bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Green Tea and EGCG on the Growth Rate and Cell Density of the Probiotic Bacteria Lactobacillus acidophilus and Lactobacillus gasseri
Authors: Story Erica N , Azcarate‐Peril Andrea , Klaenhammer Todd R , Harris Gabriel K
Published: June 2021

Green tea and probiotic bacteria have been reported to have beneficial health effects individually. The purpose of this study was to determine if green tea (GT) or epigallocatechin‐3‐gallate (EGCG), the main flavonoid component of GT, would stimulate the growth rate and increase the cell density in planktonic cultures of the probiotic bacterial strains Lactobacillus acidophilus NCFM (L. acid.) and Lactobacillus gasseri ATCC 33323 (L. gas.). Aqueous GT and EGCG extracts were prepared and matched for total phenol content. Growth rate was determined using a 96‐well microtiter plate assay. Cell density was assessed via optical density at 600nm. GT (1, 2, 10, 20, 30 and 40%) and EGCG (1, 2 and 10%) enhanced the maximum specific growth rate (MSGR) of L. acid. vs. the control. GT (4, 10, 20, 30, and 40%) and EGCG (1, 2, 4, 10, and 20%) also enhanced the MSGR of L. gas. relative to the control. GT (10 and 30%) and EGCG (1% only) increased the cell density of both L. acid. and L. gas. relative to the control. In summary, in preliminary results, GT and EGCG increased the growth rate and final cell densities of both L. acid. and L. gas., suggesting that combinations of probiotic cultures with tea components may promote survival, growth or activity in the gastrointestinal tract. This project was supported by North Carolina State University, the NC Dairy Foundation, and the Southeast Dairy Foods Research Center.
Fructooligosaccharide supplementation improved blood antioxidative status in the constipated elderly subjects
Authors: Wu Wentzu Irene , Tseng Yun‐Hua , Yen Chi‐Hua , Chen Hsiao‐Ling
Published: June 2021

Fructooligosaccharide (FO) has been shown to stimulate the growth of bifidobacteria in men which may beneficially exert antioxidative effect. We have demonstrated FO supplementation promote fecal bifidobacteria population in constipated age population. This study further investigated effects of FO supplementation on blood antioxidative status in these subjects. Ten elderly adults (6 males) aged 74.0 ± 3.3 (mean ± SD) completed the single‐blind, placebo‐ and diet‐controlled study that consisted a 4‐wk placebo (3 g/d fructose syrup), a 4‐wk FO (10 g/d oligosaccharides) and a 4‐wk post period. Fasting bloods were collected at the end of each period for analysis of antioxidants, trolox equivalent antioxidant capacity (TEAC), thiobarbitituric acid‐reactive substances (TBARS) in the plasma. DNA strand breakage of whole blood, indicator of blood peroxidation, was determined using single‐cell electrophoresis (comet) assay. Results (means ± SDs) indicated that FO supplementation significantly increased plasma vitamin C level from 4.5 ± 1.1 to 11.9 ± 3.4 μM (P < 0.05 vs placebo) and tended to increase the plasma TEAC, vitamin E and GSH levels (P > 0.05). Plasma TBARS level was 13.1 ± 1.5 mM in the placebo period, which was significantly reduced to be 11.0 ± 1.6 mM in the FO period (by 16%, P < 0.05) and 10.3 ± 1.3 mM in post period (P < 0.05). The DNA strand breaks of whole blood was significantly reduced by 56% (P<0.05) with FO supplementation, and this effect lasted through the post period. Therefore, this study suggested that supplementation of FO exerted prolonged beneficial effects on plasma antioxidant capacity in constipated elderly subjects. This research was supported by the National Science Council 96‐2320‐B‐040‐031‐MY3, Taiwan.
Unlocking the Archives: Genomic Analysis of Formalin‐Fixed Paraffin Embedded Tissue
Authors: Monzon Federico Alberto , Alvarez Karla , Lyons‐Weiler Maureen A , Kash Shera , Kim Hyun‐Jung , Hagenkord Jill M
Published: June 2021

Background

Virtual karyotypes derived from SNP microarrays can be performed on formalin‐fixed paraffin embedded (FFPE) tissue samples.

Methods

284 archival FFPE human tissue samples (tumor and normal) were processed to obtain virtual karyotypes with Affymetrix 10K 2.0 or 250K Nsp SNP microarrays. Tissue was macro‐dissected from 10µm sections and DNA extraction was performed. Data analysis was performed with the CNAG 3.0 software.

Results

226 samples (79.6%) yielded adequate virtual karyotypes for interpretation. Importantly, 43% of failed samples belong to one specific source where tissue blocks were subject to extreme temperature variation. Parameters for selecting samples for hybridization based on PCR product size range for the 10K 2.0 arrays were developed which obtained 80‐90% success rate on hybridizations. 37 samples were repeated (2 to 4 times) and in all instances results from all successful repeats from one sample showed identical virtual karyotypes. In 15 samples two or more tumor regions were assayed separately and in 53% of these, tumor heterogeneity in chromosomal imbalances was observed.

Conclusion

Virtual karyotyping with SNP microarrays is a robust technique that shows good performance and excellent reproducibility when applied to the analysis of FFPE tissues.
Effects of blueberries in prevention of atherosclerosis in ApoE knockout mice
Authors: Wu Xianli , Ferguson Matthew E , Wilkes Samuel E , Nagarajan Shanmugam
Published: June 2021

ApoE knockout (ApoE−/−) mice were fed AIN‐93G diet (CD) or CD formulated to contain 1% freeze‐dried whole wild blueberries (CD1% BB). Mice were sacrificed after 20 weeks on the specified diet. Atherosclerotic lesions in aortic sinus were determined by staining cryosections (10 μm) with Oil Red O. The mean lesion area for ApoE−/− mice fed the CD1% BB was reduced by 39% (P <0.01) compared to CD fed animals. Serum LDL‐cholesterol and triglyceride levels were slightly lower in ApoE−/− mice fed CD1%BB (NS) compared to CD fed animals. Serum paraoxonase 1 activities in serum of CD1%BB animals were higher than that in CD animals (P<0.05). Superoxide dismutase activities in both serum and liver were found to be increased (P<0.05) in CD1%BB‐fed animals. Serum total antioxidant capacity measured by ORAC was not different between CD and CD1%BB fed animals, though a slight increase in CD1%BB‐fed animals was observed. These results indicated that anti‐atherogenic effects of BB are probably independent of changes in serum lipid profile. Furthermore, in addition to directly scavenging free radicals, BB in the diet altered antioxidant status by increasing antioxidant enzymes. (USDA‐CRIS‐6251‐5100002‐06S)
A systematic overview and meta‐analysis of genetic variation within the folate metabolic network and cardiovascular disease (CVD) risk
Authors: Wernimont Susan M. , Stover Patrick J. , Wells Martin T. , Cassano Patricia A.
Published: June 2021

Dysfunctional folate metabolism has been implicated in chronic diseases including CVD. The relation of the methylene‐tetrahydrofolate reductase enzyme to CVD risk is the subject of several meta‐analyses, yet much less is known about variation in other folate network genes in relation to CVD. Thus, a systematic overview and meta‐analysis of genetic variation in the folate network in relation to CVD was conducted. Fifty‐two genes in the folate network were identified, representing key reactions and linked steps. Four genes had an evidence base sufficient to summarize: cystathionine‐beta‐synthase (CBS, 25 studies), methionine synthase (MTR, 16 studies), methionine synthase reductase (MTRR, 9 studies) and transcobalamin II (TCN2, 4 studies). In CBS, 844ins68 had a differential effect by CVD subtype: for heart disease the variant decreased risk (OR 0.77; 95% CI 0.6, 1.0; I2 24.2%), for stroke & other vascular disease it increased risk (OR 1.30; 95% CI 1.0, 1.7; I2 0%). In MTRR, rs1801394 increased the risk of CVD (OR 1.27; 95% CI 0.9, 1.7; I2 19.3%), and the number of publications precluded subtype analysis. For CBS rs5742905, MTR rs1805087, and TCN2 rs1801198, little or no association with CVD was observed. Thus, the association of genetic variation in the folate network with CVD differs by gene and outcome, and few variants have been studied sufficiently to allow meta‐analysis. Funding: NIH T32 DK007158‐33 (SMW).

Grant Funding Source

NIH T32 DK007158‐33 (SMW)
Selenium status and erythropoiesis in mice
Authors: Kaushal Naveen , Hegde Shailaja N , Gandhi Ujjawal H , Paulson Robert F , Prabhu K. Sandeep
Published: June 2021

Reduced hematocrit has been associated with selenium deficiency in many epidemiological studies in animal and human subjects. However, the events leading to such hematological changes are not well understood. Recent studies have shown that oxidative stress plays an important role in the regulation of erythropoiesis. Selenoproteins, such as glutathione peroxidases, can effectively scavenge peroxides and mitigate cellular oxidative stress. Foxo3, a key transcription factor of the forkhead family that regulates expression of selenium‐dependent glutathione peroxidase‐1, has been reported to be vital for erythroid development. Given the importance of antioxidants in the regulation of erythropoiesis, time seems propitious to study the role of selenium in erythroid development. As a consequence of increased oxidative stress in erythrocytes isolated from selenium‐deficient mice, a significantly higher levels of denatured hemoglobin (as Heinz bodies) were seen; however, such Heinz bodies were absent in the erythrocytes in selenium‐adequate (0.1 ppm) and selenium‐supplemented (0.4 ppm) mice. Our studies indicate that selenium is essential during erythrocyte development.
Anti‐inflammatory potential of Selecoxib
Authors: Kaushal Naveen , Desai Dhimant , Arner Ryan J , Gandhi Ujjawal H , Amin Shantu G , Prabhu K. Sandeep
Published: June 2021

Celecoxib is a selective cyclooxygenase (COX)‐2 inhibitor that has also shown promise as a chemopreventive agent. Previous reports have demonstrated the ability of celecoxib to inhibit COX‐2 expression by targeting upstream kinases. Given the parallels between selenium and celecoxib in inhibiting COX‐2 expression and activity, two seleno‐derivatives of celecoxib, 4‐[5‐(4‐methylphenyl)‐3‐(methylselenocyano)‐1H‐pyrazol‐1‐yl]benzene‐sulfonamide (Selecoxib‐CN) and 4‐[5‐(4‐(methylselenomethylene)phenyl)‐3‐(trifluoromethyl)‐1H‐pyrazol‐1‐yl]benzene‐sulfonamide (Selecoxib‐Me) were synthesized. The two derivatives were compared with the parent celecoxib in terms of their ability to inhibit the activity of COX‐2 as well as transcription of proinflammatory genes such as COX‐2. Selecoxib‐CN appeared to be a better inhibitor of COX‐2 activity. A significant decrease in LPS‐induced COX‐2 expression was observed in Selecoxib‐CN treated RAW 264.7 macrophages; while Selecoxib‐Me was ineffective. NF‐kB activation was also found to be significantly reduced in cells treated with 0.1 uM Selecoxib‐CN when compared with the other two compounds. In conclusion, we demonstrate that Selecoxib‐CN potentiates the anti‐inflammatory efficacy of parent coxib. These studies also open new vistas towards effective chemopreventive therapeutics with novel selenium‐derivatives. NIH CA128045 (KSP)
Relative distribution of protein and non‐protein bound Se in liver and muscle of growing pigs fed two sources of dietary Se
Authors: Lei X G , Li J G , Wang K N , Xia X J
Published: June 2021

Our objective was to determine effects of dietary Se source and concentration on tissue distributions of protein bound Se (PBSe) or non‐protein bound Se (NPBSe) in pigs. Two trials were conducted with 36 weanling pigs fed a corn (from Se‐deficient area in Sichuan)‐soy basal diet (0.04 mg Se/kg) added with 0, 0.3, or 3.0 mg Se/kg as Se‐enriched yeast (SeY) or sodium selenite for 8 wk. At the end, all pigs were killed to collect liver and muscle for Se analysis using hydride‐generation atomic fluorometric spectrophotometer (AFS‐830, Titan Instr, China). The 2 forms of Se were separated by centrifugation after the tissue homogenates were treated with 10% TCA. Total Se concentrations in the two tissues of pigs fed either source of Se showed dose‐dependent increases (P < 0.05) with dietary Se levels. Relative percentages of the NPBSe and the PBSe to total tissue Se in liver were increased (P < 0.05) and decreased (P < 0.05), respectively, by the increases of dietary Se levels. This was also true for the relative distribution of the two forms of Se in muscle of pigs fed selenite. In contrast, the NPBSe and the PBSe remained constant at 6 and 94% of total tissue Se, respectively, in muscle of pigs fed the three levels of SeY. In conclusion, the relative distributions of the protein and non‐protein bound Se in liver and muscle were affected differently by dietary Se source (Chinese Natural Science Foundation Projects 30628019 & 30700585).
The effect of manganese exposure on endogenous markers of oxidative stress in astrocytes
Authors: Fordahl Steve , Anderson Joel , Milatovic Dejan , Aschner Michael , Erikson Keith
Published: June 2021

Manganese (Mn) is an essential trace element; however, accumulation of Mn in the brain can propagate cellular damage leading to neuronal dysfunction and symptoms analogous to neurodegenerative disorders (i.e. Parkinson's disease). Previously our lab has shown that iron deficiency significantly increases Mn accumulation decreasing glutathione (GSH) functionality. The resulting oxidative damage may alter the neuronal environment leading to dysfunction. Our goal is twofold; to characterize how Mn accumulation in astrocytes leads to lipid peroxidation (LP), and to test the efficacy of á‐tocopherol or N‐acetyl cysteine therapy in attenuating the production of F2Isoprostanes (F2Isop), a marker of LP. Primary rat astrocytes were treated with 100 or 300 ìM Mn with or without antioxidant therapy. GSH, F2Isop, and Mn levels were measured to assess overall oxidative stress. Mn exposure significantly increased GSH levels in the absence of antioxidant treatment (p<0.005), though no difference in GSH was seen in any antioxidant treatment compared to control. Significant increases in F2Isop (p<0.05) were present in Mn treated cells and attenuated by antioxidant pretreatment. These data imply that Mn induced LP is due to alterations in the GSH protective system, but may be mitigated by antioxidant therapy.

Funded by NINDS 1R15NS061309‐01
Effect of Coenzyme Q10 and green tea on plasma and liver lipids, platelet aggregation, TBARS production and erythrocyte Na leak in simvastatin treated hypercholesterolemic rats
Authors: Kim Yanghee , Kang Younghee , Kang Jungsook
Published: June 2021

Forty Sprague Dawley rats were divided into four groups and fed 0.5% cholesterol for the control; control plus 30 mg/kg simvastatin; statin plus 15mg/kg BW CoQ10 or 5% green tea powder for 4 weeks. There was no difference in plasma total cholesterol among groups, but liver total cholesterol was significantly decreased in green tea group compared with the others (p<0.05). Plasma triglyceride was significantly decreased in statin group compared with green tea group (p<0.05), and liver triglyceride was significantly decreased in green tea groups compared with the control (p<0.05). Platelet aggregation of green tea group was tended to be lower in the maximum aggregation with the higher in initial slope. Intracellular Na in green tea group was significantly higher than the control or statin group (p<0.05). Na leak in intact and AAPH treated cells was significantly decreased in statin group compared with the control (p<0.05). TBARS production in platelet rich plasma was significantly decreased in groups with CoQ10 and green tea compared with the control and statin group (p<0.05), and liver TBARS was significantly decreased in green tea group compared with statin group (p<0.05). In present study, simvastatin at dose 30 mg/kg did not show cholesterol lowering effect in rat. However, CoQ10 and green tea had antioxidant effects in rats treated with simvastatin which is known to deplete antioxidant capacity.
Does vitamin D status predict outcomes of experimentally‐induced muscle pain and weakness in healthy young volunteers?
Authors: Peterson Catherine A , Ring Susan M , Dannecker Erin A
Published: June 2021

Vitamin D receptor's presence in skeletal muscle indicates a role in muscle function and clinical symptoms of vitamin D deficiency include muscle weakness and pain. No one has yet examined the association of vitamin D status and experimentally‐induced muscle pain or weakness in healthy people.

Methods

Muscle damage to the elbow flexors was induced with eccentric exercise (EE) in 27 men (mean age 22.5 yr) and 21 women (mean age 22.6 yr). Muscle pain ratings from unloaded movement and isometric contractions and peak isometric force (IF) were collected before EE and for 4 days post‐EE. Serum 25‐hydroxy vitamin D (25OHD) was assayed 2 days post‐EE. Linear regression was used to determine if 25OHD was a predictor of any outcome.

Results

Serum 25OHD did not predict any of the pain or strength measures. In men: R2 for pain ratings ranged from 0 to 0.02, and p‐values from 0.48 to 1.00. R2 for IF ranged from 0 to 0.02 and p‐values from 0.48 to 1.00. In women: R2 for pain ratings ranged from 0.01 to 0.21, and p‐values from 0.14 to 0.74 . R2 for IF ranged from 0 to 0.04 and p‐values from 0.41 to 0.90.

Conclusion

Serum 25OHD did not predict muscle pain or strength after EE‐induced muscle damage in young healthy men and women. Support: Dept. of Nutritional Sciences, Univ. of Missouri, CA Peterson; and National Institute of Arthritis and Musculoskeletal and Skin Diseases (KO1 AR050146) and the Univ. of Missouri, EA Dannecker.
Hepatoprotective effects of Nigella sativa and bees' honey on hepatotoxicity induced by administration of sodium nitrite and sunset yellow
Authors: EL‐Kholy Wafaa M , Hassan Hanaa A , Nour Samar E , Abe Elmageed Zakaria E , Matrougui Khalid
Published: June 2021

Background

The study was conducted to shed the light on adverse effects of food additive such as sodium nitrite (NaNO2; as preservative) and sunset yellow (as color) on the rat liver. Furthermore, the study was extended to show the protective role of Nigella sativa (black seed) and bees' honey in modulating the toxic effects induced by these additives.

Methods‐results

Data show that the administration of NaNO2 and sunset yellow caused significant increase in serum and liver total lipids, total cholesterol, riglycerides and phospholipids levels. Also, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities were increased in serum and liver of rats. Oxidative stress markers; lipid peroxidation product and protein carbonyl group were increased in the liver. However, the antioxidants glutathione content, glutathione‐S‐transferase and catalase activities were decreased significantly in the liver tissue. Interestingly, a complete recovery of most of biochemical abnormalities was observed when black seed and bees' honey were administered, in combination, to rats intoxicated with NaNO2 and Sunset yellow.

Conclusion

We conclude that bees' honey is more hepatoprotective than black seed but the administration of both agents together has a better liver‐protection effect rather. Black seed and bees' honey should be used in Human food additives based on their protector effect
Assessment of self‐efficacy and its effect on plasma lipid profile in Hispanic diabetics
Authors: Batech Michael , Wheeler Gina , Ojo Emmanuel , Beeson Lawrence , DeLeon Marino , Balcazar Hector , Cordero‐MacIntyre Zaida
Published: June 2021

O: To evaluate the effect of self‐efficacy on diet, blood glucose and plasma lipids among Hispanics with diabetes.

M: Thirty four subjects (9 M & 25 F), ages 39 ‐ 69 years, participated in a 3‐month follow‐up study. "My Family Habits" questionnaire assessed changes in dietary self‐efficacy. Wilcoxon's Signed Rank and Paired

t‐Tests assessed changes between baseline and follow‐up and Spearman's correlation assessed associations between self‐monitored dietary intake and laboratory measurements.

R: In all subjects, there was a significant increase in self‐efficacy in choosing foods labeled low sodium, sodium free or no salt added (p=0.031), filling salt‐shakers with a mixture of herbs and spices (p=0.018), choosing fruits and vegetables instead of high fat foods (p=0.0198), and baking instead of frying fish (p=0.0084). After three months, HbA1c (p=0.0027), plasma total cholesterol (p=0.0006), plasma LDL cholesterol (p=0.0009), and blood glucose (p=0.0043), were inversely associated with choosing fruits and vegetables instead of high fat foods. A negative correlation was observed between plasma total cholesterol (p=0.012) and reading labels to choose foods lower in calories.

C: After a three‐month culturally and language‐sensitive diabetes education program, subjects with improved dietary choices had lower HbA1c, total cholesterol, LDL cholesterol and blood glucose.
Obesity and Health Risk Factors for Employees at a Major University in Rural Appalachian Ohio
Authors: Teeters Melissa Lea , Berryman Darlene E. , Holben David H. , Brannan Grace
Published: June 2021

Obesity is a major health concern in the U.S. Susceptibility to weight‐related problems is influenced by numerous factors such as dietary intake and emotional wellbeing. Work environment and job status likely contribute to obesity and its comorbidities. Although studies are limited, research shows that worksite interventions can be cost effective and have a positive effect on the overall health of the employees. The purpose of this cross‐sectional study was to determine if there was a significant difference between job classification and weight status or health risk for employees of Ohio University (OU), a large university located in the rural Appalachian region of the state. All employees were invited to participate in the study. Participants completed a health screening and a survey assessing the individual's wellness profile (WP). Data collected from the health screening included blood pressure, fasting blood lipids and glucose, and anthropometrics. Data from the WP included individual coronary risk, nutrition and fitness status, and emotional health. A total of 566 OU employees (226 staff, 81 faculty, 259 administrators) completed the study. Data for clinical parameters and survey findings will be presented based on job classification and weight status. The results from this study will benefit OU in its attempts to foster a culture of wellness and may help other large employers in rural settings.
Dairy Products Consumption in African American Women at Risk for Type 2 Diabetes Participating in a Nutrition and Lifestyle Education Program
Authors: Scripa Ioana , Cherry Carinthia , Taylor Martha
Published: June 2021

The objective of this study was to investigate the consumption of dairy products by African American women at risk for type 2 diabetes, participating in the D.R.E.A.M. study, a nutrition and lifestyle education program. A convenience sample of 29 women, aged 45 years or older was recruited from two churches in Greensboro, NC: n = 18 usual care and n =11 intervention group. Women in the intervention group participated in eight, one‐hour sessions that focused on implementing lifestyle changes. Classes were delivered by two women trained as peer educators. Participants in the usual care group received the same educational handouts, but did not attend classes. Face‐to‐face interviews with all participants, consisting of several questionnaires and a 24‐hour recall, were conducted at baseline, 8 weeks, and 12 weeks. Demographic characteristics of the women were similar, with the exception of more women from the intervention being in the > 200 % poverty level category (p=0.001). Group means for dairy product consumption were below the 2005 MyPyramid recommendation of 3 cups per day. All participants consumed more high‐fat dairy products versus low‐fat. No significant improvement was seen with intake of dairy products in either group. Mean consumption of nutrients associated with dairy products (vitamin D, calcium, and magnesium) was below the DRI for both groups. Supported by NCMHD/NIH 1P20MD002289‐01
Volume and Variety of Beverages Consumed by Third‐and‐Fourth‐Grade Urban Schoolchildren in Quetzaltenango, Guatemala
Authors: Montenegro‐Bethancourt Gabriela , Vossenaar Marieke , Solomons Noel W. , Doak Colleen M
Published: June 2021

Background

Within the context of what children consume across their entire diet has come a concern for what is consumed in liquid form. Beverage consumption is relevant both to the adequacy of hydration and the genesis of overweight/obesity.

Aim

To describe the volume, variety and nutrient contribution of the beverages consumed by 3rd and 4th grade urban schoolchildren.

Methods

We conducted a cross‐sectional study in 449 students. Intake data comprised a single 24‐h pictorial self‐recording, complemented by a nutritionist to quantify portions. Nutritional values for foods and beverages were calculated using the INCAP and USDA food composition tables.

Results

54 beverage items were consumed across 12 categories of drinks. A mean of 1185±425 mL of beverages were drunk on the evaluated day; 21% of all dietary energy was consumed in liquid form. Plain water was the only non‐caloric beverage. Coffee contributed the largest volume (27%), followed by plain water (14%) and commercial fruit drink (7%). Carbonated soda drinks provided 10% of beverages energy, less than the 25% from grain‐based gruels. The contribution of micronutrients from beverages ranged from 7% for vit B2 to 55% for vit A.

Conclusions

The dominance of sweetened drinks in the beverage profile of these urban schoolchildren is motive for public health concern.

Funded in part by Sight & Life, Basel and Nestlé Waters Co, Paris
Food insecurity is associated with pregnancy outcomes among low‐income Latinas
Authors: Hromi‐Fiedler Amber , Bermúdez‐Millán Angela , Chapman Donna , Segura‐Pérez Sofia , Damio Grace , Melgar‐Quiñonez Hugo , Pérez‐Escamilla Rafael
Published: June 2021

The objective of this study was to evaluate the relationship of food insecurity at two time periods, the year before pregnancy and during pregnancy, with pregnancy outcomes among low income Latinas. Food insecurity was assessed using a modified version of the U.S. Household Food Security Scale. Path analysis evaluated the direct and indirect effects of food insecurity on pregnancy outcomes. Findings showed a 1 point increase in the total food security score before pregnancy (indicating worsening food insecurity) directly increased pregravid BMI by 0.185 kg/m2 and directly increased the total food security score during pregnancy by 0.360 points. Food insecurity before pregnancy was also indirectly associated with gestational weight gain as well as infant birthweight. The total net indirect effect of a 1 point increase in food insecurity before pregnancy on gestational weight gain was ‐0.032 kg and on infant birthweight was 0.054 kg. Among food secure women, the predictive prevalence rate of macrosomia increased while the rate of low birthweight decreased with each hypothetical point increase in food insecurity before pregnancy. These findings suggest food insecurity before pregnancy may be important when evaluating the risk of suboptimal pregnancy outcomes among Latinas. Funded by Connecticut NIH EXPORT Center of Excellence for Eliminating Health Disparities among Latinos (NIH‐NCMHD Grant # P20MD0017650).
Activation of glutamate dehydrogenase increases renal ammoniagenesis: implications for the HI/HA syndrome
Authors: Brosnan John T , Treberg Jason R , Greene Katie , Clow Kathy , Brosnan Margaret E
Published: June 2021

Children with gain‐of‐function mutations in Glutamate Dehydrogenase (GDH) display hyperinsulinemia (HI) and hyperammonemia (HA). The HI has been clearly linked to an effect of increased GDH flux on insulin secretion. However, the origin of the HA is uncertain, particularly because hepatic GDH is considered to be close to thermodynamic equilibrium in vivo. We found increased ammonia release into the renal vein of rats infused with β‐2‐aminobicyclo[2.2.1]heptane‐2‐carboxylic acid (BCH), an activator of GDH. BCH infusion had no effect on the hepatic handling of ammonia as portal venous ammonia was effectively removed by the liver. BCH also caused increased ammonia production by isolated rat proximal tubules incubated with glutamine. BCH also increased ammonia production and flux through GDH in isolated rat kidney mitochondria incubated with glutamine. We conclude that activation of renal GDH may be responsible, at least in part, for the HA of the HI/HA Syndrome. (Supported by IGTC and CIHR).
Induction of macroautophagy by exogenously introduced calcium
Authors: gao wentao , Ding Wen‐Xing , Stolz Donna B.
Published: June 2021

Macroautophagy can be activated by a broad range of agents and cellular manipulations. In performing cellular transfection using the calcium phosphate method, we noticed that the calcium phosphate precipitates (CPP) could induce LC3 punctation. Because of the wide use of this transfection method in mammalian cells and the potential significance of calcium in autophagy induction, we investigated whether CPP could specifically induce macroautophagy. We found that CPP‐induced LC3 punctation was dependent on calcium and could be neutralized by an extracelluar or intracellular calcium chelator. The punctation was not due to nonspecific aggregation of LC3 since it depended on the amino acid residue Glycine120, which is specifically required for LC3 to conjugate to phosphatidylethanolamine (PE). Consistently, there was also a significant increase of the PE‐conjugated form of LC3. Electron microscopy confirmed the accumulation of typical autophagosomes following CPP treatment. Flux analysis indicated that CPP induced but did not inhibit autophagic degradation. Finally CPP‐induced autophagy depended on the classical macroautophagy machinery including Beclin 1, the class III phosphoinositide‐3 kinase and Atg5. Our studies thus indicate that exogenously introduced calcium in the form of CPP could specifically induce macroautophagy, which may have the practical significance in the use of this agent for introducing genes into cells, and for studying the mechanism of autophagy as a model system.
The Effects Of Palmitic Acid Concentrations On A549 Cellular Incorporation And Cellular Function
Authors: Benghuzzi Ham A , Tucci Michelle A , Cameron Joseph A
Published: June 2021

Neonates exhibit a high risk of developing acute and/or chronic lung disorder, often associated with surfactant deficiency. Alveolar type II cells (A549) synthesize dipalmitoyl phosphatidylcholine as the main surfactant. The objective of our study was to administer palmitic acid (PA) to A549 cells and determine the level of cellular viability, cellular damage, cellular morphology, and degree of surfactant production at 24, 48 and 72 hours of incubation. The results of our study show incorporation of 3H‐palmitic was approximately 96% after 24 hours. Our results also demonstrated concentrations of 0.01 M and 0.1 M PA caused marked dose dependent reductions in cell number as early as 24 hours. Markers of membrane cellular damage also were elevated in all treatment groups after 24 hours and remained elevated for the duration of the study. Cellular morphology revealed cells treated with PA initially appeared in clusters, with hyperchromatic nuclei compared with control. No differences in nuclear/cytoplasmic ratios were observed. After 72 hours the PA treated cells showed evidence of scant cytoplasm and hyperchromasia when compared to control. Overall, the results indicate that incorporation of palmitic acid caused increases in cellular damage and cellular death. This is most likely due to changing the distribution of the phosphatidyl moieties on the cellular membrane.
Polychlorinated biphenyls induce adhesion of breast cancer cells to human brain endothelium through lipid raft‐dependent upregulation of cell adhesion molecules
Authors: Eum Sung Yong , Choi Yean Jung , Radakovic Masa , Andras Ibolya E , Hennig Bernhard , Toborek Michal
Published: June 2021

During blood‐borne metastasis, upregulation of endothelial cell adhesion molecules can accelerate metastatic processes through increased adhesion of tumor cells to the endothelium. Chronic exposure to polychlorinated biphenyls (PCBs) produces a variety of effects including tumor‐promoting effects. Because the cerebrovascular endothelium can play a regulatory role in tumor metastatic processes in the brain, we have explored whether PCB 153 can upregulate adhesion of breast cancer cells to the brain endothelium. Exposure to PCB 153 increased expression of ICAM‐1 and VCAM‐1, and increased adhesion of MDA‐MB‐231 cells to endothelial cells. PCB 153‐induced ICAM‐1 expression was blocked by pretreatment with lipid rafts disrupting agent, methyl‐beta‐cyclodextrin (MβCD) or chemical inhibitors against the Src family kinases or PI3K/Akt. MβCD also inhibited PCB 153‐induced phosphorylation of Src kinase and Akt. Knockdown of caveolin‐1 using siRNA interference did not affect PCB153‐mediated upregulation of ICAM‐1 and VCAM‐1. Results of the present study indicate that PCB 153 can increase adhesion of tumor cells to brain microvascular endothelium and transendothelial migration of tumor cells through increased expression of ICAM‐1 and VCAM‐1 via lipid rafts‐dependent activation of the Src family kinases and/or PI3K/Akt signaling pathways. Supported in part by P42 ES 07380, MH63022, MH072567, and NS39254.
Aspirin‐triggered lipoxins override the apoptosis‐delaying action of myeloperoxidase in human neutrophils
Authors: El Kebir Driss , Jozsef Levente , Pan Wanling , Petasis Nicos A , Serhan Charles N , Filep Janos G
Published: June 2021

Myeloperoxidase (MPO), a heme protein abundantly expressed in the azurophilic granules in neutrophils generates cytotoxic oxidants and signals through the adhesion molecule CD11b/CD18 (Mac‐1) to activate and rescue neutrophils from apoptosis. Since aspirin‐triggered 15‐epi‐lipoxin A4 (15‐epi‐LXA4) inhibits Mac‐1‐mediated neutrophil adhesion, we studied its impact on MPO suppression of neutrophil apoptosis. Pretreatment of neutrophils with 15‐epi‐LXA4 or its metabolically stable analog 15‐epi‐16‐p‐fluorophenoxy‐LXA4 through downregulation of surface expression of Mac‐1 and inhibition of MPO release overcame the powerful anti‐apoptosis signal from MPO. 15‐epi‐LXA4 promoted apoptosis by attenuating MPO‐induced concurrent activation of ERK and phosphatidylinositol 3‐kinase/Akt‐mediated phosphorylation of Bad and reducing the expression of the anti‐apoptotic protein Mcl‐1. These led to collapse of mitochondrial transmembrane potential, cytochrome c release, resulting in increased caspase‐3 activity. The pro‐apoptotic action of 15‐epi‐LXA4 was predominant over MPO‐mediated effects even when 15‐epi‐LXA4 was added at 4‐hour post‐MPO. 15‐epi‐LXA4 did not inhibit the catalytic activity of MPO. Our results indicate that through overriding the MPO survival signal, aspirin‐triggered lipoxins may prevent neutrophil‐mediated tissue injury. (Grant support: CIHR MOP‐64283).
Olfactory Dysfunction and Olfactory Bulb Pathology induced by Urban Air Pollution
Authors: Villarreal‐Calderon Rafael , Osnaya Norma , Medina‐Cortina Humberto , Maronpot Robert , Calderon‐Garciduenas Lilian
Published: June 2021

Mexico City (MC) residents are exposed to severe air pollution and exhibit olfactory bulb inflammation. We provide evidence that chronic exposure to severe air pollution is associated with decreased smell function and the olfactory bulb accumulation of beta amyloid1‐42 and alpha‐synuclein. Sixty‐two MC young adults and 25 matched controls were administered the University of Pennsylvania Smell Identification Test (UPSIT). UPSIT deficits were present in 35.5% MC and 12% of controls. APOE e 4 MC residents scored significantly lower than APOE 2/3 or 3/3 carriers on 10 UPSIT items known to be particularly sensitive to Alzheimer's disease [respective mean (SD) scores = 7.67 (0.56) & 8.66 (0.16), p = 0.02]. The olfactory bulbs of 35 MC / 9 controls and 26 MC / 6 young control dogs were assessed histopatologically. MC subjects exhibited olfactory bulb endothelial hyperplasia and accumulation of particulate matter, βA42 (29/35) and/or α‐synuclein (4/35), while 69% of exposed dogs, but not controls, had Aβ42 in their olfactory bulbs. Ultrafine particles < 30 nm were seen in olfactory bulb human endothelial cytoplasm and basement membranes. Air pollution exposure is associated with olfactory dysfunction and olfactory bulb pathology and the APOE 4 allele may confer greater susceptibility to such abnormalities.
The G12 family proteins upregulate matrix metalloproteinase‐2 and invasion in human breast epithelial cells
Authors: Kim Eun‐Sook , Jeong Jae Boon , Kim Seonhoe , Lee Kyung‐Min , Noh Dong‐Young , Ha Ji Hee , Dhanasekaran Danny N. , Lee Chang Ho , Kim Sang Geon , Moon Aree
Published: June 2021

ABSTRACT

Mounting evidence suggests a role for the G12 proteins, Gα12 and Gα13, in the metastatic tumor progression. A direct role of G12 proteins in malignant phenotypic changes, however, has not been determined. This study aims to elucidate the molecular mechanism for a metastatic potential of Gα12 and Gα13 in MCF10A human breast epithelial cells using GTPase‐deficient active Gα12 (Gα12QL) and Gα13 (Gα13QL). Here we report, for the first time, that Gα12/13 induce upregulation of matrix metalloproteinase (MMP)‐2, leading to the invasive/migratory phenotypes in MCF10A cells while MMP‐9 is affected by neither Gα12QL nor Gα13QL. We further show that p53 is an important transcription factor for induction of MMP‐2 transcriptional activation by Gα12 and Gα13. MKK3/6, p38 MAPK and Akt were required for the Gα12/13‐induced MMP‐2 upregulation, invasion and migration of MCF10A cells. Taken together, this study elucidated a role of Gα12/13 in regulating process for MMP‐2 expression and malignant phenotypic conversion of MCF10A human breast epithelial cells, providing a molecular basis for the promoting role of Gα12 and Gα13 in breast cell invasion. [Supported by the KOSEF grant (MEST, No. R11‐2007‐107‐01002‐0), and by the KOSEF NRL Program grant funded by the Korea government (MEST, No. ROA‐2008‐000‐20070‐0).]
EGF Receptor Ligands Differentially Promote the Migration and Invasion of Malignant Peripheral Nerve Sheath Tumor Cells
Authors: Byer Stephanie , Eckert Jenell M , Watkins Stacey M , Carroll Steven L
Published: June 2021

Aggressive invasion of adjacent tissues is characteristic of malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy occurring in neurofibromatosis type 1 (NF1). These neoplasms often aberrantly express epidermal growth factor receptors (EGFRs), leading us to hypothesize that EGFR ligands present in MPNSTs and/or adjacent tissues promote MPNST invasion. We have found that EGF promotes MPNST migration in a substrate‐specific manner, enhancing migration on laminin and collagen type I relative to fibronectin. Induction of EGFR shRNA expression in MPNST cells stably transfected with a tetracycline‐regulatable lentivirus reduces baseline migration 40‐60%. Comparing the effects of the known EGFR ligands [EGF, betacellulin, epiregulin, heparin‐binding EGF (HB‐EGF), TGFα, amphiregulin] on MPNST cell lines derived from NF1‐associated (ST88‐14) or sporadic (STS‐26T) neoplasms, we found that these ligands promote migration in a concentration‐dependent manner, with EGF acting in a chemotactic fashion. However, these factors differ in their relative ability to induce migration. Further, although ST88‐14 cells are responsive to all 6 ligands, the STS‐26T migration is not enhanced by HB‐EGF or amphiregulin. These findings suggest that although EGFR ligands enhance MPNST migration and invasion, MPNST responses to these growth factors vary. Supported by grants CA122804 and NS048353.
Definitive Criteria for Ambiguous Lineage Leukemias
Authors: Cruse Julius M , Lewis Robert E , Coker John , Singleterry Will L , Suggs Jeanann L
Published: June 2021

Biphenotypic leukemias are acute leukemias of ambiguous lineage in which there is proliferation of more than one distinct cell type. In this case, both myeloid and lymphoid phenotypes are present in the blast population. As opposed to leukemias in which one specific myeloid or lymphoid population is found, these biphenotypic leukemias present a unique diagnostic challenge in these patients. Treatment is determined by identification of the predominant lineage. This study explores the successful use of the European international scoring system to define biphenotypic acute leukemias. Of nine cases of leukemias of mixed phenotype, determined by flow cytometric analysis, three were scored as biphenotypic by traditional 2001 WHO standards, whereas six were of ambiguous lineage but did not meet the scoring criteria for mixed phenotype. However, on re‐evaluation using the 2008 WHO guidelines, three of these cases were reclassified as biphenotypic based on the increased significance of myeloperoxidase (MPO) and combined CD14/CD64 positivity for myeloid lineage. Considering the worse prognosis of biphenotypic leukemia than AML or ALL, early identification of mixed lineage is critical for appropriate treatment.
Production of IL‐6 by hepatocytes as a general response to injury
Authors: Mars Wendy M. , Norris Callie , He Mu , Paranjpe Shirish , Michalopoulos George K. , Stolz Donna B.
Published: June 2021

IL‐6 is synthesized during the general acute phase response and, the hepatic response to IL‐6 is thought to be paracrine. For general injuries, provision of IL‐6 to the liver is thought to occur via NFkappaB‐dependent synthesis and release from immune cells at the injury site; IL‐6 is discharged into the circulation, travels to the liver, and stimulates the hepatocytes. When the site of injury is the liver itself, the IL‐6 is thought to be provided by resident hepatic immune cells. As LPS injection is used to simulate systemic bacterial infections, it was surprising to note that mice with hepatocellular‐specific inactivation of NFkappaB have significantly lower hepatic IL‐6 transcripts following LPS injection. Consequently, we hypothesized that hepatocytes can also synthesize IL‐6 in response to injury. Herein, we provide irrefutable evidence that normal hepatocytes in serum‐free cultures are capable of producing both IL‐6 mRNA and protein. Furthermore, injection of LPS into animals leads to production of hepatocellular IL‐6 and, hepatocytes from regenerating livers synthesize IL‐6 following hepatic resection. Finally we demonstrate that, HGF, an important monitor of hepatic function, regulates IL‐6 production by the hepatocytes both in vitro and in vivo. Combined, these results indicate that production of acute phase proteins in response to general injury can be autocrine.
Memantine and dizocilpine differ in acute and chronic interactions with morphine
Authors: Chen Yukun , Evola Marianne , Young Alice
Published: June 2021

Memantine (MEM) is a NMDA channel blocker that binds to dizocilpine (DZ) sites, is well tolerated, and has positive cognitive effects. Because published studies suggest NMDA antagonists prevent development of tolerance to effects of morphine (MS) or other psychoactive drugs by altering learning, we sought to compare effects of MEM to those of the more frequently studied DZ. To examine effects of DZ or MEM on discriminative stimulus effects of MS, Sprague‐Dawley rats were trained to discriminate 3.2 mg/kg MS and saline under fixed ratio 15 schedules of food delivery. Potency and maximal stimulus or rate‐altering effects of cumulative doses of MS were examined 30 min after pretreatment with DZ or MEM, or after chronic co‐treatment of DZ or MEM with 10 mg/kg MS, b.i.d., for 7 days. Effects of DZ or MEM on MS antinociception were examined in a 55°C water tail withdrawal assay with drug treatments parallel to those in discrimination studies. Acutely, 0.032 mg/kg DZ potentiated the MS cue by 1.6 fold, and 0.10 mg/kg potentiated MS antinociception by 2 fold; 10 mg/kg MEM attenuated both effects. Neither chronic DZ nor MEM blocked development of tolerance to the MS cue. In contrast, co‐treatment with 0.1 mg/kg DZ blocked tolerance to MS antinociception, whereas 7.5 to 10 mg/kg MEM produced non‐significant blockade. Thus, MEM differs from DZ in ability to modify stimulus and antinociceptive effects of MS. Supported by USPHS grant DA03796.
Monocarboxylate transporter (MCT)‐mediated transport of γ‐hydroxybutyric acid in human intestinal Caco‐2 cells
Authors: Felmlee Melanie Ann , Lam Wing Ki , Morris Marilyn E.
Published: June 2021

Purpose

To evaluate the expression of monocarboxylate transporters (MCTs) 1‐4 and characterize the intestinal transport of the known MCT substrates, γ‐hydroxybutyric acid (GHB) and D‐lactate.

Methods

The mRNA and protein expression of MCT1‐4 were determined by RT‐PCR and western blotting. GHB and D‐lactate uptake and directional flux kinetics were analyzed in Caco‐2 cells. Transport properties were determined with specific inhibitors and different pH and sodium conditions.

Results

MCT1‐4 mRNA was expressed in Caco‐2 cells; however, protein expression was observed for only MCT1, 2 and 4. GHB and D‐lactate uptake was pH‐ and concentration‐dependent, but sodium‐independent. Uptake was characterized by simple Michaelis‐Menton kinetics. Km, and Vmax estimates were 42.9 ± 9.4 mM, and 57.6 ± 10.3 nmol/mg/min for GHB. GHB was transported primarily in the apical to basolateral direction and was inhibited by the known MCT inhibitor α‐cyano‐4‐hydroxycinnamate, consistent with the apical localization of MCTs.

Conclusions

MCTs contribute significantly to the transport of GHB in Caco‐2 cells. Further studies are needed to determine the contributions of MCT1, 2 and 4 to the intestinal transport of GHB.

Support

NIH grant DA023223 and a fellowship for MAF from Pfizer Inc.
Subchronic treatment with 17alpha‐ethynil estradiol partially recovers the ability of ovariectomized rats to learn an autoshaped task
Authors: Marquez Sandra , Picazo Ofir , Suarez Jorge
Published: June 2021

Estrogen induces cyclic changes in synapse formation and spine density of the hippocampus and increases the synthesis of acetylcholine in basal forebrain. This information leads one to consider that estrogen could have effect on hippocampus‐dependent cognitive functions such as memory and learning. In contrast, ovariectomy‐induced (OVX) long‐term absence of estrogens seems to be responsible for deterioration in cognitive processes.

Removal of ovaries in rats was early used as a model for post‐menopausal osteoporosis. Recently, this surgery has been proposed to study the human post‐menopause. Since cognitive abilities decrease during this non reproductive condition of human females, it is likely that rats display a similar decrease of cognitive capabilities after long‐term OVX. This study was designed to analyze the performance of rats in an autoshaped task at different times after OVX. Under these experimental circumstances, the role of the synthetic estrogen 17alpha‐ethynil estradiol was tested. Results show a loss of the capacity of learning in the aforementioned task 12 weeks after OVX. At the same time, ethynilestradiol partially reduced these actions. These long‐term effects of OVX support the idea that this surgical manipulation could be a useful model for understanding some alterations associated to human post‐menopause. Support; COFAA and SIP‐IPN.