were significantly reduced (−32%, P<0.05) in human apoE2 transgenic mice. Mouse hepatic transcriptome profiling with oligonucleotide microarray showed that fatty acid synthesis and β‐oxidation pathways were significantly altered. The rate of β‐oxidation, quantified with [1‐14C]palmitate, was not changed with MOEO in HepG2 cells, however, the expressions of SREBP‐1c and its target genes in the fatty acid synthesis including ACC2, FAS, and SCD1 were reduced in mouse livers assessed by quantitative PCR. The nuclear SREBP‐1c was reduced as well (−30%, P<.05). Chromatin immunoprecipitation results suggested that the bindings of PCAF, a coactivator of SREBP‐1c, and its H3K14 acetylation on the promoter of ACC2 (−9% for H3K14ac and −21% for PCAF binding) and FAS (−37% for H3K14ac and −10% for PCAF) were reduced. These suggest that MOEO may reduce plasma triglyceride levels by multiple mechanisms. The reduction of SREBP‐1c and its target gene expressions, decreasing nuclear translocation of SREBP‐1c, and the epigenetic down‐regulation of genes in fatty acid synthesis may result in net hypotriglyceridemic effects.
Concentration of milk free fatty acids is increased during lactational mastitis
Authors: Hunt Katherine Mary , Williams Janet E , Hunt Martha K , Ting Robert , Behre Rebecca , McGuire Michelle K , Shafii Bahman , McGuire Mark A
Published: June 2021

Free fatty acids (FFA) are minor constituents of human milk lipids, but may have important antibacterial properties. The objective of this study was to investigate whether lactational mastitis alters the total lipid (TL), FFA, and phospholipid (PL) contents of human milk. Participants (n = 13) were women with diagnosed mastitis referred to us by physicians and lactation consultants. Complete breast expressions were collected from infected and non‐infected breasts, with the healthy milk of each sample pair serving as the control. TL was extracted from each sample and fractionated using solid phase extraction. TL, FFA, and PL were then converted into methyl esters and analyzed by gas chromatography. Statistical analysis was performed using the Wilcoxon Signed‐Rank Test. There was no difference in the fatty acid profiles or overall amounts of TL and PL. However, percent FFA was greater (P = 0.0007) in infected milk compared with the non‐infected milk (1.33 ± 0.195 vs 1.07 ± 0.122%, respectively). This was accompanied by minor changes in the fatty acid profile of the FFA fraction with a decrease (P < 0.05) in lauric acid (12:0) and an increase in α‐linolenic acid (18:3ω3) in infected milk. This increase in FFA and the lack of change in TL indicate the potential role of increased lipolysis during mastitis as either a promoter of or response to inflammation. Supported by NIH‐NRRI grant P20 RR15587.

Grant Funding Source: NIH‐NRRI grant P20 RR15587
The effects of acculturation on the health status of Haitian‐American mothers
Authors: Filemon Johane Morose , Chakraborty Priyanka , Anderson Alex Kojo
Published: June 2021

Objective

To examine the effects of acculturation on the health status of Haitian‐American mother living in the United States

Method

This was a cross‐sectional study of 81 women of Haitian origin residing in Georgia and Florida. Information on various acculturation variables and health outcomes were obtained by trained bilingual/bicultural interviewers.

Result

Average age of the participants was 46.8±10.6 yrs with 98.8% identifying themselves as 1st generation American. Average number of yrs lived in the United States (US) was 15.3 yrs. Participants self identified themselves as Black (12.3%), Haitian‐American (13.6%) or Haitian (74.1%). The majority (64.0%) of the Haitian‐Americans were obese as compared to Blacks (30.0%) and Haitians (50.8%). While hypertension (high blood pressure) prevalence was similar in all the 3 groups, a higher proportion of Black (60.0%) and Haitian‐American (54.5%) participants were diabetic (higher blood glucose) as compared to Haitians (35.0%). Analysis with respect to number of yrs lived in the US showed that obesity and diabetes were equally prevalent amongst all the participants. On the contrary, hypertension was more prevalent (66.7%) among those who have lived in the US for < 5yrs.

Conclusion

These findings suggest that while acculturation may increase the risk of obesity and diabetes, it has a protective effect against hypertension among Haitian women living in the US.

Funding: Dept of Foods & Nutr, UGA
Intakes of sugars, sodium, and potassium through school lunch meals by elementary and junior high school students
Authors: Lim Hyeon‐Sook , Heo Young‐Ran
Published: June 2021

This study was performed to determine the intakes of sugars, sodium (Na), and potassium (K) through school lunch meals. Eighty‐five students in the 5th grade from three elementary schools and one hundred and eight students in the 8th grade from three junior high schools located in Gwangju, Korea were enrolled in this study. All the dishes, about 250 kinds, provided to the subjects were collected from the six schools for 2 weeks and analyzed the contents of sugars, Na, and K. The intake of each dish by each subject was determined by a weighing method. The daily intakes of sugars, Na, and K by the 5th grade students were 8.7 ± 7.3 g, 840 ± 467 mg, and 286 ± 137 mg, respectively and those by the 8th grade students were 12.0 ± 9.9 g, 927 ± 562 mg, and 245 ± 115 mg, respectively. The results showed the ratios of Na/K of the 5th and 8th graders were 2.94 and 3.95, respectively. Sugar intakes of the 5thand 8th graders were within the one third of the recommended level, < 50 g/day and those contributed 2.0% and 2.6% to total energy intakes, respectively. Their Na intakes were higher than the one third of the Adequate Intake for Na, 1,500 mg. On the other hand, K intakes of them were lower than the one third of the Adequate Intake for K, 4,700 mg. Thus, the Na/K ratios were considerably high. The results indicated that the students in the 5thand 8th grade students consumed more Na and less K through school lunch meals, however, their sugar intake was fairly appropriate.
Food insecurity in female Vietnamese marriage immigrants in South Korea
Authors: Choi Ha Ney , Lee Yo A , Hwang Ji‐Yun , Chung Hey Won , Kim Wha Young , Chang Namsoo
Published: June 2021

Previous studies have reported that the nutritional status of Vietnamese female marriage immigrants in Korea is inadequate; however no study has been conducted on food insecurity or insufficiency among them. This study presents food insecurity data from 322 Vietnamese female immigrants recruited from 8 local health centers between May and August in 2009 as part of a larger study of the Cohort of Intermarried Women in Korea. Four food insecurity questions of economic reasons and lack of adjustment to unfamiliar Korean foods were asked by face to face interviews. About 34.5% of subjects cut the size of meals or ate less than they felt and 40.7% of them ever skipped meals, because there was not enough money for food in the last one year. About 30.1% of subjects felt hungry and 46.3% of them had ever skipped meals (especially 10.6% of subjects skipped meals almost every month), because there was no food that they wanted to eat or no food for their appetite at home in the last one year. Both economic and adjustment difficulties may make these females food‐insecure. Our results point to the need for program outreach for low income, immigrant Vietnamese females in Korea.

This work was supported by the Korea Centers for Disease Control and Prevention and the Brain Korea 21 project.
Dietary behaviors are associated with anxiety and depression of high school girls
Authors: Shin Sanghee , Kwon Kyoung Nam , Kim Hyemi , Joung Hyojee
Published: June 2021

The purpose of this study was to investigate the association between depression, anxiety and dietary behaviors among Korean high school girls. The subjects were 1922 high school students in Seoul and Daejeon, Korea. The data was collected through self‐reported questionnaires which included general characteristics, dietary intake, Bulimia (Bulimia Test‐R), depression and anxiety assessment (HADS). Twenty nine percent of the girls had depression disorder (mild 20.3%, moderate 8.1%, and severe 1.3%) and 42% of the subjects showed anxiety disorder (mild 22.1%, moderate 15.3%, severe 4.6%). The proportion of girls with smoking, alcohol drinking, low appetite, and skipping breakfast were significantly higher among those who had anxiety and depression disorder (p<0.001). Anxiety and depression scores were positively correlated with intake frequency of soda and fast food but negatively associated with vegetable and fruit intakes (p<0.001). In summary, the prevalence of anxiety and depression disorder was high among Korean girls and associated with unhealthy dietary pattern. Mental health care programs are necessary for better dietary behaviors of girl adolescents. (This work was supported by the Brain Korea 21 Project in 2009.)
Weight change patterns in Mexican college student applicants
Authors: Teran‐Garcia Margarita , Wang Yingying , Aradillas‐Garcia Celia , Andrade Flavia Cristina Drumon ,   UPAMIGOS group
Published: June 2021

We investigated self‐reported body weight changes and macronutrient intake in applicants to the Universidad Autónoma de San Luis Potosí (UASLP), Mexico. This is a preliminary report on a subset of 346 young applicants (37.6% males, 16 to 20 yrs) with complete data from a Willett FFQ adapted for the Mexican population and self‐reported body weight changes in the year before their college application. Weight and height were measured at the University Health Center and BMI was calculated (kg/m2). According to their BMI, 69% of this subset had normal weight (NW, n=239, 46% females), 20.8% (n=72) were overweight (OW) and 10.1% obese (OB, n= 35). One third of the individuals (33.2%, n=113) reported weight gain in past year and most of them (53.8%), reported a 2 to 5kg gain. Among those who reported weight loss (n=106), 40.2% lost less than 2 kg and 38.2% 2 to 5kg. Few applicants indicated to be on a diet (10.9%), and that was concordant with a reported decrease in their total calorie (p=0.01), protein (p=0.008) and fat intake (p=0.02) in OB individuals compared to NW or OW. There were no differences in reported macronutrient intake among the 3 BMI categories for those that did not report to be on a dietary regime. We emphasize that this data is preliminary and will analyze information in most of the applicants (expected ~8,000) to confirm our observations.
Human intestinal ischemia/reperfusion‐induced inflammation characterized: experiences from a new translational model
Authors: Lenaerts Kaatje , Grootjans Joep , Derikx Joep PM , Matthijsen Robert A , de Bruïne Adriaan P , van Bijnen Annemarie A , van Dam Ronald M , Dejong Cornelis HC , Buurman Wim A
Published: June 2021

A new unique in vivo human model was used to investigate the inflammatory response following intestinal ischemia/reperfusion (I‐IR).

In this model, an isolated part of jejunum, to be removed during a standard surgical procedure, was exposed to 45 minutes of ischemia, followed by 30 and 120 minutes of reperfusion. At all time points tissue and blood was collected.

Histology revealed intestinal barrier integrity loss after ischemia, which further aggravated during reperfusion. This was reflected by massive leakage of intestinal fatty acid binding protein and soluble cytokeratin 18 (p<0.01) from damaged enterocytes, accompanied by increased arteriovenous concentration differences of endotoxin (p<0.05). Western blot for C3c and immunohistochemistry for activated C3 revealed complement activation after IR. During reperfusion, enhanced tissue mRNA expression of interleukin (IL)‐6 and IL‐8 (p<0.05) was accompanied by increased IL‐6 and IL‐8 release into the circulation (p<0.01). Furthermore, expression of intercellular adhesion molecule‐1 was markedly increased, facilitating the observed influx of neutrophils into damaged villus tips.

This study shows for the first time the sequelae of human I‐IR‐induced inflammation, which is characterized by complement activation, production and release of cytokines into the circulation, endothelial activation, and neutrophil influx into IR‐damaged tissue.
Pentoxifylline (PTX) ameliorates acute renal ischemia‐reperfusion (IR) injury
Authors: Grande Joseph Peter , Cheng Jingfei , Yin Ping
Published: June 2021

We have previously demonstrated that, in vitro, c‐AMP specific PDE3 inhibitors block mitogenesis of mesangial cells (Am J Physiol Renal Physiol, 2004) and PDE4 inhibitors block cytokine stimulated MCP‐1 expression (Am J Physiol Cell Physiol, 2005). The in vivo relevance of these findings has not been previously established. Mice were treated with the nonselective cAMP PDE inhibitor pentoxifylline (PTX) prior to bilateral clamping of the renal arteries for 30 minutes, followed by reperfusion for 1 and 4 days. PTX blunted the increase in BUN and creatinine after 1 day (−38% and −43%, respectively, p<0.05), and after 4 days (−80% and −44%, respectively, p<0.05). PTX reduced the extent of tubular necrosis (1 day: 39.13% vs. 52.5%; 4 days: 2.5% vs. 23.33%, p<0.05, p=NS. % cortical area in PTX vs. IR). PTX reduced PCNA expression 4 days after IR, as assessed by Western blot (−43%, p<0.05), and reduced caspase 3 activity one day after IR (−43%, p<0.05). PTX markedly reduced expression of MMP10 and Cox‐2 one day after IR (26 and 4 folds, respectively, p<0.05), which are induced in response to acute inflammation. PTX significantly reduced cyclin F, cyclin A2 and Ki67 expression 4 days after IR (124, 7 and 9 folds, respectively, p<0.05), which are induced in response to proliferation. We conclude that PTX ameliorates IR injury through c‐AMP mediated reduction in proliferative and inflammatory responses to acute injury.
Ultrastructural differences in the endoplasmic reticulum among various pituitary tumor types
Authors: Sharma Soniya , Rotondo Fabio , Kovacs Kalman , Horvath Eva
Published: June 2021

Our aim was to reveal ultrastructural differences in the endoplasmic reticulum (ER) among surgically removed human pituitary tumors. More than 2000 pituitary tumors were studied by electron microscopy. In growth hormone (GH) adenomas, the ER is well developed and consists mainly of rough surfaced endoplasmic reticulum (RER) and few ER membranes without ribosomes, called smooth surfaced endoplasmic reticulum (SER). In the sparsely granulated GH adenomas, the ER is less prominent and is seen in fibrous bodies containing keratin immunopositive microfilaments. In prolactin (PRL) adenomas, the RER is conspicuous, forming concentric whorls. In adenocorticotropin (ACTH) and thyroid stimulating hormone (TSH) adenomas, the ER and consists of RER and to a lesser extent, SER. In gonadotroph adenomas and null cell adenomas, the ER is poorly developed. In GH adenomas exposed to somatostatin analogs and in prolactin adenomas exposed to dopamine agonists, regression of ER is noted. In pituitary carcinomas, the ER is recognizable but it is less extensive than in the benign neoplasms. In conclusion, the ultrastructural investigation of ER provides valuable information on the cytogenesis and cellular composition of pituitary tumors. There is also a mild correlation between endocrine activity and extent of ER. However, no correlation exists between invasive and non‐invasive tumors and growth potential. Pituitary carcinomas cannot be distinguished from benign adenomas based on the ultrastructural features of ER.
Expression profiling of intestinal ischemia/reperfusion: first human in vivo findings
Authors: Lenaerts Kaatje , Grootjans Joep , Derikx Joep PM , van Dam Ronald M , Dejong Cornelis HC , Buurman Wim A
Published: June 2021

To better understand the molecular mechanisms associated with intestinal ischemia/reperfusion (IR) in man, gene expression profiles were studied in a unique in vivo human experimental model.

In this model, an isolated part of jejunum, to be removed during a standard surgical procedure, was subjected to 30 or 45 minutes of ischemia, followed by 30 and 120 minutes of reperfusion. Jejunal tissue exposed to IR as well as control tissue was collected. Total RNA was prepared and whole‐genome expression was assessed using Illumina HT‐12 expression beadchips containing 48,803 probes. GeneSpring X10 was used to identify differences in gene expression.

Expression of 661 genes was significantly changed (p<0.05) during intestinal IR with a fold change of at least 1.5. The most highly upregulated genes code for heat shock proteins and members of the Fos and Jun families. Accordingly, overrepresented gene ontology categories (p<0.05) in the list of genes include stress response and regulation of cell proliferation. Furthermore, mapping changed genes within a pathway database showed that the EGFR1, TGFBR and TNFalpha/NF‐kB pathways are significantly affected in response to IR.

This is the first study that examines global gene expression changes in the human intestine in response to IR. Identification of these transcriptional changes provides new targets to reduce intestinal IR‐associated morbidity and mortality.
Stathmin expression in breast cancer patients treated with anti‐tubulin drugs
Authors: Lu Ting‐Wei , Beedupalli Kavitha , Johnson Wendy , Luduena Richard , Yeh I‐Tien
Published: June 2021

Objective

Stathmin is a protein that inhibits microtubule assembly and is over expressed in highly aggressive and tubulin‐drug resistant breast cancers. This study examines stathmin expression in breast cancers from patients treated with anti‐tubulin chemotherapy.

Methods

We reviewed breast cancers from 44 women enrolled in a randomized trial of neoadjuvant doxorubicin and cyclophosphamide +/− docetaxel, including 39 with invasive ductal carcinoma and 5 with invasive lobular carcinoma. Microarray blocks were constructed from pre‐ and post‐treatment tissues and assayed for stathmin by IHC. Analyses of the stained slides were performed using Aperio Scanscope CS/GL® and TMALab® software. Tissues were evaluated for % staining of strong positive cells, with 4% used as a cut‐off value for high vs. low expression.

Results

The percentage of strong positive staining of stathmin in invasive ductal carcinomas ranged from 0.5% to 62% with mean 14.4%. Invasive lobular carcinomas had significantly less strong positive stathmin staining, from 0.07% to 3.3% (p = 0.00016, Student's t‐test, two‐tailed). Comparison of the recurrences in high vs. low stathmin was 47% to 21%. There was no correlation with survival or response to chemotherapy.

Conclusion

Invasive lobular carcinomas had lower intensity stathmin expression than ductal carcinomas. Stathmin expression tended to be higher in tumors that recurred.
Capsaicin: a potential therapeutic agent for human small cell lung cancer
Authors: Dom Aaron M. , Brown Kathleen C. , Witte Ted R. , Hardman W. Elaine , Dasgupta Piyali
Published: June 2021

Capsaicin the major active ingredient of chili peppers can induce apoptosis in multiple human cancer cell lines in cell culture and animal models. The present study examines the anti‐neoplastic activity of capsaicin in human small cell lung cancer (SCLC). SCLC is characterized by rapid progression, early metastasis and low survival rates. Our study showed that capsaicin induced 5–6 fold increase in apoptosis in multiple human SCLC cell lines. Most interestingly, the apoptotic activity of capsaicin was only displayed in SCLC cells and not in normal human lung epithelial cells. Capsaicin also suppressed the invasion of human SCLC cells as determined by Boyden Chamber assays. The dietary administration of capsaicin decreased the growth of human SCLC tumors xenotransplanted in nude mice. The growth‐inhibitory activity of capsaicin was independent of TRPV1, which is known to be the classical receptor for capsaicin. In contrast, the growth‐inhibitory activity of capsaicin requires the TRPV6 receptor, and depletion of TRPV6 by siRNA ablated the growth‐inhibitory activity of capsaicin. Our findings suggest that capsaicin may have potential applications as a novel agent for management and therapy of human SCLCs. Funding for our study was supported by a COBRE Pilot Grant, CDDC Pilot Grant, an MU‐ADVANCE Fellowship, and the Flight Attendant Medical Research Institute YCSA Grant.
Forming and Patterning the Rudiments of the Inner Ear
Authors: Schoenwolf Gary
Published: June 2021

The inner ear begins its development as a plate of cells (the otic placode) formed from the surface ectoderm of the embryo, which quickly internalizes to form a vesicle called the otocyst. The otocyst in turn forms the developing membranous labyrinth, which subdivides into dorsal vestibular and ventral auditory components. Two aspects of inner ear development will be discussed: induction of the otic placode; and initial dorsal patterning of the otocyst. Induction of the otic placode involves a cascade of growth factors secreted during gastrulation/early neurulation by all three germ layers: the neuroectoderm (secretes WNT8a and FGF3), the mesoderm (secretes FGF3, 4, and 19), and endoderm (secretes FGF8). Gain‐of‐function and loss‐of‐function experiments demonstrate the importance of these factors in establishing a hierarchy of interactions that lead to otic induction. Initial dorsal patterning of the otocyst‐‐manifested by rapid thinning and expansion of the otocyst wall‐‐is controlled by BMP signaling that results in a dramatic change in cell shape. Loss of adherens junctions and redistribution of E‐Cadherin play important roles in this process. As a result of these changes, dorsoventral regionally specific morphogenesis of the otocyst occurs, leading to structural and functional differences that define the vestibular and auditory components of the developing inner ear.
Age‐Associated Decline in Erectile Function: The Confounding Influence of Obesity
Authors: Maio Maria Tina , Komolova Marina , Smallegange Corry , Adams Michael A
Published: June 2021

Although there is a well‐established link between aging and erectile dysfunction (ED), the differential contribution of obesity, specifically visceral adipose tissue (VAT), as a causal factor in ED at a given age has not been determined. Caloric restriction (CR) can prolong lifespan and is a powerful tool that we use in our research to delineate the effects of aging on erectile function distinct from obesity.

Methods

3 groups of male Sprague‐Dawley rats (10–30 wks) were used: (10 and 20% CR), and ad libitum (control) Body weigh (Bwt), length, and abdominal girth (AG) were taken throughout. Full body MRI, was performed at 4 time points. The apomorphine bioassay (80 ug/kg, s.c.) was used to assess erectile function at 30wks of age in Study 1, whereas cavernous nerve stimulation was used in Study 2. Total VAT fat pads were weighed upon sacrifice.

Results

Final Bwt.'s (30wks) were Study 1/2: 659/660g (control), CR10% 537g, and CR20% 410/400g. VAT (% Bwt.) was Study 1/2: 6.2/7.5%(control), CR10% 5.8%, CR20% 3.8/2.2%. Erectile responses were 0.6±0.7 in controls, 0.9±1.1 in CR10% and 1.8±1.0 in CR20%. The CR‐induced reduction in VAT was well correlated with centrally mediated erectile responses (R2=0.7).

Conclusions

The age related decline in erectile responses was prevented via CR20%. There was a positive correlation between a reduction in VAT and improvements in sexual function. (Funds: HSFO, MK:CIHR‐DRA)
C‐peptide restores mitochondrial complex 1 activity and lowers superoxide levels in high glucose‐treated murine renal microvascular endothelial cells
Authors: Vejandla Himani L. , Dabkowski Erinne R. , Hollander John M. , Brock Robert W.
Published: June 2021

C‐peptide has been shown to protect against renal dysfunction and other diabetic microvascular complications. High glucose‐mediated microvascular damage, in endothelial cells, is based on excess generation of mitochondrial superoxide. The mitochondrial membrane potential (Δψm) and the amplitude of electrochemical proton gradient regulate superoxide production. The main objective of this study was to determine the effect of C‐peptide on overall mitochondrial function as well as the levels of superoxide in renal microvascular endothelial cells exposed to high glucose (HG ‐ 25 mM) for 24 and 48 h. Using JC‐1 to assess Δψm, we observed that C‐peptide (6.6 nM) restored the HG‐induced hyperpolarization at 24 h, and depolarization at 48 h, back to the normal Δψm levels measured with low glucose (5.5 mM). Respiratory control ratio, a measure of electrochemical coupling determined by polarography, was significantly higher in HG cells treated with C‐peptide compared to HG alone (24 h: p<0.0002 and 48 h: p<0.0155). C‐peptide also prevented HG‐mediated superoxide (p<0.05), as measured by mitosox red fluorescence using flow cytometry. In addition, C‐peptide ameliorated HG‐induced reductions in mitochondrial complex 1 activity. Together, these data demonstrate that C‐peptide protects against endothelial mitochondrial dysfunction during hyperglycemia.

Funded, in part, by NIH Grant RO1 DK067582.
Hypoxia‐inducible factor 1α is critically involved in metallothionein protection against diabetic cardiomyopathy
Authors: Feng Wenke , Xue Wanli , Zhao Jingchan
Published: June 2021

Previous studies have shown that metallothionein (MT) protects against diabetic cardiomyopathy (DCM) in mice. The current study was undertaken to test the hypothesis that the protective role of MT against DCM is mediated by hypoxia‐inducible factor ‐1 (HIF‐1) pathway leading to an increased angiogenesis and a normalization of glucose metabolism in a MT cardiac specific over‐expression mouse model and a rat embryonic cardiac fibroblast H9c2 cell line. Streptozotocin‐induced diabetes decreased cardiac HK‐II protein level, a HIF target and an important glycolysis enzyme; and cardiac‐specific MT over‐expression relieved this suppression. MT over‐expression increased HK‐II mRNA level nder both non‐diabetic and diabetic conditions. In vitro analysis showed that MT over‐expression increased and normalized the hyperglycemia‐reduced glycolysis. MT over‐expression significantly prevented the diabetes‐induced reduction in angiogenesis. Further studies showed that MT over‐expression increased HIF‐1α mRNA and protein level in diabetic heart and in MT stable over‐expressing H9c2 cells, indicating the transcriptional modulation of HIF‐1α by MT. This study demonstrated that MT increased HIF‐1 transcriptional activity leading to the normalization of glycolysis and angiogenesis in cardiomyocytes under diabetic conditions. Supported by a grant from American Diabetes Association (W.F)