bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterologous expression of human phosphodiesterase 3A enhances oxidative stress resistance in yeast
Authors: Rhee Dong Keun , Lim Jung Chae , Hockman Steven C. , Ahmad Faiyaz , Manganiello Vincent C.
Published: June 2021

All organisms have evolved to overcome environmental stress via protective antioxidant activity, which slows ageing or senescence and extends life. cAMP/PKA signaling pathways are directly related to increased resistance to H2O2 and to the extension of life span in yeast cells. PDEs control cAMP pools that are involved in regulating the cell cycle, and they are components of the RAS/cAMP pathway that mediates general stress responses. Using the yeast two‐hybrid system to study the interaction of human PDE3A (hPDE3A) and human RMND5A (hRMND5A), a E3 ubiquintin ligase, we noticed that expression of hPDE3A and an ubiquitinylation site mutant K13R hPDE3A (which did not interact with hRMND5A) altered yeast growth in response to environmental stresses. For our current studies we therefore used S. cerevisiae as a model system to study effects of exogenous WT hPDE3A and on H2O2‐mediated stress responses in yeast. Our results suggest that hPDE3A enhances calcineurin activity and upregulates YAP1 and YAP1‐dependent gene expression, which in turn leads to increased expression of cellular target genes involved in recovery from oxidative stress, including up‐regulation of SRX1 and resulting in reduction of Tsa1p.
Who is undernourished and who is overweight in Nigeria?
Authors: Adeyemi Olutayo , Stoltzfus Rebecca J. , Devine Carol M. , Pelletier David L. , Pinstrup‐Andersen Per
Published: June 2021

The rising prevalence of overweight and obesity in low and middle income countries has been documented, but the development of appropriate policy responses requires an understanding of the geographic and social distribution of these conditions in relation to that of undernutrition. This need is especially great in countries with marked social, cultural and economic diversity. This study examined the distribution of undernutrition and overweight in women and children in Nigeria. The anthropometric status of 27,304 women 15–49 years and 18,893 children 0–59 months in the 2008 Nigerian Demographic Health Survey was examined using complex survey design in Stata 12.1. In general, undernutrition in women and children was higher in the three northern regions, overweight in women was higher in the three southern regions and child overweight was similar across all six regions. Also, undernutrition in women and children was inversely associated with wealth quintile in all six regions, overweight in women was positively associated with wealth quintile in all six regions, and child overweight was not associated with wealth quintile in any of the regions. Relative to other Sub‐Saharan African countries, Nigerian subpopulations, including the poorest children, had a higher prevalence of both undernutrition and overweight.

Research support: Division of Nutritional Sciences, Cornell University

Grant Funding Source: None
The impact of long‐term storage on fermentability of human fecal bacteria
Authors: Racicot Kenneth , Arcidiacono Steven , Chen C.Y. (Oliver) , Soares Jason
Published: June 2021

In vitro fermentation using human feces as inoculums is a useful tool to evaluate microbially catalyzed bioconversion of dietary components. However, the influence of storage duration on fecal fermentability has not been fully examined even though such information is crucial to generation of consistent results from in vitro experiments conducted over many months. The objective of this study was to determine the effect of storage at −20°C on the fermentability of human fecal bacteria. Freshly voided feces of 3 people were stabilized within 4 h using a reduced anaerobic phosphate buffer. The resulting fecal slurries were preserved with glycerol, frozen at −20°C, and evaluated monthly for 4 mo. Anaerobic fermentation was performed with 2% inoculum in batch style at 37°C and starting pH 6.8 under anaerobic mixed gas. A complex colonic medium supported bacterial growth for 48 h. Fermentability was monitored by changes in pH and protein content and production of short chain fatty acids. Our results show that fermentability of fecal bacteria that were properly preserved and stored at −20°C was maintained. The addition of cranberry proanthocyanidins prior to the start of fermentation appeared to increase bacterial growth by >; 20%. Our results are in support of the feasibility of using feces properly preserved and stored for long duration for in vitro fermentation experiments. Funded by US Army Natick Soldier Center.
Changes in coffee intake and subsequent risk of type 2 diabetes in women
Authors: Bhupathiraju Shilpa N , Pan An , Willett Walter C , van Dam Rob M , Hu Frank B
Published: June 2021

Epidemiological data have consistently found an inverse association between coffee consumption and risk of type 2 diabetes (T2D). It is unclear whether changes in coffee consumption are associated with subsequent risk of T2D. Therefore, we analyzed whether 4‐year changes in coffee and tea consumption predicted subsequent risk of T2D among 48,721 women from the Nurses’ Health Study (1986–2006) who were free of cardiovascular disease and cancer at baseline. Diet was assessed using a validated FFQ and updated every 4 years. We documented 3482 cases of T2D during 20 years of follow‐up. In Cox proportional hazards regression analyses, adjusting for baseline and 4‐year changes in dietary and lifestyle variables, we found that women who decreased their coffee intake by 1 serving/day, over a 4‐year period, had a 17% higher risk for T2D (RR=1.17, 95% CI: 1.06–1.30) compared to those who made no changes in coffee consumption. Conversely, those who increased their coffee intake by 1 serving/day had a 13% lower risk for T2D (RR=0.87, 95% CI: 0.77–0.99). We did not observe any significant associations between changes in tea intake and T2D. There was no evidence that these associations were modified by baseline coffee/tea intake, changes in smoking status, body weight, hypertension, or high cholesterol. Our data provide novel evidence that changes in coffee consumption habits influence subsequent risk of T2D in women.

Grant Funding Source: Supported by NIH grants CA87969, CA055075, DK58845, HL60712
Iodine and Iron deficiency and Parasites in children of Arandas, Mexico during the nutrition transition
Authors: Vasquez‐Garibay Edgar Manuel , Barrera Liliana R Campos , Velarde Enrique Romero , Cosio Maria Eugenia Nuño , Sanroman Rogelio Troyo , Rios Lizette Miranda , Rodriguez Francisco Napoles , Del Angel Alma Rosa , Velarde Fernando
Published: June 2021

With the purpose to demonstrate changes on nutritional and health status a comparison was made in two studies 2000 and 2010. In the earlier, a cross sectional design carried out in children (60–120 months) of Instituto Alteño para el Desarrollo de Jalisco (INADEJ); in the latter a case‐control study with 102 children from 60 to 144 months of age from INADEJ (cases) and 206 children (controls) with similar age and sex randomly selected from the education system. Demographic, socioeconomic, parasites, iodine/iron indicators were included. Chi square test and odds ratio were estimated.

During the last decade, the social, demographic and nutritional indicators of children living in Arandas, Jalisco are being significantly changed during the social & nutrition transition. This study was sponsored by National Council for Science and Technology, Mexico & Teasdale Corti Grant # 103460–044, Canada.
The effects of dairy intake among preschool aged girls and boys on their weight status
Authors: Cohen Tamara R , Hazell Tom J , Jean‐Philippe Sonia , Pham Thu , Vanstone Catherine A. , Rodd Celia R , Weiler Hope A.
Published: June 2021

Intakes of milk and alternatives may affect body weight, but their associations with weight status in preschool aged children are unclear. This study assessed whether gender differences exist among milk intakes and if milk intake is related to body mass index‐for‐age z‐score (BAZ) in 483 children (3.74 ± 1.00 y) from Montreal, QC. Dietary intakes were assessed by direct observation at daycares and by telephone recalls to caregivers. At daycares, height and weight were measured. According to BAZ, 28% were classified as overweight/obese with no gender differences [total: boys (n=257); girls (n=230); (BAZ p=0.648)]. Dietary intake did not differ between genders (mean for group 1490.64 ± 395.64 kcal/d [17% protein, 56% carbohydrate and 27 % fat]); however, girls consumed significantly higher servings of dairy/d (p=0.018) and dietary calcium (mg/d) (p=0.008) but not dietary vitamin D (ug/d) (p=0.143) compared to boys. As a group, BAZ and milk intake did not correlate (rho= 0.076, p= 0.096), however a positive correlation was seen in girls milk intake and BAZ (rho= 0.161, p=0.015), but not in boys. These preliminary results suggest that milk intake differs among genders. Future analyses should include other food groups and test their associations to BAZ, taking into account gender differences. Funded by Dairy Farmers of Canada.
Use of digital messages to increase parental engagement in an after‐school obesity prevention program
Authors: Miesel Lindsay , Spence Marsha , Perry‐Burst Carolyn , McDonald Aneisa , Beason Jill
Published: June 2021

Research shows that parental engagement in childhood obesity prevention programs is key for children's healthy eating and activity. However, parental participation is difficult to achieve. The aim of this study was to test if the use of personalized digital nutrition and physical activity messages delivered to parents via a digital home message center impacted children's reported food intake and child/parent goal‐setting. Results from the intervention group (n = 34) were compared to a historical control (n = 34) without the parental engagement component. Results show a total increase in healthy breakfast intake (mean pre‐post difference: treatment [T] = −2.04, control [C] = −8.98, p = .03). The treatment group decreased intake of sugar‐sweetened beverages (T = .16, C = −5.75, p < .001), but increased intake of solid fats and sugars (T = − 2.14, C = −1.34, p < .001) compared to the control group. The control group increased intake of 1% (T = ‐.34, C = −6.79, p = .02) and fat‐free milk (T = −1.91, C = −2.21, p = .01) compared to the intervention group. Children whose parents were involved in the treatment group were more likely to return goal cards than children in the control group (percent returned: T = 44%, C = 24%, p < .001). Although child food intake results were mixed, parent engagement increased significantly as evidenced by the increase in returned goal cards.

Funding Source: Mercy Health Partners
The Relevances of Metabolic Syndrome with Dietary Habit and Lifestyle in Korean middle‐aged Women
Authors: LEE HYE JIN , LEE KYUNG‐HEA
Published: June 2021

The aim of this study was to research the relationship of metabolic syndrome (MS) with dietary habit and lifestyle in 45–60 years aged Korean women who visited the Changwon Hanheart hospital for medical examination from July to September, 2012(IRB 2012–1, Hanheart hospital) using SPSS statistics version 20.0 program. The subjects were divided into the following two groups: MS group (≥ 3 among 5 indices: waist circumference, triglyceride, HDL‐cholesterol, glucose and blood pressure) and none MS group (< 3 among 5 indices). Fourteen subjects 117 participants had metabolic syndrome (12%). BMI (p<0.05) and smoking ratio (p<0.01) in MS group were significantly higher, but self‐rated health status was significantly lower (p<0.05) than in none MS group. The subjects having MS showed a significantly negative correlation with ‘meal regularity’ (p<0.01), ‘constant food intake’ (p<0.05), ‘having enough meal time’ ( p<0.01), ‘fruits intake frequency’ (p<0.05), ‘adequate energy intake’ (p<0.05), ‘total dietary habit score’ (p<0.001), but showed a significantly positive correlation with ‘frequency of meats intake’ (p<0.01), ‘frequency of high cholesterol foods intake’ (p<0.001) and ‘frequency of salty foods intake’ (p<0.01). In conclusion, the risk of the metabolic syndrome is substantially lower in individuals who have healthful dietary habit.

This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology(2012–0004233)
Metabolomic profiling of the small for gestational age piglet
Authors: Getty Caitlyn M , Baratta Alyssa A , Dilger Ryan N
Published: June 2021

Human infants born small for their gestational age (SGA), as associated with intrauterine growth restriction, are at increased risk of morbidity and mortality during early life and beyond. As an animal model, the domestic piglet (Sus scrofa) provides many benefits for studying developmental aspects of the SGA condition. Our objective was to assess global metabolomic profiles of SGA (≤ 0.9kg body weight) and average for gestational age (AGA, 1.3–1.5kg body weight) piglets. Piglets were selected in littermate pairs, weighed daily to assess growth rate, and blood was collected at 15–17 days of age; piglets remained with their mother throughout the study. Following stringent quality assurance procedures on multiple analytical platforms, a total of 323 named biochemicals were identified in plasma samples, with significant effects noted in metabolic pathways involving energy (i.e., TCA cycle), amino acids, nucleotides, and fatty acids. Most notably, de novo synthesis of nicotinamide derivatives was higher (P < 0.05) in SGA piglets, suggesting a deficiency in cofactors important for energy metabolism and biosynthetic reactions. Moreover, changes in glucose metabolism suggested the ability to extract energy from dietary sources may have been compromised in the SGA piglet. We conclude that a significant reduction in the growth potential of SGA piglets is associated with perturbations in multiple metabolic pathways.

ACES James Scholar Honors Program, College of ACES, University of Illinois, Urbana‐Champaign
A comparison of American and Canadian RBC folate concentrations
Authors: Colapinto Cynthia K , Tremblay Mark S , Aufreiter Susanne , Bushnik Tracey , Pfeiffer Christine M , O'Connor Deborah L
Published: June 2021

In North America, folic acid fortification and supplementation policies have improved folate status and reduced the incidence of poor birth outcomes. This research aimed to compare RBC folate (RBF) concentrations in two nationally representative surveys: the 2007–2008 US NHANES and the 2007–2009 Canadian Health Measures Survey (CHMS). RBF was assessed in participants aged 6 to 79 years and in a subset of women of childbearing age (WCBA). Two different folate assay methods were employed— microbiologic assay (NHANES) and Immulite 2000 immunoassay (CHMS)—necessitating the application of a conversion equation to adjust the CHMS RBF data. T‐tests were used to examine country differences. RBF concentrations ≥906 nmol/L (considered optimal for neural tube defect risk reduction) were explored with a multiple logistic regression model. Median Canadian RBF (adjusted) were lower than those of Americans (988 nmol/L and 1106 nmol/L, respectively), but unadjusted Canadian median RBF values were higher (1248 nmol/L). Canadian WCBA (adjusted RBF) were less likely than American WCBA to have RBF ≥906 nmol/L (OR 0.58; 95% CI 0.37, 0.92), though Canadian WCBA with unadjusted RBF values were more likely to achieve this cut‐off than American WCBA (OR 1.90; 95% CI 1.03, 3.49). Harmonization of folate measurement procedures in future surveillance efforts would support comparisons and inform policy directions.

Grant Funding Source: Canadian Institutes for Health Research Fellowship (180375) to C.K.C and Operating Grant (218776) to M.S.T, D.L.O and C.K.C.
Effects of milk and carbonated beverage consumption on ambulatory blood pressure and cardiovascular responses to stress: a pilot study
Authors: Kynast‐Gales Susan Anne , Johnson Emily Carolyn , Massey Linda K.
Published: June 2021

Bioactive components of milk (Ca, K, Mg, a‐lactalbumin) reduce blood pressure (BP) and reactivity to stress. This study was undertaken to similarly explore effects of milk consumption versus a common alternative, soda. In a randomized crossover, 10 prehypertensive men consumed either 3 servings of milk or noncaffeinated regular soda daily for 2 wk with their customary diet. Free‐living 24 h ambulatory blood pressure (ABP) was recorded. In an exercise physiology laboratory, automated BP was measured at baseline; after 2‐min isometric handgrip pre‐ and post‐prandial, and post‐caffeine; and during submaximal cycle ergometry. Individual mean 24‐h ABPs clustered into 2 response categories, with participants displaying lower systolic ABP with milk (MC, n=4) or with soda (SC, n=3) consumption, and a non‐responding category (n=3). Applying the 24‐h ABP categorization, data collected in response to dynamic cycle ergometry substantially reflected the bimodal response to beverage. Isometric handgrip exercise elicited greater BP differences between beverages and in reactivity in MC after fasting; post‐prandial responses and reactivity were reversed.

Conclusion

Results suggest heterogeneous BP response to beverage in pre‐hypertensive men.

Supported by Washington Dairy Products Commission
Immunostimulatory effects of Curcuma longa L, Mulberry leaves, and Purple sweet potato extracts : Modulation of immune functions during murine leukemia virus infection
Authors: Yoo Seon‐A , Kim Ok‐kyung , Nam Da‐eun , Park Soo‐Jeung , Han Dong‐kyu , Kwon Han‐Ol , Lee Jeong‐min
Published: June 2021

Curcuma longa L(CL) is well‐known as oriental traditional medicinal plant. Curcumin, the active component of CL, is known to have a wide array of bioactivity including anti‐oxidant, antiinflammatory. Mulberry leaves(ML) improve immunity and influences anti‐inflammation function. Purple sweet potato(PSP) is also well known anti‐inflammatory. LP‐BM5 murine leukemia virus induces immune dysfunction leading to B cell leukemia and murine AIDS with cytokine dysregulation. The purpose of this study was the effects of CL, ML, and PSP extracts on immune dysfunction in a murine model of leukemia were investigated. Has been infected by a virus, the immune system collapsed, C57BL/6 mice for 12 weeks a diet containing CL, ML, and PSP extracts. CL ML, and PSP extracts were extracted by hot water, 10% EtOH and 80% EtOH, yielding respective extracts. These extracts are largely prevented the retrovirus induced splenomegaly, lymphadenopathy, reduction in B and T cell proliferation, and suppression of Th 1 cytokines(IL‐2, IFN‐gamma) secretion. It also suppressed Th2 cytokines(TNF‐alpha, IL‐10) production, which was otherwise stimulated by retrovirus infection. In conclusion, these data suggest that immune dysfunction, induced by murine retrovirus infection, was largely prevented by CL, ML, and PSP extracts.
The Efficacy of Some Common Vegetables in Ameliorating the Impact of Cement Dust Selected Enzymes in Wild and Laboratory Rats.
Authors: Okpuzor Joy Elizabeth , Tajudeen Yahaya
Published: June 2021

Cement dust poses a great problem to humans and the environment as a result of constant emission of dust and gas from cement facility. Exposure to cement dust could cause myriad of diseases including multi‐organ damage. Therefore, the effect of some food plants on the hepatic and antioxidant enzymes were investigated.

The phytoconstituents from Hibiscus sabdariffa, Moringa oleifera, Zingiber officinale, Telfairia Occidentalis were extracted with 95% ethanol. Two sets of rats referred to as the wild rats collected from the vicinity of the cement factory and normal laboratory rats Rattus norvegicus were used for the study. They were distributed into six groups each. Different plants extract and a mixture of all the plants extract were administered to the rats at a dose of 200 mg kg −1 for 180 days.

The results showed that there were significant decreases in the levels of ALT, AST and ALP of both the wild and laboratory rats that received all the plant extracts compared to the negative control that received no extract. However, the highest decrease in enzyme activity was observed in the rats the received the mixture of all the extracts followed by the rats that received only Zingiber officinale. The activity of GST in some of the extract treated rats was elevated compared control.

The study affirms that these plants have a positive influence on the hepatic and antioxidant enzyme of rats in cement polluted environments.
Ex vivo anti‐adhesion activity of a proanthocyanidin standardized cranberry powder beverage
Authors: Kaspar Kerrie L , Howell Amy B , Khoo Christina
Published: June 2021

Cranberry bioactives have been studied for their bacterial antiadhesion effect, which may prevent uropathogenic Escherichia coli (E. coli) from entering epithelial cells in the bladder. In this study, we compared the ex vivo urinary anti‐adhesion activity of a lowcalorie cranberry powder beverage (CPB) to a low‐calorie cranberry juice cocktail (LCJC) in healthy adults. The CPB was standardized to be equivalent to LCJC on a proanthocyanidin basis. Fifty‐nine volunteers participated in a double‐blind, randomized, placebo‐controlled, cross‐over study. Clean‐catch urine samples collected at baseline and 0–6 h were tested for anti‐adhesion activity utilizing a mannose‐resistant human red blood cell hemagglutination assay specific for P‐fimbriated E. coli. Compared to placebo, 0–6 h post‐consumption urines from the CPB and LCJC groups had significantly higher (p<0.05) antiadhesion activity compared to baseline. Although the CPB beverage demonstrated a greater anti‐adhesion activity post‐consumption compared to LCJC, there were no significant differences between these treatments (p=0.14), indicating a similar effect. Acute cranberry beverage consumption increased urinary anti‐adhesion activity ex vivo. This research was supported by Ocean Spray Cranberries, Inc.
Single dose oral toxicity of the Lotus(Nelumbo Nucifera) root ethanol extract in ICR mice
Authors: You Jeong Soon , Kim Sung Hoon , Lee Yun Ju , Kim So Young , Zhao Xu , Chang Kyung Ja
Published: June 2021

Lotus(Nelumbo Nucifera) root has been used as a familiar edible vegetable in east Asia for thousands of years. This study was performed to evaluate the single dose oral toxicity of lotus root ethanol extract(LREE) in male and female ICR mice. In order to observe the 50% lethal dose (LD50), 0(control), 2000 and 5000 mg/kg of LREE were orally administered to 12 male and 12 female ICR mice. After single oral administration of LREE to ICR mice, we monitored number of the death, clinical signs, changes of body weight during 14 days. Compared with the control group, we could not find any toxic signs in the mortalities, clinical signs, body weight changes in all treated groups (2000 and 5000 mg/kg). In addition, there were no abnormal changes in the organ weight and no pathological changes in macroscopic examination at necropsy. These results indicate that the single oral administration of LREE may have no side toxic effect at the dose of 5000 mg/kg body weight for both female and male ICR mice and LD50 value of LREE may be over than 5000 mg/kg body weight. This research was supported by the Globalization of Korean Foods R&D program, funded by MIFAFF, Republic of Korea
Effects of a high fat or a high carbohydrate diet and exercise on energy substrate utilization in rat brain
Authors: Minjun Xu , Sonou Tomohiro , Fujii Takako , Nakashima Ayumi , Tanaka Chihiro , Okamura Koji
Published: June 2021

The effects of a high fat (HF) or a high carbohydrate (HC) diet and endurance exercise training on energy substrate utilization in the rat brain were examined. Three‐wk‐old male rats were separated into four groups for 8 wk intervention: sedentary with a HF diet; exercise (15 m/min for 50 min, 3 d/wk) with the HF diet; sedentary with a HC diet; exercise with the HC diet. Each group was pair‐fed. After the intervention, all rats were sacrificed after a bout of exercise (15 m/min for 90 min) to measure the cerebral arteriovenous (AV) differences of lactate, glucose and ketone body (KB) as well as the KB production/consumption by homogenate of the brain and skeletal muscle. The final body weight and the AV‐difference of lactate and glucose did not significantly differ among the groups. The AV‐difference of KB showed net uptake and the HF diet increased the uptake. Exercise increased the AV‐difference of KB in the HC diet group but decreased the difference in the HF diet group. Exercise increased KB consumption by the homogenate of the brain in both the HF and high C diet groups. The consumption of KB by the brain homogenate tended to be higher in the HF diet than the HC diet (P = 0.076). These results showed that 8 wk HF diet increased the consumption of KB in the rat brain, and exercise increased the net cerebral uptake of KB, while no effects were observed in lactate and glucose utilization.
High resolution in vivo micro‐computed tomography is preferential over dual energy X‐ray absorptiometry for detecting bone loss in the orchidectomized guinea pig
Authors: Mak Ivy Lynn , DeGuire Jason R , Lavery Paula , Agellon Sherry , Weiler Hope A
Published: June 2021

Monitoring longitudinal skeletal changes in small animals requires sensitive and precise imaging tools. This study compares two in vivo imaging modalities, dual energy X‐ray absorptiometry (DXA) and micro‐computed tomography (μCT) for assessing bone quality in the guinea pig. Middle‐aged male guinea pigs (n=40; 70 wks) were randomized into orchidectomized (ORX) or SHAM groups for 16 weeks. At termination, femurs were scanned in vivo using DXA (DXAin vivo, QDR 4500A, Hologic). Excised bones were scanned again using DXA (DXAex vivo), and μCT (LCT‐200, Aloka). Bone mineral content (BMC) was assessed by ashing. Independent t test was used to compare differences in SHAM vs ORX; and agreement between methods assessed with Bland‐ Altman plots. Substantial bias (7–60%) was observed in all measured variables except areal bone mineral density (aBMD). As shown by DXAin vivo and μCT, whole bone aBMD was significantly higher in SHAM vs ORX. DXAin vivo also suggested higher BMC but smaller bone in SHAM vs ORX, such differences were not observed in DXAex vivo, μCT or ashing; indicating the lower aBMD in ORX observed in DXAin vivo is likely an artifact resulting from variations in nearby tissues and positioning. Also, compartmental changes in volumetric BMD and bone volume fraction shown by μCT are masked if only DXA was used. These data suggest that μCT is a more sensitive and reliable tool for capturing skeletal changes in the guinea pig.
EXPRESSION OF CARDIOLIPIN BIOSYNTHESIS AND REMODELING ENZYMES IN ADULT HEART FAILURE
Authors: Grudis Jonathan E. , Chatfield Kathryn C. , Sparagna Genevieve C. , Hijmans Jamie , Sobus Rebecca D. , Sucharov Carmen C. , Miyamotto Shelley D. , Stauffer Brian L.
Published: June 2021

Background

Cardiolipin (CL) is a unique phospholipid that is an essential component of the inner‐mitochondrial membrane critical for normal energy metabolism. Biosynthesis of CL occurs via an enzymatic pathway or through remodeling of existing CLs. The content of total CL and (18:2) 4CL (tetralinoleic form, normally predominant in the heart) are lower in ventricular tissue from adults with heart failure secondary to idiopathic dilated cardiomyopathy (IDC).

Purpose

The aim of this study was to determine the expression levels of CL biosynthetic and remodeling enzymes associated with CL content changes in IDC.

Methods

mRNA was isolated from the left ventricle (LV) of adult IDC patients at transplant (n= 27; mean age = 51±14) and non‐failing control LV from donor hearts (n= 15, mean age = 43±8). RT‐PCR was used to measure expression of CL biosynthesis and remodeling enzymes.

Results

Expression of biosynthetic enzymes, CDP diacylglycerol synthase 2 and phosphatidylglycerolphosphate synthase, were both 33% lower in IDC LV (p<0.05). Remodeling enzymes, monolyso‐CL acyltransferase and tafazzin, were also down‐regulated (66% and 43% respectively, p<0.01) in IDC LV compared to controls.

Conclusions

These results demonstrate that biosynthetic and remodeling CL abnormalities are present in failing IDC hearts and may contribute to mitochondrial CL abnormalities in heart failure. Supported by NIH/NCATS Colorado CTSI Grant Number UL1 TR000154.
PGC‐1 isoforms modulate the antioxidant response of photoreceptors to photo‐oxidative stress
Authors: Iacovelli Jared , Arany Zoltan , Saint‐Geniez Magali
Published: June 2021

Photoreceptors (PRs) are sensitive to oxidative stress due high oxygen consumption, high levels of light irradiation, and outer segments abundant in readily oxidized poly‐unsaturated fatty acids. This study examines expression of peroxisome proliferator‐activated receptor‐gamma coactivator 1 α and β (PGC‐1α/β), regulators of cellular metabolism and antioxidant response, in retina and their role in PR oxidative stress response in vitro. Mouse retina PGC‐1α/β□expression was studied by in situ hybridization, immunofluorescence and qPCR. 661w, photoreceptor‐like cells, were exposed to bright light, and reactive oxygen species (ROS) and cell death were analyzed. Knock‐down of PGC‐1α/β was performed using siRNA. PGC‐1α/β and antioxidant enzyme gene expression was analyzed by qPCR. PGC‐1α/β□expression increased during postnatal retinal development in mice, coinciding with increased mitochondrial gene expression. Bright light exposure increased ROS, up‐regulated PGC‐1α expression, and following prolonged exposure, caused cell death. Increased PGC‐1α/β expression may regulate the mitochondria burst associated with postnatal PR development. The photo‐oxidative stress induced increase in PGC‐1α levels and increased cell death following PGC‐1α/β knock‐down implies a role for PGC‐1α/β in PR antioxidant response. Funding was from T32‐EY007035‐30 (JI) and Schepens “Start‐up” package (MSG).
MG624, a synthetic small molecule alpha7 receptor antagonist, inhibits growth of human small cell lung cancer
Authors: McNees Christopher A , Brown Kathleen C , Lau Jamie K , Dom Aaron M , Shiflett Brandon , Witte Theodore R , Hardman W Elaine , Luo Haitao , Chen Yi C , Carpenter A Betts , Dasgupta Piyali
Published: June 2021

Small cell lung cancer (SCLC) is characterized by early dissemination, aggressive clinical course and low survival rates. Smoking is correlated to 90% of all reported SCLC cases, suggesting that tobacco components like nicotine contribute to the pathophysiology of this disease. Nicotine promotes the proliferation of human lung cancer cells via the α7‐nicotinic acetylcholine receptors (α7‐nAChRs). Therefore, we hypothesized that α7‐nAChR antagonists should be useful in attenuating the growth of human SCLCs. We observed that the small molecule α7‐nAChR antagonist MG624 induced robust apoptosis in human SCLC cells as measured by TUNEL and caspase‐3 cleavage assay. Furthermore, the administration of MG624 suppressed nicotine‐induced growth of H69 human SCLC xenografts in athymic mice models. Immunohistochemical staining of the H69 tumor sections isolated from MG624‐treated from athymic mice show the presence of apoptotic bodies. Our data suggest that MG624 may have potential applications for the treatment of human SCLCs.
Differential contribution of pannexin‐1 channels to agonist and neurogenic constriction of mesenteric arteries and veins from normotensive and DOCA‐salt hypertensive rats
Authors: Hernandez Jessica , Xu Hui , Sangsiri Sutheera , Galligan James
Published: June 2021

Norepinephrine (NE) and ATP are constrictor transmitters released from perivascular sympathetic nerves. ATP efflux through smooth muscle pannexin‐1 channels contributes to á1 adrenergic receptor (α1‐AR) mediated arterial constriction. We tested the hypotheses that pannexin‐1 contributes to: 1) α1‐AR mediated constriction of mesenteric veins (MV); 2) neurogenic constriction of mesenteric arteries (MA) and MV; 3) pannexin‐1 mechanisms are impaired in DOCA‐salt hypertension in rats. We used MA and MV in vitro. Drugs were added to organ bath solutions. Constrictions were measured using video microscopy. Perivascular nerves were activated by focal electrical stimulation. Western blot was used to measure pannexin‐1 protein. Phenylephrine (PE) concentration‐response curves (CRCs) were similar in MA and MV from sham and DOCA‐salt rats. PE‐CRCs were right‐shifted to a similar extent by mefloquine (1 μM, pannexin‐1 blocker) in MA but not MV from sham and DOCA‐salt rats. Mefloquine did not alter neurogenic constrictions in MA or MV. Pannexin‐1 protein was expressed in MA and MV. These data indicate that pannexin‐1 mechanisms contribute to agonist but not neurogenic constriction of MA in normotensive and hypertensive rats. This mechanism does not contribute to adrenergic constriction of MV. Nerve released and exogenous NE may access different constrictor mechanisms in MA. (Supported by P01HL070687)
Signaling pathways in control of gastric acid secretion and food‐stomach‐bone axis revealed by gene expression profiling in the stomach of genetically targeted mice deficient in CCK1 receptor and gastrin/CCK2 receptor
Authors: Chen Duan , Zhao Chun‐Mei
Published: June 2021

Stomach plays important roles in the regulations of digestion, food intake, and mineral homeostasis, which involve CCK1 and gastrin/CCK2 receptors. The aim of this study was to reveal signaling pathways for drug development. Genome‐wide gene expression profiling was performed in the stomachs of wild‐type (WT) and CCK1 and/or CCK2 receptor knockout (KO) mice in response to food intake. The results showed that the KEGG “gastric acid secretion pathway” was neither altered in CCK1 receptor KO, CCK2 receptor KO nor in CCK1+2 receptor double KO mice, which was in line with normal ultrastructural appearance of the parietal cells in all the three mutant strains. A novel “ECL cell pathway” was found and it was inhibited in CCK2 receptor KO mice, but not in CCK1 receptor KO nor CCK1+2 receptor double KO mice. The typical WT ECL cells remained in CCK1 receptor KO mice, disappeared in CCK2 receptor KO mice, and re‐appeared in CCK1+2 receptor KO mice. The ECL cells contain pthlh gene‐related peptide gastrocalcin, a PTH‐like hormone, which was up‐regulated by food intake in WT mice but downregulated in both CCK2 receptor KO and CCK1+2 receptor double KO mice compared with WT mice. In addition, immune signaling pathways, TFF2, BMP, vitamin D synthesis and A‐like cell ghrelin were found to be altered. Perturbation of these signaling pathways might lead to the development of osteoporosis, which is a phenotype of CCK2 receptor KO mice. In conclusion, the revealed signaling pathways represent new targets for the control of acid secretion and for the bone metabolism and mineral homeostasis.
Melatonin Accelerates the Re‐entrainment Rate of Multiple Spontaneous Homecage Behavioral Rhythms in the C3H/HeN Mice
Authors: Adamah‐Biassi Ekue B , Stepien Iwona , Hudson Randall L , Dubocovich Margarita L
Published: June 2021

Activation of MT1 receptors by melatonin (MLT) accelerates the re‐entrainment of circadian rhythms of wheel running activity after an abrupt advance of the dark cycle (Dubocovich et al., 2005). Here, we investigated the effects of melatonin on the re‐entrainment rate of multiple spontaneous homecage behaviors after a 6hr advance of the dark onset in C3H/HeN mice. The 15 behaviors assessed include activity (i.e. comedown, jump, hang, walk), exploration (i.e. dig, groom, rearup, sniff, stretch), ingestion (i.e. drink, eat) and resting (i.e. awake, remainlow, rest, twitch). Mice (n=8 per group) were treated for three consecutive days with either vehicle (VEH) (3% ethanol in saline) or MLT (3 mg/kg in VEH, s.c.) at the new dark onset. MLT significantly decreased the number of days (accelerate) necessary for re‐entrainment of the spontaneous behaviors including activity (e.g. Walk: VEH, 8.3 ± 0.3d & MLT, 6.2 ± 0.2d, p<0.001), exploration (e.g. Groom: VEH, 8.8 ± 0.7d & MLT, 5.80 ± 0.2d, p<0.01), ingestion (e.g. Eat: VEH, 9.0 ± 0.4d & MLT, 6.6 ± 0.4d, p<0.005) and resting (e.g. RemainLow: VEH, 9.167 ± 0.7d & MLT, 6.8 ± 0.5d, p<0.05). We concluded that MLT acting at MT1 melatonin receptors accelerates the re‐entrainment rate of spontaneous homecage behavioral rhythms. We suggest that MLT or MLT agonists could be useful in the treatment of circadian related disorders including jet lag, circadian sleep and mood disorders.
Effect of AXOS on fecal water cytotoxicity and genotoxicity: a randomized, double‐blind, placebo‐controlled, cross‐over study
Authors: Windey Karen , De Preter Vicky , Broekaert Willem , Herman Jean , Louat Thierry , Verbeke Kristin
Published: June 2021

This study evaluated the effect of wheat bran derived arabinoxylan‐oligosaccharides (AXOS) on fecal water (FW) cytotoxicity and genotoxicity in healthy subjects.

Twenty healthy subjects performed a double‐blind, cross‐over RCT in which they ingested AXOS (10g/d) or placebo (maltodextrine, 10g/d) for 3 weeks. The intervention periods were separated by a 3‐week wash‐out period. At the end of the run‐in, intervention and wash‐out periods the subjects collected feces for 72h. Metabolite profiles were analyzed in fecal samples using GC‐MS. FW cytotoxicity was assessed using the WST‐1 assay and FW genotoxicity using the Comet Assay. Metabolite profiles were correlated to cytotoxicity and genotoxicity using cluster analysis.

AXOS did not differentially affect FW cytotoxicity and genotoxicity as compared to placebo. Cluster analysis of metabolite profiles in fecal samples according to both cytotoxicity and genotoxicity revealed a separation between the high toxicity samples and the low toxicity samples. The separation according to cytotoxicity was mainly due to the presence of alcohols and acids in the high toxicity samples, while the separation according to genotoxicity was mainly due to the presence of aldehydes and branched chain fatty acids in the very genotoxic samples.

Presence of specific fermentation metabolites was associated with FW cytotoxicity and genotoxicity.

Support: Fund for Scientific Research‐Flanders, Belgium (FWO project G.0674.10)
Prescription analysis for patients with upper respiratory tract infections at tertiary referral center in Anand
Authors: Patel Kartik J , Leuva Alpa , Rangoonwala Arohi
Published: June 2021

It is a cross sectional study conducted at outpatient department (OPD) in Shree Krishna Hospital, Anand, Gujarat during the month of September to October, 2012. Patients, who have temperature greater than or equal to 99°F analyzed by the physician in Medicine OPD.

A total of 451 medicines were prescribed to 101 patients during the 2 months study period. The mean number of medicines per prescription was found to be 4.46. Oral route was the most preferred mode of administration. Monotherapy therapy (95.50%) was more prevalent than combination therapy (4.50%). An overwhelming tendency for prescribing medicines by brand names (58%) was observed by the physicians. The most frequently prescribed class of medicines were antipyretics>;antihistaminic>;anti‐ulcer >;antimicrobials >; gargles >; expectorants. Non traditional methods of treatment such as warm saline gargles and steam inhalation was profoundly practiced.

There is a considerable scope of improvement in the existing prescribing practice, especially prescribing by generic names, needs to be encouraged and a hospital formulary has to be upgraded accordingly. The number of medicines to be included per prescription should be judged and polypharmacy ought to be curbed. Usage of medicines also needs to be rationalized as over usage may lead to the drug interactions and noncompliance.
Human pharmacokinetics of xanthohumol, a flavonoid from hops with anti‐diabetic activity
Authors: Legette LeeCole , Reed Ralph , Miranda Cristobal , Karnpracha Chanida , Christensen J. Mark , Stevens J. Fred
Published: June 2021

Current findings suggest flavonoids might aid in prevention and/or mitigation of cardiovascular disease and type II diabetes. Specifically, xanthohumol (XN), a prenylflavonoid from hops, has recently been shown to improve glucose and lipid homeostasis in obese rodents. However, there is limited data on XN metabolism in humans. A study was conducted in healthy men (n=24) and women (n=24) to determine basic aspects of XN pharmacokinetics (PK). Subjects were randomized on age and gender and given one of the following oral doses: 20, 60, or 180 mg XN. Blood was collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, and 120 h. Plasma samples were analyzed for XN and its metabolites: isoxanthohumol (IX), 8‐prenylnaringenin (8PN) and 6‐prenylnaringenin (6PN) using LC‐MS/MS. PK parameters were estimated by fitting a non‐compartmental model to the experimental results. XN and IX were the dominant circulating metabolites among all subjects. Levels of 8PN were very low in some subjects (n=5) and not detectable in others. Levels of 6PN were not detectable in all subjects. The Cmax was 41±30 μg/L for the 20 mg dose, 67±40 μg/L for the 60 mg dose, and 133±97μg/L for the 180 mg dose. The AUC0→∞was 84±68 h*μg/L, 286±155 h*μg/L, and 809±384 h*μg/L for the 20, 60, and 180 mg dose, respectively. This work was supported by National Institutes of Health (R21AT005294).
Contrasting pharmacodynamic requirements of disease models revealed through characterization of a novel and selective M1 agonist
Authors: Wood Michael , Martino Giovanni , Coupal Martin , Lindberg Mattias , Schroeder Patricia , Santhakumar V , Valiquette Manon , Sandin Johan , Widzowski Daniel , Laird Jennifer
Published: June 2021

A new class of selective M1 muscarinic allosteric agonists has emerged. Reported here, is the in vitro and in vivo characterization of a novel M1 agonist, PPBI, a new member of that family and the clear demonstration that the biological effects of PPBI are mediated through M1. PPBI reverses d‐amphetamine locomotor activity, but fails to do so in transgenic mice that do not express M1. At much lower doses, PPBI reverses a natural deficit in a rat cognition model, occurring at an exposure level which is also shown to activate cortical circuitry as measured by phMRI. Most importantly, PPBI is analgesic in a variety of rat and mouse models and the analgesic effect of PPBI is reversed by an M1‐preferring antagonist and an M1‐selective toxin. Finally, the pharmacokinetic/pharmacodynamic measures of this highly characterized tool are compared across multiple endpoints and it is concluded that models of psychosis and pain require greater M1 receptor activation by PPBI than that required in the cognition model.
Chronic Treatment with NaF Promotes Dyslipidemia in Rats
Authors: Sumida Doris Hissako , Garbin Cléa Adas Saliba , Colombo Natália Helena , Astolphi Rafael Dias , Chiba Fernando Yamamoto
Published: June 2021

The present study aimed to evaluate the chronic effect of NaF on: 1) inhibitory pathway of insulin signal transduction in liver (L) and muscle (M); 2) plasma concentration (PC) of triglycerides (TGL); 3) total cholesterol (TC); 3) high‐density lipoprotein cholesterol (HDL‐C); 4) low‐density lipoprotein cholesterol (LDL‐C); 5) very low‐density lipoprotein cholesterol (VLDL‐C). Seven‐week‐old castrated male Wistar rats were randomly divided into two groups: 1) control group (CN); 2) fluoride group (FN), which was treated with NaF in drinking water and F in food pellets (4.0 mgF/kg bw/day). After 42 days, PC of TGL, TC, HDL‐C, LDL‐C and VLDL‐C quantification analysis, and insulin receptor substrate‐1 (IRS‐1) serine phosphorylation status tests in L and M were performed by Western Blotting method. The FN group showed a significant increase (p<0.05) in PC of TGL (CN: 30.7 + 3.6 vs FN: 46.9 + 2.7), TC (CN: 76.1 + 2.1 vs FN: 87.0 + 4.2), and VLDL‐C (CN: 6.1 + 0.7 vs FN: 9.4 + 0.5), in comparison with the CN group. However, the treatment with NaF didn't promote alteration in PC of HDL‐C or LDL‐C, or in IRS‐1 serine phosphorylation status in L or in M. The chronic treatment with F promoted: 1) increase in PC of TGL, TC, and VLDL‐C; 2) no alteration in PC of HDL‐C or LDL‐C; 3) no alteration in inhibitory pathway of insulin signal in L or in M. Financial support: FAPESP (2010/10664–5).
Effect of Milk Consumption and the Glycemic Response on Healthy College Aged Subjects
Authors: Fodstad Terra M. , Ackermann Kristin C. , Wilson Ted
Published: June 2021

Evening dietary habits may affect endocrine activity and glycemic response the following morning. This may influence the high fasting glucose levels often observed in type 2 diabetics (Dawn Effect). This study determined the effect of evening milk consumption on morning glycemic response. Healthy subjects (19 ± 1 yr; BMI 23 ± 1) were randomized into groups that consumed either 355 mL of 2% cow's milk (n=43; 183 Cal) or 355 mL water (control; n=42) nine hours prior to an oral glucose tolerance test (OGTT=50g/255 ml). Following an overnight fast from all foods/beverages except water and a 15‐minute acclimation period after lab arrival, baseline blood glucose was measured (0 min). Blood glucose was re‐assessed 30, 60, 120 minutes post‐OGTT. Blood glucose in evening milk consumers at 0, 30, 60, and 120 min was 84.6 ± 1.4, 136.8 ± 3.7, 138.1 ± 4.0, and 103.8 ± 2.8 mg/dL, respectively. Control blood glucose was 82.4 ± 1.5, 130.8 ± 3.3, 130.7 ± 4.2, and 105.0 ± 3.0 mg/dL, respectively. Blood glucose AUC for milk‐ and water‐ pre‐OGTT was 13710.8 ± 316.6 and 14089.7 ± 313.0. Glycemic responses displayed no significant differences between milk and control treatments. Evening milk consumption does not appear to alter morning glycemic response in healthy, non‐diabetic subjects. However, influence of evening milk on AM glycemic status remains to be tested in type 2 diabetics.
Renal autoregulation dynamics monitored across the renal surface
Authors: Scully Christopher , Mitrou Nicholas , Braam Branko , Cupples William , Chon Ki
Published: June 2021

We extended dynamic analysis of renal autoregulation across a spatial surface using laser speckle perfusion imaging (LSPI) of an area of the renal cortex. Anaesthetized (isoflurane) male Long‐Evans rats (N=8) had left kidneys exposed and an occluder placed around the renal artery. Monitoring included LSPI of the renal cortex, renal blood flow (RBF) and blood pressure (BP) under BP forcing during NOS inhibition by intrarenal infusion of L‐NAME (10 μg/min × 20 min then 3 μg/min i.r.a.) followed by rho‐kinase inhibition by intrarenal infusion of Y‐27632 (to achieve 10 μmol/L in RBF). Transfer function analysis was performed with either RBF or LSPI as output signals and BP as the input. Using both pairs of transfer functions, we found a significant increase in coherence (0.05 – 0.08 Hz) and a significant decrease in gain slope (0.05 – 0.15 Hz) and phase (0.1 Hz) from L‐NAME to Y‐27632. These results indicate LSPI detected decreased tubuloglomerular feedback and myogenic activity during rho‐kinase inhibition. Additionally, using LSPI we were able to identify changes at all locations within the imaging window, and using time‐varying analysis we were able to identify them temporally. We conclude that transfer function analysis of LSPI can be used to monitor renal autoregulation across spatial and temporal dimensions. This work was performed under CIHR Grant MOP‐102694, and CS was supported by an AHA predoctoral fellowship.