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Chest Pain Risk Scores Can Reduce Emergent Cardiac Imaging Test Needs With Low Major Adverse Cardiac Events Occurrence in an Emergency Department Observation Unit.

Recent Research Articles from UNTHSC - Wed, 11/16/2016 - 07:32

Chest Pain Risk Scores Can Reduce Emergent Cardiac Imaging Test Needs With Low Major Adverse Cardiac Events Occurrence in an Emergency Department Observation Unit.

Crit Pathw Cardiol. 2016 Dec;15(4):145-151

Authors: Wang H, Watson K, Robinson RD, Domanski KH, Umejiego J, Hamblin L, Overstreet SE, Akin AM, Hoang S, Shrivastav M, Collyer M, Krech RN, Schrader CD, Zenarosa NR

Abstract
OBJECTIVE: To compare and evaluate the performance of the HEART, Global Registry of Acute Coronary Events (GRACE), and Thrombolysis in Myocardial Infarction (TIMI) scores to predict major adverse cardiac event (MACE) rates after index placement in an emergency department observation unit (EDOU) and to determine the need for observation unit initiation of emergent cardiac imaging tests, that is, noninvasive cardiac stress tests and invasive coronary angiography.
METHODS: A prospective observational single center study was conducted from January 2014 through June 2015. EDOU chest pain patients were included. HEART, GRACE, and TIMI scores were categorized as low (HEART ≤ 3, GRACE ≤ 108, and TIMI ≤1) versus elevated based on thresholds suggested in prior studies. Patients were followed for 6 months postdischarge. The results of emergent cardiac imaging tests, EDOU length of stay (LOS), and MACE occurrences were compared. Student t test was used to compare groups with continuous data, and χ testing was used for categorical data analysis.
RESULTS: Of 986 patients, emergent cardiac imaging tests were performed on 62%. A majority of patients were scored as low risk by all tools (85% by HEART, 81% by GRACE, and 80% by TIMI, P < 0.05). The low-risk patients had few abnormal cardiac imaging test results as compared with patients scored as intermediate to high risk (1% vs. 11% in HEART, 1% vs. 9% in TIMI, and 2% vs. 4% in GRACE, P < 0.05). The average LOS was 33 hours for patients with emergent cardiac imaging tests performed and 25 hours for patients without (P < 0.05). MACE occurrence rate demonstrated no significant difference regardless of whether tests were performed emergently (0.31% vs. 0.97% in HEART, 0.27% vs. 0.95% in TIMI, and 0% vs. 0.81% in GRACE, P > 0.05).
CONCLUSIONS: Chest pain risk stratification via clinical decision tool scores can minimize the need for emergent cardiac imaging tests with less than 1% MACE occurrence, especially when the HEART score is used.

PMID: 27846006 [PubMed - in process]

Thiopurine Prodrugs Mediate Immunosuppressive Effects by Interfering with Rac1 Protein Function.

Recent Research Articles from UNTHSC - Fri, 11/11/2016 - 07:31
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Thiopurine Prodrugs Mediate Immunosuppressive Effects by Interfering with Rac1 Protein Function.

J Biol Chem. 2016 Jun 24;291(26):13699-714

Authors: Shin JY, Wey M, Umutesi HG, Sun X, Simecka J, Heo J

Abstract
6-Thiopurine (6-TP) prodrugs include 6-thioguanine and azathioprine. Both are widely used to treat autoimmune disorders and certain cancers. This study showed that a 6-thioguanosine triphosphate (6-TGTP), converted in T-cells from 6-TP, targets Rac1 to form a disulfide adduct between 6-TGTP and the redox-sensitive GXXXXGK(S/T)C motif of Rac1. This study also showed that, despite the conservation of the catalytic activity of RhoGAP (Rho-specific GAP) on the 6-TGTP-Rac1 adduct to produce the biologically inactive 6-thioguanosine diphosphate (6-TGDP)-Rac1 adduct, RhoGEF (Rho-specific GEF) cannot exchange the 6-TGDP adducted on Rac1 with free guanine nucleotide. The biologically inactive 6-TGDP-Rac1 adduct accumulates in cells because of the ongoing combined actions of RhoGEF and RhoGAP. Because other Rho GTPases, such as RhoA and Cdc42, also possess the GXXXXGK(S/T)C motif, the proposed mechanism for the inactivation of Rac1 also applies to RhoA and Cdc42. However, previous studies have shown that CD3/CD28-stimulated T-cells contain more activated Rac1 than other Rho GTPases such as RhoA and Cdc42. Accordingly, Rac1 is the main target of 6-TP in activated T-cells. This explains the T-cell-specific Rac1-targeting therapeutic action of 6-TP that suppresses the immune response. This proposed mechanism for the action of 6-TP on Rac1 performs a critical role in demonstrating the capability to design a Rac1-targeting chemotherapeutic agent(s) for autoimmune disorders. Nevertheless, the results also suggest that the targeting action of other Rho GTPases in other organ cells, such as RhoA in vascular cells, may be linked to cytotoxicities because RhoA plays a key role in vasculature functions.

PMID: 27189938 [PubMed - indexed for MEDLINE]

Super Skin.

Recent Research Articles from UNTHSC - Thu, 11/10/2016 - 07:33
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Super Skin.

JAMA Dermatol. 2016 Nov 1;152(11):1208

Authors: Roman J, Reynolds SD

PMID: 27829109 [PubMed - in process]

Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1).

Recent Research Articles from UNTHSC - Thu, 11/10/2016 - 07:33
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Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1).

Int J Mol Sci. 2016 Nov 03;17(11):

Authors: Liu X, Xavier C, Jann J, Wu H

Abstract
Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG) between cysteine residues and glutathione (GSH), can lead to cell death. Glutaredoxin 1 (Grx1) is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B), a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE) cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H₂O₂-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2), the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of Grx1 by small interfering RNA (siRNA) significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H₂O₂-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage.

PMID: 27827892 [PubMed - in process]

Sex-specific and genotype-specific differences in vocalization development in FMR1 knockout mice.

Recent Research Articles from UNTHSC - Wed, 11/09/2016 - 16:45
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Sex-specific and genotype-specific differences in vocalization development in FMR1 knockout mice.

Neuroreport. 2016 Dec 14;27(18):1331-1335

Authors: Reynolds CD, Nolan SO, Jefferson T, Lugo JN

Abstract
Fragile X syndrome is a neurodevelopmental disorder caused by a trinucleotide (CGG) hyperexpansion in the FMR1 gene, functionally silencing transcription of the fragile X mental retardation protein (FMRP). This disorder is characterized by impaired cognition, communication, and social behavior. The aim of this study was to investigate the development of ultrasonic vocalization (USV) behavior in a Fmr1-deficient mouse model. On postnatal days (PD) 9-14, separate cohorts of FVB/NJ pups were removed from their homecage and isolation-induced USVs were recorded. There were significant genotype-dependent and sex-dependent differences in USV behavior across the different testing days. Fmr1 knockout (KO) mice showed a significant reduction in vocalizations across all days. There was also a significant difference in vocalizations between male and female mice. We found a significant decrease in the total number of calls for KO males on PD9 and PD13 as well as an increase in the total number of calls for KO males on PD12. The KO males also showed a significant increase in the total call duration on PD12 and a reduction on PD13. The KO female showed a significant decrease in the total number of calls on PD9 and PD10. They also showed a significant decrease in the total call duration on PD9 and a marginal decrease in the total call duration on PD10. These results provide additional evidence for communication deficits in Fmr1 deficient mice and provide new insight suggesting sexually dimorphic vocalizations during the neonatal period.

PMID: 27824730 [PubMed - in process]

Aerobic Exercise Training Improves Orthostatic Tolerance in Aging Humans.

Recent Research Articles from UNTHSC - Wed, 11/09/2016 - 16:45
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Aerobic Exercise Training Improves Orthostatic Tolerance in Aging Humans.

Med Sci Sports Exerc. 2016 Nov 7;

Authors: Xu D, Wang H, Chen S, Ross S, Liu H, Olivencia-Yurvati A, Raven PB, Shi X

Abstract
PURPOSE: This study was designed to test the hypothesis that aerobic exercise training of the elderly will increase aerobic fitness without compromising orthostatic tolerance (OT).
METHODS: Eight healthy sedentary volunteers (67.0±1.7 years old, 4 women) participated in 1-year of endurance exercise training (stationary bicycle and/or treadmill) program at the individuals' 65%-75% of peak heart rate (HRpeak). Peak O2 uptake (VO2peak) and HRpeak were determined by a maximal exercise stress test using a bicycle ergometer. Carotid baroreceptor reflex (CBR) control of HR and mean arterial pressure (MAP) were assessed by a neck pressure-neck suction (NP/NS) protocol. Each subject's maximal gain (Gmax), or sensitivity, of the CBR function curves were derived from fitting their reflex HR and MAP responses to the corresponding NP/NS stimuli using a logistic function curve. The subjects' OT was assessed using lower-body negative pressure (LBNP) graded to -50 mmHg; the sum of the product of LBNP intensity and time (mmHg•min) was calculated as the cumulative stress index (CSI).
RESULTS: Training increased VO2peak (before vs after: 22.8±0.92 vs 27.9±1.33 ml/min/kg, P < 0.01) and HRpeak (154±4 vs 159±3 beats/min, P < 0.02); and decreased resting HR (65±5 vs 59±5 beats/min, P < 0.02) and MAP (99±2 vs 87±2 mmHg, P < 0.05). CBR stimulus-response curves identified a leftward shift with an increase in CBR-HR Gmax (from -0.13±0.02 to -0.27±0.04 bpm/mmHg, P = 0.01). CSI was increased from 767±68 mmHg•min pre-training to 946±44 mmHg•min post-training (P < 0.05).
CONCLUSION: Aerobic exercise training improved the aerobic fitness and OT in elderly subjects. An improved OT is likely associated with an enhanced CBR function that has been reset to better maintain cerebral perfusion and cerebral tissue oxygenation during LBNP.

PMID: 27824693 [PubMed - as supplied by publisher]

In vitro and in vivo neuroprotective effects of cJun N-terminal kinase inhibitors on retinal ganglion cells.

Recent Research Articles from UNTHSC - Wed, 11/09/2016 - 16:45
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In vitro and in vivo neuroprotective effects of cJun N-terminal kinase inhibitors on retinal ganglion cells.

Mol Neurodegener. 2016 Apr 21;11:30

Authors: Kim BJ, Silverman SM, Liu Y, Wordinger RJ, Pang IH, Clark AF

Abstract
BACKGROUND: The c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in neuronal pathophysiology. Using JNK inhibitors, we examined involvement of the JNK pathway in cultured rat retinal ganglion cell (RGC) death and in mouse retinal ischemia/reperfusion (I/R) injury of the visual axis. The in vitro effects of JNK inhibitors were evaluated in cultured adult rat retinal cells enriched in RGCs. Retinal I/R was induced in C57BL/6J mice through elevation of intraocular pressure to 120 mmHg for 60 min followed by reperfusion. SP600125 was administered intraperitoneally once daily for 28 days. Phosphorylation of JNK and c-Jun in the retina was examined by immunoblotting and immunohistochemistry. The thickness of retinal layers and cell numbers in the ganglion cell layer (GCL) were examined using H&E stained retinal cross sections and spectral domain optical coherence tomography (SD-OCT). Retinal function was measured by scotopic flash electroretinography (ERG). Volumetric measurement of the superior colliculus (SC) as well as VGLUT2 and PSD95 expression were studied.
RESULTS: JNK inhibitors SP600125 and TAT-JNK-III, dose-dependently and significantly (p < 0.05) protected against glutamate excitotoxicity and trophic factor withdrawal induced RGC death in culture. In the I/R model, phosphorylation of JNK (pJNK) in the retina was significantly (p < 0.05) increased after injury. I/R injury significantly (p < 0.05) decreased the thickness of retinal layers, including the whole retina, inner plexiform layer, and inner nuclear layer and cell numbers in the GCL. Administration of SP600125 for 28 days protected against all these degenerative morphological changes (p < 0.05). In addition, SP600125 significantly (p < 0.05) protected against I/R-induced reduction in scotopic ERG b-wave amplitude at 3, 7, 14, 21 and 28 days after injury. SP600125 also protected against the I/R-induced losses in volume and levels of synaptic markers in the SC. Moreover, the protective effects of SP600125 in the retina and SC were also detected even with only 7 days (Days 1-7 after I/R) of SP600125 treatment.
CONCLUSIONS: Our results demonstrate the important role the JNK pathway plays in retinal degeneration in both in vitro and in vivo models and suggest that JNK inhibitors may be a useful therapeutic strategy for neuroprotection of RGCs in the retina.

PMID: 27098079 [PubMed - indexed for MEDLINE]

C1q propagates microglial activation and neurodegeneration in the visual axis following retinal ischemia/reperfusion injury.

Recent Research Articles from UNTHSC - Wed, 11/09/2016 - 16:45
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C1q propagates microglial activation and neurodegeneration in the visual axis following retinal ischemia/reperfusion injury.

Mol Neurodegener. 2016 Mar 24;11:24

Authors: Silverman SM, Kim BJ, Howell GR, Miller J, John SW, Wordinger RJ, Clark AF

Abstract
BACKGROUND: C1q represents the initiating protein of the classical complement cascade, however recent findings indicate pathway independent roles such as developmental pruning of retinal ganglion cell (RGC) axons. Furthermore, chronic neuroinflammation, including increased expression of C1q and activation of microglia and astrocytes, appears to be a common finding among many neurodegenerative disease models. Here we compare the effects of a retinal ischemia/reperfusion (I/R) injury on glial activation and neurodegeneration in wild type (WT) and C1qa-deficient mice in the retina and superior colliculus (SC). Retinal I/R was induced in mice through elevation of intraocular pressure to 120 mmHg for 60 min followed by reperfusion. Glial cell activation and population changes were assessed using immunofluorescence. Neuroprotection was determined using histological measurements of retinal layer thickness, RGC counts, and visual function by flash electroretinography (ERG).
RESULTS: Retinal I/R injury significantly upregulated C1q expression in the retina as early as 72 h and within 7 days in the superficial SC, and was sustained as long as 28 days. Accompanying increased C1q expression was activation of microglia and astrocytes as well as a significantly increased glial population density observed in the retina and SC. Microglial activation and changes in density were completely ablated in C1qa-deficient mice, interestingly however there was no effect on astrocytes. Furthermore, loss of C1qa significantly rescued I/R-induced loss of RGCs and protected against retinal layer thinning in comparison to WT mice. ERG assessment revealed early preservation of b-wave amplitude deficits from retinal I/R injury due to C1qa-deficiency that was lost by day 28.
CONCLUSIONS: Our results for the first time demonstrate the spatiotemporal changes in the neuroinflammatory response following retinal I/R injury at both local and distal sites of injury. In addition, we have shown a role for C1q as a primary mediator of microglial activation and pathological damage. This suggests developmental mechanisms of C1q may be re-engaged during injury response, modulation of which may be beneficial for neuroprotection.

PMID: 27008854 [PubMed - indexed for MEDLINE]

Expression of Mutant Myocilin Induces Abnormal Intracellular Accumulation of Selected Extracellular Matrix Proteins in the Trabecular Meshwork.

Recent Research Articles from UNTHSC - Tue, 11/08/2016 - 07:33

Expression of Mutant Myocilin Induces Abnormal Intracellular Accumulation of Selected Extracellular Matrix Proteins in the Trabecular Meshwork.

Invest Ophthalmol Vis Sci. 2016 Nov 1;57(14):6058-6069

Authors: Kasetti RB, Phan TN, Millar JC, Zode GS

Abstract
Purpose: Abnormal accumulation of extracellular matrix (ECM) in the trabecular meshwork (TM) is associated with decreased aqueous humor outflow facility and IOP elevation in POAG. Previously, we have developed a transgenic mouse model of POAG (Tg-MYOCY437H) by expressing human mutant myocilin (MYOC), a known genetic cause of POAG. The purpose of this study is to examine whether expression of mutant myocilin leads to reduced outflow facility and abnormal ECM accumulation in Tg-MYOCY437H mice and in cultured human TM cells.
Methods: Conscious IOP was measured at various ages of Tg-MYOCY437H mice using a rebound tonometer. Outflow facility was measured in 10-month-old Tg-MYOCY437H mice. Selected ECM proteins were examined in human TM-3 cells stably expressing mutant myocilin and primary human TM cells (n = 4) as well as in the TM of Tg-MYOCY437H mice by real-time PCR, Western blotting, and immunostaining. Furthermore, TM cells expressing WT or mutant myocilin were treated with 5 mM sodium 4-phenylbutyrate (PBA), and ECM proteins were examined by Western blot and immunostaining.
Results: Starting from 3 months of age, Tg-MYOCY437H mice exhibited significant IOP elevation compared with wild-type (WT) littermates. Outflow facility was significantly reduced in Tg-MYOCY437H mice (0.0195 μl/min/mm Hg in Tg-MYOCY437H vs. 0.0332 μl/min/mm Hg in WT littermates). Increased accumulation of fibronectin, elastin, and collagen type IV and I was observed in the TM of Tg-MYOCY437H mice compared with WT littermates. Furthermore, increased ECM proteins were also associated with induction of endoplasmic reticulum (ER) stress markers, GRP78 and CHOP in the TM of Tg-MYOCY437H mice. Human TM-3 cells stably expressing DsRed-tagged Y437H mutant MYOC exhibited inhibition of myocilin secretion and its intracellular accumulation compared with TM cells expressing WT MYOC. Expression of mutant MYOC in TM-3 cells or human primary TM cells induced ER stress and also increased intracellular protein levels of fibronectin, elastin, laminin, and collagen IV and I. In addition, TM-3 cells expressing mutant myocilin exhibited reduced active forms of matrix metalloproteinase (MMP)-2 and MMP-9 in conditioned medium compared with TM-3 cells expressing WT myocilin. Interestingly, both intracellularly accumulated fibronectin and collagen I colocalized with mutant myocilin and also with ER marker KDEL further suggesting intracellular accumulation of these proteins in the ER of TM cells. Furthermore, reduction of ER stress via PBA decreased selected ECM proteins in primary TM cells.
Conclusions: These studies demonstrate that mutant myocilin induces abnormal ECM accumulation in the ER of TM cells, which may be responsible for reduced outflow facility and IOP elevation in myocilin-associated glaucoma.

PMID: 27820874 [PubMed - in process]

Clear cell "sugar" tumor of the lung: benign or malignant?

Recent Research Articles from UNTHSC - Tue, 11/08/2016 - 07:33
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Clear cell "sugar" tumor of the lung: benign or malignant?

Int Surg. 2015 May;100(5):924-6

Authors: Olivencia-Yurvati AH, Rodriguez AE

Abstract
Clear cell "sugar" tumors of the lung are rare pulmonary tumors. This case study illustrates a patient who was found to have a persistent nodule in the left-upper lobe of the lung. Positron emission tomographic scanning showed mild-moderate 18-fluorodeoxyglucose uptake. Based on these findings, a video-assisted resection of the tumor was undertaken. The mass was identified histologically, as a clear cell "sugar" tumor of the lung. This case report discusses the benign versus malignant nature of this rare tumor.

PMID: 26011217 [PubMed - indexed for MEDLINE]

Dysregulated corticostriatal activity in open-field behavior and the head-twitch response induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine.

Recent Research Articles from UNTHSC - Mon, 11/07/2016 - 10:32
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Dysregulated corticostriatal activity in open-field behavior and the head-twitch response induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine.

Neuropharmacology. 2016 Nov 2;:

Authors: Rangel-Barajas C, Estrada-Sánchez AM, Barton SJ, Luedtke RR, Rebec GV

Abstract
The substituted amphetamine, 2,5-dimethoxy-4-iodoamphetamine (DOI), is a hallucinogen that has been used to model a variety of psychiatric conditions. Here, we studied the effect of DOI on neural activity recorded simultaneously in the primary motor cortex (M1) and dorsal striatum of freely behaving FvB/N mice. DOI significantly decreased the firing rate of individually isolated neurons in M1 and dorsal striatum relative to pre-drug baseline. It also induced a bursting pattern of activity by increasing both the number of spikes within a burst and burst duration. In addition, DOI increased coincident firing between simultaneously recorded neuron pairs within the striatum and between M1 and dorsal striatum. Local field potential (LFP) activity also increased in coherence between M1 and dorsal striatum after DOI in the low frequency gamma band (30-50 Hz), while corticostriatal coherence in delta, theta, alpha, and beta activity decreased. We also assessed corticostriatal LFP activity in relation to the DOI-induced head-twitch response (HTR), a readily identifiable behavior used to assess potential treatments for the conditions it models. The HTR was associated with increased delta and decreased theta power in both M1 and dorsal striatum. Together, our results suggest that DOI dysregulates corticostriatal communication and that the HTR is associated with this dysregulation.

PMID: 27816502 [PubMed - as supplied by publisher]

Deciphering the Role of Emx1 in Neurogenesis: A Neuroproteomics Approach.

Recent Research Articles from UNTHSC - Wed, 11/02/2016 - 07:33
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Deciphering the Role of Emx1 in Neurogenesis: A Neuroproteomics Approach.

Front Mol Neurosci. 2016;9:98

Authors: Kobeissy FH, Hansen K, Neumann M, Fu S, Jin K, Liu J

Abstract
Emx1 has long been implicated in embryonic brain development. Previously we found that mice null of Emx1 gene had smaller dentate gyri and reduced neurogenesis, although the molecular mechanisms underlying this defect was not well understood. To decipher the role of Emx1 gene in neural regeneration and the timing of its involvement, we determine the frequency of neural stem cells (NSCs) in embryonic and adult forebrains of Emx1 wild type (WT) and knock out (KO) mice in the neurosphere assay. Emx1 gene deletion reduced the frequency and self-renewal capacity of NSCs of the embryonic brain but did not affect neuronal or glial differentiation. Emx1 KO NSCs also exhibited a reduced migratory capacity in response to serum or vascular endothelial growth factor (VEGF) in the Boyden chamber migration assay compared to their WT counterparts. A thorough comparison between NSC lysates from Emx1 WT and KO mice utilizing 2D-PAGE coupled with tandem mass spectrometry revealed 38 proteins differentially expressed between genotypes, including the F-actin depolymerization factor Cofilin. A global systems biology and cluster analysis identified several potential mechanisms and cellular pathways implicated in altered neurogenesis, all involving Cofilin1. Protein interaction network maps with functional enrichment analysis further indicated that the differentially expressed proteins participated in neural-specific functions including brain development, axonal guidance, synaptic transmission, neurogenesis, and hippocampal morphology, with VEGF as the upstream regulator intertwined with Cofilin1 and Emx1. Functional validation analysis indicated that apart from the overall reduced level of phosphorylated Cofilin1 (p-Cofilin1) in the Emx1 KO NSCs compared to WT NSCs as demonstrated in the western blot analysis, VEGF was able to induce more Cofilin1 phosphorylation and FLK expression only in the latter. Our results suggest that a defect in Cofilin1 phosphorylation induced by VEGF or other growth factors might contribute to the reduced neurogenesis in the Emx1 null mice during brain development.

PMID: 27799894 [PubMed - in process]

Joint pain in a man with lung cancer.

Recent Research Articles from UNTHSC - Wed, 11/02/2016 - 07:33
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Joint pain in a man with lung cancer.

Cleve Clin J Med. 2015 Jan;82(1):18-9

Authors: Jernigan E, Siddiqi N, Peddi P

PMID: 25552621 [PubMed - indexed for MEDLINE]

Association Between Alcohol Outlets and HIV Prevalence in U.S. Counties.

Recent Research Articles from UNTHSC - Tue, 11/01/2016 - 07:33

Association Between Alcohol Outlets and HIV Prevalence in U.S. Counties.

J Stud Alcohol Drugs. 2016 Nov;77(6):898-903

Authors: Rossheim ME, Thombs DL, Suzuki S

Abstract
OBJECTIVE: The current study examines associations between on- and off-premise alcohol retail outlets and HIV prevalence in counties across the United States during a 3-year period.
METHOD: Health department and U.S. Census Bureau surveillance data were analyzed from 1,523 counties in 47 states, representing more than 86% of the U.S. population. Multilevel Poisson regression models were used to examine the association between the number of on- and off-premise alcohol outlets in a county and HIV prevalence in the same county, adjusting for the between-year correlation of HIV prevalence within each county.
RESULTS: When we adjusted for potential confounders, number of on-premise alcohol outlets within a county was positively associated with HIV prevalence, whereas off-premise alcohol outlets were negatively associated with HIV prevalence.
CONCLUSIONS: The relations observed in this study are consistent with the niche theory of assortative drinking, which maintains that drinkers who are prone to risk taking may be attracted to alcohol outlets where they can expand their social networks to include similarly high-risk individuals who engage in both heavy drinking and sexual risk taking. This is the largest study conducted to date to examine the association between alcohol retail outlet types and HIV prevalence. Natural experiments are needed to examine specific policy changes that reduce outlet density and its association with HIV incidence.

PMID: 27797691 [PubMed - in process]

Contra-directional Coupling of Nur77 and Nurr1 in Neurodegeneration: A Novel Mechanism for Memantine-Induced Anti-inflammation and Anti-mitochondrial Impairment.

Recent Research Articles from UNTHSC - Tue, 11/01/2016 - 07:33
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Contra-directional Coupling of Nur77 and Nurr1 in Neurodegeneration: A Novel Mechanism for Memantine-Induced Anti-inflammation and Anti-mitochondrial Impairment.

Mol Neurobiol. 2016 Nov;53(9):5876-5892

Authors: Wei X, Gao H, Zou J, Liu X, Chen D, Liao J, Xu Y, Ma L, Tang B, Zhang Z, Cai X, Jin K, Xia Y, Wang Q

Abstract
Recent evidence suggests that nerve growth factor IB (Nur77) and nuclear receptor related1 (Nurr1) are differentially involved in dopaminergic neurodegeneration. Since memantine has shown clinically relevant efficacy in Parkinson's disease (PD) and displayed a potent protective effect on dopaminergic neurons in experimental PD models, we asked if it exerts its neuroprotection by regulating Nur77 and Nurr1 signaling. We adopted a well-established in vitro PD model, 6-hydroxydopamine (OHDA)-lesioned PC12 cells, to test our hypothesis. Different concentrations of memantine were incubated with 6-OHDA-lesioned PC12 cells, and Nur77/Nurr1 and their related signaling molecules were examined by Western blot and immunocytochemistry. Nur77-deficient PC12 cells were used to verify the influences of Nur77 on neurodegeneration and memantine-mediated neuroprotection. We found that memantine reversed Nur77 upregulation and restored Nurr1 downregulation in 6-OHDA-lesioned PC12 cells. 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and induced co-localization of Cyt c/HSP60/Nur77 in the cytosol. Memantine strongly reduced the sub-cellular translocations of Nur77/Cyt c/HSP60 under 6-OHDA-induced oxidative condition. Knockdown of Nur77 enhanced the viability of PC12 cells exposed to 6-OHDA, while memantine-induced neuroprotection was much less in the cells with Nur77 knockdown than in those without it. We conclude that Nur77 plays a crucial role in modulating mitochondrial impairment and contributes to neurodegeneration under the experimental PD condition. Memantine effectively suppresses such Nur77-mediated neurodegeneration and promotes survival signaling through post-translational modification of Nurr1. Nur77 and Nurr1 present a contra-directionally coupling interaction in memantine-mediated neuroprotection.

PMID: 26497037 [PubMed - in process]

Modified DOP-PCR for improved STR typing of degraded DNA from human skeletal remains and bloodstains.

Recent Research Articles from UNTHSC - Tue, 11/01/2016 - 07:33
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Modified DOP-PCR for improved STR typing of degraded DNA from human skeletal remains and bloodstains.

Leg Med (Tokyo). 2016 Jan;18:7-12

Authors: Ambers A, Turnbough M, Benjamin R, Gill-King H, King J, Sajantila A, Budowle B

Abstract
Forensic and ancient DNA samples often are damaged and in limited quantity as a result of exposure to harsh environments and the passage of time. Several strategies have been proposed to address the challenges posed by degraded and low copy templates, including a PCR based whole genome amplification method called degenerate oligonucleotide-primed PCR (DOP-PCR). This study assessed the efficacy of four modified versions of the original DOP-PCR primer that retain at least a portion of the 5' defined sequence and alter the number of bases on the 3' end. The use of each of the four modified primers resulted in improved STR profiles from environmentally-damaged bloodstains, contemporary human skeletal remains, American Civil War era bone samples, and skeletal remains of WWII soldiers over those obtained by previously described DOP-PCR methods and routine STR typing. Additionally, the modified DOP-PCR procedure allows for a larger volume of DNA extract to be used, reducing the need to concentrate the sample and thus mitigating the effects of concurrent concentration of inhibitors.

PMID: 26832369 [PubMed - indexed for MEDLINE]

A triazine-based BODIPY trimer as a molecular viscometer.

Recent Research Articles from UNTHSC - Tue, 11/01/2016 - 07:33
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A triazine-based BODIPY trimer as a molecular viscometer.

Phys Chem Chem Phys. 2016 Feb 14;18(6):4535-40

Authors: Raut SL, Kimball JD, Fudala R, Bora I, Chib R, Jaafari H, Castillo MK, Smith NW, Gryczynski I, Dzyuba SV, Gryczynski Z

Abstract
Photophysical behaviour of a novel trimeric BODIPY rotor with a high extinction coefficient is reported. Steady state and time resolved fluorescence measurements established that the trimer could be used as a viscometer for molecular solvents, membrane-like environments and several cancer cell lines.

PMID: 26795882 [PubMed - indexed for MEDLINE]

Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells.

Recent Research Articles from UNTHSC - Tue, 11/01/2016 - 07:33
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Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells.

Mol Cell Biochem. 2016 Jan;411(1-2):221-33

Authors: Shetty P, Bargale A, Patil BR, Mohan R, Dinesh US, Vishwanatha JK, Gai PB, Patil VS, Amsavardani TS

Abstract
Overexpression and activation of tyrosine kinase receptors like EGFR and Src regulate the progression and metastasis of Her-2 negative breast cancer. Recently we have reported the role of cell membrane interaction of phospholipid-binding protein annexin A2 (AnxA2) and EGFR in regulating cellular signaling in the activation of angiogenesis, matrix degradation, invasion, and cancer metastasis. Beta-galactoside-specific animal lectin galectin-3 is an apoptosis inhibitor, and cell surface-associated extracellular galectin-3 also has a role in cell migration, cancer progression, and metastasis. Similar expression pattern and membrane co-localization of these two proteins made us to hypothesize in the current study that galectin-3 and AnxA2 interaction is critical for Her-2 negative breast cancer progression. By various experimental analyses, we confirm that glycosylated AnxA2 at the membrane surface interacts with galectin-3. N-linked glycosylation inhibitor tunicamycin treatment convincingly blocked AnxA2 membrane translocation and its association with galectin-3. To analyze whether this interaction has any functional relevance, we tried to dissociate this interaction with purified plant lectin from chickpea (Cicer arietinum agglutinin). This highly specific 30 kDa plant lectin could dissociate AnxA2 from endogenous lectin galectin-3 interaction at the cell surface. This dissociation could down-regulate Bcl-2 family proteins, cell proliferation, and migration simultaneously triggering cell apoptosis. Targeting this interaction of membrane surface glycoprotein and its animal lectin in Her-2 negative breast cancer may be of therapeutic value.

PMID: 26438086 [PubMed - indexed for MEDLINE]

Regulatory Roles of Glutathione-S-Transferases and 4-hydroxynonenal in Stress-mediated Signaling and Toxicity.

Recent Research Articles from UNTHSC - Mon, 10/31/2016 - 07:35

Regulatory Roles of Glutathione-S-Transferases and 4-hydroxynonenal in Stress-mediated Signaling and Toxicity.

Free Radic Biol Med. 2016 Oct 26;:

Authors: Awasthi YC, Ramana KV, Chaudhary P, Srivastava SK, Awasthi S

Abstract
Glutathione-S-Transferases (GSTs) have primarily been thought to be xenobiotic metabolizing enzymes that protect cells from toxic drugs and environmental electrophiles. However, in last three decades, these enzymes have emerged as the regulators of oxidative stress-induced signaling and toxicity. 4-Hydroxy-trans 2-nonenal (HNE) an end-product of lipid peroxidation, has been shown to be a major determinant of oxidative stress-induced signaling and toxicity. HNE is involved in signaling pathways, including apoptosis, proliferation, modulation of gene expression, activation of transcription factors/repressors, cell cycle arrest, and differentiation. In this article, available evidence for a major role of GSTs in the regulation of HNE-mediated cell signaling processes through modulation of the intracellular levels of HNE is discussed.

PMID: 27794453 [PubMed - as supplied by publisher]

Stage Validity of the Health Action Process Approach in African American Breast Cancer Survivors.

Recent Research Articles from UNTHSC - Fri, 10/28/2016 - 07:32
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Stage Validity of the Health Action Process Approach in African American Breast Cancer Survivors.

J Immigr Minor Health. 2016 Oct 26;

Authors: Meadows R, Paxton RJ

Abstract
The Health Action Process Approach (HAPA) has been applied in a number of populations because it proposes to overcome limitations from previous health behavior theories. However, it has yet to be applied to cancer survivors or racial/ethnic minorities. In this study, we examined the construct validity of the HAPA phase and stage algorithms in a sample of African American breast cancer survivors. A total of 259 African American breast cancer survivors (mean age = 54 years) participated in a Web-based survey that assessed sociodemographic and medical characteristics, physical activity, and HAPA constructs. Analysis of covariance was used to compare mean differences between HAPA phase/stage. Statistical significance was determined at p < 0.017 due to multiple comparisons. Phase and stage inconsistencies were observed for most constructs. However, adequate distinctions were made for motivational self-efficacy and intentions (i.e., P = I < A) by phase, and both action and coping planning (i.e., P < I < A) by stage. Our data indicate partial support of the HAPA algorithm to classify African American breast cancer survivors according to stage or phase. Modifying the staging algorithm or constructs are needed if stage- or phase-based interventions can be designed for this population.

PMID: 27785639 [PubMed - as supplied by publisher]

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