bluuebunny/crossref_metadata_2025 huggingface dataset:
It is not the freshmen 15
Authors: Gropper Sareen S. , Drawdy Kelly , Gaines Alisha , Connell Lenda Jo , Simmons Karla , Ulrich Pam , Zizza Claire
Published: June 2021

The “freshmen 15” weight gain is a commonly cited phenomenon in the popular press. Yet, surprisingly little solid scientific evidence supports this claim. This study examined changes in body weight and % body fat in 36 college freshmen. Subjects were measured using standard anthropometric techniques three times during the 2006–07 academic year. Mean initial weight of the females (n = 26) was 124.9 ± 16.6 lbs and significantly increased to 126.9 ± 16.4 lbs after one semester. Mean female body fat and body mass index (BMI) increased significantly from 22.2 ± 4.1% to 23.2 ± 3.9% and from 21.0 ± 2.2 to 21.4 ± 2.2 kg/m2, respectively. Mean body fat in the 10 males increased significantly from 14.2 ± 5.4% to 15.1 ± 4.8% in the first semester. Over the academic year, weight gain for the females averaged 3.2 ± 5.1 lbs and 5.4 ± 4.5 lbs for the males. Mean body fat and BMI increased significantly by 1.1% and 0.7 kg/m2, respectively. While 76% of these students gained weight during their freshmen year, the weight change ranged from a loss of 5.8 lbs to a gain of 13 lbs. These findings support the notion that most college students gain weight during their freshmen year; however, weight gain was about 4 lbs, and not the popularized 15 lbs. A larger study of 240 freshmen is now underway to more broadly examine weight change and the factors influencing weight change in college freshmen. This research was funded by USDA AL Agricultural Experiment Station 013‐020.
Differences in body weight loss practice according to age and gender
Authors: Doo Miae , Kim Yangha
Published: June 2021

In this study, the recognition of a person's current body weight and previous experiences of body weight loss according to age and gender are investigated. The subjects of the study were 360 males and females respectively, aged between 10–60 years, with previous experiences of body weight loss during a period of 6 months prior to this study. Anthropometrics, general characteristics, recognition of one's current body weight, and the degree of satisfaction concerning body weight loss were analyzed through a questionnaire. Approximately 73% of the subjects recognized themselves as obese, and 85% wished to lose weight. Results showed that the older the subject, the lower the frequency of body weight loss trial; however, the period of body weight loss maintenance was longer. Female subjects showed a higher frequency of body weight loss trial, with a shorter maintenance period of the reduced body weight, in comparison with male subjects. Female subjects aged between 10~20 yrs showed the highest frequency of body weight loss trial and the shortest period of maintenance of the reduced body weight. It can be derived from these results that attitudes concerning a person's current body weight and body weight loss practice vary according to age and gender. Accordingly, consideration of these individual differences may be vital in the development of a nutritional education program aiming for body weight loss for obese people.
Influence of bone age and allelic variants of the vitamin D receptor (VDR) gene on bone mass indices in adolescent boys
Authors: Diógenes Maria Eduarda Leão , Oliveira Karla F. , Bezerra Flávia F. , Koury Josely C. , Oliveira‐Junior Astrogildo Vianna , Cabello Giselda M.K. , Cabello Pedro , Mendonça Laura M.C. , Donangelo Carmen M.
Published: June 2021

The aim of this study was to evaluate the influence of bone age and FokI polymorphism on bone mass indices in healthy adolescent boys (11–14y, n=47). Bone age was assessed by left hand x‐ray. Total body bone mineral density (TBMD) and content (TBMC) were assessed by DXA. Plasma testosterone and serum PTH were measured by radioimuno‐ and chemiluminescent assay – respectively. VDR genotypes were determined by PCR amplification and enzymatic digestion of the products with FokI.

These results indicate that bone age is the main factor affecting bone indices. Moreover, differences in TBMD, TBMD‐Zscore and TBMC due to bone age appear to be less pronounced in adolescents with FF compared to those with Ff + ff genotypes.

Financial support: CNPq and FAPERJ (Brazil).
25‐hydroxyvitamin D inhibits differentiation of 3T3‐L1 preadipocytes
Authors: Natarajan Radhika , Ronnenberg Alayne G , Wood Richard J , Lee Ok‐Hwan , Kim Young‐Cheul
Published: June 2021

INTRODUCTION: Adipogenesis is a key process in the development of obesity as well as normal development and function of adipose tissue. Some evidence in humans suggests an inverse association between adiposity and serum 25‐hydroxyvitamin D (25‐D), the circulating form of vitamin D. Recent studies in the murine 3T3‐L1 preadipocyte cell line indicate that 1,25‐dihydroxyvitamin D (1,25‐D), the active hormonal form of vitamin D, inhibits adipogenesis, but no studies have investigated the role of 25‐D, the prohormone form, which is converted to 1,25‐D by CYP27B1. PURPOSE: This study was designed to investigate whether 25‐D treatment affects adipocyte differentiation in murine 3T3‐L1 cells. METHODS: 3T3‐L1 preadipocytes were treated with various concentrations of 1,25‐D and 25‐D for up to 6 days following standard induction of differentiation. The degree of differentiation, lipid accumulation (oil red O) and expression of various adipogenic genes was assessed. RESULTS: Both 1,25‐D and the 25‐D prohormone inhibited adipocyte differentiation, lipid accumulation and expression of the key adipogenic transcription factor PPARγ. CONCLUSION: 25‐D is biologically active in 3T3‐L1 cells, which is consistent with a possible direct role of vitamin D status on fat cell biology. The effects of 25‐D may reflect the intracellular conversion of the prohormone to the active 1,25‐D hormone form in differentiating preadipocytes.
The effects of excessive selenium metabolism on protein expression of HepG2 cells
Authors: Chen Yu Hsin , Chen Han‐Min , Shui Hao‐Ai , Yang Feili Lo
Published: June 2021

High selenium (Se) level in the culture medium was reported to delay cell growth and to cause morphological changes of HepG2 cells in our previous study. The purpose of this study was to use proteomic technique to explore the influence of excessive Se metabolism on the protein expression of HepG2 cells. After 24 hr of exposure in 20 μM of sodium selenite in medium, the expression of at least 30 proteins was significantly altered. Nine of the up‐regulated proteins included those participated in immune response (immunoglobulin heavy chain), collagen formation (proline 4‐hydroxylase), energy metabolism (mitochondrial ATP synthase), tumor suppressor protein (prohibitin), cell growth (FUBP1 protein, galectin‐3 carbohydrate recognition domain), and cell differentiation (human nucleoside diphosphate kinase, galectin‐3 carbohydrate recognition domain). The expression of 21 proteins was down regulated, which also included some proteins in the cellular activities such as energy metabolism, immune response, DNA replication (EF‐Tu) and cytoskeleton. Therefore alterations in protein expression occurred in the early phase of high Se exposure may be related to the later changes in the growth and morphology of HepG2 cells. Further analysis regarding the systemic relationship among the aforementioned proteins and many others is currently underway. (Sponsored by Office of Research and Development, Fu Jen Catholic University, Project 409531060439)
Dietary proteins alter tissue‐specific gene expression and adiposity in male Sprague‐Dawley rats
Authors: Simmen Frank A , Greenway Amy D , Bowman Margaret T , Su Ying , Kang Ping
Published: June 2021

Dietary soy protein elicits anti‐obesity effects in rodents. This study examined adiposity and gene expression in male Sprague‐Dawley rats lifetime‐fed diets containing casein (CAS), soy protein isolate (SPI), or casein supplemented with genistein (250 mg/kg diet; GEN). At 48 days of age, retroperitoneal fat weight (normalized to BW) was reduced in SPI vs. CAS and GEN groups. Expression profiling identified 28 SPI up‐regulated and 52 SPI down‐regulated jejunum transcripts (relative to CAS). A subset of these genes was examined for dietary protein regulation in jejunum, liver and abdominal fat pad. In jejunum, Stearoyl‐CoA desaturase 2 (Scd2) and Kruppel‐like factor 15 (Klf15) mRNAs were SPI‐induced and Malic enzyme 1 (Me1) and Iodothyronine deiodinase type I (Dio1) mRNAs were SPI‐suppressed (compared to CAS), with no effects of GEN observed. In liver, Scd2, thyroid receptors (TR)alpha 1 and beta 1, and Dio1 were SPI‐induced and Me1 was SPI‐suppressed, with no effects of GEN observed. In adipose tissue, Klf15 and Klf9 mRNAs were suppressed by GEN but not SPI. Results identify metabolic (Me1, Scd2), transcriptional (Klf15, Klf9, TRs), and thyroid hormone system (TRs, Dio1) genes affected in complex tissue‐specific fashion by SPI that may contribute to anti‐obesity in rats. These newly described effects of SPI appear to be unrelated to the major soy isoflavone GEN. Supported by CRIS 6251‐51000‐005‐3S
Effects Sulforaphane on IMR‐90 Phase II Enzyme Induction and Cell Senescence
Authors: Hintze Korry Joseph , Nabor Darren
Published: June 2021

Sulforaphane (SF) derived from cruciferous vegetables induces expression of phase II antioxidant and detoxification enzymes including: quinone reductase (QR), ferritin and thioredoxin reductase. Aging cells accumulate iron, oxidized proteins and the cellular redox potential shifts to become increasingly oxidative. To study the effects of SF on aging cells, the IMR‐90 cell model of aging was used. IMR‐90 lung fibroblast cells are a non‐transformed cell line that exhibit the hallmarks of aging over time and become senescent after a finite number of culture passages. Moreover, time until IMR‐90 senescence can be modulated by oxidative stressors. Under standard culture conditions (19% O2) SF treatment (1, 2 and 4 μM) of IMR‐90 cells significantly increased QR reporter expression over controls by: 2.5±0.2, 2.9±0.1 and 3.2±0.2 respectively (P <0.001 for all treatments). When cells were cultured at 2% O2, SF treatment (1, 2 and 4 μM) induced reporter expression over controls by; 1.3±0.1 (P=0.011), 2.5±0.3 (P <0.001), and 3.3±0.3 (P <0.001) respectively. To determine the effect of SF on time until cell senescence, IMR‐90 cells were continuously cultured with 2 μM SF and subcultured weekly. Compared to controls, SF treatment delayed senescence by 2 cell culture passages. These preliminary data indicate that SF induces the IMR‐90 phase II enzyme system regardless of O2 tension and increases time until cell senescence.
The Adipocyte Renin Angiotensin System (RAS) Mediates the Effects of Calcitriol on Oxidative Stress and Cytokine Expression
Authors: Caserio Christina M , Zemel Michael B
Published: June 2021

We recently demonstrated calcitriol to stimulate adipocyte reactive oxygen species (ROS) production and inflammatory stress (IS), while dietary calcium suppression of calcitriol exerted the opposite effect. These effects are mediated, in part, by calcitriol modulation of Ca2+ signaling and mitochondrial potential. However, adipocytes contain a functional RAS, and angiotensin II (AT) modulates ROS and IS. Accordingly, we investigated the role of AT in mediating calcitriol effects. Calcitriol (1 nM) stimulated NOX4 expression and ROS production in 3T3‐L1 adipocytes by 67% (p<0.01), while these effects were reversed by ACE inhibition (enalapril) or antagonism of either AT receptor1 (AT1R) or AT2R, antagonism. Similarly, AT (0.1 – 1.0 nM) stimulated NOX4 expression (p<0.03), and this effect was reversed by AT1R or AT2R antagonism. Calcitriol and AT both suppressed adiponectin expression (p<0.04) and increased IL6 and MCP‐1 expression ∼ 2‐fold (p<0.03), and these effects were reversed with enalapril or AT2R, but not AT1R, antagonism. These data demonstrate that calcitriol modulation of adipocyte ROS production and IS is modulated, in part, by the adipocyte RAS.
Dehydrocostus lactone (DHCL) isolated from the root of Saussurea lappa inhibits the migration and invasion of DU145 human prostate cancer cells
Authors: Hong Ji Eun , Kim Eun Ji , Lim Soon Sung , Shin Hyun‐Kyung , Kim Jong‐Sang , Park Jung Han Yoon
Published: June 2021

Saussurea lappa has been used in traditional herbal medicine and shown to exert anti‐inflammatory and anti‐carcinogenic effects. In present study, we investigated the effects of the hexane extracts of SL (HESL) on the migration and invasion characteristics of DU145 cells. DU145 cells were cultured in the presence of 0 – 4 μg/mL HESL with or without 10 ng/mL EGF. HESL inhibited the basal and EGF‐induced cell migration, invasion and adhesion in dose‐dependent manners. Active fractions were isolated by column chromatography and the structure of the active principle was determined using 1H NMR and 13C NMR. The active compound DHCL inhibited the basal and EGF‐induced migration, invasion and cell adhesion in dose‐dependent manners. DHCL decreased secretion of matrix metalloproteinase (MMP)‐9 and tissue inhibitor of metalloproteinase (TIMP)‐1 but increased TIMP‐2 levels in concentration‐dependent manners. We have shown that HESL and its active principle DHCL inhibit the metastasis potential of DU145 human prostate cancer cells. Our results indicate that inhibition of MMP‐9 secretion and stimulation of TIMP‐2 expression contribute to decreased migration and invasion of DU145 cells treated with HESL and DHCL.
Intrinsic carbon‐13 labeling of red cabbage anthocyanins for human nutrition studies
Authors: Charron Craig S. , Britz Steven J. , Mirecki Roman M. , Harrison Dawn J. , Clevidence Beverly A. , Novotny Janet A.
Published: June 2021

Although health benefits of dietary anthocyanins (ACN) have received significant attention, scientific progress has been slowed by an incomplete understanding of ACN absorption and metabolism. Thus, we developed a system to produce carbon‐13 labeled ACNs in red cabbage to enable study of ACN fate after ingestion. Twenty‐eight ‘Super Red’ red cabbage seedlings were grown in an inorganic growth medium in 10.1 cm pots. Upon appearance of the first true leaves, pots were placed in a gas‐tight acrylic box located in a walk‐in growth chamber. Nutrient solution was delivered hydroponically. Temperature was maintained at 22.0 ± 0.5 °C until day 26, then at 10.5 ± 1.5 °C until plants were harvested on day 34. 13CO2 concentration in the box was monitored with an infrared gas analyzer, and 13CO2 (99.3% pure) was injected when concentration was < 390 μL L−1. ACNs were analyzed by HPLC‐MS/MS. Carbon sites of the predominant nonacylated ACN, cyanidin 3‐diglucoside‐5‐glucoside, and the predominant acylated ACN, cyanidin 3‐(feruloyl)(sinapoyl) diglucoside‐5‐glucoside, were > 98% labeled. This high incorporation rate of 13C favors precise tracing of ACNs and ACN metabolites in upcoming feeding studies. Funded by the USDA/ARS.
Green tea extract (GTE) is more effective than epigallocatechin gallate (EGCG) and epicatechin (EC) in inhibiting the lymphatic absorption of cholesterol (CH) and other lipids
Authors: Koo Sung I , Noh Sang K
Published: June 2021

This study was conducted to determine whether green tea catechins, EGCG and EC, inhibit the absorption of CH and other lipids and compare their relative inhibitory potencies with that of GTE. Male rats with lymph cannula were infused at 3.0 mL/h for 8 h via a duodenal catheter with a lipid emulsion containing 14C‐CH, triolein (OA), α‐tocopherol (αTP), and Na‐taurocholate in PBS buffer (pH, 6.0), with 153 μmol EGCG, EC, 207 mg GTE containing 153 μmol EGCG, or no catechin (control). The absorption of 14C‐CH was significantly lower in rats infused with EGCG (27.7 ± 1.6% dose), EC (29.9 ± 4.5% dose), and GTE (19.5 ± 1.4%) than in those infused with the lipid emulsion alone (39.4 ± 3.0%). EGCG and EC did not significantly affect the lymphatic outputs of αTP, whereas GTE markedly lowered its output (EGCG, 17.0 ± 1.6%; EC, 19.5 ± 2.8%; GTE, 5.5 ± 2.2%) compared with control (22.1 ± 2.8% dose). Similarly, the lymphatic outputs of OA and phosphatidylcholine also were significantly lowered by GTE, but not affected by EGCG or EC. The results indicate that both EGCG and EC, when singly administered, inhibit the intestinal absorption of CH with little effect on other lipids. However, GTE is effective in inhibiting the absorption of all lipids tested, indicating that catechins and other constituents, as present in GTE, have a synergistic and more potent inhibitory effect on intestinal lipid absorption. Supported in part by NIH NCCAM R21AT001363‐01A2 to SIK.
Effects of Chrysanthemum indicum Linne Flowers on the Acetylcholinesterase Activity and the Learning Performance of Mouse
Authors: Yim Hyun Jae , Kim Hye Mi , Jeon Young Eun , Kang Young‐Hee , Chung Cha‐Kwon , Kang Il‐Jun
Published: June 2021

Alzheimer's disease is the most common neurodegenerative disorder responsible for more than 50% of all dementia cases. There is significant interest in finding new sources of acetylcholinesterase inhibitor for use in treating Alzheimer's disease, since only a few acetylcholinesterase inhibitors are available for clinical use, such as galanthamine, physostigmine, and tacrine. In the present study, ICR (International Cancer Research) mice were treated with a dose of scopolamine, 1 mg/kg, which was able to cause impaired cognitive ability. The daily consumption of the water extract of Chrysanthemum indicum Linne flowers (0.1 mg/ g body weight) for three months could significantly prevent the scopolamine induced deficit of the spatial cognitive capability of mouse and improve long‐term memory in amnestic mice induced by scopolamine in Morris water maze and passive avoidance tests. In addition, the water extract consumption significantly decreased acetylcholinesterase activity in mouse brain, leading to inhibit the acetylcholine hydrolysis. Supported by Brain Korea 21.
Effects of bitter melon on inflammatory molecules induced by lipopolysaccharides (LPS) on RAW 264.7 murine macrophage cells
Authors: Seewald Amy , Pina Fatima , Beverly Kandice , Smith Brenda Jane , Lucas Edralin
Published: June 2021

Bitter melon or Momordica Charantia is a widely consumed vegetable in South Asia. One of the most notable health benefits of bitter melon is its role in lowering blood glucose as demonstrated in both animal and clinical studies. These effects on glucose appear to be mediated by activation of peroxisome proliferator‐activated receptor (PPAR)‐α and ‐γ, members of the steroid hormone nuclear receptor family involved in the regulation of lipid and glucose homeostasis. The objective of this research was to explore the anti‐inflammatory properties of bitter melon using the RAW 264.7 murine macrophage cell line. Bitter melon was deseeded, the edible portion was blended, and the pulp was separated to obtain the juice. Cells were plated at a density of 10,000 cells/well in a 96‐well plate and then treated with bitter melon at concentrations of 0, 0.125, 0.25, 0.5, 1% (v/v) for 24 hours. Cells were then stimulated with 500 ng/mL of LPS for another 24 hours and the supernatants were collected for determination of nitric oxide (NO), prostaglandin E2 (PGE2) and interleukin (IL)‐6. All experiments were repeated three times and cell viability was assessed using the resazurin‐based assay. Cell viability was not affected by any of the bitter melon juice concentrations used in the study. The LPS‐induced increase in NO production was dose‐dependently down‐regulated by bitter melon. PGE2 and IL‐6 were also elevated by LPS and bitter melon also reduced these inflammatory molecules. Bitter melon, which has been reported to activate both PPAR‐α and PPAR‐γ, suppresses the production of inflammatory mediators brought about by LPS and these anti‐inflammatory effects should be further evaluated using in vivo models. (Supported by College of Human Environmental Sciences, Oklahoma State University)
Docosahexaenoic Acid (DHA) Supplementation Benefits Pregnancy Complicated with Gestational Diabetes Mellitus (GDM)
Authors: Lammi‐Keefe Carol J. , Rozowski Jaime , Parodi Carmen Gloria , Sobrevia Luis , Foncea Rocio
Published: June 2021

GDM, characterized by an alteration of glucose regulation which is first detected during pregnancy, is associated with elevated blood glucose, insulin resistance, pro‐inflammatory agents, and increased nitric oxide (NO) synthesis. Our purpose was to assess supplementation of mothers with GDM with 600 mg/day DHA (randomized to receive DHA or placebo, corn oil) (week 24 of pregnancy‐delivery, GDM mothers, n=31). Blood samples were collected at weeks 24 and 36 in pregnancy. At delivery, blood from the mother and umbilical cord were collected to assess transfer of DHA from mother to fetus and placental tissue for NO synthesis. DHA supplementation significantly increased maternal red blood cell (RBC) DHA concentration but not fetal RBC DHA. Supplementation reduced fasting glucose in GDM compared to controls and insulin resistance tended to decrease substantially more in supplemented mothers than controls. Inflammatory markers were not different between the groups, likely explained on the basis of small sample size. Placental endothelial cells from controls had increased L‐arginine utilization and elevated NO synthesis compared to the DHA supplementation group. We hypothesize that DHA decreased expression of L‐arginine transport protein and/or diminished activity of endothelial NO synthase. In conclusion, DHA supplementation of women with GDM demonstrated favorable effects regarding glucose metabolism and the NO synthetic pathway compared to controls, underscoring the importance of this n‐3 long chain fatty acid in pregnancy complicated by diabetes. (Fondo Nacional de Innovacion en Salud de Chile and Nestle)
Changes of biochemical components during the fermentation process of dark tea, a microbial fermented tea
Authors: Han Seon Kyeong , Ma Seung‐Jin , Cho Jeong‐Yong , Park Keun‐Hyung , Jeong Jae‐Cheon , Hong Hee‐Cheol , Jung Soon‐Teck , Jeong Byeong‐Choon
Published: June 2021

Dark tea, which is made by the fermentation of microorganisms without the action of endogenous enzyme of tea leaves, is a popular beverage in Asia. To understand fermentation mechanism of dark tea, three different species of tea leaves were fermented and microorganisms related the tea fermentation were screened. Aspergillus and Penicillium were identified to be main fungi. Each tea sample also was collected during fermentation process and then investigated to the changes of chemical constituents such as amino acid, caffeine, chlorophyll, and four kinds of catechin. (−)‐Epicatechin and epigallocatechin were increased and then decreased during the fermentation, although chlorophyll, (+)‐catechin, epicatechingallate, and epicatechingallate were decreased. These results suggested that the gallate group of epicatechingallate and epigallocatechingallate are hydrolyzed by the action of microorganism. Changes of biological activities including antioxidant were also investigated in this study.
SOX2 immunoreactivity in cortical dysplasia and in tumors with composite glial and neuronal histologic features: Evidence for a common route of histogenesis
Authors: Eschbacher Jennifer Mary , Coons Stephen William
Published: June 2021

A number of tumors, most commonly dysembryoplastic neuroepithelial tumor (DNET) and ganglioglioma, demonstrate histologic and/or immunohistochemistry features suggesting both glial and neuronal differentiation. The lineage and etiology of these low‐grade glioneuronal tumors is unclear. Based on their similar immunohistochemistry features and common association with cortical dysplasia, we hypothesize that these entities may share a common route of histogenesis. Pleomorphic xanthoastrocytoma (PXA) also demonstrates both glial and neuronal markers. The basis for this, along with its lineage and relation to ganglioglioma, is also unclear. Using immunohistochemistry analysis, we evaluated for expression of SOX2, a neural stem cell marker, in 27 tumors with glioneuronal features and 7 cases of cortical dysplasia. We found scattered SOX2 immunoreactive cells in 22/27 tumors, including 10/10 DNETs, 8/10 PXAs, and 4/7 gangliogliomas. All 7 cases of cortical dysplasia demonstrated SOX2 immunoreactivity in dysplastic areas only. In uninvolved cortex, and in eight normal control autopsy brain sections, we found no SOX2 positive cells. Our results suggest that these entities may share a common lineage and may arise from a multipotent stem cell.

This research was funded and supported by Barrow Neurological Institute.
Prognostic value of tumor microinvasion and metalloproteinases expression in intracranial pediatric ependymomas
Authors: Snuderl Matija , Chi Susan N. , DeSantis Stacia , Stemmer‐Rachamimov Anat , Betensky Rebecca A. , DeGirolami Umberto , Kieran Mark W.
Published: June 2021

Ependymomas often appear well circumscribed on imaging and histology, but many recur despite gross total resection (GTR). The current WHO histologic grading system does not accurately predict the clinical behavior. The aim of this study is to determine histological and immunohistochemical features that would better correlate with prognosis of ependymomas treated with GTR. In a retrospective study, we analyzed 41 pediatric ependymomas for microinvasion and for expression of invasion associated proteins, metalloproteinases MMP2 and MMP14 and correlated the findings with clinical outcome. We found GTR to have significant positive influence on both overall survival (OAS) and progression free survival (PFS). In 28 patients that underwent GTR, microinvasion was a predictor of poor OAS (p= 0.003) as well as PFS (p=0.03). Furthermore, GTR tumors with high expression of MMP2 and MMP14 had significantly shorter OAS (p= 0.02 and p=0.002 respectively). Our data show that tumor microinvasion into adjacent brain and tumor expression of MMP2 and MMP14 are significant predictors of both OAS and PFS in pediatric ependymomas and these are useful prognostic markers that may help stratify patients for adjuvant treatments.

Research support: DFCI BTCF 9999056.
Tau Negative FTLD Without Abnormal TDP‐43 Immunoreactivity
Authors: Josephs Keith A. , Stroh Alex , Dickson Dennis W.
Published: June 2021

Objective: To determine whether all cases of tau‐negative frontotemporal lobar degeneration (FTLD) show abnormal TDP‐43 immunoreactivity.

Design/methods: The neuropathological database at Mayo Clinic, Florida, was queried to identify all cases of tau‐negative FTLD. Forty cases were identified that underwent analysis with TDP‐43 immunohistochemistry. Cases without abnormal TDP‐43 immunoreactivity were further analyzed with H&E, PAS and silver stains, and with immunohistochemistry for phosphorylated tau, alpha‐synuclein, ubiquitin, neurofilament, alpha‐internexin and p62.

Results: Of the 40 cases, 3 did not show abnormal TDP‐43 immunoreactivity. Cases 1 and 3 had clinical features of behavioral variant FTD while case 2 had features of the corticobasal syndrome. Case 3 had a positive family history. Case 1 had a pathological diagnosis of dementia lacking distinctive histology (DLDH) and case 2 basophilic inclusion body disease. Case 3 had ubiquitin‐positive but TDP‐43 negative neuronal inclusions and dystrophic neurites.

Conclusion: Not all cases of tau‐negative FTLD have abnormal TDP‐43 immunoreactivity; basophilic inclusion body disease and DLDH are rare examples that do not. Given the positive family history and histological findings in case 3, there likely exists a yet to be identified gene and protein associated with tau negative FTLD.
Diagnosis and grading of the Parkinson's disease phenotype
Authors: Richfield Eric Karl , Prasad Kavita , Rhodes Roy , Beach Tom , Zhang Jing
Published: June 2021

We examined criteria for the diagnosis and grading of the Parkinson's disease phenotype (PDP) using postmortem tissue and clinical features.

We used cases of the PDP, incidental Lewy body disease (ILBD), other neurodegenerative diseases and control subjects. We stained paraffin slides and free‐floating tissue sections from different academic centers for H&E. StereoInvestigator (MBF, Williston VT) was used for counting. Features counted included: neuromelanin (NM) containing neurons, NM+ cells, NM– neurons, NM+ macrophages (MPs), NM+ clusters of MPs, free NM, LBs, pale bodies and other intraneuronal inclusions. Principle component analysis followed by linear discriminant analysis will be used with other clinical features to compare the levels of these morphological factors.

Data presented will include cases not used, counts from paraffin and free‐floating sections, repeat counting, inter‐rater reliability, and statistical analysis.

Disagreements were identified. Criteria, counts, morphology, and time required for counting varied between the two methods. Both methods have advantages and disadvantages. The use of additional cases to refine this approach may demonstrate which method is superior and how they relate to each other.
Neuroprotective effects of pyruvate and piroxicam in animals treated with 1‐methyl‐4‐phenyl‐1, 2, 3, 6 tetrahydropyridine (MPTP)
Authors: Soliman Yousef I , Mazzio Elizabeth A , Soliman Karam F
Published: June 2021

MPTP (1‐methyl‐4‐phenyl‐1, 2, 3, 6 tetrahydropyridine) is a prototypical toxin used to induce Parkinsonism in experimental animal models and is known to involve mitochondrial complex I inhibition, oxidative stress and robust gliosis with inflammation. In this study, neuroblastoma N2A cell line was used to investigate the neuroprotective effects of pyruvate and piroxicam. The results demonstrate that pyruvate as well as piroxicam were capable of sparing neuronal damage. In another study to examine the extent to which each of these compounds may prevent the loss of SN dopaminergic neurons induced by administration of MPTP in C57/B6 mice. The administration of pyruvate 150‐mg/kg and piroxicam 20 mg/kg I.P, 3 days pre and post MPTP administration, were effective in reducing the loss of locomotive function, SN tyrosine hydroxylase concentration and attenuating the loss of dopamine. These data suggest that pyruvate, which is a non‐toxic food derived carboxylic acid, may have therapeutic value in the treatment of PD. The data also support previous studies reporting that COX inhibitors attenuated MPTP toxicity in animal models. It was concluded from these study that pyruvate as well as piroxicam may be used in PD prevention and therapy. (Supported by NIH Grant RR03020)
Severe cerebral amyloid angiopathy in Alzheimer's disease is associated with frequent old microinfarcts
Authors: Soontornniyomkij Virawudh , Lynch Matthew D. , Pomakian Justine , Clare Ryan , Vinters Harry V.
Published: June 2021

To investigate whether the presence of severe cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD) was associated with a higher prevalence of old microinfarcts (OMIs) than in AD without significant CAA, 6 AD brains with severe CAA were selected, together with 12 age‐matched AD brains without significant CAA, from the Alzheimer's Disease Research Center Tissue Bank. Immunohistochemistry for CD68 was employed to highlight ≤5 mm foci of macrophage‐infiltrated tissue destruction (i.e. OMIs) in formalin‐fixed paraffin‐embedded tissue blocks taken from various regions of the cerebral cortex/white matter and cerebellum (range 13–21, mean 16.3 blocks per brain in the AD/CAA group; range 7–21, mean 14.7 blocks per brain in the AD group; p = 0.39, 2‐tailed Student's t‐Test). OMIs, manually counted by light microscopy, were observed in all of 6 AD/CAA brains, and in 2 out of 12 AD brains (p = 0.0015, 2‐tailed Fisher's Exact Test). The number of OMIs per block ranged from 0.14 to 1.76 (mean 0.74) in the AD/CAA group, and from 0 to 0.12 (mean 0.02) in the AD group (p = 0.02, 1‐tailed Student's t‐Test). Using Perl's iron staining, old microhemorrhages were occasionally seen in both groups. In conclusion, OMIs are frequent in AD with severe CAA, which may contribute to a vascular component of cognitive impairment. This work was supported by the grants P50 AG16570, P01 AG12435 and the Sarkaria Chair in Diagnostic Medicine (H.V.V.).
Altering Agrin Expression Influences Aβ Deposition in APP(Swe)/PS1(ex9) Transgenic Mice
Authors: Donahue John Edward , Stopa Edward G. , Johanson Conrad E. , Chaudhry Hira , Miller Miles C. , Fallon Justin R. , Ruegg Markus , Rauch Steven M. , Burgess Robert W.
Published: June 2021

The heparan sulfate proteoglycan agrin binds to amyloid‐β (Aβ) found in senile plaques and cerebral vessels in Alzheimer disease. Aβ has also been shown to directly interact with heparan sulfate, which may affect Aβ fibril formation, proteolysis, and clearance. In the brain, neurons express agrin, suggesting that neuronal agrin can influence Aβ. Agrin is also present in the basement membrane of blood‐brain‐barrier (BBB) capillaries. Thus, BBB dysfunction may influence brain Aβ levels. We have tested the in vivo significance of agrin's interaction with Aβ using Tg mice that over‐ and underexpress agrin, combined with APP/PS1 Tg mice that form Aβ plaques. Increasing expression of both agrin isoforms caused a reduction of insoluble Aβ in the brain by ELISA and filter‐trap assays. Altering neuronal agrin did not change Aβ levels. However, the deletion of vascular agrin using an agrin conditional allele and cre expressed by the Tie2 promoter caused an increase in insoluble Aβ. Immunostaining showed reduced agrin in vessels and increased agrin in A plaques. Thus, vascular agrin loss exerts the greatest influence on Aβ deposition, and that BBB compromise may contribute to AD pathology. (Alz Assoc)
Immune reconstitution inflammatory syndrome of the brain: clinicopathological study of six cases
Authors: Rushing Elisabeth J. , Liappis Angelike , Smirniotopoulos James D , Smith Alice B. , Henry James M. , Nelson Ann M.
Published: June 2021

OBJECTIVES:

Immune reconstitution inflammatory syndrome (IRIS) represents a spectrum of clinicopathological entities encountered in HIV‐infected patients who have received highly active, antiretroviral therapy (HAART). Diagnosis of is often challenging, treatment options are limited, and the prognosis variable. We present our experience with six cases, including one autopsy, with central nervous system (CNS) involvement. METHODS: All patients met the clinicopathological criteria for the diagnosis of IRIS. The study included 5 males and one female, ranging in age from 34 to 47 (mean, 41, S.D. 5.39) years. RESULTS: The spectrum of underlying CNS lesions included necrotizing meningoencephalitis in two cases, progressive multifocal leukoencephalopathy, and cryptococcal meningitis. In several patients, the disease had unusual features, and in some cases, this delayed the diagnosis. DISCUSSION: Greater awareness of IRIS may hasten accurate diagnosis and appropriate treatment. Although nonspecific, imaging findings reflect the underlying histopathologic conditions and may yield important clues to early diagnosis. In order to capture all suspected cases, early biopsy is recommended.
Cryptic Unbalanced t(4q;18q) In A Pediatric Patient with Neuropathologic Findings
Authors: Horbinski Craig Michael , Cody Jannine D. , Gunn Shelly R. , Sathanoori Malini , Hu Jie , Vockley Gerard , Surti Urvashi
Published: June 2021

Objective: To determine whether a pediatric patient with a phenotype resembling the 18q deletion syndrome but a normal karyotype had any cryptic genetic aberrations.

Methods: High‐resolution G‐band chromosome analysis, array comparative genomic hybridization (aCGH), and telomeric fluorescence in situ hybridization (FISH) were performed on DNA obtained from a peripheral blood sample.

Results: FISH and aCGH detected a cryptic unbalanced translocation between 4q and 18q [der(18)t(4;18)(q35;q23)(4qtel+,18qtel‐)].

Conclusions: Two other similar patients were identified in the literature. The known genes gained and deleted by this unbalanced translocation are enumerated, including deletion of myelin basic protein. An assessment of candidate genes for particular characteristics, including neurologic and developmental abnormalities (such as abnormal white matter myelination), is also included.

Source of support: This data was collected as part of the patient's routine workup; no designated research support was utilized.
ROLE OF CARBONIC ANHYDRASE EXPRESSION IN HEPATOCYTE PROTECTION BY LATE PRECONDITIONING
Authors: Ndoungue Valerie , Alchera Elisa , Imarisio Chiara , Ponte Caterina Dal , Monga Guido , Albano Emanuele , Carini Rita
Published: June 2021

Liver ischemic preconditioning improves reperfusion damage during hepatic surgery and transplantation. However, the mechanisms involved are still poorly understood. This study investigated the role of carbonic anhydrase IX (CAIX), a transmembrane enzyme that catalyzes bicarbonate production, in the protective effects associated with the late phase of liver preconditioning.

Late preconditioning was induced in primary cultured rat hepatocytes by a transient (10 min) hypoxic stress or by 15 min incubation with the adenosine A2A receptors agonist CGS21680 (5μ mol/L) 24 h before the exposure to 90 min hypoxia.

Late preconditioning prevented hepatocytes killing and ameliorated intracellular acidosis and Na+ accumulation during hypoxia. Such effects were associated with the expression of CAIX. Blocking the transduction of preconditioning signals by PKC and PI3‐kinase with chelerythrine or wortmannin abolished CAIX expression and the protective action of late preconditioning. The inhibition of CAIX with acetazolamide or the block of bicarbonate influx through the Cl−/HCO−3 exchanger with SITS also reverted the protective effects of late preconditioning on intracellular acidosis and Na+ accumulation.

We conclude that the induction of late preconditioning in liver cells involve the expression of CAIX that increases hepatocyte tolerance to ischemia by maintaining intracellular Na+ homeostasis.
Asymmetric Dimethylarginine Levels in the Plasma Are Elevated in Non‐Alcoholic Fatty Liver Disease
Authors: Kasumov Takhar , Edmison John M. , Bennett Carole , Dasarathy Srinivasan , Lopez Rocio , McCullough Arthur J. , Kalhan Satish C.
Published: June 2021

Asymmetrical dimethylarginine (ADMA) and symmetrical dimethylarginine (SDMA) are produced by the breakdown of proteins that have been methylated post translationally at an arginine residue. Plasma levels of ADMA are elevated in insulin resistant states. ADMA is metabolized in the liver, while SDMA cleared by the kidney. Non‐alcoholic fatty liver disease (NAFLD) is the most common liver disease in humans and is associated with insulin resistance. We hypothesized that plasma levels of ADMA will be increased in subjects with NAFLD and with the progression of NAFLD from hepatic steatosis to non alcoholic steatohepatitis (NASH). Plasma levels of ADMA and SDMA were measured by HPLC in 48 patients with histologically confirmed NAFLD (16 steatosis and 32 NASH) and 29 healthy controls. Estimates of kidney function in all subjects were in normal range. Plasma ADMA levels were significantly higher (P<0.002) in patients with NAFLD compared with controls. SDMA levels were not different between any groups. ADMA/SDMA ratio was significantly higher in patients with NASH compared with controls (1.7±0.5 vs. 1.4±0.3, p<0.05). Estimates of insulin resistance as measured by HOMA, did not correlate with plasma levels of ADMA or SDMA. ADMA/SDMA ratio correlated with plasma insulin levels and with insulin resistance. We conclude that ADMA and ADMA/SDMA ratio can be used as an additional biomarker of NASH in combination with measures of insulin resistance. Since ADMA is an inhibitor of nitric oxide synthase, high levels of ADMA in NASH may contribute to the vascular abnormalities in NASH.
Diallyl Sulfide Inhibits Lipid Peroxidation by increasing Superoxide dismutase and Glutathione S Transferase Gene Expression in the Liver of Male Sprague Dawley Rats.
Authors: Newell Oneil George , Darling‐Reed Selina , Thomas Ronald
Published: June 2021

Diethylstilbestrol (DES), a synthetic estrogen, is associated with liver cancer in rats and humans. DES undergoes redox cycling producing free radicals which can react with lipids causing lipid peroxidation. Lipid peroxides causes DNA damage, mutations and ultimately cancer. Dially sulfide has been shown to inhibit various types of cancers presumably by metabolic modulation. We hypothesize that DAS will inhibit lipid peroxidation by increasing gene expression of superoxide dismutase (SOD) and Glutathione S Transferase (GST) in the liver of male Sprague Dawley rats. To test this hypothesis four groups of five male Sprague Dawley rats were treated as follows: (1) control (corn oil), (2) 50 mg/kg DAS (3) 50 mg/kg DES, (4) 50 mg/kg DAS, 50mg/kg DES. RNA was extracted from the liver using the trizol. SOD and GST gene expression was assed by real time RT‐PCR. The Folch Method was used to extract lipids from the liver and lipid peroxidation was determined by PeroxiDirect Kit, (Sigma). Animals treated with DES resulted in lipid peroxide formation of 14.5 nmoles/gram of tissue. Co‐administration of DAS and DES attenuated DES‐induced lipid peroxidation by 90%. No lipid peroxides were detected in the control and the DAS treated animals. DES, DAS and a combination of DES and DAS resulted in increases of SOD expression by 2.2, 10.1 and 18.1 fold respectively. Similar results were seen with GST. DES, DAS, and a combination of DES and DAS resulted in GST expression of 0.78, 8.1, and 13.2 fold respectively. Our results demonstrate that DAS inhibits DES induce lipid peroxidation. These data suggest that diallyl sulfide may prevent DES induced cancer and be used to develop potent chemopreventive compounds. Supported in part by NIH grantsRR08111 and RR03020.
Chlorella vulgaris protects against lead‐induced hepatic toxicity in rats
Authors: Jang Mi Kyung , Kim In Hye , Hong Sung Yi , Om Ae Son
Published: June 2021

This study was accomplished to investigate the effect of Chlorella vulgaris against lead‐induced oxidative stress especially associated with the liver fibrosis. Six weeks old Sprague‐Dawley male rats (n=10/group) were randomly divided into control group (Control; treated with drinking water) and lead‐chlorella groups (Pb+C0, Pb+C2, Pb+C5 and Pb+C10; treated with drinking water containing 200 ppm lead acetate + different concentrations of chlorella 0, 2, 5 and 10% by diet for 4 weeks). Superoxide dismutase activity was decreased in Pb+C0 compared to Control but increased in Pb+C2, Pb+C5 and Pb+C10 (128.9, 165.8 and 167.4% respectively) compared to Pb+C0 (P<0.05). And also glutathione peroxidase and glutathione reductase activity were increased in lead‐chlorella groups compared to Pb+C0 (P<0.05). The glutathione contents were decreased in Pb+C0 compared with other groups (P<0.05). But contents of thiobarbituric acid reactive substances were increased in Pb+C0 (P<0.05). The protein expression of transforming growth factor β1 and matrix metalloproteinase‐2 was significantly increased in Pb+C0 compared to Control but decreased in lead‐chlorella groups. These results indicate that chlorella may have protective effect against lead‐induced hepatic toxicity in rats. [This study was supported by Daesang Co. Ltd. WelLife Health Business.]
Inhibition of tumor necrosis factor alpha secretion by a 27‐mer siRNA in rat Kupffer cells
Authors: Ponnappa Biddanda C , Jing Yawu , Shishkov Andrei
Published: June 2021

Tumor necrosis factor alpha (TNF‐α) plays a major role in the pathogenesis of many inflammatory diseases. Neutralizing TNF‐α by antibodies or antisense oligodeoxynucleotides, alleviate disease symptoms. Earlier studies show that two daily doses (1.5 mg/kg body wt.) of an antisense oligonucleotide against rat TNF‐α mRNA, reduced lipopolysaccharide (LPS)‐induced liver injury by 60%. In this study, we introduce the new generation of gene‐silencing molecules, namely the short interfering RNA (siRNA), to reduce TNF‐α levels. Although siRNAs of 19‐21 base pairs are commonly used, it is reported that longer siRNAs may have much higher efficacies. In this study, we report the identification of a 27‐mer anti‐TNF‐α siRNA and compare its properties with a recently identified 21‐mer anti‐TNF‐α siRNA, SSL3. Primary cells of rat Kupffer cells were transfected with of three 27‐mer siRNA constructs (si27‐1, si27‐2 and si27‐3) for 24 h, following which, TNF‐α secretion was induced by exposure to LPS (0.1 ug/ml) for 2 h. TNF‐α released to the medium was measured by ELISA. Of the three si27 constructs two (si27‐2 and si27‐3) had profound inhibitory effect on TNF‐α secretion and the third had no effect at all. At 5 nM, si27‐3, almost totally (>97%) inhibited TNF‐α secretion compared to an 85% inhibition by the 21‐mer (SSL3); at 1 nM, si27‐3 was still inhibitory at 95% after 48 h whereas the inhibitory effect of SSL3 was lower at 75%. These data demonstrate the identification of a highly efficacious siRNA, which can be used in the treatment of TNF‐α mediated diseases (Supported by Grant AA 015081).
Signaling through CXCR2 delays liver regeneration after ischemia/reperfusion in mice
Authors: Kuboki Satoshi , Shin Thomas , Huber Nadine , Eismann Thorsten , Blanchard John , Schuster Rebecca , Lentsch Alex B
Published: June 2021

Ligands of the CXC chemokine receptor, CXCR2, are critical for neutrophil recruitment during hepatic ischemia/reperfusion (I/R) injury. Hepatocytes also express CXCR2, however, direct effects of CXC chemokines on hepatocyte function or recovery during I/R injury is unknown. We sought to determine the role of CXCR2 signaling in injury and recovery from hepatic I/R in mice. Male wild‐type or CXCR2−/− mice were subjected to 90 minutes of partial hepatic ischemia followed by up to 96 hours of reperfusion. Some wild‐type mice were treated with a CXCR2 antagonist after 24 hours of reperfusion. CXCR2−/− mice had less liver injury and accelerated recovery after I/R compared to wild‐type mice. There were no differences noted between groups in the expression of TNFα or IL‐6. Acute neutrophil recruitment was blocked in CXCR2−/− mice, but after 24 or 48 hours of reperfusion, neutrophil accumulation between the groups was similar. Hepatocyte proliferation, measured by PCNA staining, was increased in CXCR2−/− mice and was associated with increased activation of NF‐κB and STAT3. Treatment of wild‐type mice with CXCR2 antagonist after initial neutrophil recruitment had similar effects on injury, proliferation, and activation of NF‐κB and STAT3. The data suggest that signaling via CXCR2 in hepatocytes after I/R prevents proliferation and delays recovery.
The role of low molecular weight hyaluronan in the pathogenesis of monocrotaline‐induced pulmonary hypertension
Authors: Ormiston Mark , Slaughter Graham , Deng Yupu , Stewart Duncan J. , Courtman David
Published: June 2021

Extracellular matrix degradation products, such as low molecular weight hyaluronan (LMW HA), have been shown to stimulate the innate inflammatory response and could play a fundamental role in the pathogenesis of pulmonary hypertension (PH). The role of LMW HA in experimental, monocrotaline (MCT)‐induced PH was investigated in Fisher 344 rats. Twenty‐four days after MCT injection (0.7mg/kg), right ventricular systolic pressure was markedly elevated in MCT treated animals (62.9 ± 5.6 mmHg) when compared to no MCT controls (24.3 ± 0.8 mmHg). Quantification of total lung HA by ELISA revealed increased HA in MCT treated animals when compared to controls (248+/−71 versus 154+/−17 ng HA/mg dry lung). This data was supported by histological analysis of lung sections, which show elevated levels of HA in association with regions of vascular occlusion as well as with inflammatory cell infiltrates. Molecular weight analysis of lung‐derived HA by agarose gel electropheresis illustrated that MCT‐induced PH is associated with an accumulation of LMW HA (>5×105 Da) and a corresponding decrease in high molecular weight HA (∼4×106 Da). Gene expression analysis of the hyaluronan synthase (HAS) genes revealed that MCT‐induced PH corresponds with increased expression of HAS1 and HAS2 (1.67+/−0.14 and 3.37+/−0.55 fold increases vs. normal, respectively) and a decrease in HAS3 expression (4.86+/−0.16 fold decrease vs. normal).