bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical Activity, Body Image and Body Mass Index: ELSA Brasil Cohort
Authors: Coelho Carolina , Barreto Sandhi , Giatti Luana , Molina Maria Del Carmen , Nunes Maria Angélica
Published: June 2021

The present study investigates whether dissatisfaction with body image, obesity and central obesity are independently associated with physical activity (PA) and if such association differ among men and women. 13,286 participants of ELSA‐Brasil cohort, aged‐35‐65 years. PA assessed by IPAQ and categorized as low, moderate and intense. Nutritional status assessed by body mass index and waist to height ratio. Body image dissatisfaction was defined by the difference between self‐reported body image and ideal body image using a validated silhouette scale. Multinomial logistic regression used to investigate whether body image dissatisfaction, obesity and central obesity are independently associated with PA, after controlling for age, schooling, income and common mental disorder. Prevalence of moderate and intense PA was lower among women than men. Prevalence of body image dissatisfaction was present even among normal weight individuals of both sexes. Body image dissatisfaction was associated with less moderate PA in women and with intense PA in men. Overweight and obese men had higher chances of high intensity PA. Obese women had lower OR of engaging in intense PA. Body image as well as nutritional status is related to PA practice in both sexes, but the association differs according to PA intensity.
Where do US Households Shop? Understanding the Sociodemographic Characteristics that Predict Shopping Pattern Membership
Authors: Stern Dalia , Ng Shu Wen , Popkin Barry
Published: June 2021

Objectives

We examined the combination of stores where US households shop for food and sociodemographic predictors of shopping patterns.

Methods

We conducted cross‐sectional analysis of US households' shopping patterns using Nielsen Homescan. Store type was classified using 2012 information into: warehouse‐club; convenience/drug/dollar; ethnic/specialty; grocery chains (蠅10 stores); mass‐merchandisers; independent (<10 stores); and other. Cluster analysis was used to derive shopping patterns (2000, 2003, 2006, 2009 and 2012). Multinomial logistic regression was used to identify whether specific subpopulations, defined by race and income characteristics, were associated with shopping patterns in 2012.

Results

From 2003 onwards, we found three shopping patterns: grocery‐chain cluster, mass‐merchandise/grocery‐chain cluster and combo store cluster. The proportion of households belonging to the grocery‐chain cluster decreased from 59.6% in 2003 to 50.7% in 2012, increased from 15.6% in 2003 to 21.9% in 2012 for mass‐merchandisers/grocery‐chain cluster and remained stable for the combo store cluster. Predicted probabilities for grocery‐chain cluster membership show no race‐ethic differences amongst low‐income households; however Hispanic/low‐income households had a significantly lower probability (vs. white‐non Hispanic/low‐income) to belong to the mass‐merchandise/grocery‐chain cluster and higher probability to belong to the combo store cluster.

Conclusions

Contrary to research on food desserts, low income and other US households shop for food at a variety of store‐types. These complex varied patterns must be considered in policy initiatives.
Assessing the content and daily intake of sodium from instant ramen in Korean adolescents and adults
Authors: Kim Yi‐Yeong , Choi Mi‐Kyeong , Bae Yun‐Jung
Published: June 2021

The production and consumption of instant ramen is constantly increasing because of its taste and convenience. However, ramen is estimated to be a major contributor to high dietary sodium intake. The purpose of this study is to assess the sodium content of ramen and its daily intake by Korean adolescents and adults. The sodium contents of 214 ramen types in the present market were surveyed, and the daily ramen intake of 405 adolescents aged 12~18 years and 1645 adults aged 19~64 years was analyzed using 2010~2012 Korean National Health and Nutritional Examination Survey (KNHANES) data. The sodium contents were 1483.7 mg/100 g for pouch‐ramen (n=65), 836.4 mg/100 g for pouch‐ramen without soup (n=25), 1752.6 mg/100 g for cup‐ramen (n=88), and 945.8 mg/100 g for cup‐ramen without soup (n=36). The daily sodium intakes from instant ramen were 1247.8 mg (24.9% of total sodium intake) for boys, 993.1 mg (24.4%) for girls, 1165.5 mg (19.7%) for adult men, and 901.5 mg (21.4%) for adult women. These results were lower than the daily sodium intake estimated in the current KNHANES.
Anti‐hyperglycemic Effect and Mode of Action of Palatinose In vitro and Animal Models
Authors: Lee Jung‐Yun , Choi Hwang‐Yong , Kang Yuri , Park Cheon‐Seok , Kim Young‐Cheul , Kwon Young‐In
Published: June 2021

Inhibition of α‐amylase and α‐glucosidase involved in the digestion carbohydrates can decrease the postprandial increase of blood glucose level after a mixed carbohydrate diet. In the course of screening these enzyme inhibitors, we screened isomaltulose (6‐0‐α‐D‐glucopyranosyl‐D‐fructose) using in‐vitro enzyme inhibition assay. Isomaltulose, known by the trade name Palatinose, is a disaccharide that is manufactured from sucrose via bacterial fermentation. Several studies showed that Palatinose had benefit effects on anti‐hyperglycemic effect in human clinical trials. However, there is limited information about the action mechanism on blood glucose lowering effect. Therefore, inhibitory activity of Palatinose against rat intestinal α‐glucosidases and porcine pancreatic α‐amylase were investigated in this study. The half‐maximal inhibitory concentration (IC50) of Palatinose on α‐amylase and α‐glucosidase were 30.8 and 91.8 mM, respectively. The postprandial blood glucose lowering effects of Palatinose was compared to a known type 2 diabetes drug (Acarbose), a strong α‐glucosidase inhibitor in the Sprague‐Dawley (SD) rat model. In rats fed on starch, the blood glucose level at 30 min after administration in Palatinose‐treated SD rats (0.1 g/kg‐body weight) was significantly lower than in untreated group (173.94 ± 10.15 vs. 195.80 ± 12.92 mg/dL, respectively). These results indicate that Palatinose may have anti‐hyperglycemic effect by suppressing carbohydrate absorption in the gastrointestinal level, and thereby reducing the postprandial increase of blood glucose.
Differential Serving Sizes of High β Glucan Oatmeal Elicit Lower Glycemic Response than Rice Cereal
Authors: Wolever Thomas , Jenkins Alexandra , Campbell Janice , Spruill Susan , Richard Black , Harkness Laura , van Klinken Jan‐Willem
Published: June 2021

To determine impact of serving size and cereal type along with addition of sugar on the glycemic response (GLR) elicited by oatmeal, we compared the GLR over 2 hr elicited by 30, 40 and 60g high β glucan (5.2%) Classic Quaker Quick Oats (18, 24 and 36g available carbohydrate (CHO), respectively) and by 30g Oats plus 9g sugar (sucrose) with those after available CHO matched portions (22, 29, 44 and 33g, respectively) of Cream of Rice cereal (Control) in 38 healthy subjects (mean±SD age 40±12 yr, BMI 26.4±3.6 kg/m²).

As serving size increased, incremental area under the curve (AUC), peak rise (PR), rate of decline (RD) and time to baseline (Tb) for blood glucose increased significantly for both cereals.

Time to peak (Tp) tended to increase with serving size (significant only for Oats).

Overall mean AUC, PR and RD, respectively for oats without sugar were 24%, 25%and 24% less than those after Control (all p<0.05). The GLR after Oats plus sugar was compared to that after 33g Control without sugar (both test meals contained 27g available CHO). After Oats plus sugar AUC, PR and RD were significantly lower than after 33g Control without sugar by 29%, 15% and 23%, respectively.

It is concluded that high β glucan Oatmeal elicits a lower glycemic response than Cream of Rice cereal. Measures of GLR tended to increase with increased serving size but the rate of change of some of the measures varied for the different cereals. Adding sugar to Oatmeal elicits a significantly lower GLR than a serving of Cream of Rice cereal containing the same amount of available carbohydrate.
Dietary Intake of Antioxidants including Vitamins C, E, and Lycopene among Normal Weight and Obese Native American Adolescents
Authors: zheng shasha , Crosby Grace , Perez Maria , Knisley Benjamin , Barth Margaret
Published: June 2021

Antioxidants are well‐known for possessing anti‐inflammatory properties which can reduce the risk of chronic disease and obesity. However, very little research has been done to examine antioxidant intake among adolescent minority populations such as Native American adolescents. Our study examined the significance of antioxidant intake among Native American adolescents at an urban residential high school in Southern California. Our study population consisted of 183 male and female Native American adolescents, 14‐18 years of age, representing 43 tribes from across the United States. Students' primary source of food was the school food service. Based on BMI measurements, we calculated the rate of obesity within our population to be 38% for males and 40% for females, more than two‐fold the national rate indicated by NHANESIII data. We used the Harvard School of Public Health Youth/Adolescent Questionnaire (HSPH YAQ), a semi‐quantitative usual food intake questionnaire, to examine antioxidant intake and to evaluate the differences in antioxidant intake between normal weight and obese weight students. The statistical analysis of the results showed that intakes of vitamins C, E, and lycopene were significantly higher in normal weight than in obese weight students (p‐values = 0.02451, 0.00847, and 0.04928, respectively). These results suggest that dietary intake of antioxidants such as vitamins C, E, and lycopene should be increased among Native American adolescents. Further research is needed to confirm our findings and to identify the most effective ways for food service companies to incorporate foods rich in vitamins C, E, and lycopene into school cafeteria menus.
Effects of high‐fat diet intake and endurance training on CLOCK gene in rat skeletal muscle
Authors: Fujii Hisao , Tamazaki Chihiro
Published: June 2021

【Objective】Excess caloric intake is associated with the development of obesity. A number of recent studies suggest that attenuation of CLOCK gene amplitude by high‐fat diet causes obesity. Normalizing to the CLOCK gene amplitude can be considered to contribute for the prevention of obesity. Also endurance training has the effect for prevention of obesity, but influence on the disorder of CLOCK gene by high‐fat diet intake is not clear. In the present study, we investigated the effects of high‐fat diet intake and endurance training on CLOCK gene in rat skeletal muscle.
【Methods】Adult male Wistar rats (∼260 g) were used. Animals were randomly divided into three groups; control diet (CON), high‐fat diet (HF) and high‐fat diet+ training (HF+Tr). The CON animals were received a standard diet. HF and HF+Tr animals were received high‐fat diet containing of 62% fat as calories. All animals were feeding two times per day. The rats of each group were provided equal food volume per day for six weeks. HF+Tr animals were exercised on treadmill (90 min/day and 5 days a week). The mRNA expression of CLOCK genes (Bmal1, Clock, and Per2 ) in skeletal muscle were tested at four points (ZT2, ZT8, ZT14 and ZT20) .
【Results and Conclusion】 The body weight of HF was heavy significantly compared with CON and HF+Tr. In skeletal muscle Bmal1 and Per2 gene expressions were not affected by high‐fat diet. On the other hand, the amplitude of Clock expression was attenuated in the HF and HF+Tr. In the present study, we consider the attenuation of Clock expression in skeletal muscle might be caused by lipid metabolism abnormality. Therefore, high‐fat diet intake was suggested to become obesity.
Comparing Effects of Native and Nanoencapsualted Epigallocatechin Gallate on Liver Fat Content in LDL Receptor Null Mice
Authors: Li Chuan , Zhang Jia , Nie Shufang , Cao Jun , Wang Shu
Published: June 2021

Objectives

We successfully synthesize epigallocatechin gallate (EGCG) nanocarriers (E‐nano), which have anti‐atherogenic and anti‐inflammatory bioactivities. But their effects on liver fat, primarily triglyceride, content have not been known yet. Therefore, we compared the effects of native EGCG and different types of E‐nano on liver fat content in LDL receptor null (LDLr‐/‐) mice.

Methods

Mice were fed an atherogenic diet and received weekly intravenous injection of the following 6 treatments for 20 weeks: saline, high dose (25 mg/kg body weight) of EGCG (EGCG‐H), E‐nano (E‐nano‐H), macrophage‐targeting E‐nano (TE‐nano‐H), and low dose (10 mg/kg body weight) of E‐nano (E‐nano‐L), macrophage‐targeting E‐nano (TE‐nano‐L). Liver lipids were extracted by a chloroform/methanol mixture. Liver triglyceride content was measured using an enzymatic method. Liver fat content was determined using an EchoMRI scanning method.

Results

Compared to other treatments, native EGCG significantly decreased liver fat content in LDLr‐/‐ mice. Both the enzymatic method and EchoMRI scanning demonstrated the similar results.

image

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Conclusions

Native EGCG, not nanoencapsulated EGCG, decreased liver fat content in LDLr‐/‐ mice fed an atherogenic diet.

Grant Funding Source: NIH 1R15AT007013‐01, Scholarship of Nanchang University.
Children with Epilepsy With Different Baseline Blood Beta‐hydroxybutyrate Have Similar Blood Beta‐hydroxybutyrate and Response on Ketogenic Therapy
Authors: Allen Hannah , Pacheco Giselle , Lennon Dylan , Lukosaityte Jurate , Borum Peggy
Published: June 2021

Background

Children with epilepsy may have fasting blood beta‐hydroxybutyrate (BOB) similar to (low BOB) or higher than (high BOB) healthy children, which could reflect differences in metabolism or usual diet. BOB increases in children with epilepsy on Ketogenic Therapy (KT), where fat is most of the Calories, but it is unclear if children with low or high BOB at baseline respond differently to KT.

Objective

To test the hypothesis that both groups of children with epilepsy (low or high BOB) can respond to KT with a reduction in seizures and need for antiepileptic drugs (meds).

Methods

Patients were divided into low or high BOB group at baseline. BOB, seizure response, and med response were collected 1.5 to 3.5 years on KT. Seizure response and med response (including aspects of seizures or meds in addition to number) were determined the month BOB was collected. Seizure response and med response are a percent change from baseline where 0% reflects 0 seizures or meds.

Results

Low BOB group was significantly different (p<0.001) from high BOB group at baseline. BOB, seizure response, and med response were not significantly different between the two groups at 1.5‐3.5 years on KT.

BOB at baseline
Baseline
1.5‐3.5 years on KT

BOB (mg/dL)
BOB (mg/dL)
Seizure Response (%)
Med Response (%)

Low (n=10)
4.2 (2.4)*
32.6 (17.6)
50.0 (86.5)
27.2 (32.2)

High (n=10)
20.7 (11.1)
41.5 (14.9)
27.2 (41.8)
60.2 (45.9)

Data are mean (± SD), * is (p<0.001) compared to high

Conclusion

Children with epilepsy with different baseline blood BOB have similar BOB, seizure response, and med response on KT for 1.5‐3.5 years on KT.

Supported in part by the NIH/NCATS CTSA to the University of Florida UL1 TR000064
Human Milk Intake and Pesticide Transfer in Agricultural and Urban Areas of Sonora, Mexico
Authors: Limon‐Miro Ana , Aldana‐Madrid Maria , Antunez‐Roman Lesley , Alvarez‐Hernandez Gerardo , Rodriguez‐Olivarria Guillermo , Valencia Mauro
Published: June 2021

Background

Breast milk is considered the best way to feed newborn babies in order to achieve optimal growth, development and health. Despite being essentially sterile and safe, people may be exposed to various pollutants when living in different environments.

Objective

To measure human milk production by isotopic techniques, mother's body composition and pesticide transfer to babies through human milk in agricultural and urban areas of Sonora, Mexico.

Methods

Human milk intake was determined by the dose‐to‐the‐mother technique using deuterium oxide dilution. Likewise, mother's body composition was assessed by the intercept method. Organochlorine pesticide residues (p,p'‐DDT, p,p'‐DDE, p,p'‐DDD) and pyrethroids (deltamethrin , cypermethrin and cyhalothrin) in breast milk samples where measured by gas chromatography.

Results

62 lactating women and their infants participated in the study, 32 where urban residents and 30 lived in the agricultural area. There was a difference of approximately 100 mL on the daily milk intake between the study areas (799 mL in the agricultural area and 707 mL in urban participants (p< 0.05)). The concentrations of DDT metabolites were higher in the urban group (p< 0.002), however none of the samples exceeded the safe limits established by the Environmental Protection Agency and FAO/WHO.

Conclusion

Breast milk intake was higher in agricultural areas in Sonora compared to the urban region. Consumption of human milk by infants, can still be considered a safe feeding practice in these environments.
Txt4HappyKids: Using text messaging to promote fruit and vegetable intake among low‐income families with young children, a pilot study
Authors: Power Julianne , Bersamin Andrea , Uliassi Daniel , Braccio Courtney
Published: June 2021

Low‐income populations, especially low‐income children, do not consume enough fruits and vegetables (F&V) and may be disproportionately affected by chronic illnesses. Interventions to increase F&V intake can be costly and time consuming. Text messaging may be a time and cost‐effective way to promote F&V intake. Our objectives were to examine the acceptability and preliminary efficacy of a text message service to promote F&V intake among low‐income families with young children using a pre‐post design. Parents (n=107) participated in an 11 week intervention that included receiving 2 texts per week designed to reduce barriers to and promote F&V intake. Parents completed a survey about F&V attitudes and behaviors before and after the intervention. Seventy‐four parents completed the post‐intervention survey, a retention rate of 69%. Analyses included descriptive statistics and a Wilcoxon Signed‐Rank Test. Approximately three‐quarters of parents found the texts very useful (72%) and agreed or strongly agreed that they were more aware of the foods their children ate (81%) and of nutrition (78%). Over 80% of parents reported trying new ways of preparing F&V. After the intervention, parents receiving food assistance in the last 12 months (n=34) reported that their children ate more than one fruit (Z = ‐2.998, p = .003) and vegetable each day (Z = ‐2.430, p = .015) significantly more often. No change was observed among parents who did not receive food assistance (n=37). These results show promise that text messaging may be an effective way to supplement food assistance programs in promoting a healthy diet.
Efficacy of Formats for Added Sugar Labeling on Pre‐Packaged Foods
Authors: Vanderlee Lana , Hobin Erin , White Christine , Bordes Isabelle , Hammond David
Published: June 2021

Most health authorities suggest limiting added sugar consumption. In Canada and the US, current nutrition labels require information for total sugars, with no differentiation between naturally occurring sugars or added sugars, and do not provide a % daily value (%DV) as a reference of recommended consumption. An online study was conducted with 2,010 young people ages 16 to 24 from across Canada. Participants were asked questions regarding perceptions of sugar and recommendations for sugar intake. Participants were then shown one of three current nutrition labels including ingredients lists labeled with information for: total sugar only; total + added sugar; or total + added sugar + %DV for added sugar, and asked if there was any added sugar in the product, and if the amount of added sugar was a little, a moderate amount, or a lot. In total, 59% reported thinking of sugar in grams, 33% in teaspoons and 8% in other measures. Overall, 3% of participants correctly reported the recommended limit for added sugar as <10% of energy intake. Participants were more likely to correctly identify that the product contained added sugar when labeled (95% in total + added sugar and 93% in total + added sugar + %DV vs. 78% total sugar only, p<0.05). When asked, 55% of participants in total + added sugar condition and 73% of those in total + added sugar + %DV condition correctly identified added sugar content as 'a lot', compared to 42% in the total sugar only condition (p<0.05). Improved labeling may improve consumer knowledge of added sugar and levels of added sugar in food products. This research may help inform recently announced reformatting of Nutrition Facts information on prepackaged food items in Canada and the US.
Overcoming Consumer Inertia to Dietary Guidance
Authors: Byrd‐Bredbenner Carol , Webb Densie
Published: June 2021

The first edition of the Dietary Guidelines for Americans laid the cornerstone of nutrition policy in the US. Yet, 35 years later, consumers' adoption of dietary practices congruent with the Guidelines remain far from ideal. Closing the gap between ideal and actual is a shared responsibility of government, industry, nutrition professionals, and others. Nutrition communicators have the responsibility for creating messages and programming that resonate with consumers and build their capacity and desire to implement dietary recommendations. However, many report continued confusion about healthy eating guidance. Application of key evidence‐based communication practices, such as the following, could improve communication and reduce confusion: aim for simplicity, conciseness, and clarity; make food‐based recommendations; use easy to understand terms and engaging writing styles; cognitive test messaging; explain why guidance evolves; position messages within modern lifestyles; keep messages actionable and realistic; use positive tones that create partnerships between the communicator and consumer; respect consumers' abilities and available resources; target and tailor guidance to consumer groups; align with consumer needs, value, motivations; remember eating enjoyment is the key driver of food choice; use explicit examples; show benefits of healthy eating; offer solutions to real or perceived barriers; expand responsibility to include the environment; build on existing positive behaviors; and celebrate progress. Improved Guidance and related communications have the potential to give consumers increased control over their diets so they can enjoy better health on their own terms. Funding:North American Meat Institute
Communities' perceptions of changes in income, women's empowerment and nutrition as a result of participating in Feed the Future activities in Rwanda
Authors: Gewa Constance , Clark Samantha , Titus Sarah
Published: June 2021

While the potential of agricultural production to improve women's and children's nutrition has been recognized, there is still limited understanding of the specific pathways through which USAID‐funded Feed the Future value chains can positively impact nutritional status in vulnerable households. The current study was conducted to document the process and progress made by two Rwanda‐based Feed the Future activities, the Integrated Improved Livelihoods Program (IILP) and the Rwanda Dairy Competitiveness Program II (RDCP II), in working along agriculture‐to nutrition pathways. Specifically, we explored how increases in income, as a result of participating in Feed the Future activities, changed purchasing and consumption patterns and how engagement in the activities affected care‐seeking and care‐giving practices and women's empowerment. Interviews and discussions were conducted with activity staff and beneficiaries and, community leaders in three districts of Rwanda. Quantitative data were summarized into means and percentages. Qualitative data were coded into specific themes. Study results indicate a general improvement in program beneficiaries' income, crop production, and women's empowerment. Despite the positive trend, IILP and RDCP II face challenges that may hinder further movement along the agriculture‐to‐nutrition pathways, including demands on women's time and energy use, low consumption of animal‐sourced foods, targeting children's nutrition within the first 1,000 days, and monitoring nutrition indicators. The research highlights gaps that need to be addressed to further improve women and children's nutrition in Rwanda.
Microengineered Human Gut‐on‐a‐Chip for Dissecting Intestinal Inflammatory Disease
Authors: Kim Hyun Jung , Ingber Donald
Published: June 2021

Human intestinal inflammatory diseases involve debilitating inflammation and mucosal injury caused by complex interactions between gut microbes, intestinal mucosa and immune components. However, it has not been possible to precisely define how these interacting factors contribute to the disease development or to responses to clinical therapies because human‐relevant experimental models that can independently control these factors do not exist. We developed a 'Gut‐on‐a‐Chip' microdevice lined by intestinal villi that mimics the structure and function of living intestine. The physiological microenvironment was recreated by flowing fluid and exerting mechanical cyclic deformations that emulate peristalsis. We used this model to independently vary potential contributors to human intestinal inflammation and epithelial injury. We found that pathological destruction of intestinal villi resulted when the villi were challenged to luminal stimulation such as lipopolysaccharide and immune cells, simultaneously. These intestinal injuries induced secretion of four proinflammatory cytokines that were necessary and sufficient to induce villus injury, which were suppressed by co‐administering probiotic or antibiotic therapy. Our results can lead to the development of a humanized in vitro disease model that faithfully mimics human intestinal pathophysiology observed in IBD patients, which can be used to dissect disease mechanisms and determine the efficacy of new drugs.
Proteome Analysis of Plasma Exosomes in a Mouse Model of Dilated Cardiomyopathy (4C30 strain)
Authors: Suzuki Osamu
Published: June 2021

Aim

The role of exosomes is focused on in various diseases. In this study, I examined protein profiles in plasma exosomes of a mouse model of dilated cardiomyopathy (4C30 strain) to discover possible protein biomarkers for cardiomyopathy in plasma exosomes.

Methods

Plasma samples were collected from 15‐week‐old male mice of cardiomyopathic 4C30 and normal C57BL/6NCr mice (five mice/strain). Plasma exosomes were collected from 1 mL of plasma, pooled from the five mice (0.2 mL/mice) in each strain using Exosome extraction kit for plasma (Invitrogen). Exosomal proteins were solubilized, cleaned up, reduced and alkylated. Approximately 50 µg of exosomal proteins were separated by isoelectric focusing and then SDS‐PAGE. After SyproRuby staining, two‐dimension electropherograms of exosomal proteins were compared between two strains. Some protein spots were punched out and their protein identities were determined by mass spectrometry.

Results and Discussion

Only a few differences were found in exosomal proteins between strains. Of proteins preferentially present in the 4C30 exosome, three spots were picked up and examined by mass spectrometry. One of them was fibrinogen gamma chain (FGG), which was thought to be a contaminant from plasma soluble components. The other two spots were under examination. Our results suggest that cardiomyopathy induces only a subtle change in exosomal proteins. This work was supported by a grant from the Ministry of Health, Labour and Welfare of Japan.
Anti‐arthritic effects of melatonin through blockade of cytonuclear shift of MMP‐13
Authors: Hong Yunkyung , Hong Yonggeun
Published: June 2021

No curative treatments for osteoarthritic cartilage have been reported. The aim of the present study was to determine the therapeutic effects of melatonin on osteoarthritic chondrocytes. Chondrocytes were isolated from the cartilage specimens of the neonatal rats, cultured in monolayer, and treated with TNF‐α (10 ng/mL) repeatedly. We added DMSO combined with or without melatonin to medium. Caspase‐3 cleavage was induced by TNF‐α within 15 min, which is consistent with reduced cell viability. Co‐treatment of TNF‐α with DMSO induced not only increases of MMP‐13, both full length pro‐ and active proteins, but also shift of cytosolic MMP‐13 into the nucleus. Also there were metabolic disruption of COL2A1, proteoglycan loss, their atypical distribution, and excessive Ca2+ deposit. Melatonin, which was treated at the concentration of 1 nM, restored aberrant levels of COL2A1. Cytonuclear translocation of MMP‐13 was blocked by nanomolar concentration of melatonin partially, although its level was still remained high. Melatonin induced increase of the amount of proteoglycan with well‐distribution in chondrocytes. Moreover, the number of cells containing Ca2+ crystals decreased by melatonin treatment. Based on these results, we suggest that melatonin might be able to inhibit turning on of catabolic switch through regulation of MMP‐13 localization.

Funding: 2012R1A1A2005089, 2013R1A2A2A01067169, KGM4611512
Building a Better Mouse Model to Understand Infant Respiratory Syncytial Virus Disease
Authors: You Dahui , Siefker David , Shrestha Bishwas , Saravia Jordy , Cormier Stephania
Published: June 2021

Respiratory syncytial virus (RSV) is the number one cause of lower respiratory tract infection in infants; and there are no vaccines or specific antiviral drugs against RSV. The pathogenesis of RSV remains elusive. This is partly due to the fact that the mouse is semi‐permissive for human RSV. The present study sought to determine if a better neonatal mouse model of RSV infection could be obtained using a recombinant virus in which the F protein of standard laboratory strain A2 was replaced with that from the line 19 isolate (rA2‐19F).

Five‐day‐old pups were infected with A2 or rA2‐19F. rA2‐19F caused significantly more lung inflammation and mucus than A2. More type II T helper (Th2) cells and less type I (Th1) cells and effector CD8+ T cells (Tc1) were observed in the rA2‐19F infected lungs compared to A2. A cohort of infected neonates were allowed to mature to adulthood and reinfected with the same strain at 4 wks post primary infection. Similarly, secondary infection with rA2‐19F caused exaggerated Th2 and reduced Th1 and Tc1 responses. These immune responses during reinfection were associated with increased airway hyperreactivity, mucus hyperproduction and eosinophilia in rA2‐19F vs. A2 infected mice. The mechanisms are unknown, but are associated with higher pulmonary viral loads in rA2‐19F vs. A2 infected mice during primary infection.

Therefore, rA2‐19F caused more severe lung pathologies and Th2 immune responses compared to A2, possibly due to higher lung titers during primary infection. The rA2‐19F strain represents a better neonatal mouse model of RSV infection.

This work is supported by U.S. National Institutes of Health.
HIV X4 Viruses as Potential Agents in the Pathophysiology of HIV‐associated Pulmonary Hypertension
Authors: Manoharan Michael , He Qianbin , Flores Sonia , Almodovar Sharilyn
Published: June 2021

Pulmonary Hypertension (PH) is a severe disease that is more frequent in HIV+ individuals even with antiretrovirals. We do not know how HIV contributes to HIV‐PH. HIV proteins like gp120 play roles in the pathogenesis of HIV‐PH. Recently, we found that CXCR4‐utilizing HIV variants (X4) are overrepresented in patients with HIV‐PH compared to CCR5‐using HIV(R5). Hence, our objective was to determine if there is a differential impact of HIV‐X4 or R5 on pulmonary endothelial cells (EC). For this, we exposed cultured human pulmonary EC to recombinant HIV gp120 X4 or R5, and PBS (mock). We measured the activity of caspases 3/7 (a marker of apoptosis) from 4‐48 hrs. We also examined gene expression in EC exposed to gp120, by PCR array. We found increased caspase 3/7 activity in all EC at 8 hrs (initial apoptotic wave); this activity decreased to baseline at 16 hrs and increased again at 24 hrs (second apoptotic wave). Compared to X4, R5 gp120 induced slightly more apoptosis in EC at 8 hrs (p=0.20) and 48 hrs (p=0.10); however, X4‐treated EC displayed less apoptosis at 48 hrs than mock or untreated EC (p=0.06). Compared to R5, we also found 8 genes significantly overexpressed in X4‐treated cells, mainly the arachidonate 5‐lipoxygenase (ALOX5) gene (5‐fold, p=0.003). Our data support that HIV‐gp120 induces apoptosis in EC. We conclude that R5 and X4 may have a differential impact on EC and that X4 induces overexpression of ALOX5. Others have shown that ALOX5 is overexpressed in PH patients and induce pulmonary artery smooth muscle and EC proliferation. It is possible that HIV‐X4 induces apoptosis‐resistance in EC after long‐term exposure. Hence, we have uncovered HIV‐X4 viruses as potential agents in HIV‐PH.
Secukinumab Reverses Disease‐Defining Psoriasis Histopathology While Retaining Full T‐cell Activation Potential
Authors: Wharton Keith , Krueger James , Fuentes‐Duculan Judilyn , Wang Claire , Hillenbrand Rainer , Li Yue , Koroleva Irina , Hueber Wolfgang
Published: June 2021

Secukinumab is an anti‐IL‐17A fully human monoclonal antibody with clinical efficacy in psoriasis. The effects of secukinumab on skin pathology and T cell activation were investigated. In a randomized double‐blinded placebo controlled study, subjects with chronic plaque‐type psoriasis received 300 mg s.c. secukinumab (n=24) or placebo (n=12) at Weeks 0, 1, 2, 3 and 4, then every 4 weeks until Week 12. Biopsies of lesional and non‐lesional skin were assessed for epidermal growth, differentiation / maturation, mitotic rate, infiltrating T‐cells, macrophages, and dendritic cell (DC) subsets. The primary endpoint was histological disease reversal at Week 12. Circulating T‐cells were evaluated by flow cytometry for the activation marker CD69. 14/23 secukinumab‐treated (61%) and 0/12 (0%) placebo‐treated subjects attained histologic disease reversal at Week 12 (p<0.001; secukinumab vs. placebo). 14/24 (58.3%) secukinumab‐treated and 0/12 (0%) placebo‐treated subjects had a PASI90 response at Week 12. Histological disease reversal was correlated with PASI score at Week 12 (r= ‐0.77, p <0.001). T‐cells, macrophages, and myeloid DC subsets were reduced by secukinumab in lesional skin, but resident immune cell populations were retained. Ex vivo, 48% of circulating T‐cells induced CD69 before vs. 46% after secukinumab treatment (p=ns). Secukinumab treatment significantly reversed skin histopathology of psoriasis while reducing pathologic infiltration by T‐cells, macrophages, and DC subsets; responses to global T‐cell activation were unimpaired. Funded by Novartis.
Factor XIII A Clone EP3372 Provides Superior Staining on FFPE Human Tissue Sections Compared to Clone AC‐1A1
Authors: Liu Haiping , Muralitharan Sharmini
Published: June 2021

Factor XIII is a plasma proenzyme essential for normal clot formation. Its 'A' subunit (Factor XIII A) exists intracellularly in cells such as dermal dendritic cells, histiocytic reticulum cells as well as megakaryocytes, macrophages and blood monocytes. Detection of Factor XIII A (FXIIIA) by Immunohistochemistry (IHC) is useful in the distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans, with DFs mostly being FXIIIA positive. However, the frequently used FXIIIA antibody, clone AC‐1A1, is associated with considerable non‐specific staining in IHC. The aim of the study is to find a good IHC assay for FXIIIA.
Clone AC‐1A1 concentrate antibody was optimized with two IHC platforms on FFPE human tissue sections. However, the non‐specific staining was lingering. A Rabbit monoclonal antibody clone EP3372 was subsequently obtained and optimized. The optimized protocols for clone EP3372 and clone AC‐1A1 were compared. It was found that clone EP3372 not only produced stronger staining on tumor cells of dermatofibroma than clone AC‐1A1, but also devoid of any non‐specific staining. To further characterize clone EP3372, multi normal tissue arrays and tumor arrays were stained. In the normal tissues interstitial macrophages and stromal fibroblasts showed strong cytoplasmic staining. They were found in abundance in skin, gastrointestinal tracts, bladder, lymphoid tissues; and scattered in other tissues. Strong staining was found in dermatofibroma, capillary hemangioblastoma and fibrosarcoma. In addition, FXIIIA was also diffusely positive in 5 of 13 lymphomas.
This study suggests that FXIIIA clone EP3372 performs superior to clone AC‐1A1. The finding that some lymphomas are FXIIIA positive needs further investigation.
Pharmacology Specialty and Brain Drain are Factors for Consideration in Improving Pharmacology Education in Nigeria ‐ Lagos State University College of Medicine (LASUCOM) as Example
Authors: John Theresa , Agaga Luther
Published: June 2021

INTRODUCTION

In Nigeria, pharmacology departments teach medical students didactically towards direct health care delivery. Is there a premise for expanding pharmacology departments' programs to include science degree curricula using LASUCOM as example?

METHODS

Medical students of LASUCOM participated in different 18‐question surveys two months apart.

RESULTS

Respondents associated pharmacology with medicine (61.3%), science (24.9%), industry (16.8 %), and government (11.1%); 32.8% want to know clinical pharmacology, 7.1% basic pharmacology; 45.8% prefer to study lecturers' notes, 26.7% textbooks, 9.8% the Internet, and 2.7% journals;primarily to be able to treat patients (40%), obtain MBBS degree (39.1%) and 8.9% to know this subject, 3.1% to make money; 0.4% would definitely and 33.8% would probably become pharmacologists, while 27.1% are uninterested and 8.4% would never be pharmacologists. Regarding Nigeria as not yet developed (51%), most would visit a developed country (61%) after MBBS (52%); some to spend professional life (59.52%); highest interests are in USA (46.7%), Canada (44.8%) and any European country (40.48%); based on scientific and technical advancement (60%). Some 23.8% consider it important for self fulfillment; 32.9%, 26.2%, and 21.9% for opportunity, bright future, and job satisfaction; 63% would necessarily return to Nigeria for roots (39%), to bring expertise (51.9%) and experience (53.3%).

CONCLUSION

Respondents relate pharmacology to MBBS requirements; pharmacology departments could include science degree programs, collaborating with advanced countries, to contribute to local scientific and technical advancement, lack of which promotes brain drain.
In silico study of the binding mode of biased agonists of the angiotensin II type 1 receptor (AT1)
Authors: Malta de Sá Matheus , Gallottini de Magalhães Juliana , Massimo Modestia Silvestre , Goulart Trossini Gustavo , Miyakawa Ayumi , de Oliveira Rangel‐Yagui Carlota , Krieger José
Published: June 2021

AT1 is a G protein‐coupled receptor (GPCR), and the interaction with angiotensin II (AngII) causes vasoconstriction by Gq protein signaling. AT1 activation leads to receptor internalization by β‐arrestin, which can also act as a second messenger. Biased agonists are pharmacologically advantageous because they can antagonize the effects of Gq without interrupting β‐arrestin beneficial effects (cellular growth and survival), however, their binding mode remains unknown. Here, we investigated how biased agonists bind to AT1 using molecular docking and molecular dynamics simulations. AT1 homology model was built based on CXCR4 crystal structure and inserted in a lipid bilayer. The binding mode of five biased agonists (TRV027, TRV023, SI, SII and DVG) and 2 full agonists (AngII and SVdF) was compared. The analysis of interatomic distances showed that biased agonists interact with Trp84, Tyr87, Glu173, Asn174, Cys180 and Tyr292, while SVdF interacts with His183 and Gln187. Ser105, Arg167, Tyr184, Glu185 and Lys199 help positioning both biased and full agonists inside the receptor pocket, not affecting their activation mechanism. Because of the different binding mode, biased agonists cause conformational changes in AT1 that block Gq actions, still keeping β‐arrestin activated.
Coumarins from Angelica decursiva Inhibit Lipopolysaccharide‐induced Nitric Oxide Production in RAW 264.7 Cells
Authors: JUNG Hyun Ah , Ishita Ishrat Jahan , Islam Md. Nurul , Kim Yeong Shik , Choi Ran Joo , Sohn Hee Sook , Jo A Ra , Oh Seo In , Choi Jae Sue
Published: June 2021

Angelica decursiva has been used in Korean traditional medicine as an antitussive, analgesic, antipyretic, and cough remedy. In a recent study, the 90% methanol fraction of the dichloromethane fraction showed the most promising anti‐inflammatory activity; however, compounds responsible for the anti‐inflammatory activity were not identified. In this study, bioactivity‐guided isolation yielded 8 coumarins along with a new coumarin, 3′‐angeloyloxy‐4′‐hydroxy‐3′,4′‐dihydroxanthyletin (4). The anti‐inflammatory activity of compounds was evaluated via inhibition of nitric oxide (NO) and tumor necrosis factor‐α (TNF‐α), as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) expression in lipopolysaccharide (LPS)‐stimulated RAW 264.7 cells. Among the tested compounds, edulisin II (1) exhibited the highest NO inhibitory activity, followed by decursidin (2), Pd‐C‐III (3), 4, Pd‐C‐I (5), and Pd‐C‐II (6). Structure‐activity relationships revealed that esterification of the hydroxyl at C‐3′/C‐4′ with an angeloyl/senecioyl/acetyl is essential for NO inhibitory activity; the number and the position of angeloyl/or senecioyl groups greatly affect the potency of coumarins. Coumarins 1~6 inhibited TNF‐α production and iNOS expression while 1~4 inhibited COX‐2 expression. Thus, coumarins isolated from A. decursiva might be used as potential leads for the development of therapeutic agents for inflammation.
Assessing the Safety and Tolerability of Long‐Term Multi Day IVM Treatment for Alcohol Use Disorder
Authors: Arabian Natalie , Huynh Nhat , Lieu Dustin , Thuy Jamie , Patel Neel , Rodgers Kathleen , Davies Daryl
Published: June 2021

Alcohol use disorder (AUD) is a health crisis of unmet need. We propose that ivermectin (IVM), an FDA approved drug, can be repurposed to address this problem. Our group recently reported that long‐term (30 day) oral administration of IVM (10 mg/kg) significantly reduces murine ethanol intake without causing any overt signs of toxicity, suggesting that IVM represents a safe, tolerable, and effective agent for the treatment of AUDs. This first longer term study focused on an alcohol drinking paradigm that resulted in levels of alcohol intake that would more closely mimic the levels one would expect from someone drinking at a moderate level (i.e., social drinker). The current study extends this investigation and further assesses the safety and utility of multi‐day oral administration of IVM using a Drinking in the Dark (DID) paradigm, where animals in a very short period of time reach blood ethanol levels that are associated with “binge” drinking in humans. This was accomplished by investigating the effects of orally delivered IVM (10 mg/kg/day) in male alcohol preferring C57BL/6 over a 6 week (30 day, M‐F drinking) treatment period. We found that IVM significantly reduces ethanol intake and preference over the 6 week study without exerting any significant signs of toxicity, which was assessed using aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzyme level measurements. Histopathology assessments are currently ongoing. Taken together, findings, to date, continue to provide support for the development of of IVM for the treatment of AUD.

Suport: Research grants SC CTSI NIH/NCRR/NCATS –UL1TR000130 (D.L. D.)
Investigations into the Antidiabetic Activities of Bitter Kola
Authors: Obih Patience , Ambush Evelyn , Jimoh Akeem , Ezebuenyi Michael
Published: June 2021

In search of antidiabetic agents with tolerable or no side effects, researchers are investigating medicinal plants for antidiabetic activities. Acarbose and miglitol are standard drugs in the market used to reduce postprandial glucose surge, they possess some side effects. Their mechanism of action involves competitive inhibition of intestinal alpha‐glucosidases. Bitter kola is used in some parts of West Africa as an oral agent for treating type 2 diabetes mellitus. Its mechanism of action has not been elucidated. The aim of this study is to evaluate the inhibitory alpha‐glucosidase activities of aqueous extracts of Bitter Kola in vitro. The aqueous extract was prepared by soaking 100g of Bitter Kola powder in 200 ml of deinonized water for 48 hours at 40C. The extract was filtered, evaporated with rotavapor, and lyophilized. The extract was then used in in vitro assay to inhibit alpha‐glucosidase. The extract was compared with acarbose, a standard antidiabetic agent that inhibits alpha‐glucosidase. The result shows that Bitter Kola inhibits alpha‐glucosidase and compares favorably with acarbose, a positive control that is already in the market. Bitter kola will be further examined by characterization, isolation, purification, and enzyme assays in order to display its maximal potential.
Sestrin2 Regulates TLR‐mediated Proinflammatory Signaling in Macrophages
Authors: Ki Sung Hwan , Yang Ji Hye
Published: June 2021

Sestrins (Sesns) are conserved antioxidant proteins that accumulate in cells in response to various stresses. However, the regulatory roles of Sesn2 in the immune system and in inflammatory responses remain obscure. In the present study, we investigated whether Sesn2 regulates TLR‐mediated inflammatory signaling and sought to identify the molecular mechanism responsible. In cells expressing Sesn2, it was found that Sesn2 almost completely inhibited lipopolysaccharide (LPS)‐induced NO release and iNOS expression. A gene knockdown experiment confirmed the role of Sesn2 in LPS‐activated RAW264.7 cells. Consistently, proinflammatory cytokine release and expression were inhibited in Sesn2‐expressing cells. Furthermore, Sesn2 prevented LPS‐elicited cell death and ROS production via inhibition of NADPH oxidase. NF‐κB and AP‐1 are redox‐sensitive transcription factors that regulate the expressions of diverse inflammatory genes. Surprisingly, Sesn2 specifically inhibited AP‐1 luciferase activity and its DNA binding, but not those of NF‐κB. AP‐1 inhibition by Sesn2 was found to be due to a lack of JNK, p38, and c‐Jun phosphorylation. Next, we investigated whether Sesn2 protects galactosamine (Gal)/LPS‐induced liver injury in mice infected with a recombinant adenovirus Sesn2 (Ad‐Sesn2). Ad‐Sesn2 present less severe hepatic injury as supported by decreases in the ALT, AST, and hepatocyte degeneration. Moreover, Ad‐Sesn2 attenuated Gal/LPS‐induced proinflammatory gene expression in mice. The study shows that Sesn2 inhibits TLR‐induced proinflammatory signaling and protects cells by inhibiting JNK‐ or p38‐mediated c‐Jun phosphorylation.

This study was supported by the National Research Foundation (NRF) funded by the Korea government (MOSIFP) (Grant No. R13‐2008‐010‐00000‐0)