Recent Research Articles from UNTHSC

Syndicate content NCBI pubmed
NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
Updated: 1 hour 40 min ago

Association between Helicobacter pylori and Barrett's Esophagus: A Case-Control Study.

Sat, 01/18/2014 - 5:30am
Related Articles

Association between Helicobacter pylori and Barrett's Esophagus: A Case-Control Study.

Am J Gastroenterol. 2014 Jan 14;ajg

Authors: Fischbach LA, Graham DY, Kramer JR, Rugge M, Verstovsek G, Parente P, Alsarraj A, Fitzgerald S, Shaib Y, Abraham NS, Kolpachi A, Gupta S, Vela MF, Velez M, Cole R, Anand B, El Serag HB

Abstract
OBJECTIVES:The estimated association between Helicobacter pylori and Barrett's esophagus (BE) has been heterogenous across previous studies. In this study, we aimed to examine the association between H. pylori and BE and to identify factors that may explain or modify this association.METHODS:We conducted a case-control study in which we used screening colonoscopy controls recruited from primary care clinics as our primary control group in order to minimize selection bias. All participants underwent an esophagogastroduodenoscopy with gastric mapping biopsies. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the association between H. pylori and BE while controlling for confounders.RESULTS:We identified 218 cases and 439 controls. The overall OR for the association between H. pylori and BE after controlling for age and white race was 0.55 (95% CI: 0.35-0.84). We observed an even stronger inverse association (OR: 0.28; 95% CI: 0.15, 0.50) among participants with corpus atrophy or antisecretory drug use ≥1 time per week (factors thought to lower gastric acidity), and no inverse association in patients without these factors (OR: 1.32; 95% CI: 0.66, 2.63).CONCLUSIONS:The association between H. pylori and a decreased risk for BE appears to occur in patients with factors that would likely lower gastric acidity (corpus atrophy or taking antisecretory drugs at least once a week).Am J Gastroenterol advance online publication, 14 January 2014; doi:10.1038/ajg.2013.443.

PMID: 24419485 [PubMed - as supplied by publisher]

An Optimal Test for Variance Components of Multivariate Mixed-Effects Linear Models.

Sat, 01/18/2014 - 5:30am
Related Articles

An Optimal Test for Variance Components of Multivariate Mixed-Effects Linear Models.

J Multivar Anal. 2014 Feb;124

Authors: Aryal S, Bhaumik DK, Mathew T, Gibbons RD

Abstract
In this article we derive an optimal test for testing the significance of covariance matrices of random-effects of two multivariate mixed-effects linear models. We compute the power of this newly derived test via simulation for various alternative hypotheses in a bivariate set up for unbalanced designs and observe that power responds sharply when sample size and alternative hypotheses are changed. For some balanced designs we compare power of the optimal test to that of the likelihood ratio test via simulation, and find that the proposed test has greater power than the likelihood ratio test. The results are illustrated using real data on human growth. Other relevant applications of the model are highlighted.

PMID: 24415807 [PubMed - as supplied by publisher]

Pyruvate-enriched resuscitation: metabolic support of post-ischemic hindlimb muscle in hypovolemic goats.

Sat, 01/18/2014 - 5:30am
Related Articles

Pyruvate-enriched resuscitation: metabolic support of post-ischemic hindlimb muscle in hypovolemic goats.

Exp Biol Med (Maywood). 2014 Jan 10;

Authors: Gurji HA, White DW, Hoxha B, Sun J, Harbor JP, Schulz DR, Williams AG, Olivencia-Yurvati AH, Mallet RT

Abstract
Tourniquet-imposed ischemia-reperfusion of extremities generates reactive oxygen and nitrogen species (RONS), which can disrupt intermediary metabolism and ATP production. This study tested the hypothesis that fluid resuscitation with pyruvate, a natural antioxidant and metabolic fuel, ameliorates the deleterious effects of ischemia-reperfusion on intermediary metabolism in skeletal muscle. Anesthetized male goats (∼25 kg) were bled to a mean arterial pressure of 48 ± 1 mmHg and then subjected to 90 min hindlimb ischemia with a tourniquet and femoral crossclamp, followed by 4-h reperfusion. Lactated Ringers (LR) or pyruvate Ringers (PR) was infused intravenous for 90 min, from 30 min ischemia to 30 min reperfusion, to deliver 0.05 mmol kg(-1) min(-1) lactate or pyruvate. Time controls (TC) underwent neither hemorrhage nor hindlimb ischemia. Lipid peroxidation product 8-isoprostane, RONS-sensitive aconitase and creatine kinase activities, antioxidant superoxide dismutase activity, and phosphocreatine phosphorylation potential ([PCr]/[{Cr}{Pi}]), an index of tissue energy state, were measured in reperfused gastrocnemius at 90 min resuscitation (n = 6 all groups) and 3.5 h post-resuscitation (n = 8 TC, 9 LR, 10 PR). PR more effectively than LR suppressed 8-isoprostane formation, prevented inactivation of aconitase and creatine kinase, doubled superoxide dismutase activity, and augmented [PCr]/([Cr][Pi]). Pyruvate-enriched Ringer's is metabolically superior to Ringer's lactate for fluid resuscitation of tourniqueted muscle.

PMID: 24414481 [PubMed - as supplied by publisher]

U.S. Population Estimates and Correlates of Sexual Abuse of Community-Dwelling Older Adults.

Sat, 01/18/2014 - 5:30am
Related Articles

U.S. Population Estimates and Correlates of Sexual Abuse of Community-Dwelling Older Adults.

J Elder Abuse Negl. 2014 Jan 10;

Authors: Cannell MB, Manini T, Spence-Almaguer E, Maldonado-Molina M, Andresen EM

Abstract
Abstract We describe the annual prevalence of sexual abuse among community dwelling older adults in the United States. We also describe factors associated with experiencing sexual abuse. We used data from 24,343 older adults from the 2005 Behavioral Risk Factor Surveillance System pooled across 18 states. We estimated prevalence of sexual abuse, bivariate distributions, and odds ratio associations across demographic, health, and contextual factors. Our results show that 0.9% of older adults reported experiencing sexual abuse in the previous year. This represents approximately 90,289 community dwelling older adults. We also report on factors associated with experiencing recent sexual abuse. There was a significant gender-by-binge drinking interaction, with a stronger association among women. There is a need for health promotion efforts targeted specifically towards older adults, encouraging them to seek services, if possible, after exposure to sexual abuse.

PMID: 24410194 [PubMed - as supplied by publisher]

Estrogen receptors and ischemic neuroprotection: who, what, where, and when?

Wed, 01/15/2014 - 9:41am
Related Articles

Estrogen receptors and ischemic neuroprotection: who, what, where, and when?

Brain Res. 2013 Jun 13;1514:107-22

Authors: Schreihofer DA, Ma Y

Abstract
Estrogens, particularly 17β-estradiol (E2), are powerful neuroprotective agents in animal models of cerebral ischemia. Loss of endogenous E2 in women at menopause or after surgical oopherectomy leads to an increase risk of stroke, neurodegenerative disease, and cognitive decline. However, several clinical trials found detrimental effects of E2 therapy after menopause, including increased stroke risk and dementia. Recent animal and human studies now support the "critical period" hypothesis for E2 neuroprotection whereby E2 therapy must begin soon after the loss of endogenous E2 production to have a beneficial effect. Although a wide array of mechanisms has been proposed for estradiol (E2)-dependent neuroprotection in cerebral ischemia and neurodegenerative disease, most of these mechanisms involve interactions of E2 with one of its cognate receptors, estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), or the G protein-coupled estrogen receptor (GPER). However, these receptors are not uniformly distributed throughout the brain, across different cell types, and within cellular compartments. Such differences likely play a role in the ability of E2 and ER selective ligands to protect the brain from ischemia. This review examines the changes in ER expression and location that may underlie the loss of E2 neuroprotection seen with aging and long-term estrogen deprivation (LTED). Recent results suggest that the loss of ERα that accompanies aging and LTED plays an important role in the loss of E2-dependent neuroprotection. This article is part of a Special Issue entitled Hormone Therapy.

PMID: 23500634 [PubMed - indexed for MEDLINE]

Does phytoestrogen supplementation affect cognition differentially in males and females?

Wed, 01/15/2014 - 9:41am
Related Articles

Does phytoestrogen supplementation affect cognition differentially in males and females?

Brain Res. 2013 Jun 13;1514:123-7

Authors: Sumien N, Chaudhari K, Sidhu A, Forster MJ

Abstract
Phytoestrogens are plant-derived compounds found mainly in soy with known estrogenic properties and a potential for benefits to human health. Increased intake in phytoestrogens stemmed from the search for safe alternatives to hormone replacement therapies. Based on epidemiologic evidence comparing Western and Asian populations and clinical studies, phytoestrogens show promise to improve health and brain function. This review is focused on the effects of phytoestrogens on cognition by examining clinical and animal studies, with special attention placed on (1) a window of therapeutic opportunity which may explain the discrepancy among studies, and (2) whether a sex/gender difference exists in response to phytoestrogen intake and what the possible underlying mechanisms may be.

PMID: 23415935 [PubMed - indexed for MEDLINE]

Progesterone-induced neuroprotection: factors that may predict therapeutic efficacy.

Wed, 01/15/2014 - 9:41am
Related Articles

Progesterone-induced neuroprotection: factors that may predict therapeutic efficacy.

Brain Res. 2013 Jun 13;1514:98-106

Authors: Singh M, Su C

Abstract
Both progesterone and estradiol have well-described neuroprotective effects against numerous insults in a variety of cell culture models, animal models and in humans. However, the efficacy of these hormones may depend on a variety of factors, including the type of hormone used (ex. progesterone versus medroxyprogesterone acetate), the duration of the postmenopausal period prior to initiating the hormone intervention, and potentially, the age of the subject. The latter two factors relate to the proposed existence of a "window of therapeutic opportunity" for steroid hormones in the brain. While such a window of opportunity has been described for estrogen, there is a paucity of information to address whether such a window of opportunity exists for progesterone and its related progestins. Here, we review known cellular mechanisms likely to underlie the protective effects of progesterone and furthermore, describe key differences in the neurobiology of progesterone and the synthetic progestin, medroxyprogesterone acetate (MPA). Based on the latter, we offer a model that defines some of the key cellular and molecular players that predict the neuroprotective efficacy of progesterone. Accordingly, we suggest how changes in the expression or function of these cellular and molecular targets of progesterone with age or prolonged duration of hormone withdrawal (such as following surgical or natural menopause) may impact the efficacy of progesterone. This article is part of a Special Issue entitled Hormone Therapy.

PMID: 23340161 [PubMed - indexed for MEDLINE]

Window of opportunity: estrogen as a treatment for ischemic stroke.

Wed, 01/15/2014 - 9:41am
Related Articles

Window of opportunity: estrogen as a treatment for ischemic stroke.

Brain Res. 2013 Jun 13;1514:83-90

Authors: Liu R, Yang SH

Abstract
The neuroprotection research in the last 2 decades has witnessed a growing interest in the functions of estrogens as neuroprotectants against neurodegenerative diseases including stroke. The neuroprotective action of estrogens has been well demonstrated in both in vitro and in vivo models of ischemic stroke. However, the major conducted clinical trials so far have raised concern for the protective effect of estrogen replacement therapy in postmenopausal women. The discrepancy could be partly due to the mistranslation between the experimental stroke research and clinical trials. While predominant experimental studies tested the protective action of estrogens on ischemic stroke using acute treatment paradigm, the clinical trials have mainly focused on the effect of estrogen replacement therapy on the primary and secondary stroke prevention which has not been adequately addressed in the experimental stroke study. Although the major conducted clinical trials have indicated that estrogen replacement therapy has an adverse effect and raise concern for long term estrogen replacement therapy for stroke prevention, these are not appropriate for assessing the potential effects of acute estrogen treatment on stroke protection. The well established action of estrogen in the neurovascular unit and its potential interaction with recombinant tissue Plasminogen Activator (rtPA) makes it a candidate for the combined therapy with rtPA for the acute treatment of ischemic stroke. On the other hand, the "critical period" and newly emerged "biomarkers window" hypotheses have indicated that many clinical relevant factors have been underestimated in the experimental ischemic stroke research. The development and application of ischemic stroke models that replicate the clinical condition is essential for further evaluation of acute estrogen treatment on ischemic stroke which might provide critical information for future clinical trials. This article is part of a Special Issue entitled Hormone Therapy.

PMID: 23340160 [PubMed - indexed for MEDLINE]

Window of opportunity for estrogen and progestin intervention in brain aging and Alzheimer's disease.

Wed, 01/15/2014 - 9:41am
Related Articles

Window of opportunity for estrogen and progestin intervention in brain aging and Alzheimer's disease.

Brain Res. 2013 Jun 13;1514:1-2

Authors: Singh M, Simpkins JW, Simpkins JW, Bimonte-Nelson HA, Bimonte-Nelson HA, Brinton RD, Brinton RD

PMID: 23726132 [PubMed - indexed for MEDLINE]

Therapeutic strategies in Friedreich's ataxia.

Wed, 01/15/2014 - 9:41am
Related Articles

Therapeutic strategies in Friedreich's ataxia.

Brain Res. 2013 Jun 13;1514:91-7

Authors: Richardson TE, Kelly HN, Yu AE, Simpkins JW

Abstract
First established as a diagnosis by Nikolaus Friedreich in 1863, Friedreich's ataxia (FA) is an autosomal recessive progressive neurodegenerative disorder cause by a trinucleotide repeat expansion. FA begins with the functional absence of the FXN gene product frataxin, a protein whose exact function still remains unknown. This absence results in impaired intracellular antioxidant defenses, dysregulation of iron-sulfur cluster proteins, depression of aerobic electron transport chain respiration, massive mitochondrial dysfunction, and ultimately cell death in the brain, spinal cord and heart. Herein, we review the molecular and cellular pathogenesis leading to widespread organ system dysfunction, as well as current therapeutic research aimed at preventing the debilitating effects of frataxin loss and preventing the signs and symptoms associated of FA. We also discuss the ongoing treatment strategies employed by our laboratory to prevent mitochondrial damage using synergistic effects of 17β-estradiol and methylene blue, previously shown by our group and others to have protective effects in human FA fibroblasts. This article is part of a Special Issue entitled Hormone Therapy.

PMID: 23587934 [PubMed - indexed for MEDLINE]

Oxidative stress defines the neuroprotective or neurotoxic properties of androgens in immortalized female rat dopaminergic neuronal cells.

Sat, 01/11/2014 - 5:31am
Related Articles

Oxidative stress defines the neuroprotective or neurotoxic properties of androgens in immortalized female rat dopaminergic neuronal cells.

Endocrinology. 2013 Nov;154(11):4281-92

Authors: Holmes S, Abbassi B, Su C, Singh M, Cunningham RL

Abstract
Males have a higher risk for developing Parkinson's disease and parkinsonism after ischemic stroke than females. Although estrogens have been shown to play a neuroprotective role in Parkinson's disease, there is little information on androgens' actions on dopamine neurons. In this study, we examined the effects of androgens under conditions of oxidative stress to determine whether androgens play a neuroprotective or neurotoxic role in dopamine neuronal function. Mitochondrial function, cell viability, intracellular calcium levels, and mitochondrial calcium influx were examined in response to androgens under both nonoxidative and oxidative stress conditions. Briefly, N27 dopaminergic cells were exposed to the oxidative stressor, hydrogen peroxide, and physiologically relevant levels of testosterone or dihydrotestosterone, applied either before or after oxidative stress exposure. Androgens, alone, increased mitochondrial function via a calcium-dependent mechanism. Androgen pretreatment protected cells from oxidative stress-induced cell death. However, treatment with androgens after the oxidative insult increased cell death, and these effects were, in part, mediated by calcium influx into the mitochondria. Interestingly, the negative effects of androgens were not blocked by either androgen or estrogen receptor antagonists. Instead, a putative membrane-associated androgen receptor was implicated. Overall, our results indicate that androgens are neuroprotective when oxidative stress levels are minimal, but when oxidative stress levels are elevated, androgens exacerbate oxidative stress damage.

PMID: 23959938 [PubMed - indexed for MEDLINE]

STRait Razor: a length-based forensic STR allele-calling tool for use with second generation sequencing data.

Thu, 01/09/2014 - 12:27pm
Related Articles

STRait Razor: a length-based forensic STR allele-calling tool for use with second generation sequencing data.

Forensic Sci Int Genet. 2013 Jul;7(4):409-17

Authors: Warshauer DH, Lin D, Hari K, Jain R, Davis C, Larue B, King JL, Budowle B

Abstract
Recent studies have demonstrated the capability of second generation sequencing (SGS) to provide coverage of short tandem repeats (STRs) found within the human genome. However, there are relatively few bioinformatic software packages capable of detecting these markers in the raw sequence data. The extant STR-calling tools are sophisticated, but are not always applicable to the analysis of the STR loci commonly used in forensic analyses. STRait Razor is a newly developed Perl-based software tool that runs on the Linux/Unix operating system and is designed to detect forensically-relevant STR alleles in FASTQ sequence data, based on allelic length. It is capable of analyzing STR loci with repeat motifs ranging from simple to complex without the need for extensive allelic sequence data. STRait Razor is designed to interpret both single-end and paired-end data and relies on intelligent parallel processing to reduce analysis time. Users are presented with a number of customization options, including variable mismatch detection parameters, as well as the ability to easily allow for the detection of alleles at new loci. In its current state, the software detects alleles for 44 autosomal and Y-chromosome STR loci. The study described herein demonstrates that STRait Razor is capable of detecting STR alleles in data generated by multiple library preparation methods and two Illumina(®) sequencing instruments, with 100% concordance. The data also reveal noteworthy concepts related to the effect of different preparation chemistries and sequencing parameters on the bioinformatic detection of STR alleles.

PMID: 23768312 [PubMed - indexed for MEDLINE]

The role of p38 in mitochondrial respiration in male and female mice.

Thu, 01/09/2014 - 12:27pm
Related Articles

The role of p38 in mitochondrial respiration in male and female mice.

Neurosci Lett. 2013 Jun 7;544:152-6

Authors: Ju X, Wen Y, Metzger D, Jung M

Abstract
p38 is a mitogen-activated protein kinase and mediates cell growth, cell differentiation, and synaptic plasticity. The aim of this study is to determine the extent to which p38 plays a role in maintaining mitochondrial respiration in male and female mice under a normal condition. To achieve this aim, we have generated transgenic mice that lack p38 in cerebellar Purkinje neurons by crossing Pcp2 (Purkinje cell protein 2)-Cre mice with p38(loxP/loxP) mice. Mitochondria from cerebellum were then isolated from the transgenic and wild-type mice to measure mitochondrial respiration using XF24 respirometer. The mRNA and protein expression of cytochrome c oxidase (COX) in cerebellum were also measured using RT-PCR and immunoblot methods. Separately, HT22 cells were used to determine the involvement of 17β-estradiol (E2) and COX in mitochondrial respiration. The genetic knockout of p38 in Purkinje neurons suppressed the mitochondrial respiration only in male mice and increased COX expression only in female mice. The inhibition of COX by sodium azide (SA) sharply suppressed mitochondrial respiration of HT22 cells in a manner that was protected by E2. These data suggest that p38 is required for the mitochondrial respiration of male mice. When p38 is below a normal level, females may maintain mitochondrial respiration through COX up-regulation.

PMID: 23603578 [PubMed - indexed for MEDLINE]

Neurogenesis in neurological and psychiatric diseases and brain injury: From bench to bedside.

Tue, 01/07/2014 - 5:18am
Related Articles

Neurogenesis in neurological and psychiatric diseases and brain injury: From bench to bedside.

Prog Neurobiol. 2013 Dec 30;

Authors: Ruan L, Lau BW, Wang J, Huang L, Zhuge Q, Wang B, Jin K, So KF

Abstract
Researchers who have uncovered the presence of stem cells in an adult's central nervous system have not only challenged the dogma that new neurons cannot be generated during adulthood, but also shed light on the etiology and disease mechanisms underlying many neurological and psychiatric disorders. Brain trauma, neurodegenerative diseases, and psychiatric disorders pose enormous burdens at both personal and societal levels. Although medications for these disorders are widely used, the treatment mechanisms underlying the illnesses remain largely elusive. In the past decade, an increasing amount of evidence indicate that adult neurogenesis (i.e. generating new CNS neurons during adulthood) may be involved in the pathology of different CNS disorders, and thus neurogenesis may be a potential target area for treatments. Although the new neurons were shown to be a major player in mediating treatment efficacy of neurological and psychotropic drugs on cognitive functions, it is still debatable if the altered production of new neurons can cause the disorders. This review hence seeks to discuss pre and current clinical studies that demonstrate the functional impact adult neurogenesis have on neurological and psychiatric illnesses while examining the related underlying disease mechanisms.

PMID: 24384539 [PubMed - as supplied by publisher]

Menu-Labeling Usage and Its Association with Diet and Exercise: 2011 BRFSS Sugar Sweetened Beverage and Menu Labeling Module.

Tue, 01/07/2014 - 5:18am
Related Articles

Menu-Labeling Usage and Its Association with Diet and Exercise: 2011 BRFSS Sugar Sweetened Beverage and Menu Labeling Module.

Prev Chronic Dis. 2014;11:E02

Authors: Bowers KM, Suzuki S

Abstract
INTRODUCTION: The primary objective of our study was to investigate the association between menu-labeling usage and healthy behaviors pertaining to diet (consumption of fruits, vegetables, sodas, and sugar-sweetened beverages) and exercise.
METHODS: Data from the 2011 Behavioral Risk Factor Surveillance System, Sugar Sweetened Beverage and Menu-Labeling module, were used. Logistic regression was used to determine the association between menu-labeling usage and explanatory variables that included fruit, vegetable, soda, and sugar-sweetened beverage consumption as well as exercise.
RESULTS: Nearly half (52%) of the sample indicated that they used menu labeling. People who used menu labeling were more likely to be female (odds ratio [OR], 2.29; 95% confidence interval [CI], 2.04-2.58), overweight (OR, 1.13; 95% CI, 1.00-1.29) or obese (OR, 1.29; 95% CI, 1.12-1.50), obtain adequate weekly aerobic exercise (OR, 1.18; 95% CI, 1.06-1.32), eat fruits (OR, 1.20; 95% CI, 1.12-1.29) and vegetables (OR, 1.12; 95% CI, 1.05-1.20), and drink less soda (OR, 0.76; 95% CI, 0.69-0.83).
CONCLUSION: Although obese and overweight people were more likely to use menu labeling, they were also adequately exercising, eating more fruits and vegetables, and drinking less soda. Menu labeling is intended to combat the obesity epidemic; however the results indicate an association between menu-labeling usage and certain healthy behaviors. Thus, efforts may be necessary to increase menu-labeling usage among people who are not partaking in such behaviors.

PMID: 24384303 [PubMed - in process]

Modulation of Cellular Signaling Pathways in P23H Rhodopsin Photoreceptors.

Sun, 01/05/2014 - 9:22am
Related Articles

Modulation of Cellular Signaling Pathways in P23H Rhodopsin Photoreceptors.

Cell Signal. 2013 Dec 27;

Authors: Sizova OS, Shinde VM, Lenox A, Gorbatyuk MS

Abstract
We previously reported activation of the unfolded protein response (UPR) in P23H rhodopsin (RHO) retinas with autosomal dominant retinitis pigmentosa (ADRP). Knowing that the UPR can trigger Ca(2+) release from the endoplasmic reticulum and regulate cellular signaling we examined the level of Ca(2+)-regulated proteins. We also looked for changes in the expression of Bcl2 family proteins, autophagy proteins and the mTOR/AKT pathways, as well as for the induction of mitochondria-associated apoptosis in the P23H RHO retina. Our data demonstrated that the elevation of calpain and caspase-12 activity was concomitantly observed with a decrease in the BCL2-XL/BAX ratio and an increase in mTor levels in the P23H-3 RHO retina suggesting a vulnerability of P23H RHO photoreceptors to apoptosis. The translocation of BAX to the mitochondria, as well as the release of cytochrome C and AIF into the cytosol supports this conclusion and indicates the involvement of mitochondria-induced apoptosis in the progression of ADRP. The level of autophagy proteins in general was found to be decreased in the P21-P30 P23H RHO retina. Injections of rapamycin, however, protected the P23H RHO rod photoreceptors from experiencing physiological decline. Despite this fact, the downregulation of mTOR did not alter the level of autophagy proteins. Our results imply that in addition to activation of the UPR during ADRP progression, photoreceptors also experience alterations in major proapoptotic pathways.

PMID: 24378535 [PubMed - as supplied by publisher]

Differentially Expressed Wound Healing-Related microRNAs in the Human Diabetic Cornea.

Sun, 01/05/2014 - 9:22am
Related Articles

Differentially Expressed Wound Healing-Related microRNAs in the Human Diabetic Cornea.

PLoS One. 2013;8(12):e84425

Authors: Funari VA, Winkler M, Brown J, Dimitrijevich SD, Ljubimov AV, Saghizadeh M

Abstract
MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC) in vitro. Total RNA was extracted from age-matched human autopsy normal (n=6) and diabetic (n=6) central corneas, Flash Tag end-labeled, and hybridized to Affymetrix® GeneChip® miRNA Arrays. Select miRNAs associated with diabetic cornea were validated by quantitative RT-PCR (Q-PCR) and by in situ hybridization (ISH) in independent samples. HCEC were transfected with human pre-miR(TM)miRNA precursors (h-miR) or their inhibitors (antagomirs) using Lipofectamine 2000. Confluent transfected cultures were scratch-wounded with P200 pipette tip. Wound closure was monitored by digital photography. Expression of signaling proteins was detected by immunostaining and Western blot. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing.

PMID: 24376808 [PubMed - in process]