bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged exercise upregulates expression of MCT1, MCT2, and MCT4 mRNA in the cerebral cortex of rat brain
Authors: Takimoto Masaki , Takeyama Mirei , Hamada Taku
Published: June 2021

Brain is capable of taking up monocarboxylates as energy substrate. The transport of monocarboxylic acids across cellular membranes is mediated by the H+/monocarboxylate transporters (MCTs). In the brain, three isoforms, MCT1, MCT2, and MCT4 have been identified. However, whether exercise upregulates the expression of MCT1, MCT2, and MCT4 at the mRNA level is unknown. We have examined the effect of a single exercise session on the mRNA expression of the MCT1, MCT2 and MCT4 in the cerebral cortex of rat brain. Cortex samples were obtained immediately and 5, 10, 18 and 24 h after 2 h of treadmill exercise (20 m/min, 8% grade). The expression of all MCTs mRNA did not change immediately after 2 h exercise bout. However, the expression of MCT1 and MCT2 mRNA significantly increased to control levels at 10 h after exercise, and, this increases maintained until 18 h after exercise. In contrast, MCT4 mRNA expression significantly increased at 18 h after exercise. These results suggest that a single bout of prolonged endurance exercise can transiently increase expression of MCT1, MCT2 and MCT4 mRNA in the brain as in the muscle of rat.
Chronic Intermittent Hypoxia Induces Airflow Limitation in a Rodent Model of Allergen‐Induced Lower Airway Inflammation
Authors: Broytman Oleg , Braun Rudolf K , Pegelow David F , Hsu Pei‐Ning , Mei Linda Song , Koya Ajay K , Bates Melissa L , Morgan Barbara J , Eldridge Marlowe , Sorkness Ronald L , Teodorescu Mihaela
Published: June 2021

Rationale

Obstructive sleep apnea (OSA) aggravates asthma, but the mechanisms are unclear. Chronic intermittent hypoxia (CIH) is one hallmark feature of OSA. We tested the effects of CIH on lower airways in an ovalbumin (OVA) rodent model.

Methods

Four groups (n=5–6/group) of Brown‐Norway rats underwent CIH (10% FiO2, 30 episodes/h, 10h/day for 30 days) vs. normoxia (NORM) and OVA vs. vehicle (VEH). Lung physiology and bronchoalveolar lavage (BAL) WBC differentials were compared between groups, 2 days after last challenge.

Results

On lung physiology: 1) CIH reduced the Forced Expiratory Volume in 0.1 second (FEV0.1) to Forced Vital Capacity (FVC) ratio (FEV0.1/FVC) (p=0.008) and peak expiratory flow (p=0.03); OVA did not affect these measures. 2) FVC was increased by CIH (p=0.0009), but reduced by OVA (p <0.0001). In the BAL: 1) CIH did not change total cell counts (p = 0.25); 2) CIH induced a 2.3‐fold reduction in % eosinophils (p = 0.001); 3) In OVA‐challenged rats, CIH increased neutrophil fraction among infiltrating granulocytes (p = 0.03, Figure).

Conclusions

CIH induces airflow limitation even in the absence of inhaled allergen. CIH induces a more neutrophil‐predominant response to allergen. These findings highlight the potential of OSA to aggravate lung dysfunction in patients with pre‐existent airway inflammation.

Supported by UW‐Madison Department of Medicine Pilot Funding.
Eccentric exercise‐induced inflammatory response is augmented in type II diabetic skeletal muscle
Authors: SUDO MIZUKI , Eshima Hiroaki , Ando Soichi , Kano Yutaka , Tanaka Hiroaki , Higaki Yasuki
Published: June 2021

Type II diabetes mellitus induces peripheral circulatory failure, neuropathy, and diabetic myoatrophy. Recent studies have shown that resistance exercise seems to be effective for maintaining muscle mass in type II diabetic patients. On the other hand, eccentric exercise (ECC) has the potential to induce severe muscle inflammation and damage, which may lead to physical inactivity. However, it is unclear whether inflammation‐regeneration response occurs in type II diabetic skeletal muscle in a similar manner as the normal one. The aim of the present study was to examine inflammation‐regeneration response after ECC in type II diabetic skeletal muscle. In anesthetized Wistar (NM) and Goto‐Kakizaki (T2D) rats, the tibialis anterior muscles were subjected to 40 times‐repeated ECC, which was evoked by surface electric stimulation with mechanical muscle stretch. The inflammatory response was examined at 1, 3, 7 and 14 days after ECC. The regenerated fibers with central nucleus were detected at 7 and 14 days after ECC. The average peak torque during ECC was significantly lower in the T2D (5.9 ± 3.7 mNm) than in the NM (11.1 ± 5.2 mNm). The inflammatory responses were significantly increased in the T2D (day 1: 14.8 ± 4.8%, day 3: 35.6 ± 7.0%) compared with the NM (day 1: 6.2 ± 2.5%,day 3: 29.6 ± 12.3%, p < 0.05, respectively). Furthermore, the regeneration fibers with central nuclei were observed at day 7 and 14 in the NM. However, we detected the regeneration fibers with central nuclei only at day 14 in the T2D. In conclusion, inflammatory response induced by mechanical stress is augmented in type II diabetic skeletal muscle as compared with normal one. This study was supported in part by a Grant‐in‐Aid for young Scientists (B).
Cardioprotection by Poloxamer 188 is Mediated by Nitric Oxide Synthase
Authors: Salzman Michele , Cheng Qunli , Matsuura Timothy , Yannopoulos Demetris , Riess Matthias
Published: June 2021

INTRODUCTION

The tri‐block copolymer Poloxamer 188 (P188) attenuates myocardial ischemia/reperfusion (I/R) injury in porcine models of acute regional myocardial infarction and cardiac arrest. We tested its cardioprotective effects in a rat isolated heart model.

METHODS:

After 35 minutes baseline perfusion, Langendorff‐prepared hearts from Brown Norway rats were subjected to 30 minutes global no‐flow ischemia. On reperfusion, hearts were randomized to receive vehicle, P188, the nitric oxide synthase inhibitor Nω‐Nitro‐L‐arginine methyl ester (L‐NAME), or P188+L‐NAME for 120 minutes. Left ventricular pressure (LVP), its derivatives, and coronary flow (CF) before, during and after I/R and infarct size (IS) were measured.

RESULTS:

Functional improvement and IS reduction by P188 were abolished by L‐NAME.

Table: Coronary & myocardial function and tissue viability after I/R

Vehicle
L‐NAME
P188
P188+L‐NAME

SysLVP
65.4±1.9
62.2±2.6
59.0±1.1
62.9±5.5

DiaLVP
32.3±4.1
33.4±3.1
19.3±2.2*†‡
29.8±2.5

DevLVP
30.7±2.1
34.5±4.3
45.4±2.2*†‡
30.4±6.4

dPdtmax
38.8±3.7
39.9±5.5
54.5±2.4*†‡
35.5±7.8

CF
64.6±5.3
77.7±3.3*†
73.0±2.5*†
64.0±4.3

IS
39.1±4.0
32.4±2.2
18.5±1.4*†‡
31.1±3.4

[Sys: systolic; Dia: diastolic; Dev: developed; all data are % baseline at 120 minutes reperfusion (except for DiaLVP in mmHg and IS in %); statistics: ANOVA and SNK, alpha .05, *vs Vehicle, †vs P188+L‐NAME, ‡vs L‐NAME]

DISCUSSION

Maintaining cell membrane integrity is critical for preservation of cellular and subcellular functions and to prevent cell death. P188 offers an efficient way to attenuate I/R injury when given upon reperfusion. Direct or indirect release of nitric oxide appears to play a decisive role.

Supported by Department of Veterans Affairs (CARA‐026‐10F), NIH and institutional funds.
Circulating Cells Contribute to Cardiac Regeneration in The Axolotl
Authors: Lauridsen Henrik , Pedersen Michael
Published: June 2021

Intro

Myocardial infarction (MI) is a leading cause of death globally. Traditional mammalian biomedical animal models all respond relatively similar to MI as humans. On the other hand salamanders, such as the axolotl, have the capacity to fully regenerate cardiac structures. Cardiac regeneration in basic animal models (i.e. salamander and zebrafish) has previously been described to rely primarily on local cardiomyocytes. To test for contribution of any circulating cells we developed a heterotopic heart transplantation (HHT) model in the axolotl in which any contributing cells originating outside the heart express GFP.

M&M: Donor hearts were excised from non GFP (GFP÷) axolotls and transplanted to the abdominal cavity of axolotls globally expressing GFP (GFP+). Inflow and outflow vessels of the transplanted heart were anastomosed to the abdominal vein. Proper conjunction of the heterotopic heart to the circulation was tested by echocardiography. MI was induced on the heterotopic heart by cryoinjury. Hearts were harvested at 3, 7, 14, 30 and 60 days post infarction, cryosectioned and thoroughly examined with confocal microscopy for GFP+ cells in the regenerate.

Results & Discussion

GFP+ cells were observed to inhabit the regenerate as elongated cells lining GFP÷ cardiomyocytes. No GFP+ cells expressed cardiomyocyte markers. The HHT model dictates that GFP+ cells in the regenerate must originate from circulating cells in the host animal, however the exact phenotype of the cells remains to be determined. These results indicate that the axolotl apply a resource of circulating stem cells and cardiac regeneration is not merely a local phenomenon.
SPARC Facilitates Inflammation in the Aging Heart and Suppresses Macrophage M2 Polarization
Authors: Toba Hiroe , de Castro Brás Lisandra , Baicu Catalin , Zile Michael , Lindsey Merry , Bradshaw Amy
Published: June 2021

Cardiac aging is characterized by inflammation and fibrosis. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein known to play a role in extracellular matrix assembly and inflammation. SPARC levels increase with age in the left ventricle. We hypothesized that SPARC might facilitate age‐related cardiac inflammation. We studied 6 groups of mice (n=7‐10/group): young (3‐5 month old), middle‐aged (10‐12 m.o.) and old (18‐29 m.o.) C57BL/6J wild type (WT) and SPARC‐null (Null). Left ventricular wall thickness and myocyte size increased in an age‐related manner in WT but not Null (both p<0.05). Expression of pro‐inflammatory markers (Ccl5, Cx3cl1, Ccr2, Cxcr3) and Adamts1were increased in middle‐aged and old WT and old Null compared to respective young (all p<0.05). Versican is a substrate of Adamts1 that when cleaved promotes cell infiltration, and it decreased with age only in WT (p<0.05). Expression of α2 integrin and macrophage infiltration were increased with age in WT, but not Null. Isolated peritoneal macrophages from young and old WT showed similar levels of pro‐inflammatory M1 markers (Ccl5, Ccl3, Tnfα); however, peritoneal macrophages from old WT mice displayed reduced anti‐inflammatory M2 markers (Arg1, Mrc1). SPARC treatment of young macrophages decreased M2 markers to levels observed in old mice. In summary, SPARC mediates age‐related cardiac inflammation by suppressing M2 macrophage polarization.
Intake of 2 Eggs or Oatmeal for Breakfast does not Increase Biomarkers for Heart Disease while Eggs Improve Liver Enzymes and Raise HDL Cholesterol in Young Healthy Individuals
Authors: Missimer Amanda , DiMarco Diana , Vergara‐Jimenez Marcela , Murillo Gabriela , Creighton Brent , Andersen Catherine , Fernandez Maria‐Luz
Published: June 2021

We hypothesized that consuming 2 eggs per day for breakfast would not increase biomarkers of heart disease in a young healthy population. We recruited 26 women and 24 men aged 18‐30 y old with healthy plasma lipid profiles and plasma glucose, a BMI of 23.3 ± 3.2 kg/m2 in addition to normal systolic and diastolic blood pressure. Participants were randomly allocated to consume a breakfast of either 2 eggs per day or a packet of oatmeal per day for 4 weeks. Following a 3 week washout participants were allocated to the alternate dietary treatment. Blood was collected at the end of each period to assess plasma lipid profiles, plasma glucose, liver enzymes and C‐reactive protein (CRP). In spite of the additional 460 mg of dietary cholesterol per day during the egg period, we observed no changes in total cholesterol, LDL cholesterol, LDL/HDL ratio, plasma triglycerides, systolic or diastolic blood pressure, body weight, plasma glucose or CRP when compared to the oatmeal breakfast. However, liver enzymes alanine amino transferase and aspartate amino transferase were lower (p < 0.05) during the egg period. Further, we observed that HDL cholesterol consistently increased after the egg period (p < 0.05) while HDL cholesterol decreased following the oatmeal period. These results indicate that for healthy young men and women consumption of two eggs per day appears to be a healthy breakfast in that eggs did not impact plasma lipids or glucose negatively but in contrast were beneficial for liver enzymes and HDL cholesterol.
Dose to the Mother Method: Milk Intake and Vitamin A Transfer to the Lactating Infant of Mexican Mothers, Using Stable Isotopes
Authors: Lopez Teros Veronica , Limón‐Miró Ana , Villegas‐Valle Rosa , Antunez‐Roman Lesley , Tortoledo‐Ortiz Orlando , Astiazaran‐Garcia Humberto , Valencia Mauro
Published: June 2021

Objective

To assess the breast milk intake and transfer of vitamin A (VA) from the mother to the breastfed child in lactating Mexican women from rural and urban areas.

Methods

Milk intake was assessed with the dose to the mother method, briefly deuterated water is administered to the mother and the appearance of the isotope is measured in the breastfed child's and mother's saliva; deuterium enrichment (stable isotope) is analyzed by FTIR. Breast milk retinol (BMR) concentration was determined by HPLC and the cutoff to define VA deficiency was 1.05 µmol/L.

Results

Subjects were 27 and 32 women‐child pairs from urban and rural areas of northwest Mexico, respectively. Mean breast milk intake 727.35 ± 224 mL and it was significantly lower in children from the rural area (P=0.04). Mean BMR concentration was 1.11 μmol/L and 53% of women had VAD. BMR concentration was lower for the rural area (P=0.038). By combining both determinations (DTM and BMR), results showed that breastfed children from the rural and urban area reached only 47% and 64% of their VA recommended dietary intake (P=0.051), respectively.

Conclusion

VAD is still a public health problem in Mexico and requires new approaches to fight it effectively.

Study supported by Universidad de Sonora.
The Safety of Green Tea Extract Supplementation in Postmenopausal Women at Risk for Breast Cancer: Results of the Minnesota Green Tea Trial
Authors: Dostal Allison , Samavat Hamed , Bedell Sarah , Torkelson Carolyn , Wang Renwei , Yuan Jian Min , Kurzer Mindy
Published: June 2021

The objective of this study was to monitor adverse events (AEs) in healthy postmenopausal women randomized to receive either green tea extract (GTE) containing 840 mg (‐)‐epigallocatechin‐3‐gallate (EGCG)/day (n=538) or placebo (n=537) for one year. Data on AEs was obtained by participant self‐report and hepatic panel assessment. AEs were recorded and graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v.4.03. 407 participants in the GTE group reported 1141 AEs; 391 participants in the placebo group reported 1031 AEs. Infections and infestations were the most common AEs (139 GTE vs. 145 placebo participants, p = 0.67) followed by gastrointestinal (GI) disorders (137 GTE vs. 123 placebo participants, p = 0.33). Nausea incidence was higher in GTE participants (55 (10.2%) vs. 26 (4.8%), p < 0.001). Diarrhea incidence was lower in the GTE group (24 (4.5%) vs. 43 (8%) participants, p = 0.02). More participants taking GTE reported dermatologic AEs (18 (3.3%) vs. 8 (1.5%), p = 0.05). Alanine aminotransferase (ALT) elevations were seen in 36 (6.7%) GTE vs. 4 (0.7%) placebo participants (p < 0.001). Twenty‐six serious adverse events (CTCAE grades 3‐5) occurred in 12 GTE vs. 8 placebo participants (p = 0.37). GTE containing 840 mg EGCG/day was associated with mainly mild, transient AEs and was well tolerated by most participants, though an association with GI and hepatic abnormalities was confirmed. This project was supported by the NIH/NCI.
Use of a Systematic 3‐Pronged Evaluation to Measure, Monitor, and Test Fidelity of the 5‐State iCook 4‐H Program
Authors: Mathews Douglas , Franzen‐Castle Lisa , Kattelmann Kendra , Colby Sarah , Olfert Melissa , White Adrienne
Published: June 2021

A 3‐pronged approach to evaluation was utilized to measure change (Program Evaluation [PE]), monitor feedback (Process Evaluation), and test Fidelity of Implementation (FOI). Family dyads (youth aged 9‐10 and adult food preparer) participated in an intervention promoting the focal areas of culinary skills, family meals, physical activity, and goal setting. The online PE tool (questions: youth=34; adult=15) was developed to measure change in focal areas and completed at pre and post‐test. Following sessions, dyads and leaders completed online process surveys (questions: youth=13; adult=21; leader=11) giving feedback on sessions and at home activities. At each session FOI (32 questions) was measured. Treatment youth increased PE scores (P<0.05). Treatment adults reported increases in family meals (P<0.05) and youth involvement in meals (P<0.05). Dyads reported more cooking, eating and playing together as the program progressed. Adults reported child's culinary skills were enhanced at each session. FOI evaluators reported session objectives were met 91% and focal areas were covered 90% of time. Dyads, leaders, and evaluators reported iCook was valuable in promoting positive learning. Using a systematic approach to design and implement evaluation tools resulted in evidence‐based outcomes to measure program impact.
Are Food Processing and Convenience Linked with the Nutritional Quality of Foods Purchased by US Households?
Authors: Poti Jennifer , Mendez Michelle , Ng Shu Wen , Popkin Barry
Published: June 2021

Processed foods' contribution to US diet and nutrient content have not been accurately assessed. Our objective was to develop a multi‐dimensional classification system for food processing, determine nationally representative trends in processed and convenience food purchasing, and compare nutrient profiles of less vs more processed foods. We analyzed food and beverage purchases of 157,142 households from the 2000‐2012 Homescan longitudinal panel. We classified each of 1.2 million items by level of processing and separately by convenience using barcode‐specific details and ingredients. We used quantile and logistic regression to compare nutrient content and adherence to nutrient recommendations.

Over 3/4 of calories purchased by US households came from processed (15.9%) and ultra‐processed (61.0%) foods and beverages in 2012 (939 kcal/d per capita). By convenience, ready‐to‐eat (68.1%) and ready‐to‐heat (15.2%) products supplied the majority of calories, with a significant upward trend in ready‐to‐heat foods between 2000 and 2012. The adjusted proportion of household‐level food purchases exceeding recommended maximums for saturated fat, sugar, and sodium densities simultaneously was significantly higher for ultra‐processed (60.4%) and ready‐to‐eat (27.1%) food purchases compared to purchases of less‐processed foods (5.6%) or foods requiring cooking (4.9%). The unshifting dominance of ultra‐processed and ready‐to‐eat foods as major calorie contributors to US diet and their poor nutrient profile support the need to incentivize food manufacturers to improve the nutritional quality of their products.

Funding source: Robert Wood Johnson Foundation (67506, 68793, 70017, 71837), NIH (R01DK098072), CPC 5 R24 HD050924
Dietary Intake and Infertility: a Review
Authors: Mendoza‐López María del Mar , Reyes‐Martin Karen Itzel , Gutiérrez‐Gómez Yareni Yunuen
Published: June 2021

Infertility is a condition that affects approximately 15% of couples on reproductive age worldwide. Among the many factors associated with it, are the dietary patterns and consumption of specific foods and nutrients. The aim of this study is to evaluate the current evidence regarding the influence of diet on infertility. Electronic search of biomedical databases as PUBMED was conducted. The reviewed evidence shows that dietary patterns attached to the fundamental principles of proper nutrition promote fertility. Alcohol, caffeine, sodas and other soft drinks increase the risk of infertility. Alcohol abuse affects sperm morphology and production and could promote hormonal fluctuations among women; caffeine is associated with an increase in the time to pregnancy; and soft drinks with ovulatory disorders. Carbohydrates, proteins and lipids impact on fertility according to their quantity, proportion and type in the case of fat, ultimately affecting women's ovulation and sperm morphology and concentration. It also has been shown that antioxidants significantly increase fertility it by a suggested reduction in oxidative stress damage. In conclusion, growing research and interest in this field has made it evident that lifestyle factors and nutrition have an impact on infertility. The mechanisms by which certain foods or nutrients affect fertility are still unknown and require further investigation.
BV‐2 Microglial Cells Used in a Model of Neuroinflammation
Authors: Ackerman Kirsten , Fiddler Joanna , Soh Traces , Clarke Stephen
Published: June 2021

Microglial cells are the resident macrophages of the central nervous system (CNS). These cells are a primary form of active immune defense in the CNS. In neurodegenerative disorders such as Alzheimer's and Parkinson's disease, microglia are chronically activated and promote the release of pro‐inflammatory cytokines which further disrupt normal CNS activity. There is considerable interest in examining the extent to which bioactive food components can mitigate the effects of inflammation by decreasing oxidative stress and/or by decreasing pro‐inflammatory gene expression.

In this study, BV‐2 cells were treated with Lipopolysaccharide (LPS) for 4 or 24 hours and total RNA was isolated from the cells for gene expression analyses. A control group was also present. The LPS‐treated BV‐2 cells did not show the robust induction of IL‐1β and TNFα that was expected at either 4 hours or 24 hours. To determine if other cells would respond to LPS, a previously characterized LPS‐responsive cell line (RAW 264.7) was examined. In RAW 264.7 cells, LPS treatment increased the expression of IL‐1β, iNOS, and TNFα. Since current research on microglial cells suggests a much larger response to LPS, additional experimentation should be done to show consistent results.
Characterization of Small Molecule Gβγ Inhibitors in the Context of Inflammation
Authors: To Jesi , Rangel‐Moreno Javier , Owen Teresa , Anolik Jennifer , Smrcka Alan
Published: June 2021

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with widespread inflammation. A significant contributor to SLE is the excessive recruitment and activation of immune cells to inflamed sites via chemokines. Chemokine receptors are G‐protein coupled receptors, which liberates free Gβγ from the heterotrimeric G‐protein. Gβγ is vital in migration of immune cells. We propose that Gβγ inhibitors could be potential therapeutic candidates for SLE treatment. The NZB/W mice develop lupus similar to human SLE such as elevated autoantibodies and immune complex‐induced nephritis. To characterize the effects of Gβγ inhibition on SLE, three groups NZB/W mice were injected with vehicle, low dose (20 mg/kg), or high dose (35 mg/kg) of the Gβγ inhibitor gallein for 19 weeks. Our results show that mice treated with gallein had lower proteinuria compared to control. Furthermore, Gβγ inhibition markedly reduced infiltration in the kidneys of gallein treated mice. Specifically, the number of T‐cell, B‐cell, and, antibody secreting plasma cells were reduced by Gβγ inhibition. Ellagic acid and F067, like gallein, are small molecule inhibitors of Gβγ that attenuate neutrophil and T‐cell migration. Upon agonist stimulation, neutrophils isolated from gallein treated mice migrate less efficiently compared to control. Furthermore, this effect persists over time after the initial treatment with gallein. Similarly, an in vitro treatment model showed inhibited neutrophil migration upon agonist stimulation, after initial treatment with gallein and F067. In conclusion, our results suggest that inhibition of Gβγ attenuates immune cell migration and have a beneficial effect against lupus nephritis.
Role of Angiotensin II‐associated Mitochondrial Superoxide in Inhibiting Ferrochelatase Activity and Disrupting Heme Biosynthesis Regulation of Coronary Artery Soluble Guanylate Cyclase Expression
Authors: Patel Dhara , Alhawaj Raed , Kelly Melissa , Sun Dong , Wolin Michael
Published: June 2021

Oxidation of the soluble guanylate cyclase (sGC) heme promotes loss of regulation by nitric oxide (NO) and the proteolytic degradation of sGC. Due to the mitochondrial heme generating enzyme ferrochelatase (FECH) having an iron‐sulfur cluster which could potentially be disrupted by superoxide, and Angiotensin II (AngII) promoting increased mitochondrial superoxide and a loss of NO‐stimulated sGC/cGMP‐mediated vasodilation, we hypothesized that AngII may influence the regulation of sGC through a superoxide‐mediated inhibition of the conversion of protoporphyrin IX (PpIX) into heme by FECH.In addition, since we previously reported that 24‐hour organoid culture of bovine arteries with δ‐aminolevulinic acid (ALA) caused an increase in sGC activity by generating PpIX, we investigated if ALA attenuates actions of AngII. Organoid culture of bovine coronary arteries (BCAs) with 0.1 µM AngII for 24‐hours caused increases in mitochondrial (MitoSox/HPLC) and extra‐mitochondrial/cytosolic superoxide (DHE/HPLC), but ALA only reversed the increase in mitochondrial superoxide. AngII also decreased FECH activity, and this was attenuated by ALA or the mitochondrial superoxide scavenger mitoTempol. Treatment of BCAs with AngII also decreased FECH and sGC expression, and ALA prevented these actions of AngII suggesting a role of increased mitochondrial superoxide in regulating the loss of FECH and sGC. These observations suggest that AngII stimulated mitochondrial superoxide generation plays an important role in inhibiting FECH activity and its influence on maintaining the expression of sGC.
N‐acetylcysteine prevents in vivo oxidation of native low‐density lipoprotein
Authors: Cui Yuqi , Narasimhulu Chandrakala , Liu Lingjuan , Zhang Qingbin , Hao Hong , Li Xin , Xiao Yuan , Zhang Jia , Xie Xiaoyun , Liu Patrick , He Guanglong , Cui Lianqun , Parthasarathy Sampath , Liu Zhenguo
Published: June 2021

Objective

Low‐density lipoprotein (LDL) is not atherogenic. Oxidized LDL (ox‐LDL) produces reactive oxidative species (ROS) and is critical to atherosclerosis. N‐acetylcysteine (NAC) has anti‐atherosclerotic effect with largely unknown mechanisms. The present study aimed to determine if NAC could attenuate LDL oxidation in vivo.

Approach and Results

Measurable serum level of human ox‐LDL was detected 30 min after a single dose intravenous injection of human native LDL into male C57BL/6 mice, reached the peak in 3 hours, then started to decline, and became undetectable in 12 hours. NAC treatment significantly reduced serum ox‐LDL level with no detectable serum ox‐LDL 6 hours after injection. No difference in ox‐LDL clearance was observed in NAC‐treated animals. NAC treatment also significantly decreased serum ox‐LDL level in patients with coronary artery disease and hyperlipidemia with no effect on LDL level. Intracellular and extracellular ROS production was significantly increased in the mice treated with native LDL, or ox‐LDL that was completely prevented with NAC treatment.

Conclusion

NAC attenuated native LDL in vivo oxidation and ROS formation from ox‐LDL.

Sources of funding

NIH R01 HL094650
Hyperbaric oxygen preconditioning attenuated high‐altitude pulmonary edema via heat shock protein 70 overexpression
Authors: Lin Hung‐Jung , Chang Ching‐Ping , Tsai Ming‐Che
Published: June 2021

Evidence has indicated that reducing pulmonary injury by HBO2P (hyperbaric oxygen preconditioning) in rats during simulated high‐altitude exposure (HAE). However, underlying mechanisms remains unclear. Rats were randomly divided into four groups: the non‐HBO2P+non‐HAE group, the non‐HBO2P+HAE group, the HBO2P+HAE group, and the HBO2P+HSP‐70 antibodies (Abs)+HAE group. The HBO2P groups were given 100% O2 at 2.0 absolute atmospheres for 1 hour per day for 5 consecutive days. The HAE groups were exposed to simulated HAE (9.7% O2 at 0.47 absolute atmospheres) in a hypobaric chamber for 3 days, HSP‐70 Abs were intravenously injected 24 hours before the HAE experiments. In non‐HBO2P+HAE group, the animals displayed higher scores of alveolar edema, neutrophil infiltration, and hemorrhage, and lower levels of aquaporin (AQP) 1 and AQP 5 proteins and mRNA expression in the lung compared with those of non‐HBO2P+non‐HAE controls. The increased lung injury scores and the decreased levels of both AQP1 and AQP5 proteins and mRNA expression in the lung caused by HAE was significantly reduced by HBO2P+HAE. Furthermore, HSP70 Abs, in addition to reducing lung HSP70 proteins, significantly attenuated the beneficial effects of HBO2P in HAE. Our results suggest that high‐altitude lung edema can be prevented by HSP‐70‐mediated HBO2P in rats.
Effects of Methotrexate on Serum Testosterone Level in Sleep‐deprived Male Wistar Rats
Authors: Akindele Opeyemi , Kunle‐alabi Olufadekemi , Oghenetega Bright , Adeyemi Damilare , Raji Yinusa
Published: June 2021

Sleep deprivation has been reported to cause reductions in testosterone levels but the mechanism(s) still remain unclear. Studies have shown that sleep deprivation increases interleukin 1 beta (IL‐1β), a pro‐inflammatory cytokine.It is also known that increase IL‐1β level causes a reduction in Leydig cell production of testosterone. This study was designed to examined the effects of methotrexate, an IL‐1β blocker, on serum testosterone levels in sleep deprived Wistar rats. Twenty four male Wistar rats were randomly assigned into four groups (n = 6); group one (Control) received 1ml of the vehicle (1% tween 80 solution), group two received 0.5mg/kg body weight of methotrexate (MTX), group three was sleep deprived (SD) and received 1ml of the vehicle and group four (MTX + SD) was sleep deprived and received 0.5mg/kg body weight of methotrexate. Sleep deprivation was induced daily using the modified multiple platform technique for 14 days. Treatments were administered twice weekly by oral gavage. Blood was collected on day 14 and serum was obtained for analyses of testosterone, LH, FSH and corticosterone levels. Testicular IL‐1β level and histology of the testis were also examined. Serum testosterone levels were significantly decreased in SD and MTX+SD groups, while corticosterone levels were increased in SD and MTX+SD. Testicular IL‐1β was increased in SD and MTX+SD groups. Mean testosterone reduction in the methotrexate treated sleep deprived rats (MTX + SD) suggests that increased IL‐1β may not be a cause of testosterone reduction in sleep deprived rats.
Gsk3a is Essential for Sperm Function and Male Fertility
Authors: Bhattacharjee R , Goswami S , Popkie A , Phiel C , Kline D , Vijayaraghavan S
Published: June 2021

The signaling enzyme glycogen synthase kinase 3 exists as two isoforms – GSK3A and GSK3B. GSK3 is part of key signaling pathways in several cells and tissues. We have previously shown that both isoforms of GSK3 are present in sperm and testis. Increase or decrease in sperm motility in vitro resulted in changes in GSK3 phosphorylation. The enzyme was also shown to activate a mammal specific protein phosphatase isoform PP1γ2, a key enzyme essential for sperm function. Here we examined the role of Gsk3a in male fertility using a targeted gene knockout approach. Gsk3 (+/‐) male and female mice are fertile. However, global knockout of Gsk3a results in male infertility, while females are normal. Testis weights and sperm numbers of Gsk3a (‐/‐) mice are comparable to the fertile Gsk3a (+/‐) controls. However sperm motility in Gsk3a (‐/‐) appears to be compromised. Strikingly, forward motility of mutant sperm is altered, characterized by markedly attenuated amplitude of flagellar beat. Sperm ATP levels were lower in Gsk3a (‐/‐) mice compared to wild type animals. PP1γ2 protein levels were unaltered, but its catalytic activity was elevated in KO sperm. Remarkably, capacitation associated changes in tyrosine phosphorylation of proteins are absent or significantly lower in Gsk3a (‐/‐) sperm. Moreover the glycolytic enzyme, hexokinase, which is constitutively tyrosine phosphorylated in WT sperm, is not phosphorylated in Gsk3 (‐/‐) sperm. The GSK3B isoform was present and unaltered in testis and sperm of Gsk3a (‐/‐) mice suggesting that GSK3B is not able to compensate for the loss of GSK3A in testis and sperm. Our studies show that GSK3A, which has a highly conserved glycine rich N‐terminus in mammals, is essential for sperm motility and male fertility.

Supported by NIH grant R15 HD068971
Predictors of Maternal Concern and Accuracy of Maternal Perceptions of Child's Weight in 1st Graders
Authors: Shriver Lenka , Rutledge Julie , Swindle Taren , Harrist Amanda , Hubbs‐Tait Laura , Topham Glade , Page Melanie
Published: June 2021

Mothers influence children's lifestyle habits and maternal concern (MC) about child weight may have negative outcomes (e.g., restriction). The purpose of this study was to identify predictors of MC about child weight in a sample of 431 mothers of 1st graders from 29 schools. The Child Feeding Questionnaire was utilized to assess MC, maternal perception (MP) of child's weight and maternal self‐reported weight status. Children's weight status was determined using direct measurements and the established BMI‐for‐age percentile cut‐offs for 3 categories: 1) normal weight; 2) overweight, or 3) obese. Linear regression was conducted to determine if MC about child weight was predicted by MP of child weight, maternal self‐reported weight status, child weight status and child gender. The regression model was significant (R2 = .33, p < .001). Maternal self‐reported weight status (β = .13), child weight (β = .51) and child gender (β = .11; all ps < .01) were significant predictors of MC but MP of child weight was not (β = ‐.003, p = .94). A secondary analysis further explored why MP of child weight was not related to MC. MP of child weight was assessed using 3 categories (overestimate; match; underestimate). Child weight was misconceived by 27% of mothers (all underestimated). Findings confirmed the hypothesized MC predictors, except for MP of child weight. Because MP of child weight may influence feeding strategies and the child's perceptions of self, further research examining weight‐related concerns and perceptions of mothers in relation to child's body or self‐esteem is warranted.
Effects of Walnut Intervention on Endothelial Function among People with Type 2 Diabetes: A Randomized Trial
Authors: Djousse Luc , Petrone Andrew , Gaziano John
Published: June 2021

Background

Limited data are available on the effects of an intervention with small amount of walnuts on endothelial function in subjects with type 2 diabetes (DM).

Objective

To test the hypothesis that a 12‐week intervention with one ounce (28 g) of walnuts per day improves endothelial function in people with prevalent DM when compared to usual diet.

Methods:

A randomized controlled trial of 26 subjects aged 30+ years with prevalent DM. Participants in the walnut group were provided with a 12‐week supply of small walnut bags, and instructed to consume one bag per day as a snack or with a meal. Participants in the control group were instructed to maintain their regular diet. Endothelial function was measured non‐invasively at baseline and after 12 weeks using endoPAT2000. We used ANOVA for repeated measures to examine the effects of the intervention on reactive hyperemia index (RHI), a measure of endothelial function.

Results:

The mean age at baseline was 64.8 ± 11.6 years, and 61.5% of participants were female. All participants had DM and 15.4% of them also had coronary disease. At baseline, mean ± SE of log‐transformed RHI were 0.64 ± 0.13 in the intervention group and 0.44 ± 0.13 in the control group. At 12 weeks, corresponding values were 0.73 ± 0.07 and 0.63 ± 0.07 suggesting no difference in slope (p =0.12) nor in time‐by‐visit (p=0.58)

image

Conclusions

Our results do not support an improvement of endothelial function with daily intake of one ounce of walnuts during 12 weeks among subjects with DM.
Effect of Maternal Multiple Micronutrients Supplementation on the Apgar Score of Indonesian Neonates
Authors: Iskandar William , Smith Emily , A Aditiawarman , Apriatni Mandri , Tjiong Roy , Shankar Anuraj
Published: June 2021

Introduction

Maternal multiple micronutrients (MMN) supplementation as compared to iron‐folic acid (IFA) can increase birth weight and decrease infant mortality, but the physiological basis remains unclear. We examined Apgar scores to assess the impact of MMN on the dynamic process of neonatal adaptation after birth.

Methods

We selected 3667 singleton live births from the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) of maternal MMN versus IFA (ISRCTN34151616) with Apgar scores at the 1st and 5th minute, after excluding those with midline anomaly, inborn diseases and if not a spontaneous vaginal birth. Mixed effect multiple linear regression models were used to adjust for clustered randomization, covariates and interactions.

Results

Overall, there were no significant differences between Apgar scores of children from the MMN and IFA groups at the 1st (adjusted β ‐0.416, 95% CI ‐0.339‐0.047) or 5th minute (adjusted β 0.077, 95% CI ‐0.097‐0.252), or changes from 1 to 5 minutes (adjusted β 0.003, 95% CI ‐0.065‐0.072), nor were there effects on specific component scores. In subgroup analysis, MMN decreased the 1st minute score for full term and small for gestational (SGA) neonates, and MMN increased improvement from 1 to 5minutes in full term and SGA neonates, and those born of well‐nourished mothers (upper arm circumference > 23.5 cm).

Discussion

We observed certain subgroups of neonates of mothers given MMN tended toward lower 1st minute Apgar scores and greater improvement of Apgar scores from the 1st to 5th minute. MMN supplementation may enhance the dynamic adaptive processes of certain neonates after delivery, thereby improving infant survival.
Is the LDL/HDL‐ Cholesterol Ratio a Better Risk Indicator for Coronary Heart Disease Than the TC/HDL‐Cholesterol Ratio?
Authors: Davis Errol , Huffman Fatma , Onuoha Egondu
Published: June 2021

Objective

In a cross‐sectional study we examined total cholesterol/high‐density lipoprotein cholesterol (TC/HDL) ratio and low‐density lipoprotein cholesterol (LDL/HDL) ratio in 66 Foreign‐born Afro Caribbean (FBAC) living in the US for less than 10 years, 62 US‐born Afro Caribbean American (USBACA) and 61 African American (AA) adults (18‐40 years).

Results

Males had significantly (p<0.01) higher mean TC/HDL and LDL/HDL ratios than females (4.0 ± 1.2 vs. 3.5 ± 1.4) and (2.62 ±1.1 vs. 2.20 ± 1.2), respectively. There were no significant statistical differences between the groups with respect to mean TC/HDL or LDL/HDL ratios. Using the TC/HDL ratio (蠅 5.0, high risk) predicted 15.3% of individuals at risk for coronary heart disease (CHD) (18.7% males and 12.2% females) whereas, using LDL/HDL ratio (蠅 3.6, high risk) predicted 14.3% of individuals at risk of CHD (16.5% males and 12.2% females). Also, more USBAC than FBAC and AA participants had elevated TC/HDL ratio 蠅 5.0 (19.4% vs. 13.6% and 13.1%) and, elevated LDL/HDL 蠅 3.6 (19.4% vs. 13.6% and 9.8%), respectively.

Conclusion

Although there were small differences between the predictive function of TC/HDL and LDL/HDL between the genders and the ethnic groups, this was not significant. However, because of ease of use (TC and HDL are measured values vs. LDL which is calculated) and TC being better reflective of the total lipid profile, we would suggest that the TC/HDL‐Cholesterol ratio be used for prediction of CHD risk.

Source of funding: Florida International University Foundation
Markers of Environmental Enteric Dysfunction (EED) are Associated with Neurodevelopment in Tanzanian Children
Authors: Etheredge Analee , Manji Karim , McDonald Christine , Kellogg Mark , Tran Hao , Gosselin Kerri , Gewirtz Andrew , Kisenge Rodrick , Aboud Said , Bellinger David , Fawzi Wafaie , Duggan Christopher
Published: June 2021

Background

Children with environmental enteric dysfunction (EED) are at increased risk for impaired growth and neurodevelopment. We conducted a study to evaluate novel biomarkers of gastrointestinal epithelial and barrier function associated with EED as predictors of neurodevelopment.

Methods

Blood samples were obtained from 107 Tanzanian infants at 6 weeks and 6 months for assay of serum citrulline (CIT) and antibodies to LPS and flagellin. Neurodevelopmental testing (Bayley Scales of Infant Development‐III) was conducted at 15 months of age.

Results

The log odds of having a below‐median raw expressive language score (< 20) was increased by 1.66 (p=0.03) for every 1 unit increase (1‐UI) in LPS IgA at 6 weeks and by 0.19 (p=0.04) per 1‐UI in CIT at 12 months; log odds were decreased by 1.54 (p=0.02) per 1‐UI in flagellin IgG and by 0.16 (p=0.02) per 1‐UI in CIT at 6 months.

Conclusion

Higher levels of LPS‐IgA at 6 weeks and CIT at 12 months, and lower levels of flagellin‐IgG and CIT at 6 months were associated with below‐median language scores. Markers of intestinal permeability and absorption are indicators of neurodevelopmental sequelae in children at risk of EED.

Funding

NICHD (R01 HD048969; K24HD058795),Bill and Melinda Gates Foundation (OPP1066203)
Impact of Eating Behaviors and Cravings on Gestational Weight Gain and Diet
Authors: Lopez‐Cepero Andrea , Leung K , Corvera S , Moore T , Rosal MC
Published: June 2021

Background

Gestational weight gain (GWG) above the Institute of Medicine guidelines is prevalent, and is associated with adverse pregnancy outcomes, and obesity. Food cravings and eating behaviors (i.e., cognitive restraint of eating, emotional eating) may influence diet during pregnancy and GWG.

Objective

To assess associations between cravings, eating behaviors, diet and GWG.

Methods: Healthy pregnant women (N=94) enrolled in care <17 weeks gestation completed survey (demographics, Three Factor Eating Questionnaire, Food Craving Inventory), dietary (three 24‐hr recalls) and anthropometric assessments between 24‐34 weeks gestational age. GWG data were obtained from medical records. Analysis included binary and multivariate logistic regressions.

Results: Participants' mean age was 28 (+5.1) years; they were 67% White, 28% Hispanic, 51% overweight/obese pre‐pregnancy, and 64% above‐guideline GWG. Sweet cravings were positively associated with, and cognitive restraint was negatively associated with, caloric intake, carbohydrates, fat and sugar sweets (p<0.03). Overall cravings and fast food cravings were positively associated with caloric and carbohydrate intake (p<0.03). Controlling for gestational age, pre‐pregnancy BMI and physical activity, emotional eating was associated with greater GWG (p=0.046) and there was a trend for a significant association between cognitive restraint and GWG. Neither cravings nor eating behaviors were associated with above‐guideline GWG.

Conclusions

Selected cravings and eating behaviors were associated with diet, and emotional eating was associated with GWG. Further research of these associations could unveil potential intervention targets to optimize GWG.
An Intervention to Co‐package Zinc and Oral Rehydration Salts (ORS) Improves Health Provider Prescription and Maternal Adherence to WHO‐recommended Diarrhea Treatment in Western Guatemala
Authors: Roche Marion , García Meza Rosario , Vossenaar Marieke
Published: June 2021

Background

Diarrhea remains the second greatest cause of child morbidity and mortality in Guatemala, yet adherence to the WHO recommended treatment of Zinc (Zn) & ORS is low.

Objective

We evaluated the effectiveness of health‐facility‐level co‐packaging of Zn and ORS to improve health provider prescription practices and caregivers' adherence to the diarrhea treatment (2 days ORS; 10 days Zn) for children 2‐59 months of age in rural Guatemala.

Methods

Zn & ORS co‐packaging development was guided by social marketing and then evaluated in a community‐randomized intervention trial. The intervention group (IG) received Zn & ORS in a graphic co‐pack with instructions and provider messages for counseling in diarrhea treatment. The control group (CG) received normative care of Zn and ORS without co‐packaging or messages. Home‐monitoring of adherence was conducting at 5 and 10 days post‐prescription in 20 health posts in San Marcos, Province.

Results

Health providers in the IG were more likely to dispense both medications than those of the CG (aOR: 2.3; 95%CI: 1.0, 5.4). IG mothers (n=123) were more likely to give the full 10 days of zinc (aOR:1.7; 95%CI; 1.0, 2.8) than CG mothers (n=138), and IG mothers provided 1 more day of Zn (p<0.01).

Conclusions

The co‐packaging intervention improved both the prescription practices and adherence to zinc. This innovation could improve diarrhea treatment in Guatemala and holds potential utility in other situations of combined therapies.

Research Support

Grand Challenges Canada & Micronutrient Initiative
Dietary Soy Protein Concentrate Suppresses Colonic Inflammation and Loss of Gut Barrier Function In Vitro and in Mice
Authors: Lambert Joshua , Bitzer Zachary , Wopperer Amy , Elias Ryan
Published: June 2021

Inflammatory bowel disease afflicts nearly 4 million people worldwide. Soy (Glycine max) is an important dietary constituent and has been reported to have beneficial effects against a number of chronic diseases including cancer. Here, we examined the efficacy of soy protein concentrate (SPC) to suppress inflammation and oxidative stress, and to improve gut barrier function in vitro and in vivo. SPC exhibited radical scavenging activity and protected Caco‐2 human colon cells from H2O2‐induced cytotoxicity. This latter effect was correlated with a SPC‐mediated decrease in intracellular reactive oxygen species. Co‐treatment of Caco‐2 cell monolayers with SPC dose‐dependently reduced dextran sulfate sodium (DSS)‐induced increases in monolayer permeability. Dietary supplementation with 6 or 12% SPC dose‐dependently reduced colonic protein levels of interleukin (IL)‐1b, IL‐6, and monocyte chemotactic protein‐1 in DSS‐induced CF‐1 mice compared to DSS‐treated controls. A similar decrease in the mRNA levels of Il1b and EGF‐like Module‐containing Mucin‐like Hormone Receptor‐Like 1 and toll‐like receptor 3 and 4 was observed. SPC treatment significantly increased colon levels of glucagon‐like peptide 1 and tended to increase the mRNA expression the tight junction proteins, claudin‐1 and occludin. Overall, our results suggest that SPC attenuates colonic inflammation in part by suppressing oxidative stress and intestinal permeability.
Development of a New Model for the Induction of Chronic Kidney Disease via Intraperitoneal Adenine Administration, and the Effect of Treatment with Gum Acacia thereon
Authors: Al Za'abi Mohammed , Ali Badreldin , Yasin Javed , Schupp Nicole , Nemmar Abderrahim
Published: June 2021

Oral adenine (0.75% w/w in feed), is an established model for chronic kidney disease (CKD). Gum acacia (GA) has been shown to be a nephroprotective agent in this model. Here we aimed at developing an adenine‐induced CKD model in rats via a systemic route (intraperitoneal, i.p.) to test it with GA to obviate the possibility of a physical interaction between GA and adenine in the gut. Adenine was injected i.p. (50/100 mg/Kg for four weeks) and GA was given concomitantly in drinking water (15%, w/v). Several plasma and urinary biomarkers of oxidative stress were measured and renal damage was assessed histopathologically. Adenine, at the two given i.p. doses, significantly reduced body weight, and increased relative kidney weight, water intake and urine output. It dose‐dependently increased inflammatory and oxidative stress biomarkers, and caused morphological and histological damage resembling that which has been reported with oral adenine. Concomitant treatment with GA significantly mitigated almost all the above measured indices. Administration of adenine i.p. induced CKD signs very similar to those induced by oral adenine. Therefore, this model is quicker, more practical and accurate than the original (oral) model. GA ameliorates the CKD effects caused by adenine given i.p. suggesting that the antioxidant and anti‐inflammatory properties possessed by oral GA are the main mechanism for its salutary action in adenine‐induced CKD, an action that is independent of its possible interaction with adenine in the gut.