bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased MMP7 expression in the aging kidney causes upregulation of collagen
Authors: Slusarz Anna , Nichols LaNita A , Grunz‐Borgmann Elizabeth A , Parrish Alan R 
Published: June 2021

MMP7 is the smallest member of the metalloproteinase family and has gained attention in the recent years for its role in abnormal tissue remodeling. The secreted protein is minimally expressed in the adult except for a few niche tissues such as the small intestine and bladder. However, MMP7 is reactivated in a host of disease states including cancer and chronic kidney disease. We have found a dramatic increase in MMP7 expression in aged rat kidneys, with significant elevation starting at 16 months, and over 500 fold up‐regulation in 2 year‐old animals compared to 4 month old rats. Interestingly, 2 year‐old animals, which were maintained on a calorie‐restricted diet, had MMP7 expression comparable to 4 month‐old controls.In order to delineate the contributions of MMP7 to renal dysfunction, we overexpressed full‐length pro‐form of MMP7, which is not processed to a catalytically active form in vitro, a constitutively catalytically active mutant MMP7, and an inactive mutant in the normal rat kidney cell line NRK‐52E. High‐throughput sequencing of the cells revealed significant changes in expression of two collagen alpha genes, Col1a2 and Col3a1, which contribute to fibrosis.Importantly, both of these genes were up‐regulated in aged rat kidneys and the increased expression temporally correlated with increased MMP7 expression and fibrosis.This study was supported by NIH AG034145.
Serum VEGF as a marker of endometrial receptivity in infertile women
Authors: Paul Shipra , Jain Pooja , Tuli Anita , Gupta Usha , Jain Manjula 
Published: June 2021

PurposeFemale infertility is multifactorial in origin and may be a reflection of suboptimal endometrial receptivity. Vascularity is an essential pre‐requisite for continuation of pregnancy. Vascular endothelial growth factor (VEGF) is a major regulator of endothelial cell proliferation, angiogenesis, vasculogenesis, and capillary permeability. We assessed the effect of serum VEGF levels on grades of endometrial receptivity.Methods60 infertile women ages 20–40 years, were enrolled in the study after local IRB approval. Time of ovulation was determined by TVS Doppler ultrasonography just prior to premenstrual biopsy for endometrial characterization and sub‐endometrial blood flow. Grading of endometrial receptivity was based on histopathological findings during mid‐luteal phase. The serum VEGF levels were estimated by ELISA.ResultsSerum VEGF levels increased with grades of endometrial receptivity: 38.48±10.60 pg/ml in Grade I, 86.75±17.25 pg/ml in Grade II, and 215.08±25.60 pg/ml in Grade III. The difference of mean serum VEGF level between grades of endometrial receptivity was highly significant p=0.001.ConclusionsSerum VEGF level of 87 pg/ml predicted adequate endometrial receptivity with a sensitivity of 89.5% and a specificity of 87.8%.
Telocytes and stem cells in regenerative medicine
Authors: Nicolescu Mihnea Ioan , Manole Catalin Gabriel 
Published: June 2021

IntroductionA newly described type of interstitial cells – the telocytes – takes part in the repair/regenerative processes in several organs, including adult mammalian heart. Telocytes form a complex interstitial network, establishing hetero‐cellular contacts with resident stem/progenitor cells.MethodsImmunohistochemistry, transmission electron microscopy and cellular electron tomography were used to identify and characterize the presence and intercellular relations of telocytes in rat heart (n=10) and human salivary glands (n=5). Experimental myocardial infarction was induced and samples from different time intervals (24h, 48h, 1 week) were compared with normal hearts.ResultsCardiac telocytes play an essential role in “nursing” progenitor cells in cardiac stem cell niches. The putative salivary stem cells are also in close contact with telocytes prolongations (telopodes), creating a specific microenvironment, in several periacinar or periductal areas.ConclusionPathology of both vital (heart) and non‐vital (salivary glands) organs may lead to mild or severe dysfunction(s). The deciphering of local tissue repair and renewal mechanisms is of utmost significance. Telocytes may have the potential to increase the efficiency of self‐healing capacity, in a close tandem with resident stem cells.Grant Funding Source: AAA
Expression of stem cell markers in beta cell of the human pancreas
Authors: Filgueira Luis , Baashar Ahmaed 
Published: June 2021

The purpose of this study was to assess the expression of embryonic stem cell and pancreas‐specific markers in insulin producing beta cells in adult human islets, including Nanog, Oct4, Sox2, menin, Ngn3 and PDX‐1.An indirect immune fluorescence staining was done on archival formalin‐fixed, paraffin‐embedded human pancreatic samples. Expression of the three beta cells precursor markers menin, Ngn3 and PDX‐1 were identified in the islets, always co‐localized with insulin. Expression of Nanog, Oct4 and Sox2 were distinctly identified in the islets of the human pancreas. Oct4 and Sox2 expression was always co‐localized with insulin, indicating that all insulin secreting beta cells do express these two markers. Nanog was mainly co‐expressed with insulin in beta cells, but there was a small number of cells in the islets expressing Nanog, but no insulin, demonstrating that Nanog might be expressed by the others endocrine cells or early precursors or tissue‐specific stem cells.These findings demonstrate that the three embryonic stem cell markers Nanog, Oct4 and Sox2 are expressed in the islets of the human pancreas. The precursor markers of beta cells such as menin, Ngn3 and PDX‐1 are always localized with insulin producing beta cells as well. Consequently, the presence of embryonic stem cell markers in the human adult pancreas may offer a new principle for regenerating and replacing ageing or damaged beta cells.
Characterization Of CD‐209 Isoforms With Carbohydrate Recognition Domain Modified Due To Alternative Splicing
Authors: Santos Luciana Lara , Pereira Lailah Horácio Sales , Taranto Alex Gutteres , Junior Moacyr Comar , Lopes Débora Oliveira , Siqueira Jaqueline Maria 
Published: June 2021

The CD‐209 gene encodes a glycoprotein expressed as soluble or membrane, mainly present in human macrophages and dendritic cells. It is responsible for initial adhesion of the dengue vírus (DENV) to these cells. This gene undergoes alternative splicing, which results in thirteen different transcript of isoforms and consequently of the glycoprotein. The aim of this study is to predict the molecular structure of CD‐209 isoforms with carbohydrate recognition domain (CRD) modified due process of splicing alternative. The isoforms were obtained from the GenBank and aligned by Multialin software. Analysis in silico was performed to verify possible differences in CRD. 3D model structures were built by homology modeling (Swiss‐Model Server). We have demonstrated three sites of Ca2+ bind in CRD and amino acids residues that take part of it. We have found five isoforms with different CDR and only two of them keep three sites of Ca2+ bind. Validation steps were done and root‐mean‐square deviation values were found below 0.6. These variations may be correlated to the pathogenesis of dengue, since the virus needs of these sites of Ca2+ bind to interact with CD‐209 receptor. If the isoforms which miss some sites of Ca2+ are frequent in some populations this could confer a certain protection against virus infection. Future population studies would be interesting to better understand these issues.Support: FAPEMIG
Use of Pseudomonas aeruginosa Chaperones in Folding an Insect Recombinant Prolyl Endoprotease (rPEP) Expressed in Escherichia coli.
Authors: Gautam Ranjeeta , Dareddy Vanitha , Clack Beatrice 
Published: June 2021

Chaperone assist in protein folding. The purpose of this study were to 1) determine if co‐expression of Pseudomonas aeruginosa GroESL or Trigger factor with prolyl endo protease (PEP) cDNA in Escherichia coli system resulted in increase amount of soluble active enzyme 2) determine if two different temperatures, 37°C for 24 hours and biphasic temperature incubation of 37°C for 6 hours followed by overnight in 28°C would increase in amount of soluble active PEP and 3) to identify which chaperone mechanism results in highest expression of active protein. GroESL and TF chaperones were cloned into pLys‐S and pLys‐E plasmid. The resulting pGROELS‐S/E plasmid or pTF‐S/E plasmid was co‐transformed into E. coli. Western Blot techniques were used to determine the level of protein expression. Enzyme activity was assayed using a synthetic chromagenic peptide. Biphasic temperature growth resulted in higher level of active than constant 37°C. pGroESL‐ E and pTF‐S resulted in highest increase in amount of soluble rPEP as compared to amount found. Expression in presence of pGroESL‐E and pTF‐S resulted in the highest levels of active soluble enzyme. P. aeruginosa GroESL and TF chaperones co‐express and assist in folding successfully expression of a large insect PEP in E. coli.Funding: Office of Research and Sponsored Projects, Stephen F Austin State University; Ed and Gwen Cole, Nacogdoches, TX.
3D geometric morphometric analysis of phenotypic plasticity in the pectoral girdle of a basal actinopterygiian fish
Authors: Du Trina Y , Standen Emily M , Larsson Hans CE 
Published: June 2021

Polypterids are a basal group of actinopterygian fishes that represent a possible living analogue for the evolutionary transition from fish to tetrapods for number of reasons, including their ability to walk on land using robustly, muscled pectoral fins. We examined the phenotypic plasticity in the pectoral anatomy of Polypterus senegalus induced by habitual terrestrial locomotion. Fish were reared in a fully terrestrial environment where they were forced to live and locomote over land for up to two years. MicroCT scans were taken of the experimental walking group and a swimming control group. 3D reconstructions of the pectoral anatomy were described using spherical harmonics, a 3D extension of elliptic Fourier analysis. Here we present a geometric morphometric analysis of morphological differences in the pectoral anatomy between swimming and walking fish, and discuss potential small‐scale morphological changes in response to the functional demands of terrestrial locomotion during the fin‐to‐limb transition.Grant Funding Source: NSERC, Canada Research Chair, Tomlinson Postdoctoral Fellowship
Determining the Mechanism of Sphingosine‐1‐Phosphate Transport Between Membranes
Authors: Massa Mitterand Nformi , Wattenberg Binks 
Published: June 2021

Sphingosine‐1‐phosphate (S1P) is synthesized from sphingosine by the enzyme sphingosine kinase (SK). The main pathways of S1P degradation occur via the action of two important enzymes; S1P phosphatase (SPP) and S1P lyase (SPL) which are both bound to the endoplasmic reticulum (ER). So the ER plays a vital role in the metabolism of S1P.The goal of these studies is to determine the mechanism of S1P transport between membranes. We are hypothesizing that this is a protein mediated transfer. Initially we have defined the parameters of S1P extraction from membranes, which is the first step in intermembrane transfer. We have used a model lipid‐binding protein, bovine serum albumin (BSA). To measure S1P extraction from membranes, membranes were first loaded with 33P‐S1P by using membranes ectopically expressing a membrane‐anchored SK construct (Lck‐SK). Extraction of S1P was measured by incubating pre‐labeled membranes in the presence or absence of fatty acid‐free BSA for various lengths of time. With this system we find that extraction of S1P is protein‐dependent, but very rapid. We then tested the ability of cytosol harvested from Hela cells to replace BSA in extracting S1P from membranes. Interestingly, results indicated the presence of an S1P transport factor(s) in the cytosol. Size‐exclusion chromatography was then used to further fractionate the cytosol and various fractions were assayed for activity. S1P extraction activity was detected to be higher in higher molecular weight fractions away from bulk protein. Concentrates of these fractions demonstrated enhanced S1P extraction activity from membranes over whole cytosol.
Retinoic acid modifies lipid metabolism in isolated adult and aged rat cerebellum nuclei
Authors: Gaveglio Virginia Lucía , Giusto Norma María , Pasquaré Susana Juana 
Published: June 2021

Nuclear lipid metabolism gives rise to several lipid second messengers that seem to be involved in the regulation of nuclear structure and gene expression. The purpose of the present research was to study the metabolic pathways involved in the metabolism of phosphatidic acid (PA) and its regulation in isolated nuclei from the central nervous system. This study was also conducted in isolated nuclei from aged animals, thus allowing us to analyze the effects of neurodegeneration processes on PA metabolism as a result of aging. Adult (4 mo) and aged (28 mo) rat cerebellums were homogenized and highly purified nuclei were isolated by sucrose‐density ultracentrifugation. Using radiolabelled substrates we demonstrated lipid phosphate phosphatase, diacylglycerol lipase (DAGL), monoacylglycerol lipase (MAGL), lysophosphatidate phosphohydrolase and phospholipase as well as phospholipase type A activities. We further studied their regulation by retinoic acid (RA) which was observed to decrease DAGL, MAGL and PA‐PLA activities. Significant aged‐related changes in the above‐mentioned enzymatic activities as well as in their regulation by RA were observed. Taken together, our results demonstrate a RA‐regulated PA metabolism in rat cerebellum nuclei which could be involved in neurodegeneration processes.This research was funded by: CONICET, FONCyT, SCyT‐UNS.
TDX, a galectin‐1 and galectin‐3‐specific inhibitor, mitigates VEGF‐A‐induced angiogenesis
Authors: Chen Wei‐Sheng , Leffler Hakon , Nilsson Ulf J , Panjwani Noorjahan 
Published: June 2021

Both galectin‐1 (Gal‐1) and galectin‐3 (Gal‐3) are vital modulators for vascular endothelial growth factors receptor‐2 (VEGFR‐2) signaling pathway. To date, TDX is the only compound that specifically targets both galectins with high affinity. Our goal is to study TDX's efficacy against VEGF‐A‐mediated pathological angiogenesis.Here we showed that Gal‐1 and Gal‐3 interact with VEGFR‐2 in a carbohydrate‐dependent manner and that TDX: (i) reduces cautery‐induced corneal neovascularization in vivo, (ii) reduces VEGF‐A‐induced sprouting of human umbilical vein endothelial cells (HUVECs) as assessed by a three‐dimensional sprouting assay, (iii) efficiently abolishes VEGF‐A‐induced HUVEC chemotaxis, (iv) has little effect on HUVEC viability, and (v) does not affect total protein expression of VEGFR‐2 in HUVECs.Our data provide proof of principle that targeting Gal‐1 and Gal‐3 by the novel, small molecule inhibitor, TDX, ameliorates pathological angiogenesis. The findings provide a new therapeutic strategy for various disease conditions, including inflammation, diabetes, cancer metastasis, age‐related macular degeneration and corneal neovascularization.This work is supported by the NIH Grant R01EY007088 to N. Panjwani.
Altered hippocampal activation during memory encoding in type 2 diabetes
Authors: Meusel Liesel‐Ann Catharine , Anderson Nicole , Tchistiakova Ekaterina , MacIntosh Brad , Greenwood Carol 
Published: June 2021

Type 2 diabetes (T2DM) increases risk for cognitive decline and dementia. While much is known about T2DM‐associated cognitive changes and brain atrophy, the impact of T2DM on brain function is underexplored. Blood oxygenation level dependent (BOLD) signal changes were compared in older adults with T2DM and hypertension (DO, n = 9) and older adults with hypertension only (HO, n = 10) during a cerebrovascular reactivity (CVR) task and a word‐list learning task. We hypothesized that memory deficits and altered BOLD signaling would be apparent in DO compared to HO but that CVR, obtained during a breath‐hold task, would be comparable. There were no group differences in performance on neuropsychological memory tests nor on the word‐list learning task. A region‐of‐interest analysis on hippocampal (HC) activation during word‐list encoding showed stronger right HC activation in the DO compared to the HO group after accounting for CVR (p < .01). Across groups, there was a significant negative correlation between right HC activation and number of words learned during encoding, controlling for performance on the first trial (r = −0.61, p < .01). Collectively these findings suggest that 1) T2DM elevates memory‐related activation of right HC independent of vascular reactivity, and 2) increases in right HC activation parallel decreased learning success and may signal efforts to compensate for cognitive decline (CIHR – MOP111244).Grant Funding Source: Canadian Institutes of Health Research
Developmental and Gender Differences in Cognitive Responses to Caffeine
Authors: Graczyk Adam , Ziegler Amanda M , Bendlin Ashley , Sion Teresa , Vattana Karina , Temple Jennifer L. 
Published: June 2021

BackgroundCaffeine is the most widely used stimulant in the world. Previous studies have shown that caffeine can enhance cognitive functioning.ObjectiveTo measure developmental and gender difference in cognitive responses to caffeine in children and adolescents.MethodsPre‐ and post‐pubertal children were given a cognitive test battery using the Automated Neurological Assessment Metrics (ANAM) before and 60 minutes after administration of placebo or caffeine (1mg/kg or 2mg/kg).ResultsCaffeine increased the number correct in the memory search task and decreased the standard deviation in the go/no‐go task. Females had more correct responses than males in simple reaction time and the Stroop color‐word task. Also in post‐pubertal females, there was an interaction between menstrual cycle phase and caffeine treatment in simple reaction time and the go/no‐go task.ConclusionsThese results are consistent with previous studies, primarily in adults, showing caffeine facilitates performance on some cognitive tasks and not others. In addition, these results are similar to previous studies showing sex differences on performance on some cognitive tasks. This study is the first to report sex differences in responses to caffeine on cognitive tasks as well as differences across the menstrual cycle in children and adolescents. This study was funded by RO1DA030386 to JLT.
Patterns of food source usage among low‐income African Americans are associated with dietary intake
Authors: Cuccia Alison , Budd Nadine , Liu Debra , Jock Brittany , Jeffries Jayne , Powell Lisa , Gittelsohn Joel 
Published: June 2021

Obesity rates among Baltimore City adult residents are 30% higher than national averages, and are highest among minorities living in low‐income areas. While food availability has been linked to obesity and nutritional adequacy, little research has examined patterns of food source usage and dietary quality. 362 low‐income African American adults recalled their 24‐hour dietary intake and past 30 day frequency of food source usage. Parallel Analysis was used to extract three significant factors (using varimax rotation and factor loadings greater than 0.30 to interpret factors). Public markets, corner stores, carryouts, and fast food restaurants loaded high on the Prepared Foods Factor; street food vendors, food pantries, and community centers loaded high on the Food Giveaway Factor; and farmers markets, horse drawn produce carts (arabbers), and specialty food stores load high on Whole Food Factor. The Prepared Food Factor was associated with decreased diet quality in women, and the Food Giveaway Factor and the Specialty Food Factor was associated with decreased diet quality in men. The Food Giveaway Factor (p=0.022) and the Whole Food Factor (p=0.003) were positively associated with education. These results may inform how food policy in Baltimore City can target low‐income men and women differently.Funded by National Health, Lung & Blood Institute, Heart Disease (NHLBIDHV), Grant #1R21HL102812–01A1.
Contribution of the ECS to COX expression and activity in myoblast cultures
Authors: Kim Jeffrey , Li Yong , Watkins Bruce A 
Published: June 2021

Cyclooxygenase (COX) possesses substrate affinity to the endocannabinoids (EC) anandamide (AEA) and 2‐ arachidonylglycerol (2‐AG). Moreover, the relationship between EC signaling (ECS) and the COX pathway is not known therefore we investigated agonist, antagonists and PUFA effects on ECS genes in myoblasts. At 50% confluency, C2C12 were pretreated with 5 μM of the CB2 antagonist, AM630, for 2 h and one with both AM630 and 1 μM of CB1 antagonist, NESS0327. Cells were then treated with 25 μM of either AA (20:4n6), EPA (20:5n3), AEA, or BSA (vehicle control) for 24 h. Western blot analysis of COX and enzyme activity were measured. qPCR analyses were performed on ECS relevant genes. Total COX activity was greater in the AM630 + AEA treated cells compared to all other cells. Further analysis revealed that COX‐1 and COX‐2 proteins were greater in the AM630 + AEA treated cells compared to all others. mRNA for the AEA synthesis enzyme, NAPE‐PLD, and 2‐AG synthesis enzymes, DAGLα and DAGLβ, were higher in AM630 + EPA treated cells compared to all other groups. The mRNA levels of CB1 and CB2 were both highest in the AM630 + EPA group. These findings suggest that COX activity and protein levels are influenced by the ECS, particularly by the activation of CB1 receptors. However, treatments of either AA or EPA did not alter COX status in C2C12 cells under testing condition.Grant Funding Source: Diet and Health Initiative, UConn, Storrs, CT, USA
Genistein reduced colon cancer metastasis to liver through regulating the expression of metastasis‐related genes in xenographed mice model
Authors: Li Qian , Chen Hong , Lezmi Stephane , Chen Danni 
Published: June 2021

This study aimed at investigating the effect of genistein (Gen) on liver metastases derived from colon cancer. Male athymic nude mice were fed with western diet (W; calories%, fat 39%, carb 50%), W diet supplemented with 100ppm Gen (GL) or 500ppm Gen (GH). After 16 weeks, all the animals were intrasplenically injected with metastatic human colon cancer cells SW620 and sacrificed 8 weeks later. GL and GH mice showed lower liver metastases (36% and 17%) compared to W group (55% of mice with metastases). Mean size of metastases in the W group (4.7 mm2) was larger than that in GL (2.1 mm2) and GH (2.0 mm2) groups. To understand the molecular mechanism of the anti‐metastatic function of Gen, the expression of multiple metastasis‐related genes were determined by real‐time PCR. mRNA of NDRG1 gene in livers was greatly decreased by 50% and 60% in GL (p=0.005) and GH group (p=0.001) compared to W group. As NDRG1 has been reported as a biomarker for metastasis and poor prognosis in hepatocellular carcinoma, the down‐regulation of NDRG1 by Gen supplementation was corresponding to decreased liver metastasis. In summary, our study indicated that dietary supplementation of Gen suppressed colon cancer metastasis, which is associated with altered expression of metastasis‐related genes by the treatment.Grant Funding Source: university of illinois