bluuebunny/crossref_metadata_2025 huggingface dataset:
Past food deprivation is related to current dietary practices and weight status in Cambodian refugee women
Authors: Peterman Jerusha Nelson , Wilde Parke E. , Liang Sidney , Bermudez Odilia I. , Silka Linda , Rogers Beatrice Lorge
Published: June 2021

Objective

We investigated the relationship between past food experience of Cambodian refugee women and current food beliefs, dietary practices, and weight status.

Methods

Survey participants (n=133) were randomly selected from a comprehensive list of Cambodian households in Lowell, MA. Height, weight, 24‐hour dietary recall, food beliefs, past food experience, and demographic information were collected Multivariate logistic and linear regression models were used to analyze relationships.

Results

Survey respondents with higher past food deprivation scores were more likely to currently report eating meat with fat (OR=1.14 for every point increase on 9–27 point food deprivation measure), and to be overweight/obese by CDC (OR=1.28) and WHO (OR=1.18) standards.

Conclusions

Refugees who experienced extensive food deprivation/insecurity may be more likely to engage in unhealthful eating practices and more likely to be overweight/obese than those who experienced less extreme food deprivation/insecurity.

Funding sources: Cambodian Community Health 2010 program (CDC Agreement Number U50/CCU12215), Blue Cross and Blue Shield of Massachusetts Foundation Catalyst Fund, The Feinstein International Center, Project Bread, and the Cambodian Mutual Assistance Association of Greater Lowell, Inc.
Effects of exercise and high carbohydrate and high protein diets on women with and without metabolic syndrome (MS)
Authors: Oliver J , Culbertson J , Cannon C , Byrd M , Mardock M , Simbo S , Jung Y , Khanna D , Koozehchian M , Dalton R , Kim H , Lockard B , Rasmussen C , Kreider R
Published: June 2021

396 sedentary women (46±11 yrs, 163±7 cm; 92±18 kg; 45±4% fat) participated in the Curves® circuit training (3 d/wk) and weight loss program (1,200 kcal/d for 1‐wk; 1,600 kcal/d for 9‐wks that was 30% fat with 55% CHO in a HC group and 50–63% protein in a HP group) for 10‐wks. Subjects were divided into those with less than (n=218) or more than (n=178) 3 NCEP‐ATP III criteria for MS. Data were analyzed by MANOVA with repeated measures and are presented as means ± SD percent changes from baseline for the non‐MS and MS groups, respectively. Subjects with MS experienced significantly greater changes in fasting glucose (1.2±17; −3.0±15 %, p=0.016), TG (4.2±40; −8.7±30 %, p=0.001), SBP (−0.5±10; −4.3±12 %, p=0.001), and DBP (−1.2±12; −4.1±13 %, p=0.02). Although time effects were observerd, no differences were seen between groups in weight loss (−3.7±3.6; −4.0±3.6 %, p=0.40), fat loss (−6.5±6.7; −7.0±6.4 %, p=0.64), waist circumference (−3.1±6.0; −2.5±5.5 %, p=0.46), total CHL (−5.7±18; −5.3±19 %, p=0.75), or HDL (−3.8±20; −1.8±18 %, p=0.23). Subjects in the HP group tended to lose more weight (p=0.10) and had a greater reduction in TG (p=0.004). No time x MS x diet interactions were observed. Results revealed that exercise and diet promoted favorable changes in markers of MS; individuals with MS may experience greater benefits; and, a HP diet may promote greater reductions in TG levels.
Cardiovascular disease risk factors among older Chinese Americans living in New York City
Authors: Wong Sally S , Dixon Beth , Gilbride Juidth A , Chin Warren W
Published: June 2021

Cardiovascular disease (CVD) is the leading cause of death in the U.S. and affects Chinese Americans disproportionately. This cross‐sectional study evaluated the dietary intake and physical activity of older Chinese Americans, and how these behaviors may be related to CVD. A total of 125 older Chinese Americans were recruited from health fairs conducted in New York City (NYC). CVD risk factors (anthropometrics, blood pressure, blood cholesterol, blood glucose), dietary intake (3 24‐hour recalls, 1 dietary supplement questionnaire), physical activity (3 24‐hour recalls), and sociodemographic data were obtained by dietitians and nurses. In this study, older Chinese Americans had a high prevalence of overweight and obesity, borderline hypertension, pre‐diabetes, and diabetes. Many participants had low intakes of several minerals and vitamins and did not meet the recommended number of servings of dairy foods. Only 1 in 4 adults took a multivitamin supplement daily. After adjusting for potential confounders, intake oil/sweets and dairy was positively associated with waist circumference. Intake of oils/sweets, meats, and grains was positively associated with systolic blood pressure. Vigorous intensity physical activity was inversely associated with waist circumference and systolic blood pressure. This study found a high prevalence of CVD risk factors among a group of older Chinese Americans living in NYC.
NF‐E2 related factor 2 activation induction by decursin and decursinol angelate protect against bete‐amyloid‐peptide‐induced oxidative stress in PC12 cells
Authors: Li Li , Li Wei , Park Sung‐ki , Kim Yong‐ho
Published: June 2021

The protective effects of decursin(D) and decursinol angelate(DA) purified from Angelica gigas Nakai on beta‐amyloid‐peptide(Aβ)‐induced neurotoxicity and the mechanism was investigated. Aβ is a pathological hallmark of Alzheimer's disease(AD) which can initiate a cascade of oxidative events. It decreased viability of PC12 cells in a concentration‐ and time‐dependent manner. Pretreatment with D and DA resulted in dose‐dependent anti‐Aβ toxicity according to MTT assay and restored the activities of key antioxidant enzymes(superoxide dismutase, glutathione peroxidase, catalase), glutathione(GSH) level and lipid peroxidation altered by Aβ. Furthermore D and DA resulted in up‐regulation of GST activity accompanied by increased transactivation of activator NF‐E2‐related factor‐2(Nrf2) which mediates GST gene transcription. Our results demonstrate activation of Nrf2/ARE pathways in PC12 cells by D and DA treatment protects cells from Aβ‐induced oxidative stress and regulated Aβ‐mediated adaptive responses in PC12 cells via translocation of Nrf2. These findings indicated D and DA might be considered as an adjunct therapeutic strategy to combat neural demise in AD and other oxidative stress‐related disease.

This research is supported by Biohealth Products Research Center (BPRC) of Inje University.
Satellite Cell Specific p‐STAT3 Signalling in Human Muscle Following Acute Muscle Damage
Authors: Toth Kyle George , McKay Bryon R. , De Lisio Michael , Tarnopolsky Mark A. , Parise Gianni
Published: June 2021

Interleukin 6 (IL6) acting through STAT3 is a known signalling cascade active in many cell types. Whether IL6 exclusively signals in satellite cells (SC) following acute myotrauma is unknown. Twelve male subjects (21 ± 2 y; 83 ± 12 kg) preformed 300 maximal muscle‐lengthening contractions of the quadriceps femoris at 180°·s−1 over a 55° range with muscle samples (vastus lateralis) and blood samples (antecubital vein) taken prior to exercise (PRE), 1h (T1), 3hrs (T3) and 24hrs (T24) post‐exercise. Cytosolic and nuclear fractions of muscle biopsies were purified and analyzed for total and p‐STAT3 using western blotting. P‐STAT3 was detected only in cytosolic fractions across the time course peaking at T24 (p<0.01 vs. PRE). Nuclear total and p‐STAT3 was not detected at any time point. However, immunohistochemical analysis revealed a progressive increase in the proportion of SC expressing p‐STAT3 with ~60% of all SC positive for p‐STAT3 at T24 (p<0.001 vs. PRE) and with cMyc, the production of which is regulated by p‐STAT3, detected in SC at T24. Whole muscle mRNA analysis revealed induction of the STAT3 target genes IL6, SOCS3, cMyc (peaking at T3, p<0.05), IL6Rα and GP130 (peaking at T24, p<0.05). Upregulation of these genes coupled with that of Myf5, (T24, p<0.05) with no appreciable change in MRF4, suggests that the IL6/STAT3 axis is active in promoting SC proliferation in the early phase following muscle damage in humans.
A bifidogenic effect is observed in young infants fed infant formula supplemented with galactooligosaccharide (GOS) and polydextrose (PDX)
Authors: Walker Donald Carey , Scalabrin Deolinda MF , Mitmesser Susan Hazels , Harris Cheryl , Marunycz John D , Tölkkö Satu , Salminen Seppo
Published: June 2021

Background

Prebiotics contribute to healthy gut and immune development in infants by promoting beneficial gut microbiota rich in Bifidobacterium, predominantly B. longum, B. infantis and B. breve.

Objective

To assess the impact of a GOS/PDX‐supplemented infant formula on fecal microbiota.

Methods

In this double‐blind study, 21 to 30‐day old healthy term, vaginally delivered infants were randomized to receive Control (Enfamil Lipil®, Mead Johnson Nutrition, CTRL) or Control + GOS/PDX (4 g/L, 1:1 ratio, GP) for 60 d; there was a breastfed (BF) reference group. Stool samples were obtained at baseline and after 30 and 60 d of feeding. Microbiota by fluorescent in situ hybridization (FISH) and quantitative polymerase chain reaction (qPCR) was analyzed by Wilcoxon rank‐sum test.

Results

230 of 289 infants completed the study (CTRL=81, GP=78, BF=71). Total bifidobacteria by FISH at 30 d was similar among groups and at 60 d lower in CTRL and GP vs. BF (P≤0.049), with it tending to be higher in GP vs. CTRL (P=0.084). By qPCR, bacterial counts at 30 d tended to be higher in GP vs. CTRL for total bifidobacteria (P=0.069) and B. longum (P=0.057); GP was higher vs. CTRL for B. infantis at 30 d and for total bifidobacteria and B. longum at 60 d (P=0.002); at 60 d CTRL, but not GP, was lower than BF for total bifidobacteria and B. longum (P≤0.009) [Table].

Mean ranks of qPCR absolute counts of total bifidobacteria, B. longum, and B infantis at 60 days of feeding.+

Total bifidobacteria
B. longum
B. infantis

BF
119
113
106

CTRL
81ab
83ab
95

GP
109
111
104

Wilcoxon rank‐sum test

CTRL < BF, P≤0.009

GP > CTRL, P=0.002

Conclusion

GOS/PDX added to infant formula has a bifidogenic effect in young infants.
3,3′‐Diindolylmethane (DIM) inhibits crosstalk between DU145 prostate cancer cells and THP‐1 monocytes in vitro and in vivo
Authors: Lim Do Young , Lee Han Na , Park Jung Han Yoon
Published: June 2021

Tumor‐associated macrophages are known to influence neoplastic growth and progression by providing a rich supply of cytokines, proteases, and growth factors. The present study examined the crosstalk between prostate cancer cells and macrophages and whether DIM inhibits these interactions. Our in vitro results revealed that the migration of DU145 cells through collagen‐coated filter paper was markedly increased when THP‐1 cells were co‐cultured in the well under the filter paper. In addition, the DU145 cell‐conditioned medium stimulated the migration of THP‐1 cells. DIM inhibited these migrations of DU145 and THP‐1 cells. The secretion of IL‐6 and IL‐8 were markedly increased when DU145 cells were co‐cultured with THP‐1 cells and DIM inhibited the secretion of these cytokines. Solid tumor growth was markedly accelerated when nude mice were co‐injected with DU145 plus THP‐1 cells compared to DU145 cells alone, and DIM inhibited the tumor growth in mice co‐injected with both cells. Immunohistochemistry of tumor tissues revealed that the expression of CD31 (an endothelial marker), vascular endothelial growth factor, and Ki67 was increased in the co‐inoculation group, which was inhibited by DIM treatment. The present results indicate that interactions between DU145 and THP‐1 cells induce angiogenesis and the migration and growth of these cells and DIM inhibits these effects.
HAIR URANIUM IS INCREASED IN THE DEPRESSED SUBJECTS
Authors: LYKKEN GLENN IRVEN , Momcilovic Berislav , Prejac Juraj , Morovic Sandra , Anatoly Skalny V
Published: June 2021

Uranium (U) is a ubiquitous radiotoxic element in the human environment. In this study we analyzed the level of U in scalp hair of occupationally non‐exposed 11 men (M) and 37 women (W) having depression (D), and in 69 M and 95 W healthy control subjects (C). We strictly adhered to the principles of Helsinki declaration on human subject research. Depression was diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) criteria. Scalp hair U was analyzed by ICP‐MS (Momčilović et al. TEM 2006;7(4):35–42). The median values of U (μg·g−1) were higher in M than in W for both C and D subjects (CM 0.0099 vs. CW 0.0083; DM 0.0142 vs. DW 0.0123). However, hair U was higher in D men and women, than in healthy C subjects (DM 0.0142 vs. DW 0.0123; CM 0.0099 vs. CW 0.0083). The data indicate that scalp hair U is a reliable marker of the U body burden after the environmental internal contamination in occupationally U non‐exposed subjects. Higher U in men than women in both C and D may reflect presumably more out‐door activities of men. Regardless of gender, higher levels of U were observed in the hair of D than in C subjects, indicating the existence of a different U metabolism in D than in C subjects. The habitual risk of low‐level radiation exposure to U and its daughters is increased in D subjects.
Evaluation of clinical efficacy of Polycan for bone metabolism in Korean women: A randomized, double‐blind, placebo‐controlled clinical study
Authors: Park Soo‐Hyun , Kim Sun‐Young , Back Hyang‐Im , Jeon Ji‐Young , Kim Min‐Gul , Chae Soo‐Wan , Kim Dal‐Sik
Published: June 2021

Osteoporosis is a metabolic bone disease that results from a disturbance in normal bone remodeling, titling the balance to bone resorption over formation. Polycan known as a suppressor of bone resorption and enhancer of bone formation in animal experiment. To investigate the effect of Polycan on bone metabolism, we carried out 12 weeks, randomized, double‐blind, placebo‐controlled clinical trial for Korean woman. Sixty subjects were randomly assigned to two treatment groups with daily doses of Polycan (n=30, 150 mg), placebo group (n=30, 150 mg). Outcomes included measures of efficacy (deoxypyridinoline [DPYR], osteocalcin [OSC]) and safety (adverse events, laboratory test, anthropometric, electrocardiogram, and vital sign). 58 subjects (29 Polycan group, 29 placebo group) finished the study. After the 12 weeks of supplementation, DPYR is significantly decreased and OSC is significantly increased in both groups. There was no significant difference between Polycan and placebo group but OSC showed a tendency to increase in Polycan group. In conclusion polycan has positive effect on bone metabolism. And there was no adverse events in both groups.
Evaluation of health, eating habits and diabetes knowledge of participants of a worksite wellness initiative
Authors: Mukwevho Peter , Haley‐Zitlin Vivian , Barron Felix , Bodine Ashby B
Published: June 2021

The purpose of this study was to evaluate the health, diabetes knowledge and food consumption patterns and behaviors of university employees who had participated in a voluntary worksite wellness screening program. Online questionnaires were used to assess the demographics, diabetes knowledge (Michigan Diabetes Knowledge Test) and food consumption habits of the participants (Block food frequency questionnaire). The results of college degree holding participants were compared with those with less than a college degree. In a multivariate statistical analysis it was shown that total calories (p<0.007); having diabetes (p<0.001); gender (p<0.046); BMI (p<0.039); calories from fat (p<0.034); and calories from carbohydrates (p<0.002) were independent factors affecting diabetes knowledge score. Income (p<0.980), age (p<0.286), and education (p<0.079) were found to be insignificant factors contributing to diabetes knowledge score. This study provides insight into factors which should be taken into consideration for the development of a successful university worksite diabetes prevention program. Supported by: CU Creative Inquiry
Information and decision‐making regarding food choices by undergraduate students
Authors: Johnson Sara E , McEligot Archana J , Cullin Jennifer , Alano Ryan , McMahan Shari , Cunningham Stephanie , Sandoval Nicole
Published: June 2021

Factors affecting the decision‐making of young adults and the relative importance they place on sources of information about food choices are addressed in a US population of undergraduate students (n = 355). Acculturation and transition to an “American” diet occurs over time and sources of information and their relative importance regarding dietary choices are expected to vary based on generational residence time, ethnicity, and age. Results indicate that students born outside the US and first generation students rate the value they place on information from the media about diet (TV, news, magazines) significantly higher than 2nd and 3rd generation students (t‐test, TV, p=0.004, news, p=0.061, magazines, p=0.019). Both recent (born outside the US and 1st generation) immigrants and established immigrants (2nd and 3rd generation) rate information from parents as the most important source of information regarding dietary choices. However, recent immigrants rate information from parents significantly higher than established immigrants (t‐test p=0.039). The value of different sources of information also varies by ethnicity (ANOVA, p=0.015). Post hoc comparisons indicate that for whites compared with Hispanic and Asians, TV is significantly (p < 0.05) less likely to influence their diet, while for Asians, the newspaper, magazines and the internet is significantly (p < 0.05) more likely to influence their diet compared with non‐Hispanic Whites and Hispanics. These results will aid in the design of nutrition intervention strategies and shed a light on the factors affecting the maturation of dietary choices and decision‐making among multi‐ethnic groups.

Supported by CDC grant # 1H75DP001814‐01.
Changes in raft hippocampus in aged rats supplemented with citrulline
Authors: Marquet Perrine , Clamagirand Christine , Cynober Luc , Moinard Christophe , Allinquant Bernadette
Published: June 2021

Rationale

Lipid rafts in brain are involved in cell signaling, and identified by the protein flottilin‐1. They contain a part of the precursor of peptide β‐amyloid (APP) and are involved in peptide β‐amyloid synthesis. Caveolae, sub‐populations of rafts, are characterized by protein caveolin‐1. Modifications in composition of rafts could be responsible of neurodegenerative diseases. The aim of this work was to evaluate the long‐term effect of citrulline (CIT) supplementation on rafts properties in healthy aged rat hippocampus.

Methods

20‐month‐old male Sprague‐Dawley rats (n=20) were randomized to be fed with chow diet or CIT‐enriched diet (1 g.kg−1.d−1) for 12 weeks. Brain hippocampi were recovered. Lipid rafts were prepared and expression of flotillin‐1, caveolin‐1 and APP was assessed by western blot. 6‐week‐old male rats were used as control.

Results

In young rats, 3 populations of rafts were pointed out (light, heavy, intermediate) considering flottilin‐1 expression. In the ageing group an increase of heavy rafts associated with a caveolin‐1 enrichment were observed at the same time that lost of both others populations. In CIT group, an intermediate pattern was pointed out: thought a same enrichment of heavy rafts was observed, some heavy and intermediate rafts populations were still remaining.

Conclusion

CIT supplementation during ageing seems to affect rafts composition.
Long‐term effect of citrulline supplementation in healthy aged rats: effect on body composition
Authors: Moinard Christophe , Le Plénier Servane , Cynober Luc , Raynaud‐Simon Agathe
Published: June 2021

Rationale

Aging is associated with a decrease in muscle mass. Citrulline (CIT) increases muscle protein synthesis. The aim of this work was to evaluate the long‐term effect of CIT supplementation on body composition in healthy aged rats.

Methods

20‐month‐old male Sprague‐Dawley rats (n=20) were randomized to be fed with chow diet or CIT‐enriched diet (1 g.kg‐1.d‐1) for 12 weeks. At sacrifice, rats were dissected and we weighed lean body mass, intra‐abdominal fat mass and cutaneous fat mass. Muscles were removed and weighed; muscle protein content was measured.

Statistics

Student t‐test.

Results

The mortality over 12 weeks was 20% (4/20) in the NEAA group whereas no mortality was observed in the CIT group (p=0.05). CIT did not affect body weight, but increased muscle weight (tibialis p=0.04 and plantaris p=0.02) and muscle protein content in the tibialis (195±4 vs 183±5 mg/g of muscle for CIT and NEAA; p=0.04). CIT induced a change in body composition with a decrease in cutaneous fat mass (24.7±0.5 vs 28.6±0.7 % of total body weight for CIT and NEAA, p=0.002) and intra‐abdominal fat mass (3.6±0.2 vs 5.1±0.3 %, p=0.0001) and an increase in lean body mass (54.8±0.6 vs 50.2±0.8 %, p<0.0001).

Conclusion

CIT supplementation is safe and is able to increase lean body mass and decrease fat mass in healthy aged rats. This is the first time that a nutritional manipulation induces such a change in body composition in aged rats.
Germination and Characterization of Bacillus anthracis and Bacillus cereus in Nematodes
Authors: Fowajuh Ann‐Desdemonia Neh , Abel‐Santos Ernesto
Published: June 2021

Bacillus anthracis is a Gram‐positive, spore‐forming, rod‐shaped bacterium known to cause anthrax. B. cereus is a related soil dwelling, beta hemolytic bacterium that can cause two food poisoning syndromes characterized by nausea and vomiting. Both species are typically present in soil as spores, yet they do not germinate in soil. We hypothesize that B. cereus and B. anthracis spores germinate in the gut of nematodes. Synchronized cultures of C. elegans were used to determine the effect of B. anthracis and B. cereus on the lifespan of nematodes: these results were inconclusive. Next, co‐plating of C. elegans with: 1) B. anthracis and B. cereus; 2) B. cereus and E. coli; and 3) B. anthracis and E. coli showed no preference as food sorces for C. elegans. B. anthracis spore germination was monitored in real time by co‐plating C. elegans with a B. anthracis strain containing the Pps12 plasmid. Insertion of this plasmid was expected to facilitate the fluorescence of B. anthracis in the gut of C. elegans upon germination. B. anthracis spores fluoresced in germination buffer supplemented with inosine and alanine; however, florescence was not detectable when ingested by C. elegans. Understanding the mechanism of B. anthracis and B. cereus germination is fundamental to preventing infection by each organism. Supported by NIH R25GM063775
Effect for insulin resistance of onion skin extract containing high quercetin in streptozotocin‐induced diabetic rats.
Authors: Jung Jiyoung , Kwon Hyeyoung , Kim Jiyeon , Kwon Oran
Published: June 2021

This study was performed to examine the effect of onion skin extract(OSE), which contains high quercetin(Q), on insulin sensitivity. To induce diabetes, 8 week‐old male Sprague‐Dawley rats (n=38) were divided into two groups. One group for control (n=10) was fed normal fat diet (16.9% energy from fat) and the other group (n=28) was injected 40mg/kg B.W. streptozotocin and fed high fat diet (41.2% energy from fat) for 3 weeks. After then streptozotocin‐induced diabetic rats were randomly divided into 4 groups according to kinds of treatment (no treatment, Q 0.1%, OSE 0.5% or 1.0%). Fasting blood glucose were measured once a week during experimental period and oral glucose tolerance test (OGTT) were performed at 7 weeks‐treatment. Although fasting blood glucose was not different among treatment groups, Incremental Area Under the Curve(IAUC) was significantly decreased in the 1.0% OSE group(p<0.05). C‐peptide and free fatty acid (FFA) concentration were significantly decreased in plasma of 1.0% OSE group(p<0.05). Insulin, HbA1c in plasma were not changed significantly by the intake of Q or OSE. However, insulin seemed to be decreased by OSE. This result indicates that OSE increase insulin sensitivity in vivo system. In conclusion, ingestion of OSE has a hypoglycemic effect in stretozotocin‐induced diabetic rats. This study suggests that OSE can be available for enhancing diabetic condition as a functional food.
Diets rich in n‐3 fatty acids but not in saturated fatty acids offer protection against lipopolysaccharide induced inflammation
Authors: Vanegas Sally M , Patel Nilam , Aitken Jessie , Vijay‐Kumar Matam , Ganji Vijay
Published: June 2021

Diet rich in n‐3 fatty acid (NF) is linked to reduced inflammation. Lipopolysaccharide (LPS), a Gram negative bacterial product, triggers inflammatory response through toll like receptor‐4 (TLR4) signaling. Objective of this study was to investigate whether diet rich NF in comparison with diet rich in saturated fatty acid (SF) would protect against LPS induced inflammation. 20 mice (BL‐10 background) were divided into 2 groups (n=10). One group received NF diet and another group received SF diet ad libitum for 60 days. Then mice were bled after overnight fasting and inflammatory markers were measured. After recuperation of 4 d, mice were challenged with 500 ng of LPS and blood was collected after 2 h. Mice fed NF diet in comparison to SF diet had significantly lower body weight (26.5 vs 28.1 g) and fasting blood glucose (71 vs 82 mg/dL) (p<0.001). After LPS challenge, mice fed NF diet in comparison to SF diet had significantly lower serum IL‐1β (15.4 vs 43.9 pg/mL), insulin (1.3 vs 3.4 ng/mL), and leptin (10.7 vs 12.9 ng/mL) (p<0.05). These data suggest that NF diet in comparison to SF diet offers protection against diet induced obesity, hyperglycemia, and some inflammatory markers when challenged with microbial LPS. Supported by Research Initiative Grant, Georgia State University.
Effect of High Protein Diet on Transgenic Sickle Mice
Authors: Capers Patrice L , Hyacinth H , Cue S , Chappa P , Archer D , Hibbert J
Published: June 2021

Sickle cell anemia (HbSS) is genetic and characterized by production of sickled erythrocytes. Key features include vascular injury and hemolysis, triggering inflammation and diverting amino acids (AA) away from normal functions, including tissue deposition for weight gain and muscle formation. It is our hypothesis that sickle cell mice on a high (35%) protein diet will show more tissue replacement and repair and improved muscle function. We are testing this hypothesis in a transgenic mouse model of human sickle hemoglobin at weaning and prospectively for three months. Experiments using protein expression, plasma AA analysis, enzyme activity, body composition, and muscle strength are used to test this hypothesis. Baseline results show that on a usual (20%) protein diet sickle mice have low body weight and muscle strength compared with controls. On the 35% protein diet, rate of weight gain (ROWG) and muscle strength increased in sickle mice by 25 and 11% respectively, whereas ROWG decreased in control mice. On both diets the sickle mice had significantly larger spleens and heart weights compared with controls. These results demonstrate that the sickle mice have enlarged organs. The high protein diet improved ROWG and may improve muscle strength in sickle mice. This is a good translational mouse model for pretesting effects of dietary intervention in HbSS patients, who frequently have low body mass and under‐nutrition.
Activity of some enzymes and electrolyte concentration in students’ serum of region of smelter Ferronikel in Glogovc – Kosovo
Authors: Gashi Agim , Bislimi Kemajl , Bajraktari Ismet D , Bojniku‐Sahiti Hazbije , Ibrahimi Ilknur , Halili Fetah
Published: June 2021

The triangle Mitrovica‐Obiliq‐Gllogovc is considered among the most polluted regions in Europe with heavy metals and toxic gases (WHO, 2002, Lunchakom P. et al. 2008). In blood serum of students exposed to pollution by the Ferronikeli smelter in Glogovc, the activity of enzymes has been investigated: alkaline phosphatase (FA), asparat aminotranspherase (AST), alanin aminotranspherase (ALT), and the concentration of electrolytes (K+, Na+, Cl−, total Ca, PO43− and Fe++). As a control group was taken a student group of the same age in Gjakova, located far from Ferronikeli. Preliminary results of research show the higher activity in significant scale of FA and significant lower values activity of AST, ALT and concentration Fe++, Cl−, total Ca++, compared with their respective values registered in the serum of control group. There is no difference between analyzed groups regarding the concentration of K+, Na+ and PO43. With the exception of FA, analyzed parameters do not exceed reference values, but in students from Gllogovc they are near the lower scale of allowed level, while in students of Gjakova near the above allowed level of the reference values.
Impact of the genetic background on immune system
Authors: Buffa Silvio , Romano Giuseppina Colonna , Bulati Matteo , Pellicanò Mariavaleria , Candore Giuseppina , Caruso Calogero
Published: June 2021

The aim of this study was to compare some immune parameters between healthy centenarian offspring (CO), healthy age‐matched old (O) and young (Y) controls to evaluate whether any difference exists in the naïve/memory compartments that might explain the familiar increased lifespan expectancy of centenarian offspring (CO). In fact it is now supposed that longevity is based on genetic background and it has been demonstrated that centenarian siblings have an increased probability to reach long life as well.

Methods

Peripheral blood mononuclear cells (PBMC) were collected from CO, O and Y donors. Lymphocyte subsets were evaluated by cytofluorimetric analysis. We have studied the naïve/memory compartment in T and B cells evaluating the expression of CD45R0, CD27, CD28 (on CD4 and CD8 T cells) and IgD and CD27 (on CD19 B cells).

Results

Our results show that O show the most differentiated phenotype, Y display the less differentiated phenotype and CO show an intermediate profile between the other two control groups.

Conclusion

These data support the hypothesis of a “familiar youth” of the immune system that can be a big advantage both to fight the main age‐related diseases, and to properly respond to vaccinations. So, T and B cell subset changes could represent an hallmark of successful or unsuccessful ageing and could be used as a biomarker of human life span.

This work was supported by the Italian Ministry of Education, University and Research grant (Does parental longevity impact on the health ageing of their offspring? An immunological and genetic study) to C. Caruso.
Thymic stromal lymphopoetin is critical for recovery from DSS induced colitis
Authors: Reardon Colin , Lechman Matthias , Mak Tak W
Published: June 2021

Thymic stromal lymphopoetin (TSLP) influences a plethora of immune functions; including in the colonic mucosa.

Aims

Here we assessed the role of TSLP in mediating recovery from colonic inflammation.

Methods

Controls (WT), mice deficient for TSLP (TSLP−/−), or bone marrow (BM) chimeric mice using TSLP receptor deficient (TSLPR−/−) BM were subjected to dextran sodium sulfate colitis (DSS; 5% w/v). Mice were assessed daily for weight loss, and inflammation assessed 8 days post‐DSS during overt disease.

Results

TSLP−/− mice do not display enhanced colonic inflammation during DSS‐induced colitis as determined by similar weight loss, TH1/TH17 cytokine production and histological damage compared to WT controls. Despite this, TSLP−/− mice failed to recover from colitis, with progressive weight loss resulting in death. Reduced collagen deposition and increased neutrophil elastase (NE) activity but not metallomatrix protease activity occurred in TSLP−/− as compared to WT mice. Increased NE activity was paralleled by a reduction in the endogenous inhibitor of this enzyme, secretory leukocyte peptidase inhibitor (SLPI). Critically, BM chimeras identified that TSLPR on non‐hematopoeitc cells were sufficient for recovery from DSS‐induced colitis. Additionally, we identified TSLPR on intestinal epithelial cells (IEC), and stimulation of this receptor induced the expression of SLPI.

Conclusion

TSLP‐elicited signaling through TSLPR on IEC is a critical mediator in wound healing that does not involve restraining of TH1/TH 17 cytokines. The disparity between TSLP−/− and TSLPR−/− mice suggests that signaling downstream of TSLPR could occur in response to cytokines other than TSLP.
Enteric Commensal Bacteria Mediates Repair of Intestinal Epithelial Wounds
Authors: Kumar Amrita , Swanson Phil , Samarin Stanislav , Matam‐Kumar Vijay , Nusrat Asma , Neish Andrew
Published: June 2021

We sought to investigate the mechanism(s) by which enteric commensal microbiota contributes to recovery of epithelial integrity post‐injury. Intestinal epithelial injury was induced in mice by oral administration of dextran sodium sulfate (DSS). After 7 days of DSS treatment, mice were orally gavaged with a single dose of 108 cfu/ml of Lactobacillus rhamnosus. 24 hrs later intestinal permeability changes in mice were monitored by quantifying uptake of FITC‐Dextran and Horseradish peroxidase. Lactobacillus treatment resulted in decreased permeability of FITC‐dextran and HRP and increased phosphorylation of Focal adhesion kinase (FAK), a key protein required for active cell migration. In cultured epithelial monolayers, we showed that Lactobacillus stimulated epithelial wound healing, motility, focal adhesion formation and FAK activation. This increase in phosphorylation of FAK was in turn mediated by generation of reactive oxygen species in intestinal epithelial cells and oxidant‐mediated inactivation of protein tyrosine kinases that constitutively dephosphorylate FAK. Overall, these results suggest that commensal bacteria can mediate repair of epithelial wounds by inducing ROS‐mediated phosphorylation of FAK.
Angiotensin converting enzyme (ACE) over‐expression in myelomonocytic cells markedly augments resistance to methicillin resistant S. aureus (MRSA) by increasing iNOS levels
Authors: Datta Vivekananda , Duodu Derrick O , Shen Xiao Gregory , Billet Sandrine , Bernstein Kenneth
Published: June 2021

Despite changing the antibiotic forms, Staphylococcus aureus has become increasingly drug resistant, including Methicillin. A recent surge of MRSA has reached endemic proportions among hospital‐acquired nosocomial infections with serious consequences among immunocompromised patients. Fatal MRSA infections of epidemic proportions needs to be tackled by newer treatment modalities.

ACE a crucial component of the Renin‐Angiotensin System, is thought to be involved in the immune modulation. The role of ACE peptidase in immunity is not well understood. We created a transgenic mouse strain, refered as ACE10, in which ACE is over‐expressed only in monocytes and macrophages, but lacks ACE expression else where. Transgenic mice when challenged with MRSA subcutaneously, produced a smaller ulcerated skin lesions compared to WT mice. Compared to WT mice, ACE10 mice has 50 times less bacterial burden in their lesions. Resistance to MRSA in ACE10 was reversed by treating these mice with ACE inhibitor. Inhibition of ACE in macrophages rendered ACE10 mice sensitive to MRSA. Although the baseline iNOS expression remains unchanged in the ACE10, ACE10 mouse strains when treated with iNOS inhibitor significantly increased the bacterial burden in the lesion.

The presence of enhanced ACE activity in ACE10 mice macrophages, increases innate inflammatory response, through induction of iNOS and augmented nitrite production.
Scedosporium apiospermum presenting as a pulmonary mycetoma in immunocompetent male
Authors: Gupta Ekta , Shibli Muhammad , Gibbons Junette
Published: June 2021

Background

Scedosporium apiospermum the anamorph of the ascomycete Pdeudoallescheria boydii, is a significant opportunist with very high levels of antifungal resistance. Colonization of Scedosporium apiospermum is a rare event, which eventually occurs on previous damaged lung tissue such as cavity or a lung cyst. We report this rare case of pulmonary scedosporiosis in an immunocompetent male treated many years ago for pulmonary tuberculosis.

Case presentation

A 42 year old Ethiopian male with past medical history of successfully treated Pulmonary Tuberculosis, presented with cough and Hemoptysis off and on for the last few months, which got worse for 3 days. Imaging showed cavitary lesion in the right upper lobe of lung. Bronchoalveolar lavage after bronchoscopy was negative for AFB smear and culture. Patient had an episode of massive hemoptysis and was electively intubated for right upper and middle lobectomy. Patient felt better after surgery, and no further episode of Hemoptysis was reported. Later, bronchoalveolar lavage cultures grew – Scedosporium apiospermum.

Conclusion

Scedosporium apiospermum infection is an emerging, potentially life‐threatening disease category which is difficult to diagnose and treat. In lungs, it is easily misidentified as Aspergillus, especially in post tubercular cavitary lesion. Even in culture, the species is frequently not recognized due to its morphological plasticity. This case is reported to highlight a rising incidence of this potentially lethal infection and the prognostic significance of early detection and therapy.
Development of a murine model of tumor promotion and progression for immunotoxicity testing
Authors: Egenolf Devon , Rafferty Patricia , Brosnan Kerry , Jordan Jarrat , Walsh Melinda , Kavalkovich Karl , Watson Sharon , Johns Laura , Makropoulos Dorie , Walker Mindi , Volk Amy , Bugelski Peter J.
Published: June 2021

Non‐selective immunosuppressive drugs are associated with an increased risk of neoplasia. Although selective immunosuppressants, e.g., monoclonal antibodies, will likely pose less of a hazard, concerns remain about an increased risk of neoplasia, particularly squamous cell carcinoma. The 2 year bioassay has been the industry standard for evaluating carcinogenicity. However, it has poor predictive value for immunosuppressive drugs, accurately identifying a hazard with only 5 of the 13 drugs tested. Thus, there is need for an alternative testing strategy. We have developed a novel 3‐stage model to study tumor promotion and progression in vivo. We chose a murine squamous skin cell carcinoma (SCC VII) cell line to study local invasion and dissemination, colonization, and tumor progression in C3H‐HeN, SCID and SCID/bg mice in the presence and absence of cyclosporin A. Local invasion and dissemination were evaluated by following emigration of quantum dot labeled tumor cells to the draining lymph node. Lung colony counts were made after iv injection of tumor cells and angiogenesis and growth fraction were evaluated morphometrically. Immunosuppression, was associated with increased local growth and lung colonization but with decreased angiogenesis and growth rates. These results suggest that a series of models described here may offer a viable alternative to the 2 year bioassay.
The Role of the Protein C System in Prostate Cancer
Authors: Glasscock Laura , Pardhanani Pooja , Brunson Lacey , Wilson Kim , VanNostern Chantelle , Teigland Chris , Wakeman Carolyn
Published: June 2021

Thrombin bound to endothelial thrombomodulin (TM) activates protein C (PC) into activated protein C (APC) with the aid of endothelial protein C receptor (EPCR). We determined if TM and EPCR are also expressed in PC‐3 and DU‐145 prostate cancer (CaP) cell lines, their ability to activate PC into APC, and how each of the proteins involved in this system regulates CaP cell proliferation and invasion. Real‐Time PCR, Western Blotting, and confocal microscopy demonstrated that TM and EPCR are expressed by both cell lines and both cell lines activated PC into APC in the presence of thrombin. PC, APC, and thrombin alone did not affect CaP cell proliferation or invasion. Since APC affects ovarian tumor cell invasion by competing with urokinase type plasminogen activator (uPA) for binding to plasminogen activator inhibitor‐I (PAI‐1), we determined if APC also regulates CaP invasion. APC competed with uPA for binding to PAI‐1 in CaP cells, enabling uPA to increase DU‐145 invasion. We conclude that the CaP cells make TM and EPCR and generate APC. Although PC, APC, and thrombin alone do not affect CaP cell proliferation or invasion, in the presence of CaP cell TM and EPCR and exogenously added thrombin, PC, PAI‐1 and uPA, APC is generated and binds to PAI‐1, freeing uPA to facilitate CaP tumor cell invasion.

This research was made possible by NIH Grant Number P20 RR‐016461, the McKay Urology Endowment Fund, and the Hemby Foundation.
The elastic fiber protein MAGP‐2 is ectopically expressed in ovarian carcinoma cells
Authors: Rigueur Diana , Garrett Erin , Miyamoto Alison
Published: June 2021

Microfibril‐associated Glycoprotein‐2 (MAGP‐2) is a secreted protein component of elastic fiber microfibril sheaths. Gene expression profiling studies have linked elevated MAGP‐2 expression to advanced stage papillary serous ovarian tumors. These tumors primarily consist of epithelial‐derived tumor cells, but stromal cells are also present, and include endothelial cells from the tumor neovasculature. Since whole tissue assays do not indicate which cells in the tumor expressed increased levels of MAGP‐2, we assayed MAGP‐2 expression by quantitative Reverse Transcriptase PCR (qRT‐PCR) in three ovarian epithelial carcinoma cell lines and normal human ovarian surface epithelial cells. Interestingly, the data revealed that two of the three carcinoma cell lines did express significantly higher levels of MAGP‐2 than the normal cells, suggesting that ectopic expression of MAGP‐2 in the tumor cells themselves may have a role in cancer progression. Our data agree with recently published work on a non‐overlapping set of ovarian epithelial carcinoma cell lines by Mok et al. (Cancer Cell 16:521 2009) showing elevated MAGP‐2 protein levels in approximately 30% of carcinoma cell lines. Studies from our lab and others indicate that ectopic MAGP‐2 can modulate signaling by Notch or integrins, and can induce angiogenesis, suggesting that MAGP‐2 may play multiple roles in ovarian cancer progression. (CSUPERB, MARC)
Nicotine provokes impulsive‐like action by stimulating α4β2 nicotinic acetylcholine receptors in the infralimbic, but not in the prelimbic cortex
Authors: Tsutsui‐Kimura Iku , Ohmura Yu , Izumi Takeshi , Yamaguchi Taku , Yoshida Takayuki , Yoshioka Mitsuhiro
Published: June 2021

Nicotine, a major addictive component of tobacco, has been suggested to provoke impulsivity by activating central α4β2 nicotinic acetylcholine receptors (nAChRs). Although lesion studies have demonstrated the involvement of the medial prefrontal cortex (mPFC) in impulsive action, the precise brain sites responsible for nicotine‐induced impulsive action have not been identified. Our goal was to determine whether α4β2 nAChRs in the prelimbic cortex (PL) and/or infralimbic cortex (IL), which are subregions of the mPFC, mediate nicotine‐provoked impulsive‐like action in the 3‐choice serial reaction time task (3‐CSRTT). The 3‐CSRTT is a rodent model of impulsive action in which the animal is required to inhibit the response until a light stimulus is presented randomly in one of three holes. Following the completion of the training, rats were bilaterally injected with dihydro‐β‐erythroidine (DHβE) (6 and 18 μg/side), a selective α4β2 nAChRs antagonist, into the PL or IL before systemic injection of nicotine (0.2 mg/kg, s.c.). Intra IL DHβE infusions dose‐dependently blocked nicotine‐induced impulsive‐like action, whereas infusions of DHβE into the PL failed to block the effects. Our data provide evidence for the involvement of α4β2 nAChRs in the IL in nicotine‐provoked impulsive‐like action.
Melatonin reduces striatal dopaminergic and mitochondrial deficits associated with chronic Parkinson's disorder
Authors: Patki Gaurav , Lau Yuen‐Sum
Published: June 2021

Neuronal oxidative stress and mitochondrial dysfunction have been implicated in Parkinson's disease (PD). We have recently correlated striatal dopaminergic (DA) neurodegeneration with mitochondrial deficit in a chronic mouse model of PD (MPD) induced by 10 injections of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine and probenecid over 5 weeks. Melatonin is a natural antioxidant and free radical scavenger, which has been shown to reduce cellular oxidative stress, protect mitochondria, and slow aging. In this study, we examined the effect of long‐term melatonin treatment (5 mg/kg/day, i.p., 5 days/week for 18 weeks) on mitochondrial and DA neuronal functions in the striatum of the chronic MPD. Melatonin alone did not alter the normal neuronal, mitochondrial and motor functions as seen in the saline‐treated control mice. The chronic MPD exhibited marked loss of DA, reduction of mitochondrial respiration and ATP level in the striatum, and impaired motor performance on the challenging beam. Interestingly, melatonin treatment for 18 weeks significantly reduced DA loss and motor impairment and prevented mitochondrial deficit as detected in the chronic MPD. This study demonstrates that long‐term melatonin is not only mitochondria‐protective but also neuroprotective in the chronic MPD supporting the hypothesis that melatonin may slow the progression of PD neurodegeneration. Supported by NINDS R01 NS47920.
Ric‐8B is a guanine nucleotide exchange factor for G alpha q, G alpha 13, and G alpha s and regulates G alpha s catalysis by a unique mechanism
Authors: Chan PuiYee , Gabay Meital , Wright Forrest A , Tall Gregory G
Published: June 2021

Ric‐8A is a non‐receptor GEF for a subset of G protein alpha subunits. Ric‐8B was discovered as a Gαs/Gαq interacting protein and through homology to Ric‐8A has been suggested to be a GEF for these subunits. Here we show in cells and in vitro the complete profile of Ric‐8 protein interactions with representatives of the four G protein alpha subunit classes. Ric‐8BFL (full length) binds Gαq = Gαs > Gα13 ⋙ Gαi, Ric‐8BΔ9 binds Gαs exclusively, and Ric‐8A binds Gαi = Gαq = Gα13. In all cases, but to varying degrees Ric‐8 proteins stimulated GTPγS binding to the G alpha subunits that each bound. Ric‐8BFL stimulated Gαq GTPγS binding and steady state GTP hydrolysis (GTPase). For Gαs, Ric‐8BFL and Ric‐8BΔ9 promoted very rapid GDP release, but delayed the rate at which the open form of Gαs bound GTPγS, although the overall rate of Gαs GTPγS binding was enhanced slightly above the intrinsic rate. Ric‐8BFL, but not Ric‐8BΔ9 also remained bound to Gαs:GTPγS after nucleotide exchange (neither bound Gαq‐GTP). The kinetics of Gαs single turnover GTPase were unaltered by Ric‐8BFL or Ric‐8BΔ9. However, Ric‐8BFL uniquely promoted Gαs futile nucleotide exchange of GTPγS for GTPγS. These collective observations explain in part, the finding that Ric‐8BFL potently inhibited Gαs steady state GTPase activity (overall catalysis), despite being a GEF for Gαs. This work was supported by NIH grant R01GM088242 to G.G.T., and NIDA grant T32 DA07232 to P.C.
Novel pharmacological insights for adenylyl cyclase 5, a gatekeeper of GPCR signaling
Authors: Siehler Sandra , Yamamoto Rina , Bergsdorf Christian , Leder Lukas , Reinhardt Juergen , Freuler Felix , Scheel Guenther
Published: June 2021

Nine mammalian adenylyl cyclase isoforms (AC1‐9) are specifically expressed and regulated by G protein‐coupled receptors (GPCRs). Full knock‐out mice for AC5 are protected from cardiac stress and aging‐induced cardiomyopathy, and reveal an increased lifespan. Pharmacological inhibition of AC5 may have therapeutic potential in the clinic. Forskolin (FSK), a natural diterpene, directly activates AC1‐9, and potently stimulated cAMP production in HEK293/human AC5 cells (EC50 = 27 nM). Human AC6 expressed in HEK293 cells revealed an 8‐fold lower FSK potency. Despite highest sequence homology (67%) AC5 inhibitors selective over AC6 were discovered. Inhibitor potencies were comparable when using either FSK or isoproterenol, a β‐adrenoceptor agonist, for stimulation. PKC activation enhanced cAMP production through AC5, but not AC6. Inhibition of PKC had no inhibitory effect on FSK‐stimulated AC5 (or AC6) activity. Using HEK293/AC5 cell membranes, some inhibitors were found to preferentially block the inactive enzyme, whereas others block the active enzyme state. Isolated catalytic domains were used to confirm inhibitors to directly affect human AC5. Potencies of known P‐site inhibitors and newly identified inhibitors were compared using HEK293 cells and membranes, and catalytic domains. This work was supported by Novartis Institutes for BioMedical Research (NIBR).