bluuebunny/crossref_metadata_2025 huggingface dataset:
Scavenger Receptor BI Mediates the Uptake and Transcytosis of HDL in Brain Microvascular Endothelial Cells Independent of PDZK1 and Nitric Oxide
Authors: Fung Karen Yin Yue , Wang Changsen , Nyegaard Steffen , Heit Bryan , Fairn Gregory , Lee Warren
Published: November 2023

The vascular endothelium supplying the brain exhibits very low paracellular and transcellular permeability which protects the brain from fluctuations in ion concentrations and exposure to circulating toxins. The blood‐brain‐barrier (BBB) consists in large part of a continuous monolayer of endothelial cells joined by intercellular tight junctions that effectively occlude the intercellular space, reducing paracellular permeability. At the same time, the impermeability of the blood‐brain barrier is not absolute, allowing the regulated transport of various molecules such as high‐density lipoprotein (HDL). HDL crosses the blood‐brain barrier by transcytosis but technical limitations have made it difficult to elucidate its regulation. Elucidating the mechanisms of HDL transcytosis across the blood‐brain barrier, in particular, may be significant pathologically as its constituent apolipoprotein ApoAI has been demonstrated to confer a protective effect against Alzheimer disease (AD). Using a combination of spinning‐disc confocal and total internal reflection fluorescence microscopy, we examined the internalization and transcytosis of fluorescently labeled HDL by human primary brain microvascular endothelial cell monolayers. Using these approaches, we report that HDL internalization requires dynamin but not clathrin heavy chain and that its internalization and transcytosis are saturable. Internalized HDL partially co‐localized with the scavenger receptor BI (SR‐BI) and knockdown of SR‐BI significantly attenuated HDL internalization. However, we observed that the adaptor protein PDZK1 ‐ which is critical to HDL‐SR‐BI signaling in other tissues ‐ is not required for HDL uptake in these cells. Furthermore, inhibition of endothelial nitric oxide synthase did not prevent HDL transcytosis but increased HDL internalization while the addition of exogenous nitric oxide had no effect on internalization. Together, these data indicate that HDL transcytosis across the blood‐brain barrier involves a non‐canonical signaling pathway downstream of SR‐BI. Our findings may facilitate manipulation of HDL transcytosis to increase delivery of ApoA1 as a potential therapeutic approach for AD and to increase transport of HDL‐like synthetic particles containing therapeutic drug across the blood‐brain barrier to treat neurodegenerative diseases.

Support or Funding Information

Karen Fung ‐ Ontario Early Researchers Award from Dr. Gregory Fairn
Effects of early prenatal food supplementation and multiple micronutrients on under‐five survival, linear growth, metabolic markers and blood pressure up to 10 years of age. The MINIMat trial in rural Bangladesh
Authors: Persson Lars Åke , El Arifeen Shams , Khan Ashraful , Rahman Anisur , Ekström Eva‐Charlotte
Published: November 2023

Nutritional deficiencies in early life may have severe short‐ and long‐term consequences. Enhanced prenatal nutrition including macro‐ and micronutrient alternatives may prevent some of these unfavorable outcomes.

In the MINIMat prenatal nutrition trial in Bangladesh (ISRCTN16581394) 4436 pregnant women were randomized into 6 equally sized groups; a double‐masked supplementation with either 30 mg Fe and 400 μg folic acid, or 60 mg Fe and 400 μg folic acid, or a multiple micronutrient supplement (MMS) containing a daily allowance of 15 micronutrients including 30 mg Fe and folic acid starting at around 14 weeks, was combined with a randomized early invitation (from around 9 weeks) or a usual invitation to start (from around 20 weeks) food supplementation (608 Kcal 6 days per week).

These women had a median height of 150 cm, and 28% had a body mass index below 18.5. Among the 3625 live births the early timing of prenatal food supplementation combined with multiple micronutrients (vs. usual timing and 60 mg Fe‐folic acid) significantly reduced the under‐five mortality (HR 0.34; 95% CI 0.18–0.65). The early invitation to prenatal food supplementation resulted in less stunting 0–5 years (4.5 percent units), while prenatal multiple micronutrients was linked to more stunting (4.8 percent units) as well as to lower IGF‐1 levels. The early timing of prenatal food supplementation resulted in significantly lower cholesterol, LDL and ApoB levels at 4.5 years of age. Supplementation with MMS was associated with lower HDL and lower glucose levels. The higher dose of prenatal iron supplementation (60 mg) as compared to 30 mg iron or MMS was associated with significantly higher systolic and diastolic blood pressure at 10 years of age with effect sizes around 0.25 SD. The early invitation to food supplementation ameliorated that unfavourable effect. These prenatal nutrition interventions resulted in major improvement in child survival and effects on linear growth, metabolic markers and blood pressure. The combination of micronutrients with improved macronutrient nutrition in early pregnancy seems to be important in a population, where maternal undernutrition still is prevalent. These findings underline the need to analyze multiple and long‐term outcomes of prenatal nutrition interventions and to identify favorable as well as unfavorable effects in order to inform policy formation.

Support or Funding Information

The 4.5 and 10‐year follow‐up was funded by Swedish Research Council
A Nutrition Education Intervention Affects the Diet‐Health Related Practices and Nutritional Status of Mothers and Children in a Pulse‐growing Community in Halaba, south Ethiopia
Authors: Ersino Getahun , Henry Carol J , Zello Gordon A
Published: November 2023

A six‐month nutrition education intervention on pulse and other food consumption was conducted in mothers of children under‐5 in the pulse‐growing region of Halaba, south Ethiopia. The intervention incorporated the health belief model, on Knowledge, Attitude and Practices (KAP), and objective measures included dietary diversity scores (DDS), dietary intakes and nutritional status. Between March 2013–April 2014, 200 mother‐child pairs, randomly selected from each of two purposively selected communities participated in an intervention‐control study. A six‐month nutrition education program, involving interactive monthly community meetings and home‐visits, was offered to one of the communities and the other served as a control. Demographics, KAP, food perceptions, DDS, dietary and anthropometric information were collected at baseline and endline. Focus group discussions (FGD) with local farmers also occurred. Significant improvements in the intervention group were found from baseline to endline for the following outcome variables: KAP and perceptions of pulse nutrition benefits among mothers; DDS and pulse and animal source food consumption indexes for both mothers and children; and mean body‐mass index‐for‐age (BMI‐for‐age) z‐score and wasting among children. Farmers in the FDG also expressed improved intention to produce and retain more pulses for home consumption. No such changes were found in the control community. Community‐based nutrition education interventions involving monthly interactive community meetings and home‐visits in traditional pulse‐growing communities could be effective in improving mothers' knowledge of pulse nutrition and consumption frequency. Such interventions can lead to increasing DDS in mothers and their children, and decreasing underweight and wasting among children in rural Ethiopia.

Support or Funding Information

The research was supported by the International Development Research Centre (IDRC) and Global Affairs Canada, Government of Canada, through the Canadian International Food Security Research Fund (CIFSRF)
Effects of Preconceptional Weekly Micronutrient Supplements on Maternal and Child Anemia during the First 2 Years of Life
Authors: Nguyen Phuong , Young Melissa , Gonzalez‐Casanova Ines , Truong Truong Viet , Nguyen Son , Martorell Reynaldo , Ramakrishnan Usha
Published: November 2023

Background

Anemia remains a major public health problem especially during the first 1000 days of life. Prenatal supplementation with multiple micronutrients (MM) and iron and folic acid (IFA) has been suggested as a potential intervention to reduce anemia in young children but little is known about the benefits of preconception micronutrient interventions. This study evaluates the impact of preconception weekly MM or IFA supplementation on maternal and child anemia during the first 2 years of age compared to folic acid (FA) alone.

Methods

We followed 1,599 offspring born to women who participated in a randomized controlled trial of preconception micronutrient supplementation in Vietnam. A total of 5011 women (18–40 y) received weekly supplements containing either 2800μg FA only, 60mg iron and 2800μg FA, or 15 micronutrients including the same amount of IFA, from baseline until conception; followed by daily prenatal supplements containing 60mg iron and 400μg FA till delivery. Hemoglobin concentrations were measured at different time points (3, 6, 12 and 24 months postpartum) using a portable field B‐Hemoglobin Analyzer. Anemia was defined as Hb value <12 g/dL and < 11 g/dL for women and children, respectively. We used ANOVA or chi‐square tests to examine group differences for both intention to treat and per protocol analyses (women consumed supplements ≥26 weeks before conception). Multivariable logistic regression analyses were used to examine factors associated with child anemia at age 2 y.

Results

The prevalence of anemia ranged from 30–40% among women during the post‐partum period and decreased from 61.4% to 41.6% among the offspring from age 3 to 24 mo. (n=1476). The groups were similar for baseline maternal and offspring characteristics at birth and there were no significant differences (p>0.05) by intervention group in mean hemoglobin concentrations or the prevalence of maternal and child anemia at various time points during the first 2 years of life in both intent‐to‐treat and per‐protocol analysis. Preconception anemia however remained a significant predictor of the risk of offspring anemia at 24 mo of age (OR: 1.88; 95% CI: 1.44 – 2.48) even after adjusting for maternal education, socioeconomic status and ethnicity.

Conclusions

Weekly supplementation with MM or IFA before conception did not affect the risk of anemia compared to FA in rural Vietnamese women and their offspring at age 2y. Preconception anemia however remained a significant predictor of offspring anemia at age 2y even after adjusting for other known determinants.

The trial was registered at ClinicalTrials.Gov as NCT01665378

Support or Funding Information

Mathile Institute for the Advancement of Human Nutrition, the Micronutrient Initiative, and the Nestle Foundation
Time‐of‐day Macronutrient Intake and Blood Pressure Levels: The Nutrition and Health Survey in Taiwan
Authors: CHEN HSIN‐JEN , Pan Wen‐Harn
Published: November 2023

Objective

To examine the association between the time of macronutrient intake and blood pressure levels based on the Nutrition and Health Survey in Taiwan (NAHSIT, 2005–2008).

Methods

The NAHSIT used a clustered stratified multistage sampling scheme to derive a representative sample of the non‐institutionalized and non‐pregnant population in Taiwan. For this cross‐sectional study, adult subjects (>19 y) who completed a 24‐hour dietary recall and had total energy intake ranged within 1500–4000 kcal, completed interview and physical examinations, and did not have diabetes, stroke or heart diseases, were included for this study. Time of energy intake were categorized into 6 intervals of a day: Morning (5:00–9:29am), late morning (9:30–10:59am), noon (11:00am–1:29pm), afternoon (1:30–5:29pm), evening (5:30–8:29pm), late night (8:30pm–4:59am). The self‐reported food intakes during these intervals were converted to energy and macronutrients based on food composition data. Blood pressures were measured three times with standard protocol. Linear regression models were applied to estimate the differences in blood pressure associated with the replacement of macronutrient intake at different time of a day, adjusting for age, sex, menopausal status, body mass index, status of taking anti‐hypertensive medications, awareness of hypertension status, the week day and the season of the dietary recall, and physical examination. The sampling weight and design effect were taken account for statistical estimation by SUDAAN 11.

Results

According to 1165 eligible participants' data, the results showed that a higher systolic blood pressure was associated with the late night fat intake (+2.4 mmHg, 95% CI:1.4–3.4, per 100 kcal fat intake). Replacing the fat intake at late night with fat intake in the earlier times of the day was associated with a lower systolic blood pressure by about 2 mmHg (per 100 kcal fat replacement). The association of diastolic blood pressure with time of macronutrient intake was similar to the findings for systolic blood pressure, despite lower statistical significance. Focusing on the late night eating, we found that replacing fat intake with carbohydrates was associated with a lower systolic blood pressure (−3.0 mmHg, 95% CI: −4.0,−2.0, per 100 kcal), which may cancel out the elevated blood pressure associated with fat intake at late night. We further excluded those who were aware of their hypertensive status (n=975 left), the patterns of association between time‐of‐day macronutrient intake and blood pressures were similar to the findings based on all eligible participants.

Conclusions

Fat intake at late night was associated with elevated blood pressures. Shifting the time of eating, especially fat intake, from late night to an earlier time of the day may prevent the elevated blood pressures associated with fat intake at late night.

Support or Funding Information

Taiwan Ministry of Science and Technology (MOST 105‐2314‐B‐010‐012)
Phytanic acid in dairy products and risk of cancer: current evidence and future directions
Authors: Takata Yumie , Zhang Zhenzhen , Garzotto Mark , Kopp Ryan , Bobe Gerd , Shannon Jackilen
Published: November 2023

Previous epidemiological studies of dairy and cancer risk reported inconsistent associations. Differences in abundance of bioactive components, such as metabolites from rumen microbiome, may explain the inconsistent associations. Among such rumen‐microbiome‐derived metabolites, this report focuses on phytanic acid, which is a 20‐carbon, methylated, branched‐chain fatty acid and a metabolite of plant‐based chlorophyll, and summarizes current evidence on its association with cancer risk through literature review and meta‐analysis. Phytanic acid has multiple functional properties linked to carcinogenesis from in vitro studies through peroxisomal function; mitochondrial function and oxidative stress; and cell signal transduction. Phytanic acid is converted in the peroxisomes to pristanic acid by multiple enzymes, including α‐methylacyl‐CoA racemase (AMACR). AMACR is overexpressed in tissues of various cancer sites, including prostate, colon, rectum, ovaries, breast, bladder, lung, and liver and in lymphoma tissues. In prostate cancer, AMACR expression is strongly linked to presence of the disease and hypothesized as a diagnostic marker. In addition, phytanic and pristanic acids are retinoid X receptor and peroxisome proliferator‐activated receptor (PPAR) agonists and thereby can alter cell proliferation and apoptosis. The association between phytanic acid and cancer risk has been examined in several epidemiological studies. Three studies examined the association between phytanic acid intake from foods or concentration in blood and risk of overall prostate cancer. When pooled, their results are summarized as no association [pooled odds ratio (OR) =1.04; 95% confidence intervals (CI)=0.90–1.17, comparing the highest category with the lowest]. Another study reported higher concentrations in cases than in controls (P‐difference=0.04). For risk of advanced prostate cancer, one of the three studies observed a positive association (OR=1.4; 95% CI=1.0–1.9). For non‐Hodgkin's lymphoma risk, only one study examined the association with phytanic acid intake and reported a positive association (OR=1.5; 95% CI=1.0–2.1). None of the previous epidemiological studies examined factors that are potentially involved in the association between phytanic acid and cancer risk such as AMACR and PPARs, which we propose for future studies. In addition, we propose to extend to other fatty acids that are unique to dairy fats such as short‐ and medium‐chain fatty acids.

Support or Funding Information

This study was funded by the Oregon Health & Science University/Oregon State University Cancer Prevention and Control Initiative (PHR030‐PV07; Lead‐PI: Y Takata).
Food Insecurity and Food Behaviors of Male Collegiate Athletes
Authors: Poll Kacie , Valliant Melinda , Joung Hyun‐Woo David , Holben David H
Published: November 2023

Collegiate athletes may have experienced food insecurity (FI), lacking access to food for an active healthy life, during high school (HS), which may negatively impact food acquisition and habits in college.

PURPOSE

To assess the relationship of HS food security status (FSS) to current food consumption behaviors in a sample of NCAA Division 1 male, collegiate athletes ≥18 years of age (y).

METHODS

A cross‐sectional survey of NCAA athletes from a Southeastern Conference (SEC) university was approved by the Institutional Review Board and conducted during August–September, 2016. The questionnaire included the USDA food security survey module and questions related to disordered eating behaviors and food hoarding. USDA methods were used to calculate FSS.

RESULTS

Participating athletes (n=93) were 19.7±1.4 y and primarily white, football players [Race: white (n=45, 48.4%); black (n=38, 40.9%); other (n=10, 10.9%)] [Sport: football (n=65, 69.9%); baseball (n=20, 21.4%); cross country/track (n=5, 5.4%); golf (n=3, 3.2%)] [HSFSS: high food security (n=73, 80.2%); marginal food security (n=4, 4.4%); low food security (n=7.7, 8%); very low food security (n=7.7, 8%). HSFSS was significantly correlated with preoccupation with food in college (taub = 0.273, P=.006) and hiding food in their athletics locker (taub=0.207, P=.048), but not with binge eating in college (taub=0.140, P=0.181).

CONCLUSION

HSFSS is associated with food hoarding and preoccupation with food in male collegiate athletes. Screening for FI and disordered behaviors in this group is warranted. Future research in a larger sample across several institutions that includes females is warranted.

Support or Funding Information

University of Mississippi Graduate School, Summer Research Assistantship, University, MS.
Social Determinants of Food insecurity in the Arab Region: A Comparative Study
Authors: Sheikomar Olfat Bakur , Wambogo Edwina , Sahyoun Nadine R. , Ghattas Hala
Published: November 2023

Background

Some countries of the League of Arab States (LAS) are exposed to urbanization, high unemployment, food price volatility, and conflicts predisposing their populations to poverty, food insecurity (FI) and malnutrition. Limited data are available on food insecurity experience in these countries, particularly, of older adults. This study estimates the prevalence and determinants of FI in countries of LAS.

Methods

We used data from the United Nations Food and Agricultural Organization, Voices of the Hungry Project (FAO‐VOH), on food insecurity, assessed using the 8‐item Food Insecurity Experience Scale (FIES) collected by the Gallup World Poll for 19 Arab countries for the years 2014 and 2015. The sample included 32,146 adults; 80.3% were 19–49 years old, of which 53.7% were men, and 19.7% were 50 years and above, of which 56.6% men. Food security thresholds were determined using Rasch modeling and participants were classified as food secure/moderately insecure (FSMI) and severely FI (SFI). Prevalence of SFI was estimated by age group, gender, and Human Development Index (HDI) categories.

Results

The overall prevalence of SFI and FSMI were 14.1% and 85.9%, respectively. There was a higher prevalence of SFI among women than men (15.8% and 12.7% respectively, p‐value <.0001), however this was reversed in high‐HDI countries where men were at higher risk of SFI than women (P <.0001). There were no significant differences in SFI prevalence by age group. Of the total population, SFI was prevalent in 21.1% of adults from low‐HDI countries and 7.1% from high‐HDI countries (P <.0001). Additionally, overall, SFI was more prevalent among adults living in rural areas, with lower educational attainment, who are poorer, and dissatisfied with their health care access compared to FSMI individuals.

Conclusion

The relationship between food security and gender is complex and needs to be further investigated. As expected, SFI is more prevalent in countries of lower human development and among vulnerable segments of the population. It is essential to understand the socioeconomic and demographic determinants of FI in this population in order to develop interventions that target the most vulnerable populations in LAS countries.
Haemodialysis, Risk of Food Insecurity, and Dietary Behaviours in Trinidad and Tobago
Authors: Nichols Selby , Prout Patrice
Published: November 2023

Objective

The treatment of chronic kidney disease requires those afflicted to pay attention to diet. In many cases, they are asked to restrict the intakes, of sodium, potassium and proteins. These have implications for food and nutrition insecurity. In this study, we evaluated dietary intake patterns and risk of food insecurity among persons on haemodialysis.

Methods

A case‐control design was used in this study. Cases consisted of persons currently requiring weekly haemodialysis. Controls consisted of persons being treated for hypertension and diabetes mellitus. Face‐to‐face interviews were conducted on participants from September 1st–October 31st, 2016 using a standardized questionnaire consisting of dietary intake, and a food security items (U.S. Household Food Security Survey 18‐item questionnaire). The latter was used to calculate a food insecurity score.

Results

390 persons (cases = 130, controls DM =130, HTN=130) participated in the study. Persons on haemodialysis consumed significantly lower amounts of fruit (p<0.001), vegetables (p<0.001), legumes (p<0.001) and staples (p<0.001) but not meat, dairy and eggs than participants who not on haemodialysis. They had significantly higher food insecurity scores than controls (p<0.001). Persons on haemodialysis were significantly more likely to be at risk for food insecurity (odds ratio (OR) = 5.0, 95% confidence intervals (CI): 3.1, 8.1) that participants who were not on haemodialysis. Food security score was inversely associated with nutrition risk scores in cases (r = −0.19; p = 0.03) and controls (r = −0.22; p <0.001)

Conclusion

Among participants, persons on haemodialysis were at increased risk for nutrient deficiency. They were also at higher risk for food insecurity. This may have implications for the overall management of persons on haemodialysis.

Support or Funding Information

none
Pancreas Development and Nutrient Uptake and Utilization Are Disrupted by Embryonic Exposures to the Environmental Toxicant Perfluorooctanesulfonic Acid in the Zebrafish
Authors: Sant Karilyn E , Jacobs Haydee M , Borofski Katrina A , Chen Phoebe , Park Yeonhwa , Timme‐Laragy Alicia R
Published: November 2023

Several persistent and ubiquitous environmental toxicants have been categorized as diabetogens or obesogens due to their numerous associations with these conditions in adult humans. These compounds often produce deleterious effects in the pancreas, which secretes glucoregulatory hormones and proteases and lipases essential for digestion. Compounds such as the surfactant perfluorooctanesulfonic acid (PFOS) have been detected in biological samples from nearly 100% of the population, and are associated with increased risk for diabetes in adults. However, the developmental consequences of these exposures which may contribute to these adult phenotypes require elucidation. We hypothesized that embryonic exposures to PFOS would alter pancreas development and disrupt embryonic nutrition processes associated with pancreas function. Zebrafish embryos were exposed to 16 or 32 μM PFOS or 0.01% DMSO (control) throughout embryonic development (3–96 hpf). Transgenic embryos from Tg(insulin:GFP) and Tg(ptf1a:GFP) strains were imaged in vivo at 96 hpf to visualize endocrine and exocrine pancreatic development, respectively. Larval morphometry was examined to probe yolk utilization and fish growth. RNA was isolated to examine expression of genes central to pancreas function, and biochemical assays were performed to quantify total embryonic nutrient concentrations. Beta cell mass and insulin gene expression were both decreased concordantly with increasing PFOS exposure at 96 hpf. Total pancreas length and expression of protease genes were also decreased by PFOS exposure. The rate of yolk utilization was increased by 6–10% due to 16 and 32 μM PFOS, respectively, suggesting increased embryonic uptake of total yolk nutrients. However, total embryonic concentrations of the bulk yolk nutrients cholesterol, triglycerides, and glucose were decreased with increasing PFOS concentrations. These PFOS‐exposed larvae were also shorter than control fish at 7 dpf. Free fatty acid profiles also differed between control and PFOS‐exposed embryos. Total embryonic concentrations of several saturated free fatty acids such as stearic acid were increased by treatment, while concentrations of beneficial unsaturated free fatty acids such as α‐linolenic acid were decreased by treatment. Overall, this work demonstrates that embryonic toxicant exposures can perturb pancreas development, and can alter the uptake and processing of yolk nutrients during development.

Support or Funding Information

This work was supported in part by the National Institutes of Health (R01 ES025748 to ART‐L), and a University of Massachusetts Amherst Commonwealth Honors College Research grant (to KAB.).
Effects of Lycium Barbarum Polysaccharides Extract and Betaine on Cell Activation and Liver Fibrosis in Rat Hepatic Stellate HSC‐T6 Cells
Authors: Chao Jane C‐J , Li Bo‐Ying
Published: November 2023

The fibrogenesis is indicated by the activation of hepatic stellate cells (HSCs) and accompanied with enhanced secretion of transforming growth factor‐β (TGF‐β) and deposition of extracellular matrix. We determined the effects of Lycium barbarum polysaccharides (LBP) and betaine on cell activation and fibrotic markers after the activation of rat HSC‐T6 cells by H2O2. The results showed that H2O2 at 5 μM activated HSC‐T6 cells by significantly increasing the expression of alpha‐smooth muscle actin (α‐SMA), TGF‐β, and matrix metalloproteinase (MMP)‐2, which were significantly reduced by LBP and betaine at 10 and/or 50 μg/mL (p<0.05). The expression of tissue inhibitor of metalloproteinase‐1 (TIMP‐1) was significantly inhibited by LBP at 10 μg/mL, however, the expression of TIMP‐2 was promoted by betaine at 10 μg/mL. Therefore, LBP and betaine, the active components in Lycium barbarum L., attenuate liver fibrosis through inhibiting cell activation of HSCs and expression of fibrotic markers under H2O2‐induced oxidative stress.

Support or Funding Information

The study is supported by the Ministry of Science and Technology, Taiwan (grant no. 105‐2320‐B‐038‐036‐MY3).
Glutathione concentration and glutathione peroxidase activity are associated with the risk of liver cirrhosis independently of oxidative stress
Authors: Huang Yi‐Chia , Cheng Shao‐Bin , Liu Hsiao‐Tien , Lai Chia‐Yu
Published: November 2023

Oxidative stress has been observed to be associated with the risk of liver cirrhosis. Glutathione is synthesized in the liver, with its dependent antioxidant enzymes play important roles in antioxidant defense system. However, the relationship between oxidative stress and the glutathione antioxidant system to mediate the risk of liver cirrhosis has not been clearly determined. We investigated whether the glutathione antioxidant system is dependent or independent of oxidative stress linked with the risks for liver cirrhosis. This was a case control study. Sixty‐eight patients with liver cirrhosis (case) and 110 healthy subjects (control) were recruited. Patients with liver cirrhosis had significantly lower glutathione concentrations and higher glutathione peroxidase (GPx) activity than healthy subjects. There was no significant difference in oxidative stress status between groups. Plasma glutathione is significantly correlated with GPx activity (r = −0.22, p < 0.05) and oxidative stress indicator (r = 0.31, p < 0.01) in all subjects. Subjects with higher plasma glutathione concentration exhibited significantly decreased risk of liver cirrhosis (odds ratio, 0.95; p = 0.01), while subjects with lower plasma GPx activity significantly increased the risk of liver cirrhosis (odds ratio, 1.03; p < 0.01) with adjustment for potential confounders. Glutathione and GPx activity plays a significant role in the risk of liver cirrhosis.

Support or Funding Information

This study was supported by the Ministry of Science and Technology, Taiwan (MOST 104‐2320‐B‐040‐009‐MY3).
In vitro anticancer efficacy of a polyphenol combination of curcumin, quercetin, green tea extract and resveratrol in human cervical cancer HeLa cells
Authors: Roomi M Waheed , Rath Matthias , Niedzwiecki Aleksandra
Published: November 2023

Cervical cancer is the third most commonly diagnosed cancer and fourth leading cause of mortality in women worldwide. Although fully treatable in the early stages, once it has metastasized, the survival rate is 68%. Based on its poor prognosis, we investigated the effect of a specific polyphenol combination (PB) of curcumin, quercetin, green tea extract and resveratrol on viability, invasion, MMPs secretion and morphology on human cervical cancer HeLa cells. Cervix HeLa cells (ATCC) were cultured in DEM media, supplemented with bovine serum and antibiotics in 24‐well tissue plates. At near confluence, cells were treated with PB at 0, 10, 25, 50, 75 and 100 μg/ml concentration in triplicate at each dose. Cells were also treated with PMA for MMP‐9 induction. Cell proliferation was evaluated by MTT assay, MMPs by gelatinase zymography, invasion by Matrigel and morphology by H&E staining. PB inhibited proliferation by 10, 25, 30, 30 and 60% at 10, 25, 50, 75 and 100 μg/ml concentration. Zymography demonstrated expression of MMP‐2 and MMP‐9, with strong induction of MMP‐9 by PMA. Both MMPs were reduced by PB with total block at 50 μg/ml concentration. PB inhibited invasion through Matrigel at 25 μg/ml concentration. H&E staining showed no morphological changes up to 50 μg/ml concentration and exhibited apoptotic changes at 75 and 100 μg/ml concentrations. These results suggest that PB has promising new therapeutic potential in treatment of cervical cancer.

Support or Funding Information

Dr. Rath Research Foundation, a non‐profit organization
Impaired Conducted Coronary Arteriole Dilation in Patients with HFpEF
Authors: Davila Alec C , Dou Huijuan , Patel Vijay , Fulton David , Weintraub Neal , Bagi Zsolt
Published: November 2023

Heart failure with preserved ejection fraction (HFpEF) is a poorly understood clinical paradigm with an incidence that is growing alarmingly (1% increase/year among HF patients) and a high mortality rate (5.2% annual death). Recently, it has been suggested that coronary microvascular dysfunction (CMD) is a key determinant of HFpEF, but this link is poorly understood. We hypothesized that vascular endothelial adenosine‐kinase (ADK) limits adenosine availability and thereby impairs conducted coronary arteriole dilation in HFpEF. Coronary arterioles (CA, ~100 μm in diameter) from right atrial appendages were obtained from patients with HFpEF (N=5) or age‐matched controls (N=8) without the clinical HFpEF diagnosis. Conduced CA dilation was examined in isolated and pressurized CA by focal application of endothelium‐dependent agonist, bradykinin and subsequent measurements of diameter at local and remote sites (500 and 1000 μm away from the focal stimulation) using videomicroscopy. We found that the magnitude of conducted, but not the local, CA dilation was significantly reduced in HFpEF patients. Incubation of the arteries with adenosine or with a specific ADK inhibitor, ABT‐702 augmented conducted CA dilation in HFpEF patients, who exhibited an increased ADK protein expression in CA, as assessed by immunohistochemistry and Western blotting. Collectively, our data demonstrate for the first time that the impaired conducted CA dilation develops in HFpEF patients, which is due to the increased expression of ADK in CA. Inhibition of ADK restores conducted vasodilation in HFpEF, likely via increasing ADO availability.
Effect of 4 weeks of high‐intensity interval training on exercise performance and markers of inflammation and oxidative stress
Authors: Zwetsloot Kevin A. , Nieman David C. , Knab Amy , John Casey S. , Lomiwes Dominic D. , Hurst Roger D. , Gillitt Nicolas D. , Lila Mary A.
Published: November 2023

Prolonged, high intensity exercise induces substantial systemic inflammatory and oxidative stress responses. High intensity interval training (HIIT) involves bursts of heavy exertion separated by short rest periods; however, there is limited research on the effect of regular HIIT on the acute immune and oxidative stress responses to exercise. The purpose of this study was to determine the acute and chronic exercise‐related physiological responses and adaptation to 4‐weeks of cycling HIIT. We hypothesized that 4 weeks of HIIT would induce an attenuated inflammatory and oxidative stress response to an acute bout of HIIT. Sixty‐one sedentary, but healthy participants (males: n=15, 21.8 ± 1.0 y, initial VO2max = 37.7 ± 1.7 ml•kg−1•min−1, body fat = 16.8 ± 1.6%; females: n=46, 20.2 ± 0.3 y, initial VO2max = 32.1 ± 0.7 ml•kg−1•min−1, body fat = 25.7 ± 0.8%) completed a maximal graded cycle ergometer test and an acute HIIT exercise bout (HIIT challenge) before and after 4 weeks of HIIT. The HIIT challenge was an acute bout of eight 60‐sec cycling intervals at 100% of Wattsmax. The 4‐week HIIT consisted of 12 sessions (3 d•wk−1) of 8 to 12 cycling intervals at 100% of Wattsmax (60‐sec intervals; 75‐sec rest in between). Standard exercise‐related physiological variables were measured during the maximal cycle ergometer test and blood samples were collected at rest, immediately, and 30 min after completion of the HIIT challenge for analysis of inflammatory cytokines and markers of oxidative stress. Participants experienced 6% and 5% increases in VO2max and Wattsmax (both p≤0.001), respectively, after 4 weeks of HIIT. The post‐exercise blood lactate response was lower after 4 weeks of HIIT (p=0.0125), compared to before training. We also observed reductions in exercise heart rate and rating of perceived exertion at various submaximal cycling workloads (all p≤0.001) after training. Plasma IL‐6 increased immediately and 30 min after the HIIT challenge (p<0.0125), but 4 weeks of HIIT reduced this response (p<0.0125). IL‐8 and MCP‐1 increased in response to the HIIT challenge (both p≤0.001), but these responses were not altered by 4 weeks of HIIT. Before training, glutathione peroxidase (GPx) activity and malondialdehyde (MDA) levels increased (p=0.020 and p<0.001, respectively), but superoxide dismutase (SOD) activity was unchanged 30 min after the HIIT challenge. However, 4 weeks of HIIT further augmented GPx activity by 8% (p=0.026), attenuated MDA levels by 60% (p<0.001), and tended to increase SOD activity by 20% (p=0.059), in response to the HIIT challenge. In conclusion, 4 weeks of HIIT improves fitness and cycling exercise performance, and moderates the systemic inflammatory and oxidative stress responses to an acute bout of HIIT in sedentary men and women.

Support or Funding Information

Dole Foods, Inc., Westlake Village, CA
Exercise Increases Brain‐Derived Neurotrophic Factor in Serum Exosomes
Authors: Saengsawang Witchuda , Kongoun Sasithorn , Chanda Metha
Published: November 2023

Brain Derived Neurotrophic Factor (BDNF) is a major neurotrophic factor that elicits several important roles in the nervous system including neuronal development, synaptic plasticity and neuronal survival. It is known that BDNF can be detected in blood circulation and its level is altered during exercise. However, which form of BDNF and how BDNF is released from the brain into blood circulation during exercise are still unknown. Exosomes are small vesicles secreted from cells and carry a number of molecules from one cell to another. Several studies showed that exosomes carry several neuronal proteins and are able to cross blood‐brain barrier. However, it is unknown whether BDNF is present in the exosomes. In the present study, we demonstrated that the truncated form of BDNF was detected in the exosomes isolated form blood obtained from the jugular vein of the horses. In addition, we found that the level of truncated BDNF was significantly higher in the exosomes obtained from the serum of active horses compared to the sedentary horses. These results suggested the possibility that truncated‐BDNF was secreted from the brain into blood circulation through the exosomes. This is the first study demonstrating the presence of truncated BDNF in the serum exsosomes. It also showed the effect of exercise on the level of truncated‐BDNF in serum exosomes. The knowledge can be applied for a better understanding on the roles of BDNF in exercise, as well as in several neurodegenerative diseases, which are related to changes in the level of BDNF.

Support or Funding Information

This work was supported by a grant from the Thailand Research Fund (TRF) to WS (TRG5880104). We also gratefully acknowledge support from the Faculty of Science, Mahidol University (to WS).
Acute Effects of Walking on Human Internal Carotid Blood Flow
Authors: Greene Ernest R. , Shrestha Kushum , Garcia Analyssa
Published: November 2023

Due to technical limitations of measuring systems, human cerebral blood flow was considered to be highly regulated and relatively constant. New data now strongly suggest that brain blood flow is very dynamic and depends directly on cyclic aortic pressures that interact with retrograde pressure pulses from foot impacts. Recently, we and others have published that ergometer exercise (bicycle, no foot impacts) increases human cerebral blood flow. We also have reported that running, with relatively high foot impacts (4–5 G forces), dramatically modulates brain blood flow with the complex interaction of central aortic pressures and stride rates. Surprisingly, the effects of walking (minimal foot impacts and G forces) on cerebral blood flow have not been reported. Accordingly, we tested the hypothesis that walking modulates cerebral blood flow. In 12 healthy young adults (20 ± 3 years, 6 males/6 females) we used noninvasive duplex ultrasound (3 ms, 0.07 mm; 40db: time, space, and dynamic resolutions; respectively) to measure internal carotid artery blood velocities (BV) and lumen diameters (LD). Internal carotid (hemispheric cerebral) blood flow (CBF, ml/min) was calculated as the product of lumen area and BV [(π × (LD2)/4 × BV)]. Control (upright, resting, and fasting) CBF was calculated and compared to values obtained during steady state walking at 1.0 m/s and 2.0 m/s. Noninvasive heart rate (HR), mean blood pressure (MBP), and cerebral vascular resistance (CVR=MBP/CBF), were also determined (mean/SD; with * = p<0.05 versus control).

HR (bpm)
Mean BP (mmHg)
CBF (ml/min)
CVR (units)

Control
75/16
97/10
449/155
0.24/0.09

1.0 m/s
87/16*
93/10
558/204*
0.20/0.11*

2.0 m/s
94/19*
94/10
602/205*
0.18/0.07*

Preliminary results suggest that relatively low foot impacts during walking significantly affect CBF. Waveform morphology is dependent on the timing convolution of the heart rate and stride rates. Thus, there is a continuum of hemodynamic effects on human brain blood flow within pedaling, walking, and running. These activities may optimize brain perfusion, function, and overall sense of wellbeing during exercise.
Troponin degradation products: more specific marker for myocardial infarction
Authors: Zahran Somaya , Figueiredo Vivian , Cembrowski George , Graham Michelle , Schulz Richard , Hwang Peter
Published: November 2023

Introduction

Myocardial infarction (MI) is the death of cardiac muscle in the setting of severe ischemia (lack of oxygen and nutrient supply). Assay of serum troponin I (TnI) is the biochemical gold standard for detecting MI. With the development of high sensitivity assays, TnI is being detected in milder conditions such as reversible tachycardia or myocardial ischemia in the absence of radiologic evidence for infarct. Different types of MI are classified clinically: type 1 MI being the classic “heart attack” where the irreversible infarct necessitates a timely intervention. In contrast, type 2 MI is precipitated by a physiologic stressor (e.g. tachyarrhythmia, sepsis, or anemia) that causes ischemia in vulnerable regions of the heart. It is very important to differentiate irreversible infarct from reversible ischemia with a novel biomarker because the treatments are very different.

Rationale

While the mechanisms leading to TnI release are poorly understood, it is generally accepted that intracellular proteases are differentially activated in ischemia and in cell death. Cardiac TnI has intrinsically disordered N‐ and C‐terminal ends that are exposed and vulnerable to proteolytic digestion. TnI proteolysis products may be more rational and specific markers for irreversible cardiomyocyte death than its total level in the blood.

Methods

We collected blood samples from 29 hospitalised patients with elevated cTnI. We quantitated proteolytic degradation using sandwich ELISAs to specifically detect the N‐terminal, core, or C‐terminal regions of TnI using commercial antibodies (M18, MF4, and 560, respectively).

Results

We observed a wide variation in the degree of proteolytic degradation of TnI across the patients' samples. Interestingly, degradation of TnI at both N‐ and C‐termini in type 1 MI samples was detected. However, the C‐terminus degradation was more robust, consistent and proportional to the severity of the infarct. On the other hand, there was less degradation observed in type 2 MI samples, indicating that TnI is released in a more intact form.

Conclusions

Proteolytic degradation of TnI at its C‐terminus is a more specific marker for clinically significant MI than total TnI level. Making a distinction between intact and degraded forms of TnI may be useful for identifying patients with focal infarct in need of urgent revascularization and monitoring intracellular proteolysis as a possible target for therapeutic intervention.

Support or Funding Information

This work was funded by the University of Alberta Hospital Foundation, CIHR, startup funds from the Department of Medicine and Faculty of Medicine & Dentistry in the University of Alberta, and the Hwang Professional Corporation
Non‐invasive Vagus Nerve Stimulation Acutely Improves Blood Pressure Control in a Placebo Controlled Study
Authors: Sabino‐Carvalho Jeann L , Antonino Diego , Teixeira André L , Maia‐Lopes Paulo M , Murray Aaron R , Deuchars Jim , Vianna Lauro C
Published: November 2023

Background

Despite positive outcomes across a variety of disease states, invasive vagus nerve stimulation (VNS) has been associated with adverse side‐effects. Given this, non‐invasive VNS (tVNS) via the auricular branch of the vagus nerve (ABVN) has been proposed as an alternative approach. However, the mechanisms underlying these positive outcomes remain unclear. Therefore, we controlled the sensory effects (placebo) to investigate if tVNS acutely improves blood pressure (BP) control.

Methods

Thirteen healthy men (23±1yrs) were randomized across three experimental visits in a random order. In active tVNS, electrodes were placed on the tragus of the ear and electrical current was applied by using a Transcutaneous Electrical Nerve Stimulation device. A time‐ control visit was performed with the electrodes placed on tragus, but no current was applied (sham‐T). Additionally, to avoid a confounding sensory effect, another sham protocol was performed with same electrical current of the active visit, but the electrodes were placed on the ear lobe (an area without cutaneous nerve endings from the vagus – sham‐L). Before interventions were applied, we inform to subjects that both active tVNS and sham‐L would not cause any harm. Beat‐to‐beat heart rate (HR) and BP were monitored at rest, during tVNS (active, sham‐T and sham‐L) and recovery. Spontaneous cardiac baroreflex sensitivity (cBRS) was measured via sequence technique. Both HR (LF/HF) and BP variability (BPV) were also measured.

Results

Arterial BP and BPV were not affected by any active or sham protocols (P>0.05). HR and LF/HF ratio decreased (Δ–3.4±1% and Δ–17±10%, P<0.05, respectively) and cBRS increased (Δ20±7%, P<0.05) only during active tVNS, but were unchanged during both sham protocols (P>0.05).

Conclusion

The results of the present study provide evidence that tVNS acutely improves neural control of BP in healthy young men. These findings allow us to suggest that spontaneous cBRS and cardiac sympathovagal balance could play a role in the mechanisms involved in previously reported beneficial outcomes caused by tVNS. Future studies are needed to confirm these findings in older and diseased populations.

Support or Funding Information

J.L.S., A.L.T., P.M.M. have been supported by scholarships from Coordination for the Improvement of Higher Education Personnel (CAPES).