Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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Updated: 2 hours 18 min ago

Antiretroviral Adherence Level Necessary for HIV Viral Suppression Using Real-World Data.

Fri, 05/15/2020 - 06:58
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Antiretroviral Adherence Level Necessary for HIV Viral Suppression Using Real-World Data.

J Acquir Immune Defic Syndr. 2019 11 01;82(3):245-251

Authors: Byrd KK, Hou JG, Hazen R, Kirkham H, Suzuki S, Clay PG, Bush T, Camp NM, Weidle PJ, Delpino A, Patient-Centered HIV Care Model Team

Abstract
BACKGROUND: A benchmark of near-perfect adherence (≥95%) to antiretroviral therapy (ART) is often cited as necessary for HIV viral suppression. However, given newer, more effective ART medications, the threshold for viral suppression may be lower. We estimated the minimum ART adherence level necessary to achieve viral suppression.
SETTINGS: The Patient-centered HIV Care Model demonstration project.
METHODS: Adherence to ART was calculated using the proportion of days covered measure for the 365-day period before each viral load test result, and grouped into 5 categories (<50%, 50% to <80%, 80% to <85%, 85% to <90%, and ≥90%). Binomial regression analyses were conducted to determine factors associated with viral suppression (HIV RNA <200 copies/mL); demographics, proportion of days covered category, and ART regimen type were explanatory variables. Generalized estimating equations with an exchangeable working correlation matrix accounted for correlation within subjects. In addition, probit regression models were used to estimate adherence levels required to achieve viral suppression in 90% of HIV viral load tests.
RESULTS: The adjusted odds of viral suppression did not differ between persons with an adherence level of 80% to <85% or 85% to <90% and those with an adherence level of ≥90%. In addition, the overall estimated adherence level necessary to achieve viral suppression in 90% of viral load tests was 82% and varied by regimen type; integrase inhibitor- and nonnucleoside reverse transcriptase inhibitor-based regimens achieved 90% viral suppression with adherence levels of 75% and 78%, respectively.
CONCLUSIONS: The ART adherence level necessary to reach HIV viral suppression may be lower than previously thought and may be regimen-dependent.

PMID: 31343455 [PubMed - indexed for MEDLINE]

Affordable Care Act and cancer stage at diagnosis in an underserved population.

Thu, 05/14/2020 - 06:27
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Affordable Care Act and cancer stage at diagnosis in an underserved population.

Prev Med. 2019 09;126:105748

Authors: Lu Y, Jackson BE, Gehr AW, Cross D, Neerukonda L, Tanna B, Ghabach B, Ojha RP

Abstract
The Patient Protection and Affordable Care Act (ACA) has increased insurance coverage among underserved individuals, but the effect of ACA on cancer diagnosis is currently debated, particularly in Medicaid non-expansion states. Therefore, we aimed to assess the effect of ACA implementation on stage at diagnosis among underserved cancer patients in Texas, a Medicaid non-expansion state. We used data from the institutional registry of the JPS Center for Cancer Care, which serves an urban population of underserved cancer patients. Eligible individuals were aged 18 to 64 years and diagnosed with a first primary invasive solid tumor between 2008 and 2015. We used a natural experiment framework and interrupted time-series analysis to assess level (i.e. immediate) and slope (over time) changes in insurance coverage and cancer stage at diagnosis between pre- and post-ACA periods. Our study population comprised 4808 underserved cancer patients, of whom 51% were racial/ethnic minorities. The prevalence of uninsured cancer patients did not immediately change after ACA implementation but modestly decreased over time (PR = 0.94; 95% CL: 0.90, 0.98). The prevalence of early- and advanced-stage diagnosis did not appreciably change overall or when stratified by screen-detectable cancers. Our results suggest that ACA implementation decreased the prevalence of uninsured cancer patients but had little effect on cancer stage at diagnosis in an underserved population. Given that Texas is a Medicaid non-expansion state, Medicaid expansion and alternative approaches may need to be further explored to improve earlier cancer diagnosis among underserved individuals.

PMID: 31195020 [PubMed - indexed for MEDLINE]

Alcohol-specific social comparison as a moderator of the norms-behavior association for young adult alcohol use.

Thu, 05/14/2020 - 06:27
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Alcohol-specific social comparison as a moderator of the norms-behavior association for young adult alcohol use.

Addict Behav. 2019 03;90:92-98

Authors: Litt DM, Waldron KA, Wallace EC, Lewis MA

Abstract
Research has indicated that individuals high in social comparison orientation (SCO) are more influenced by the behavior and perceived norms of others. However, despite research indicating that behavior is more closely influenced by and modeled on more socially proximal reference groups, most social comparison research to date has utilized global measures of social comparison. As such, research has not examined whether domain-specific (i.e. alcohol-specific social comparisons) and their relation with norms are more predictive of alcohol-related outcomes than global comparisons. As such, the present study aimed to determine whether the previously found relationships between global SCO, descriptive drinking norms and their interaction are still significant when accounting for alcohol-specific SCO and its interaction with descriptive norms in the prediction of drinking willingness and behavior. Results from 355 young adults age 18-20 indicated that the association of alcohol-specific SCO and its interaction with descriptive norms for drinking predicts alcohol-related outcomes (drinking willingness and alcohol consumption), but not alcohol-related negative consequences above and beyond global SCO. Thus, alcohol-specific SCO may be of particular importance when determining for whom normative based preventive interventions may be the most efficacious.

PMID: 30384190 [PubMed - indexed for MEDLINE]

Delayed capsular bag akreos IOL opacification after vitrectomy and gas tamponade.

Wed, 05/13/2020 - 06:14
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Delayed capsular bag akreos IOL opacification after vitrectomy and gas tamponade.

Am J Ophthalmol Case Rep. 2020 Jun;18:100676

Authors: Shakibai N, Chavala SH

PMID: 32395667 [PubMed]

Inhibition of interleukin-6 on matrix protein production by glomerular mesangial cells and its pathway involved.

Tue, 05/12/2020 - 05:55

Inhibition of interleukin-6 on matrix protein production by glomerular mesangial cells and its pathway involved.

Am J Physiol Renal Physiol. 2020 May 11;:

Authors: Chaudhari S, Yazdizadeh Shotorbani P, Tao Y, Davis ME, Mallet RT, Ma R

Abstract
Activation of immunologic pathways and disturbances of the extracellular matrix (ECM) dynamics are important contributors to the pathogenesis of chronic kidney diseases. Glomerular mesangial cells (MCs) are critical for homeostasis of glomerular ECM dynamics. Interleukin-6 (IL6) can act as a pro/anti- inflammatory agent relative to cell types and conditions. This study investigated if IL6 influenced ECM protein production by MCs and the regulatory pathways involved. Experiments were carried out in cultured human MCs (HMCs) and in mice. We found that overexpressing IL6 and its receptor decreased the abundance of fibronectin and collagen IV in MCs. Enzyme-linked immunosorbent assay and immunoblot analysis demonstrated that thapsigargin (an activator of store-operated Ca2+ entry, SOCE), but not endoplasmic reticular stress inducer tunicamycin, significantly increased IL6 content. This thapsigargin effect was abolished by GSK-7975A, a selective inhibitor of SOCE, and by silencing Orai1 (the channel protein mediating SOCE). Furthermore, inhibition of NFκB pharmacologically and genetically significantly reduced SOCE-induced IL6 production. Thapsigargin also stimulated the nuclear translocation of p65 subunit of NFκB. Moreover, MCs overexpressing IL6 and its receptor in HMCs increased the content of the receptor for glucagon-like peptide-1 (GLP-1R), and IL6 inhibition of fibronectin was attenuated by the GLP-1R antagonist, exendin 9-39. In agreement with the HMC data, specific knockdown of Orai1 in MCs using the targeted nanoparticle delivery system in mice significantly reduced glomerular GLP-1R level. Taken together, our results suggest a novel SOCE/NFкB/IL6/GLP-1R signaling pathway which inhibits ECM protein production by MCs.

PMID: 32390515 [PubMed - as supplied by publisher]

Cell-free mitochondrial DNA increases in maternal circulation during healthy pregnancy: a prospective, longitudinal study.

Tue, 05/12/2020 - 05:55
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Cell-free mitochondrial DNA increases in maternal circulation during healthy pregnancy: a prospective, longitudinal study.

Am J Physiol Regul Integr Comp Physiol. 2020 02 01;318(2):R445-R452

Authors: Cushen SC, Sprouse ML, Blessing A, Sun J, Jarvis SS, Okada Y, Fu Q, Romero SA, Phillips NR, Goulopoulou S

Abstract
Mitochondrial DNA (mtDNA) exposed to the extracellular space due to cell death has immunostimulatory properties. Case-control studies reported a positive association between odds of developing preeclampsia and circulating mtDNA. These findings are based on relative quantification protocols that do not allow determination of absolute concentrations of mtDNA and are highly sensitive to nuclear DNA contamination. Furthermore, circulating mtDNA concentrations in response to normal pregnancy, which is an inflammatory state characterized by continuous placental cell apoptosis, have not been established. The main objective of this study was to determine longitudinal changes in circulating mtDNA from preconception to first trimester, third trimester, and postpartum in healthy pregnant women. Absolute real-time PCR quantification of mtDNA and nuclear DNA (nDNA) was performed on whole genomic extracts from serum using TaqMan probes and chemistry. Serum cell-free mtDNA and nDNA concentrations were greater in late pregnancy as compared with early pregnancy and postpartum. Pregnant women carrying neonates at the upper quartile of birth length distribution had higher concentrations of mtDNA in late pregnancy compared with pregnancies carrying neonates at the lower quartile. The correlation between circulating mtDNA and nDNA concentrations varied by sex (i.e., pregnancies carrying female vs. male fetuses). This study is the first to establish temporal patterns of circulating cell-free mtDNA concentrations in normal human pregnancy using absolute DNA quantification techniques. Concentrations of circulating mtDNA in normal pregnancy may be used as reference values for the development of clinical prognostic or diagnostic tests in pregnant women with, or at risk of developing, gestational complications.

PMID: 31913687 [PubMed - indexed for MEDLINE]

Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats.

Tue, 05/12/2020 - 05:55
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Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats.

Am J Physiol Heart Circ Physiol. 2020 01 01;318(1):H34-H48

Authors: Marciante AB, Wang LA, Little JT, Cunningham JT

Abstract
Obstructive sleep apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into the waking hours. Chronic intermittent hypoxia (CIH), which models the hypoxemia associated with sleep apnea, is sufficient to cause a sustained increase in blood pressure that involves the central nervous system. The median preoptic nucleus (MnPO) is an integrative forebrain region that contributes to blood pressure regulation and neurogenic hypertension. The MnPO projects to the paraventricular nucleus (PVN), a preautonomic region. We hypothesized that pathway-specific lesions of the projection from the MnPO to the PVN would attenuate the sustained component of chronic intermittent hypoxia-induced hypertension. Adult male Sprague-Dawley rats (250-300 g) were anesthetized with isoflurane and stereotaxically injected bilaterally in the PVN with a retrograde Cre-containing adeno-associated virus (AAV; AAV9.CMV.HI.eGFP-Cre.WPRE.SV40) and injected in the MnPO with caspase-3 (AAV5-flex-taCasp3-TEVp) or control virus (AAV5-hSyn-DIO-mCherry). Three weeks after the injections the rats were exposed to a 7-day intermittent hypoxia protocol. During chronic intermittent hypoxia, controls developed a diurnal hypertension that was blunted in rats with caspase lesions. Brain tissue processed for FosB immunohistochemistry showed decreased staining with caspase-induced lesions of MnPO and downstream autonomic-regulating nuclei. Chronic intermittent hypoxia significantly increased plasma levels of advanced oxidative protein products in controls, but this increase was blocked in caspase-lesioned rats. The results indicate that PVN-projecting MnPO neurons play a significant role in blood pressure regulation in the development of persistent chronic intermittent hypoxia hypertension.NEW & NOTEWORTHY Chronic intermittent hypoxia associated with obstructive sleep apnea increases oxidative stress and leads to chronic hypertension. Sustained hypertension may be mediated by angiotensin II-induced neural plasticity of excitatory median preoptic neurons in the forebrain that project to the paraventricular nucleus of the hypothalamus. Selective caspase lesions of these neurons interrupt the drive for sustained hypertension and cause a reduction in circulating oxidative protein products. This indicates that a functional connection between the forebrain and hypothalamus is necessary to drive diurnal hypertension associated with intermittent hypoxia. These results provide new information about central mechanisms that may contribute to neurogenic hypertension.

PMID: 31675258 [PubMed - indexed for MEDLINE]

Arterial Baroreflex Resetting During Exercise in Humans: Underlying Signaling Mechanisms.

Tue, 05/12/2020 - 05:55
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Arterial Baroreflex Resetting During Exercise in Humans: Underlying Signaling Mechanisms.

Exerc Sport Sci Rev. 2019 07;47(3):129-141

Authors: Raven PB, Young BE, Fadel PJ

Abstract
The arterial baroreflex (ABR) resets during exercise in an intensity-dependent manner to operate around a higher blood pressure with maintained sensitivity. This review provides a historical perspective of ABR resetting and the involvement of other neural reflexes in mediating exercise resetting. Furthermore, we discuss potential underlying signaling mechanisms that may contribute to exercise ABR resetting in physiological and pathophysiological conditions.

PMID: 30921029 [PubMed - indexed for MEDLINE]

Identification of long non-coding RNA-related and -coexpressed mRNA biomarkers for hepatocellular carcinoma.

Tue, 05/12/2020 - 05:55
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Identification of long non-coding RNA-related and -coexpressed mRNA biomarkers for hepatocellular carcinoma.

BMC Med Genomics. 2019 01 31;12(Suppl 1):25

Authors: Zhang F, Ding L, Cui L, Barber R, Deng B

Abstract
BACKGROUND: While changes in mRNA expression during tumorigenesis have been used widely as molecular biomarkers for the diagnosis of a number of cancers, the approach has limitations. For example, traditional methods do not consider the regulatory and positional relationship between mRNA and lncRNA. The latter has been largely shown to possess tumor suppressive or oncogenic properties. The combined analysis of mRNA and lncRNA is likely to facilitate the identification of biomarkers with higher confidence.
RESULTS: Therefore, we have developed an lncRNA-related method to identify traditional mRNA biomarkers. First we identified mRNAs that are differentially expressed in Hepatocellular Carcinoma (HCC) by comparing cancer and matched adjacent non-tumorous liver tissues. Then, we performed mRNA-lncRNA relationship and coexpression analysis and obtained 41 lncRNA-related and -coexpressed mRNA biomarkers. Next, we performed network analysis, gene ontology analysis and pathway analysis to unravel the functional roles and molecular mechanisms of these lncRNA-related and -coexpressed mRNA biomarkers. Finally, we validated the prediction and performance of the 41 lncRNA-related and -coexpressed mRNA biomarkers using Support Vector Machine model with five-fold cross-validation in an independent HCC dataset from RNA-seq.
CONCLUSIONS: Our results suggested that mRNAs expression profiles coexpressed with positionally related lncRNAs can provide important insights into early diagnosis and specific targeted gene therapy of HCC.

PMID: 30704465 [PubMed - indexed for MEDLINE]

Association of magnesium intake and vitamin D status with cognitive function in older adults: an analysis of US National Health and Nutrition Examination Survey (NHANES) 2011 to 2014.

Mon, 05/11/2020 - 05:40

Association of magnesium intake and vitamin D status with cognitive function in older adults: an analysis of US National Health and Nutrition Examination Survey (NHANES) 2011 to 2014.

Eur J Nutr. 2020 May 09;:

Authors: Peeri NC, Egan KM, Chai W, Tao MH

Abstract
PURPOSE: Reduced cognitive function associated with aging has gained increasing attention as the US population ages. Magnesium plays a critical role in vitamin D biosynthesis and metabolism; and deficiencies in magnesium and vitamin D show associations with poor cognition. However, no study has examined their interaction. This study aimed to evaluate the associations of magnesium intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, indicating vitamin D status, with cognition, and interaction between these nutrients in older adults.
METHODS: Based on the National Health and Nutrition Survey (NHANES) 2011-2014, the study included 2466 participants aged ≥ 60 years who completed the Digit Symbol Substitution Test (DSST) and had data available on serum 25(OH)D and magnesium intake. Cognitive impairment was defined as a DSST score lower than the lowest quartile. Serum 25(OH)D concentrations were measured by HPLC-tandem mass spectrometry.
RESULTS: Higher total magnesium intake was independently associated with higher DSST scores (highest quartile vs lowest: β = 4.34, 95% CI 1.14-7.54). The association of total magnesium intake with high DSST score was primarily observed among women, non-Hispanic whites, physically active participants and those with sufficient vitamin D status, although the interactions were not significant. The odds of cognitive impairment was reduced with increasing intake of total magnesium (p trend < 0.01) and higher level of serum 25(OH)D (p trend = 0.05).
CONCLUSIONS: Findings suggest that high magnesium intake alone may improve cognitive function in older adults, and the association may be stronger among subjects with sufficient vitamin D status. Further studies are needed to confirm these findings.

PMID: 32388734 [PubMed - as supplied by publisher]

Temperature- and Pressure-Regulating Insoles for Prevention of Diabetic Foot Ulcers.

Mon, 05/11/2020 - 05:40

Temperature- and Pressure-Regulating Insoles for Prevention of Diabetic Foot Ulcers.

J Foot Ankle Surg. 2020 May 06;:

Authors: Yavuz M, Ersen A, Monga A, Lavery LA, Garrett AG, Salem Y, Hirschman GB, Myers R

Abstract
Diabetic foot ulcers (DFUs) pose a major threat to the United States healthcare system as well as patients and their families. High ulcer recurrence rates indicate that existing preventive measures are not effective. A new generation of multimodal preventive devices may reduce ulceration and amputation rates. Because previous research has revealed that tissue maintained at cooler temperatures is more resistant to breaking down, the evaluated technology may prevent foot ulceration. The purpose of this study was to test previously designed Temperature and Pressure Monitoring and Regulating Insoles (TAPMARI) in diabetic neuropathic and healthy subjects. A cooling unit, a mini-water pump, a battery pack, and a microcontroller (or simply thermostat) were placed inside a box attached to the subjects' calf, which provided cooling inside the shoe. The microcontroller was set at 28°C. Eight subjects provided informed consent, 3 of whom had diabetic neuropathy. Subjects used the instrumented shoe on the right foot and the matching control shoe on the left and walked on a treadmill for 5 minutes at self-selected speeds. Baseline and postwalking thermographs were obtained with a thermal camera. At the 2-hour midpoint, subjects again walked on the treadmill for 5 minutes at self-selected speeds. Second baseline and postwalking thermographs were captured. Plantar pressure distributions were also quantified. The TAPMARI successfully regulated foot temperatures at or below the target temperature. The mean baseline temperature of the right (regulated) and left (control) feet were 28.1 ± 1.9°C (mean ± standard deviation) for all subjects. The mean temperatures at the end of the study were 25.9 ± 2.5°C (right) and 31.7 ± 1.6°C (left) in all subjects. In the diabetic neuropathy group, the final mean temperatures were 27.5 ± 2.4°C (right) and 31.6 ± 0.8°C (left), which indicated that the temperature goal was met inside the instrumented shoe. By regulating temperatures, TAPMARI may reduce the metabolic demands in the foot and prevent cell autolysis by eliminating the imbalance between oxygen demand and supply. This study warrants further development and testing of TAPMARI as well as investigating the clinical effectiveness in preventing DFUs.

PMID: 32386918 [PubMed - as supplied by publisher]

Differentiation of Hispanic biogeographic ancestry with 80 ancestry informative markers.

Sun, 05/10/2020 - 05:29

Differentiation of Hispanic biogeographic ancestry with 80 ancestry informative markers.

Sci Rep. 2020 May 08;10(1):7745

Authors: Setser CH, Planz JV, Barber RC, Phillips NR, Chakraborty R, Cross DS

Abstract
Ancestry informative single nucleotide polymorphisms (SNPs) can identify biogeographic ancestry (BGA); however, population substructure and relatively recent admixture can make differentiation difficult in heterogeneous Hispanic populations. Utilizing unrelated individuals from the Genomic Origins and Admixture in Latinos dataset (GOAL, n = 160), we designed an 80 SNP panel (Setser80) that accurately depicts BGA through STRUCTURE and PCA. We compared our Setser80 to the Seldin and Kidd panels via resampling simulations, which models data based on allele frequencies. We incorporated Admixed American 1000 Genomes populations (1000 G, n = 347), into a combined populations dataset to determine robustness. Using multinomial logistic regression (MLR), we compared the 3 panels on the combined dataset and found overall MLR classification accuracies: 93.2% Setser80, 87.9% Seldin panel, 71.4% Kidd panel. Naïve Bayesian classification had similar results on the combined dataset: 91.5% Setser80, 84.7% Seldin panel, 71.1% Kidd panel. Although Peru and Mexico were absent from panel design, we achieved high classification accuracy on the combined populations for Peru (MLR = 100%, naïve Bayes = 98%), and Mexico (MLR = 90%, naïve Bayes = 83.4%) as evidence of the portability of the Setser80. Our results indicate the Setser80 SNP panel can reliably classify BGA for individuals of presumed Hispanic origin.

PMID: 32385290 [PubMed - as supplied by publisher]

Community-Based Eye Health Screening Study in the Elderly Hispanic Population in North Texas.

Fri, 05/08/2020 - 08:01
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Community-Based Eye Health Screening Study in the Elderly Hispanic Population in North Texas.

Tex Public Health J. 2020;72(2):19-21

Authors: Mozdbar ST, Deakins J, Terrell J, Johnson LA, Clark AF

Abstract
The Hispanic population is underserved and underrepresented in health care. Epidemiological studies are cmcial for providing insight to identify disparities and unmet eye health needs in this vulnerable group. The purpose of our study is to examine the prevalence of ocular conditions in the elderly Hispanic population in North Texas and identify the frequency in which these conditions were undiagnosed. This study was ancillary to the Health and Aging Brain study among Latino Elders (HABLE). Seventy-three HABLE participants (aged > 50 years) underwent neuropsychological evaluation and an eye health screening at the University of North Texas Health Science Center study site. Descriptive analyses were performed for prevalence of ocular conditions, as well as a comparison of self-reported conditions and ocular Endings. Our results suggest the prevalence patterns for undetected ocular disease in the Hispanic population of North Texas are comparable with the epidemiological trends for this population group in other concentrated areas in the United States.

PMID: 32377644 [PubMed]

Reply to authors.

Fri, 05/08/2020 - 05:00

Reply to authors.

Clin Infect Dis. 2020 May 07;:

Authors: Ruan L, Zeng Q, Feng Y, Jin K, ZhuGe Q

PMID: 32379864 [PubMed - as supplied by publisher]

Pharmacologic fibroblast reprogramming into photoreceptors restores vision.

Fri, 05/08/2020 - 05:00
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Pharmacologic fibroblast reprogramming into photoreceptors restores vision.

Nature. 2020 May;581(7806):83-88

Authors: Mahato B, Kaya KD, Fan Y, Sumien N, Shetty RA, Zhang W, Davis D, Mock T, Batabyal S, Ni A, Mohanty S, Han Z, Farjo R, Forster MJ, Swaroop A, Chavala SH

Abstract
Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision1,2. Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss; however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells. The transplantation of these chemically induced photoreceptor-like cells (CiPCs) into the subretinal space of rod degeneration mice (homozygous for rd1, also known as Pde6b) leads to partial restoration of the pupil reflex and visual function. We show that mitonuclear communication is a key determining factor for the reprogramming of fibroblasts into CiPCs. Specifically, treatment with these five compounds leads to the translocation of AXIN2 to the mitochondria, which results in the production of reactive oxygen species, the activation of NF-κB and the upregulation of Ascl1. We anticipate that CiPCs could have therapeutic potential for restoring vision.

PMID: 32376950 [PubMed - in process]

Neutrophils Are More Effective than Monocytes at Phagosomal Containment and Killing of Listeria monocytogenes.

Wed, 05/06/2020 - 07:29
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Neutrophils Are More Effective than Monocytes at Phagosomal Containment and Killing of Listeria monocytogenes.

Immunohorizons. 2019 12 13;3(12):573-584

Authors: Okunnu BM, Berg RE

Abstract
Neutrophils and inflammatory monocytes are innate immune cells essential for protection during Listeria monocytogenes infection. Although certain functions have been generally assigned to each of the cells, similarities and differences in functions necessary for bacterial clearance have not previously been investigated. In the current study, phagocytosis, phagosomal containment, bacterial killing, and cytokine production by neutrophils and monocytes during L. monocytogenes infection were studied. Data obtained via in vitro studies show that neutrophils are more effective at L. monocytogenes uptake, phagosomal containment, and killing than monocytes. However, monocytes were found to be more effective at cytokine production during L. monocytogenes infection, in vivo. Additionally, the data demonstrated that neutrophils and monocytes are also capable of producing IL-1α, a cytokine that does not yet have a clearly defined role during infection with L. monocytogenes Furthermore, we were able to demonstrate a population of monocytes producing both TNF-α and IL-α, concurrently. This study highlights the multifunctional capabilities of neutrophils and monocytes, further adding to our knowledge of these innate immune cells during L. monocytogenes infection.

PMID: 31836639 [PubMed - indexed for MEDLINE]

Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases.

Wed, 05/06/2020 - 07:29
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Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases.

Oxid Med Cell Longev. 2019;2019:9613090

Authors: Nandi A, Yan LJ, Jana CK, Das N

Abstract
Reactive species produced in the cell during normal cellular metabolism can chemically react with cellular biomolecules such as nucleic acids, proteins, and lipids, thereby causing their oxidative modifications leading to alterations in their compositions and potential damage to their cellular activities. Fortunately, cells have evolved several antioxidant defense mechanisms (as metabolites, vitamins, and enzymes) to neutralize or mitigate the harmful effect of reactive species and/or their byproducts. Any perturbation in the balance in the level of antioxidants and the reactive species results in a physiological condition called "oxidative stress." A catalase is one of the crucial antioxidant enzymes that mitigates oxidative stress to a considerable extent by destroying cellular hydrogen peroxide to produce water and oxygen. Deficiency or malfunction of catalase is postulated to be related to the pathogenesis of many age-associated degenerative diseases like diabetes mellitus, hypertension, anemia, vitiligo, Alzheimer's disease, Parkinson's disease, bipolar disorder, cancer, and schizophrenia. Therefore, efforts are being undertaken in many laboratories to explore its use as a potential drug for the treatment of such diseases. This paper describes the direct and indirect involvement of deficiency and/or modification of catalase in the pathogenesis of some important diseases such as diabetes mellitus, Alzheimer's disease, Parkinson's disease, vitiligo, and acatalasemia. Details on the efforts exploring the potential treatment of these diseases using a catalase as a protein therapeutic agent have also been described.

PMID: 31827713 [PubMed - indexed for MEDLINE]

Letter to the editor.

Wed, 05/06/2020 - 07:29
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Letter to the editor.

J Paediatr Child Health. 2019 11;55(11):1407-1408

Authors: Henson R, Collins A, Zia S, Coplin B, Akkad R, Hamby T

PMID: 31691417 [PubMed - indexed for MEDLINE]

Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment.

Wed, 05/06/2020 - 07:29
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Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment.

Surgery. 2020 01;167(1):189-196

Authors: Guenter R, Aweda T, Carmona Matos DM, Jang S, Whitt J, Cheng YQ, Liu XM, Chen H, Lapi SE, Jaskula-Sztul R

Abstract
BACKGROUND: Neuroendocrine tumors are found throughout the body, including the pancreas. These tumors are phenotypically and genetically heterogeneous and can be difficult to accurately image using current imaging standards. However, positron emission tomography/computed tomography with radiolabeled somatostatin analogs has shown clinical success because many neuroendocrine tumors overexpress somatostatin receptor subtype 2. Unfortunately, patients with poorly differentiated neuroendocrine tumors often have a diminished level of somatostatin receptor subtype 2. We found that histone deacetylase inhibitors can upregulate the functional expression of somatostatin receptor subtype 2.
METHODS: We evaluated the effect of histone deacetylase inhibitors on somatostatin receptor subtype 2 expression at the mRNA and protein level in neuroendocrine tumor cell lines. The effect of histone deacetylase inhibitors on surface somatostatin receptor subtype 2 was also investigated by fluorescence-activated cell sorting analysis. Changes in somatostatin receptor subtype 2 expression in neuroendocrine tumor xenografts after treatment were imaged using Ga68-DOTATATE positron emission tomography/computed tomography.
RESULTS: The functional increase of somatostatin receptor subtype 2 in neuroendocrine tumors after histone deacetylase inhibitor treatment was confirmed through in vitro experiments and small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging. Histone deacetylase inhibitors increased somatostatin receptor subtype 2 transcription and protein expression in neuroendocrine tumor cell lines. Small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging confirmed the enhancement of radiopeptide uptake after histone deacetylase inhibitor administration.
CONCLUSION: This study demonstrates a new method to potentially improve imaging and treatments that target somatostatin receptor subtype 2 in neuroendocrine tumors.

PMID: 31629542 [PubMed - indexed for MEDLINE]

Editorial overview: Allosteric assemblies.

Tue, 05/05/2020 - 07:10
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Editorial overview: Allosteric assemblies.

Curr Opin Struct Biol. 2020 Apr 30;:

Authors: Liu J, Lai L

PMID: 32362348 [PubMed - as supplied by publisher]

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