bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a High‐Carbohydrate Diet on the Proinflammatory Interleukin Levels of Older Adults
Authors: Maddy LaDonna , Gordon Scott E , Tharrington India H , Macesich Jennifer L , Harper Bradley M , Heidal Kimberly , Pofahl Walter E , Wall‐Bassett Elizabeth D 
Published: June 2021

Immunosenescence involves changes on the cellular and molecular levels in the immune system, and is associated with aging. Higher incidence of autoimmune disorders and other inflammatory conditions, as well as increased rates of infectious disease, cancer, and mortality have been linked to these conditions. Proinflammatory interleukins (IL‐6) have been shown to increase while anti‐inflammatory interleukins (IL‐4, IL‐10) decrease with age. Energy restriction has been associated with altered cytokine production; thus, the purpose of this study is to examine the effects of a prescribed diet on immunosenescence in older adults.IL‐6 concentrations were analyzed from venous samples of 10 older adults (46–85 yrs) and compared to 9 younger adults (18–45 yrs). Five older adults consumed a high‐carbohydrate diet for three days. All other subjects consumed a normal diet. Older adults who consumed less than the Acceptable Macronutrient Distribution Range for fat (20–35% of total calories) had lower IL‐6 levels comparable to younger subjects. Contrary to our hypothesis, a high‐carbohydrate diet did not lower IL‐6 levels however fat intake may contribute to a reversal of immunosenescence. Further investigation is warranted to investigate anti‐inflammatory factors contributing to changes in immunosenescence.This research was supported by the East Carolina University Division of Research and Graduate Studies.
Characterization of Gene Targets Regulated by Lmx1b during Limb Dorsalization
Authors: Feenstra Jennifer M , Pira Charmaine U , Kanaya Kohei , Hoffman Sarah E , Eppey Rick J , Oberg Kerby C 
Published: June 2021

Lmx1b is a homeodomain transcription factor that regulates dorsal identity during limb development and Lmx1b knockout (KO) mice develop nearly symmetrical ventral‐ventral limbs with hypoplastic scapulae. Currently, downstream targets of Lmx1b within dorsal mesoderm that impart the limbs' unique dorsal asymmetry are unknown.To identify genes targeted by Lmx1b, we compared gene arrays from Lmx1b KO and wild type (WT) mouse limbs during limb outgrowth and patterning, i.e., 11.5, 12.5, and 13.5 days post coitum (dpc). Real‐time PCR confirmed microarray results and whole mount in situ hybridization was used to localize and verify differential dorsal‐ventral expression.Microarray analysis identified 23 targets differentially expressed in all three arrays. Real‐time PCR confirmed 17 up‐regulated and 2 down‐regulated targets. Whole mount in situ hybridization of WT 12.5 dpc embryos demonstrated a dorsal‐ventral asymmetric pattern for the validated targets, further categorized as skeletal, soft tissue or other. Skeletal targets, including Emx2, Matrilin1 and Matrilin4, demonstrated a loss of scapular expression in the Lmx1b KO mice. Soft tissue targets which demonstrated dorsal mesodermal staining in WT were drastically reduced in KO limbs. This study provides the most comprehensive characterization of skeletal and soft tissue genes regulated by Lmx1b during limb development to date. Our data also suggest targets which Lmx1b may augment to ensure proper scapular development. Further studies are warranted to determine the mechanism of Lmx1b target regulation during limb dorsalization. NIH HD39421
Is FFM the best factor to predict the resting energy expenditure (REE) in children with obesity or leanness?
Authors: Kim Myung‐Hee , Kim Eun‐Kyung 
Published: June 2021

The purpose of this study was to compare REE between obese and nonobese children. Subjects were 24 obese (12 boys, 12 girls) and 45 normal weight (16 boys, 29 girls) Korean students aged 7–12y. REE was measured by indirect calorimetry(TrueOne 2400). REE were significantly higher in obese groups(boys 1448±211 kcal/day, girls 1291±132 kcal/day) than in nonobese groups(boys 1157±84 kcal/day, girls 1122±108 kcal/day). But, REE/weight of obese students(boys 27±2 kcal/day, girls 29±3 kcal/day) were significantly lower than that of nonobese students(boys 36±4 kcal/day, girls 31±3 kcal/day). And, there was no significant difference in REE/fat‐free mass(FFM) between obese and nonobese groups. FFM was also positively correlated with REE(r=0.84, p<0.001). These data explain that FFM is one of the most important factors which influence on REE. Therefore, to prevent the reduction of REE during weight loss, it is necessary to maintain or increase the percentage of FFM.This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education, Science and Technology(2010‐0004472).
Human cadaveric tissue is suitable for histological, immunohistochemical and ultrastructural analysis
Authors: Jensen Cynthia Graham , Slim M. Atif Mohd , Wang Tom A , Al‐Ali Saad , McGlashan Susan R 
Published: June 2021

ObjectiveThis study examined the use of cadaveric material for morphological and pathological studies using histology, immunohistochemistry and TEM.MethodsParaffin‐embedded sections of liver, myocardium, kidney, testis and trachea were prepared from cadavers embalmed using the Dodge arterial injection method. Sections were either stained with H&E or incubated with antibodies against α‐smooth muscle actin (α‐SMA), acetylated α‐tubulin or connexin 43 and detected using either DAB or fluorescence. In addition, some samples were processed for TEM.ResultsAll tissues showed excellent histological morphology comparable to freshly‐fixed tissue; ultrastructural samples yielded moderate resolution. DAB‐positive labelling was observed for α‐SMA and α‐tubulin in all tissues. For immunofluorescence, all tissues were autofluorescent in the yellow‐green spectrum. However, we found that red fluorescent secondary antibodies positively labelled tubulin in tracheal cilia, sperm flagella and kidney primary cilia, as well as connexin 43 in myocardial intercalated disks and α‐SMA in all blood vessels.ConclusionAlthough it is often believed that there is poor microstructural preservation during embalming, we have shown that cadaveric tissues are an excellent source of ethically‐approved human tissue for histological and immunohistochemical studies in biomedical research. Funded by U of Auckland.
The Role of Estrogen in Gender Differences in Adipocyte Biology
Authors: Stubbins Renee Elaine , Holcomb Valerie , Hong Jina , Nunez Nomeli P 
Published: June 2021

BackgroundIt has been established that males and females differ in their adipose tissue deposition; however, a full understanding of the adipocyte biology involved is needed. The objective of our study is to explore the role estrogen plays in gender differences in obesity, specifically in adipocyte biology.MethodsTo determine the role of estrogen in gender differences in the susceptibility to obesity we used C57BL/6J mice (15/group): 1) males 2) nonovariectomized females 3) ovariectomized females and 4) ovariectomized females supplemented with estrogen, which were randomized to the following diets: 30% calorie‐restricted, low‐fat or high‐fat diet. We measured weight gain, percent body fat, abdominal adipose tissue, and adipocyte size. Additionally, we assessed adipocyte biology by using QRTPCR to detect mRNA levels of key adipocyte biology genes.ResultsMale mice were more susceptible to diet induced obesity compared to female mice. Removal of the ovaries caused the female mice to mimic the males' susceptibility to obesity, and supplementation of estrogen to the ovariectomized females restored their protection to obesity. In the high‐fat diet groups, males and ovariectomized females gained more abdominal adipose tissue due to increased adipocyte size. Moreover, males and ovariectomized females had significantly higher peroxisome proliferator‐activated receptor‐gamma and leptin mRNA levels. Male mice also had significantly higher lipin1 and Ccaat‐enhancer‐binding protein‐beta mRNA levels compared to intact females and ovariectomized females supplemented with estrogen.ConclusionEstrogen protects female mice from obesity by modulating adipocyte biology thru key adipogenic genes.Grant Support: This work was supported by American Cancer Society grant.
Estrogen receptor‐alpha genotype affects exercise‐related bone mass in young healthy women
Authors: Kondo Hiroyo , Fujino Hidemi , Murakami Shinichiro , Fujita Naoto , Nagatomo Fumiko , Ishihara Akihiko 
Published: June 2021

Osteoporosis is a systemic skeletal disease characterized by low bone mass and/or fragile bone. The estrogen receptor alpha (ESR1) is a good genetic candidate for a prime regulator of bone metabolism. The purpose of this study was to assess the interactive effects of exercise and/or calcium intake and ESR1 polymorphism on bone mass.Eighty healthy young women (20–23 yr) were recruited in this study. Bone mass and body composition were measured. Food frequency and exercise‐related questionnaires were used to estimate calcium intake and exercise intensity. The ESR1 polymorphisms at intron 1(rs2234693 and rs9340799) were genotyped using the TaqMan‐based SNP method.Exercise and milk‐intake were significantly associated with bone mass in the whole subjects. The bone mass in non‐exercised participants with CC homozygote was lower than that in TT homozygote. The bone mass in high‐intensity exercised participants with CC homozygote was higher than that in low‐intensity. The bone mass in high‐intensity exercised participants carrying both CT and AG heterozygotes was significantly higher than that in low‐intensity.These results suggest that exercise attenuates are the increase of peak bone mass in young women carrying both C allele and AG heterozygote in estrogen receptor alpha.This study was supported by Grants for Research and Education from Nagoya Women fs University.
The knock‐down of Caveolin‐1 inhibits STAT3 signaling in human metastatic lung cancer in vitro
Authors: Gasperi‐Campani Anna , Pancotti Fabia , Maggiolini Marcello , Roncuzzi Laura 
Published: June 2021

Caveolin‐1 (Cav‐1) is an essential structural constituent of caveolae, implicated in mitogenic signaling, oncogenesis, neurodegenerative diseases and senescence. A complex role is exerted by Cav‐1 in human malignancies, which seems to be dependent on histotype, stage and grade of each neoplastic disease. As regards lung cancer, emerging evidence indicates a close relation between Cav‐1 and the development of it. In the present study we investigated the role of Cav‐1 in metastatic lung cancer proliferation. Cell lines were from metastatic lesions of lung adenocarcinoma (RAL) and of small cell lung carcinoma (SCLC‐R1), in which Cav‐1 protein was expressed at high levels. Results show that siRNA‐mediated down‐regulation of Cav‐1 caused stable arrest of cell cycle in both cell lines. A marked reduction of cyclin D and of CDK2‐CDK4 expressions were evident in the cells transfected with Cav‐1 siRNA and consequently of phosphoRb on ser795 and ser780. A significant decrease of the expression of phosphorylated Akt and its down‐stream effectors phosphorylated ERK and STAT3 was also evident. This is the first report of a block of metastatic lung proliferation obtained by Cav‐1 silencing, in the same time suggesting a new cell cycle inhibiting pathway, mediated by Cav‐1 knock‐down, in lung cancer and providing new insights into the molecular mechanism underlying the pro‐survival and tumor‐promoting functions of Cav‐1Grants from MIUR (RFO, PRIN), Pallotti's Legacy for Cancer Research, University of Bologna, Italy
Development stages of anaplastic liver cancer in the experiment at rats
Authors: Manekenova K. , Omarov T. , Peradze M. , Suleymanova A. , Sakipova A. 
Published: June 2021

Development stages of anaplastic liver cancer were investigated in the experiment at rats. Carcinogen (DMBA) diluted in the solution of medical bile, used as cocancirogen, injected intrahepatically. Histologic discomplexation signs of stringer structures in the liver lobules were revealed after 30 days from the beginning of experiment, mostly, subcapsular zones, hyperplasia of hepatocytes with enlargement nuclear‐cytoplazmatic correlation. Formation trabecular and tubular structures from large hepatocytes with large hyperchomic nuclears and signs of hepatocytes' dysplasia of different expressed degree was marked on 60 day of the experiment. Singular massy hepatocytes proliferation with signs of cells' atipism was revealed after 90 days from the beginning of experiment. Trabecular and tubular structures from hepatic cells in the condition of severe dysplasia are remained among massy foci. Morphologic picture of anaplastic cancer is observed after 120 days in the liver of rats.Research results confirm hepatocellular origin of anaplastic liver cancer.Development stages of anaplastic liver cancer of rats are following: progressing dysplasia of hepatocytes; formation of atypical trabecular and tubular structures from large hepatocytes, discomplexation of tubular and trabecular structures with hepatocytes' anaplasia.
A Novel Epithelial Proallergic Cytokine IL‐33 Serves As A Biomarker For Ocular Allergic Inflammation
Authors: zhang lili , zhao Guiqiu , De Paiva Cintia S. , Pflugfelder Stephen C. , Li De‐Quan 
Published: June 2021

PurposeTo explore a novel role of interleukin (IL)‐33 in Th2‐dominant allergic inflammation on ocular surface.MethodsIL‐33 and its signaling molecules were evaluated in patients with atopic conjunctivitis and in experimental allergic conjunctivitis (EAC) mice induced by short ragweed (SRW). Human corneal epithelial cells (HCECs) were cultured for IL‐33 regulation.ResultsIL‐33 and ST2 were highly detected in conjunctival impression cytology samples from atopic conjunctivitis patients. In the SRW‐induced EAC mice, IL‐33 and ST2 transcripts and immunoreactivity significantly increased in the corneal and conjunctival epithelia with largely infiltrated CD11c+/OX40L+ dendritic cells. Th2 cell infiltration was evidenced by increased transcripts and immunoreactivity of CD4, IL‐4, IL‐5 and IL‐13 in the conjunctiva, with increased expression of OX40, STAT6 and GATA3. In culture model, IL‐33 was dramatically stimulated in HCECs exposed to microbial ligands through toll‐like receptor (TLR) and NF‐kB pathways.ConclusionsOur findings demonstrate an important role of mucosal epithelial cells in initiating Th2‐dominant ocular allergic inflammation by IL‐33‐ST2 signaling pathways.
Triptolide‐Induced Expression of MicroRNA‐142‐3p Mediates Apoptosis of Pancreatic Cancer Cells by Inhibition of HSP70
Authors: MacKenzie Tiffany Noelle , Mujumdar Nameeta , Banerjee Sulagna , Sarver Aaron , Subramanian Subree , Sangwan Veena , Vickers Selwyn , Saluja Ashok 
Published: June 2021

Triptolide inhibits cancer cell growth in vitro and blocks growth and metastatic spread in vivo. Our lab has shown that triptolide triggers apoptosis via inhibition of heat shock protein 70 (HSP70). As regulators gene expression, microRNAs (miRNAs) are increasingly recognized as powerful gatekeepers of apoptosis.ObjectiveWe would like to understand how triptolide affects miRNA expression and to identify miRNAs that mediate apoptosis. We hypothesize that triptolide inhibits HSP70 expression via a novel mechanism of inducing the expression of miR‐142‐3p.MethodsWe performed miRNA microarray analysis of human pancreatic cancer cells before and after triptolide treatment. We transfected miR‐142‐3p mimics and measured cell viability, caspase‐3 activation and HSP70 levels.ResultsMicroRNA‐142‐3p, predicted to target HSP70, was found in our miRNA microarray analysis to increase immediately after treatment. This finding has been validated by qRT‐PCR. Overexpression of miR‐142‐3p decreases cell viability, triggers caspase‐3 activation and decreases HSP70 expression.ConclusionsTriptolide triggers the expression of miR‐142‐3p. Whether altered miR‐142‐3p expression may manipulate chemosensitivity to triptolide would be interesting to investigate.This research is funded in part by the PharmacoNeuroImmunology Training Grant: T32 DA07097
Selection of Food and Vitamins during Pregnancy to Prevent Hypervitaminosis A and Congenital Defects
Authors: Raja Dewan Saiful , Sultana Bahar 
Published: June 2021

IntroductionA pregnant woman consumes a variety of food. Pregnancy is a critical period of life. Pregnant women need more than a person does on the average diet. Vitamin A is essential for growth of the developing embryo and fetus. Supplementing with certain vitamins can prevent congenital defects. On the other hand, excessive consumption of certain vitamins may cause congenital defects. Vitamin A is a potential teratogen.MethodMultiple literatures from Web sites and textbooks are explored, and the information is summarized.DiscussionVitamin‐rich and nutritious food are expected by pregnant women. There are multiple sources of vitamin A. Vitamin A derivatives are sometimes used to treat acne. Acne is common among young women. Many women do not know the source of vitamin A in their food. Vitamin and food supplement is a fashion among rich and educated pregnant women. Certain groups of pregnant women used to take previtamin A‐rich–food like liver without knowing the consequences of vitamin‐A–related congenital defects.ConclusionsIt is advised to avoid vitamin A–rich previtamin food like liver and cod‐liver oil to prevent possible congenital defects. Vitamin A–derivative like Accutane is contraindicated during pregnancy.
The ATPase motor of the Chd1 chromatin remodeler is negatively regulated by a pair of N‐terminal chromodomains
Authors: Bowman Gregory D. , Hauk Glenn , McKnight Jeffrey , Nodelman Ilana 
Published: June 2021

ATP‐dependent chromatin remodeling complexes play a central role in the assembly, disassembly, and repositioning of nucleosomes. While the remodeling reaction is driven by a conserved ATPase motor, it is not known how this motor is regulated by auxiliary domains. We have solved the crystal structure of the Chd1 chromodomains coupled to the ATPase motor, which suggests that the chromodomains negatively regulate the ATPase motor. In the crystal, a conserved acidic helical linker between the chromodomains contacts a DNA‐binding surface on the ATPase motor, blocking DNA access to the motor. Naked DNA is a poor substrate for the Chd1 ATPase, and we find that disruption of this chromodomain‐ATPase interface permits naked DNA to stimulate ATPase activity to the same extent as nucleosome substrates. Small‐angle X‐ray scattering (SAXS) experiments suggest that in solution the chromodomains are not rigidly fixed against the ATPase motor but instead may occupy conformations distinct from that observed in the crystal structure. We propose that the chromodomains allow Chd1 to distinguish between nucleosomes and naked DNA by physically gating access to the ATPase motor.This work was supported by the NIGMS.
Evaluation of Voltage‐Activated Calcium Channel α‐1G Subunit Expression in Genetic Absence Epilepsy Rats
Authors: AKIN DEMET , KETENCI SEMA , SIRVANCI SERAP , ONAT FILIZ 
Published: June 2021

T‐type voltage‐activated calcium channels play an essential role in the generation of absence seizures. It is well known that thalamocortical circuit is critically involved in the propagation of spontaneous spike and wave discharges (SWDs) in Genetic absence epilepsy rats from Strasbourg (GAERS).Calcium channel α‐1G subunit expression was studied by immunohistochemical methods in the hippocampus (CA1, CA3, dentate gyrus), lateral and medial thalamic regions, globus pallidus and striatum of control Wistar rats (n=5) and GAERS (n=4). The brains were removed after perfusion and brain slices (40 mm) were incubated with antibodies against calcium channel α‐1G subunit. Peroxidase activity was visualized by 0.03 % 3‐3‐diaminobenzidine. We used semi‐quantitative scoring and analyzed the data with unpaired t test.We found decreased α‐1G subunit immunolabeling in the lateral thalamic region of GAERS animals compared with control Wistar rats. No difference was observed in any of the other areas between Wistar rats and GAERS.These results show that decreased calcium channel α‐1G subunit expression in lateral thalamic regions may play a role in the mechanisms underlying absence seizures. Further experiments will be performed to investigate the expression of other calcium channel subunits.Supports: Istanbul Bilim University and Marmara University S.R.C.SAG‐A 090409‐0072
Early Heparin Administration Increases Plasma Tissue Factor Pathway Inhibitor and Attenuates Tissue Factor Mediated Thrombin Generation During Simulated Cardiopulmonary Bypass
Authors: Morizumi Sei , Hiramatsu Yuji , Matsuzaki Kanji , Sato Shoko , Abe Masakazu , Sakakibara Yuzuru , Matsushita Shonosuke 
Published: June 2021

BackgroundWe tested the hypothesis that early treatment with heparin prior to the emergence of tissue factor (TF) would boost plasma tissue factor pathway inhibitor (TFPI) levels and attenuate TF mediated thrombin generation during simulated cardiopulmonary bypass (CPB).MethodsFour study groups were examined: Control group (heparin 3.75 U/ml blood, n=7), rTF group (heparin + recombinant human TF 1000 pg/ml, n=7), TFPI boost group (heparin, in pre‐heparinized donor blood, n=8), and TFPI boost + rTF group (heparin + rTF, in pre‐heparinized donor blood, n=7). In the two TFPI boost groups, 50U/kg of heparin was given to the donors intravenously five minutes before donation to elevate plasma TFPI levels.ResultsPre‐heparinization increased total plasma TFPI levels by a factor of 8.0 when compared to non‐heparinized donor blood. Administration of rTF significantly enhanced the generation of prothrombin fragment (F1 {2) (p<0.0001). The boost of TFPI reduced F1+2 to Control group levels in TFPI boost + rTF group (p=0.0178), and in TFPI boost group (p<0.0001 ).ConclusionsHeparin induced TFPI elevation results in attenuation of tissue factor mediated thrombin generation during simulated CPB. Early heparin administration prior to emergence of plasma TF may represent a novel strategy for the control of thrombin generation initiated by extrinsic coagulation pathway during CPB.
Role of sex in telomere attrition with advancing age in human arteries
Authors: Morgan Garrett , Ives Stephen J , Lesniewski Lisa A , Andtbacka Robert H.I. , Noyes R. Dirk , Richardson Russell S. , Donato Anthony J. 
Published: June 2021

Arterial aging is an important risk factor for cardiovascular disease. Telomeres are non‐coding DNA repeats that protect coding DNA and shorten with each cell cycle in all mitotic tissues. Telomere length progressively declines over time in human leukocytes, but little is known regarding human arteries. Sixty‐two human arteries (~425 μM) were obtained during outpatient surgeries (35 males; 24–93yrs, 27 females; 21–79yrs), dissected and total genomic DNA extracted. Mean telomere length (mTL) was negatively correlated with age (r= −0.38, p< 0.01), as assessed by multiplex qPCR telomere length assay. The mTL for subjects in their 20's was 11% greater than those in their 30's, 31% greater than those in their 40's, 39% greater than those in their 50's (p= 0.03), 34% greater than those in their 60's (p= 0.07), and 56% greater than those in their 70's (p= 0.01). Age was a better predictor of mTL in women than in men (r= −0.58, p<0.01 and r=−0.27, p= 0.05, respectively). The predicted rate of decline in mTL was 9% per decade in all subjects, with a predicted decline of 12% in women and 7% in men. Furthermore, the predicted decline was 41% lower than that predicted from studies in human leukocytes using the same mTL assay. These results demonstrate that telomere length declines progressively with advancing age in human arteries and suggest that telomere length declines faster in women than in men.Support: NIA‐AG029337, NHLBI‐HL09183