Recent Research Articles from UNTHSC

Genome-Wide Methylation of Mild Cognitive Impairment in Mexican Americans Highlights Genes Involved in Synaptic Transport, Alzheimer's Disease-Precursor Phenotypes, and Metabolic Morbidities.

Tue, 12/01/2020 - 09:29
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Genome-Wide Methylation of Mild Cognitive Impairment in Mexican Americans Highlights Genes Involved in Synaptic Transport, Alzheimer's Disease-Precursor Phenotypes, and Metabolic Morbidities.

J Alzheimers Dis. 2019;72(3):733-749

Authors: Pathak GA, Silzer TK, Sun J, Zhou Z, Daniel AA, Johnson L, O'Bryant S, Phillips NR, Barber RC

Abstract
The Mexican American population is among the fastest growing aging population and has a younger onset of cognitive decline. This group is also heavily burdened with metabolic conditions such as hypertension, diabetes, and obesity. Unfortunately, limited research has been conducted in this group. Understanding methylation alterations, which are influenced by both genetic and lifestyle factors, is key to identifying and addressing the root cause for mild cognitive impairment, a clinical precursor for dementia. We conducted an epigenome-wide association study on a community-based Mexican American population using the Illumina EPIC array. Following rigorous quality control measures, we identified 10 CpG sites to be differentially methylated between normal controls and individuals with mild cognitive impairment annotated to PKIB, KLHL29, SEPT9, OR2C3, CPLX3, BCL2L2-PABPN1, and CCNY. We found four regions to be differentially methylated in TMEM232, SLC17A8, ALOX12, and SEPT8. Functional gene-set analysis identified four gene-sets, RIN3, SPEG, CTSG, and UBE2L3, as significant. The gene ontology and pathway analyses point to neuronal cell death, metabolic dysfunction, and inflammatory processes. We found 1,450 processes to be enriched using empirical Bayes gene-set enrichment. In conclusion, the functional overlap of differentially methylated genes associated with cognitive impairment in Mexican Americans implies cross-talk between metabolically-instigated systemic inflammation and disruption of synaptic vesicular transport.

PMID: 31640099 [PubMed - indexed for MEDLINE]

A Comparison of Protocols for Simulating Hemorrhage in Humans: Step vs. Ramp Lower Body Negative Pressure.

Fri, 11/20/2020 - 14:56
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A Comparison of Protocols for Simulating Hemorrhage in Humans: Step vs. Ramp Lower Body Negative Pressure.

J Appl Physiol (1985). 2020 Nov 19;:

Authors: Rosenberg AJ, Kay VL, Anderson GK, Sprick JD, Rickards CA

Abstract
Lower body negative pressure (LBNP) elicits central hypovolemia, and has been used to simulate the cardiovascular and cerebrovascular responses to hemorrhage in humans. LBNP protocols commonly employ progressive stepwise reductions in chamber pressure for specific time periods. However, continuous ramp LBNP protocols have also been utilized to simulate the continuous nature of most bleeding injuries. The aim of this study was to compare tolerance and hemodynamic responses between these two LBNP profiles. Healthy human subjects (N=19; age, 27±4 y; 7F/12M) completed a 1) step LBNP protocol (5-min steps), and; 2) continuous ramp LBNP protocol (3 mmHg/min), both to presyncope. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), middle and posterior cerebral artery velocity (MCAv and PCAv), cerebral oxygen saturation (ScO2), and end-tidal CO2 (etCO2) were measured. LBNP tolerance, via the cumulative stress index (CSI, summation of chamber pressure*time at each pressure), and hemodynamic responses were compared between the two protocols. The CSI (Step: 911±97 mmHg*min vs. Ramp: 823±83 mmHg*min; P=0.12) and the magnitude of central hypovolemia (%Δ SV, Step: -54.6±2.6 % vs. Ramp: -52.1±2.8 %; P=0.32) were similar between protocols. While there were no differences between protocols for the maximal %Δ HR (P=0.88), the %Δ MAP during the step protocol was attenuated (P=0.05), and the reductions in MCAv, PCAv, ScO2,and etCO2 were greater (P≤0.08) when compared with the ramp protocol at presyncope. These results indicate that when comparing cardiovascular responses to LBNP across different laboratories, the specific pressure profile must be considered as a potential confounding factor.

PMID: 33211600 [PubMed - as supplied by publisher]

Improvements in Retention in Care and HIV Viral Suppression Among Persons with HIV and Comorbid Mental Health Conditions: Patient-Centered HIV Care Model.

Fri, 11/20/2020 - 14:56
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Improvements in Retention in Care and HIV Viral Suppression Among Persons with HIV and Comorbid Mental Health Conditions: Patient-Centered HIV Care Model.

AIDS Behav. 2020 Dec;24(12):3522-3532

Authors: Byrd KK, Hardnett F, Hou JG, Clay PG, Suzuki S, Camp NM, Shankle MD, Weidle PJ, Taitel MS, Patient-Centered HIV Care Model Team

Abstract
The Patient-centered HIV Care Model (PCHCM) integrated community-based pharmacists with medical providers and required sharing of patient clinical information and collaborative therapy-related action planning. We determined the proportions of participants with HIV and mental health conditions who were retained in care and the proportion virally suppressed, pre- and post-implementation. Overall, we found a relative 13% improvement in both retention [60% to 68% (p = 0.009)] and viral suppression [79% to 90% (p < 0.001)]. Notable improvements were seen among persons triply diagnosed with HIV, mental illness and substance use [+ 36% (50% to 68%, p = 0.036) and + 32% (66% to 86%, p = 0.001) in retention and viral suppression, respectively]. There were no differences in the proportions of persons adherent to psychiatric medications, pre- to post-implementation, nor were there differences in the proportions of persons retained in care or virally suppressed by psychiatric medication adherence, post-implementation. PCHCM demonstrated that collaborations between community-based pharmacists and medical providers can improve HIV care continuum outcomes among persons with mental health conditions.

PMID: 32415615 [PubMed - indexed for MEDLINE]

Comment on: The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis.

Wed, 11/18/2020 - 06:55
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Comment on: The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis.

Pediatr Blood Cancer. 2020 Nov 16;:e28813

Authors: Vicenzi P, Jiwani Z, Guirola R, Hamby T, Ray A

PMID: 33200506 [PubMed - as supplied by publisher]

Editorial: New Insights Into Thymic Functions During Stress, Aging, and in Disease Settings.

Tue, 11/17/2020 - 14:15
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Editorial: New Insights Into Thymic Functions During Stress, Aging, and in Disease Settings.

Front Immunol. 2020;11:591936

Authors: van Oers NSC, Su DM, Chidgey AP, Dudakov J

PMID: 33193434 [PubMed - in process]

The Effect of IDO on Neural Progenitor Cell Survival Under Oxygen Glucose Deprivation.

Tue, 11/17/2020 - 14:15
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The Effect of IDO on Neural Progenitor Cell Survival Under Oxygen Glucose Deprivation.

Front Cell Neurosci. 2020;14:581861

Authors: Wang J, Wang B, Jiang L, Zhou K, Yang GY, Jin K

Abstract
Objective: Indoleamine 2,3-dioxygenase (IDO) activity plays an important role in many neurological disorders in the central nervous system, which may be associated with immunomodulation or anti-inflammatory activity. However, the action of IDO in the ischemic condition is still poorly understood. The purpose of the present study is to explore the expression and action of IDO in stem cell culture under oxygen and glucose deprivation. Methods: Neural progenitor cells were obtained from the human embryonic stem cell line BG01. These cells underwent oxygen and glucose deprivation. We examined the IDO expression at 3 and 8 h of oxygen and glucose deprivation and then examined neuronal progenitor cell viability in the normal and oxygen and glucose deprivation condition using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. In addition, we studied the effect of IDO inhibition and the expression of TNF-α, IGF-1, VEGF, IL-6, FGFβ, TGFβ, EGF, and Leptin to explore the mechanism of IDO under the oxygen and glucose deprivation. Results: IDO expression in neural progenitor cells increased under oxygen and glucose deprivation, which is closely associated with cell death (p < 0.05). Inhibiting IDO did not affect cell survival in normal neural progenitor cells. However, inhibiting IDO could attenuate cell viability under oxygen and glucose deprivation (p < 0.05). Further study demonstrated that IDO expression was closely associated to the growth factor's leptin expression. Conclusions: Our results demonstrated that an increase of IDO under oxygen and glucose deprivation was associated with cell death, suggesting that inhibiting IDO could be a target for neuroprotection.

PMID: 33192328 [PubMed]

Association of Serum Levels of Antioxidant Micronutrients with Mortality in US Adults: National Health and Nutrition Examination Survey 1999-2002.

Tue, 11/17/2020 - 06:56
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Association of Serum Levels of Antioxidant Micronutrients with Mortality in US Adults: National Health and Nutrition Examination Survey 1999-2002.

Public Health Nutr. 2020 Nov 13;:1-26

Authors: Peeri NC, Chai W, Cooney RV, Tao MH

Abstract
OBJECTIVES: To examine associations between serum antioxidant levels and mortality (all-cause, cancer, and cardiovascular disease (CVD)) among U.S. adults.
DESIGN: We examined the risk of death from all-cause and cause-specific mortality associated with serum antioxidant (vitamin E and carotenoids) and vitamin A levels using Cox regression models to estimate hazards ratios (HR) and 95% confidence intervals (CIs).
SETTING: The National Health and Nutrition Examination Survey (NHANES) 1999-2002 were follow-up through December 31, 2015.
PARTICIPANTS: The NHANES 1999-2002 cohort included 8,758 participants aged ≥20 years. Serum carotenoid levels were only assessed for the 1999-2000 cycle. Therefore, sample size for each assessed antioxidant ranged from 4,633 to 8,758.
RESULTS: Serum vitamin E level was positively associated with all-cause mortality (HR= 1.22, 95% CI: 1.04, 1.43, highest vs. lowest quartile). No other antioxidants were associated with mortality in overall analysis. In race/ethnicity-specific analyses, high vitamin E and α-tocopherol levels were associated with increased risk of all-cause mortality among non-Hispanic Whites. Among non-Hispanic Blacks, serum α-tocopherol level was associated with decreased risk of cancer mortality (HR= 0.30, 95% CI: 0.12-0.75, third vs. first quartile), and total carotenoids levels with reduced risk of CVD mortality (HR=0.26; 95% CI: 0.07, 0.97, second vs. lowest quartile). Hispanics with high β-carotene levels had reduced risk of CVD mortality.
CONCLUSIONS: Serum antioxidant levels may be related to mortality; these associations may differ by race/ethnicity and appeared to be non-linear for all-cause and cause-specific mortality. Further studies are needed to confirm our results.

PMID: 33183381 [PubMed - as supplied by publisher]

Paradoxical modulation of influenza by intranasal administration of non-replicating adenovirus particles.

Fri, 11/13/2020 - 06:55
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Paradoxical modulation of influenza by intranasal administration of non-replicating adenovirus particles.

PLoS One. 2020;15(11):e0241266

Authors: Tang DC

Abstract
Respiratory mucosal infection by airborne microbes is a common event that occurs every day. We report here that intranasal administration of non-replicating adenovirus (Ad) particles to mice could either confer rapid protection against influenza virus (IFV) challenge independent of adaptive immunity, or exacerbate influenza by triggering rapid death. The life-or-death outcome hinges on the time interval between Ad administration and IFV challenge in conjunction with specific mouse/IFV strains. Intranasal instillation of Ad particles 1-47 days prior to IFV challenge conferred rapid protection against influenza in Balb/c mice whereas exposure to Ad 39 days prior to challenge with a specific IFV strain or 1 day post-challenge with that IFV strain induced rapid death in C57BL/6 mice. Notably, consecutive administrations of Ad prior to IFV challenge conferred a synergy in triggering a potent anti-influenza state; even a detrimental Ad exposure 39 days before challenge with the deadly IFV strain was reversed to a beneficial one by subsequent Ad boosts. Results revealed an intricate relationship between infection and innate immunity that is a linchpin around which effects revolve from protective immunity to collateral damage. It is urgent to repeat the experiments with an expanded scope for characterizing the status that defines susceptibility or resistance to IFV infection and subsequently reveal the underlying mechanisms. Whether broad heterologous protective effects induced by AdE and adaptive immunity elicited by vaccination could confer synergy during mitigation of a pandemic remains to be seen.

PMID: 33180828 [PubMed - as supplied by publisher]

Wuqinxi Exercise Improves Hand Dexterity in Patients with Parkinson's Disease.

Fri, 11/13/2020 - 06:55
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Wuqinxi Exercise Improves Hand Dexterity in Patients with Parkinson's Disease.

Evid Based Complement Alternat Med. 2020;2020:8352176

Authors: Wang T, Xiao G, Li Z, Jie K, Shen M, Jiang Y, Wang Z, Shi X, Zhuang J

Abstract
Objective: This study was designed to evaluate the effect of Wuqinxi after one session and 12-week intervention on hand dexterity in patients with Parkinson's disease (PD).
Methods: Forty-six elderly participants with mild-to-moderate PD were randomly assigned to the groups trained with Wuqinxi (n = 23) or stretching (n = 23). All participants practiced 60 min session of either of these exercises, 2 sessions a week for 12 weeks in standing position. The score of Purdue Pegboard Test (PPT) and time for Soda Pop Test (SPT) were performed to assess hand dexterity and motor function along assessing the 39 items of Parkinson's Disease Questionnaire before and after 12-week interventions. In addition, the PPT scores were compared before vs. after one session of either of these two exercise modes.
Results: Single session with either Wuqinxi or stretching exercise tended to improve PPT scores in PD patients. Furthermore, the improved SPT time was significant (P < 0.01) following 12-week training interventions with Wuqinxi (-1.32 ± 0.38 sec) or stretching (-0.89 ± 0.16 sec), which showed no group difference (P=0.734). However, only the participants in Wuqinxi group significantly improved the PPT scores of the dominant hand (+0.61 ± 1.34), both hand (+1.83 ± 3.13) and assemble (+2.04 ± 3.44) performance after 12-week training intervention. In parallel with improved hand dexterity and motor function, 12-week Wuqinxi training also significantly improved the patient's emotional wellbeing.
Conclusion: The Wuqinxi intervention could be safely and effectively applied to improve hand dexterity following single-session exercise or 12-week training, which were accompanied by improved quality of life in patients with mild-to-moderate PD.

PMID: 33178323 [PubMed]

Social Determinants of Health and Health Disparities: COVID-19 Exposures and Mortality Among African American People in the United States.

Thu, 11/12/2020 - 14:59
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Social Determinants of Health and Health Disparities: COVID-19 Exposures and Mortality Among African American People in the United States.

Public Health Rep. 2020 Nov 11;:33354920969169

Authors: Maness SB, Merrell L, Thompson EL, Griner SB, Kline N, Wheldon C

PMID: 33176112 [PubMed - as supplied by publisher]

Application of Nanotechnology in Cancer Diagnosis and Therapy - A Mini-Review.

Thu, 11/12/2020 - 14:59
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Application of Nanotechnology in Cancer Diagnosis and Therapy - A Mini-Review.

Int J Med Sci. 2020;17(18):2964-2973

Authors: Jin C, Wang K, Oppong-Gyebi A, Hu J

Abstract
Cancer is a leading cause of death and poor quality of life globally. Even though several strategies are devised to reduce deaths, reduce chronic pain and improve the quality of life, there remains a shortfall in the adequacies of these cancer therapies. Among the cardinal steps towards ensuring optimal cancer treatment are early detection of cancer cells and drug application with high specificity to reduce toxicities. Due to increased systemic toxicities and refractoriness with conventional cancer diagnostic and therapeutic tools, other strategies including nanotechnology are being employed to improve diagnosis and mitigate disease severity. Over the years, immunotherapeutic agents based on nanotechnology have been used for several cancer types to reduce the invasiveness of cancerous cells while sparing healthy cells at the target site. Nanomaterials including carbon nanotubes, polymeric micelles and liposomes have been used in cancer drug design where they have shown considerable pharmacokinetic and pharmacodynamic benefits in cancer diagnosis and treatment. In this review, we outline the commonly used nanomaterials which are employed in cancer diagnosis and therapy. We have highlighted the suitability of these nanomaterials for cancer management based on their physicochemical and biological properties. We further reviewed the challenges that are associated with the various nanomaterials which limit their uses and hamper their translatability into the clinical setting in certain cancer types.

PMID: 33173417 [PubMed - in process]

β-Catenin Regulates Wound Healing and IL-6 Expression in Activated Human Astrocytes.

Thu, 11/12/2020 - 14:59
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β-Catenin Regulates Wound Healing and IL-6 Expression in Activated Human Astrocytes.

Biomedicines. 2020 Nov 06;8(11):

Authors: Edara VV, Nooka S, Proulx J, Stacy S, Ghorpade A, Borgmann K

Abstract
Reactive astrogliosis is prominent in most neurodegenerative disorders and is often associated with neuroinflammation. The molecular mechanisms regulating astrocyte-linked neuropathogenesis during injury, aging and human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) are not fully understood. In this study, we investigated the implications of the wingless type (Wnt)/β-catenin signaling pathway in regulating astrocyte function during gliosis. First, we identified that HIV-associated inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced mediators of the Wnt/β-catenin pathway including β-catenin and lymphoid enhancer-binding factor (LEF)-1 expression in astrocytes. Next, we investigated the regulatory role of β-catenin on primary aspects of reactive astrogliosis, including proliferation, migration and proinflammatory responses, such as IL-6. Knockdown of β-catenin impaired astrocyte proliferation and migration as shown by reduced cyclin-D1 levels, bromodeoxyuridine incorporation and wound healing. HIV-associated cytokines, IL-1β alone and in combination with TNF-α, strongly induced the expression of proinflammatory cytokines including C-C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)8 and IL-6; however, only IL-6 levels were regulated by β-catenin as demonstrated by knockdown and pharmacological stabilization. In this context, IL-6 levels were negatively regulated by β-catenin. To better understand this relationship, we examined the crossroads between β-catenin and nuclear factor (NF)-κB pathways. While NF-κB expression was significantly increased by IL-1β and TNF-α, NF-κB levels were not affected by β-catenin knockdown. IL-1β treatment significantly increased glycogen synthase kinase (GSK)-3β phosphorylation, which inhibits β-catenin degradation. Further, pharmacological inhibition of GSK-3β increased nuclear translocation of both β-catenin and NF-κB p65 into the nucleus in the absence of any other inflammatory stimuli. HIV+ human astrocytes show increased IL-6, β-catenin and NF-κB expression levels and are interconnected by regulatory associations during HAND. In summary, our study demonstrates that HIV-associated inflammation increases β-catenin pathway mediators to augment activated astrocyte responses including migration and proliferation, while mitigating IL-6 expression. These findings suggest that β-catenin plays an anti-inflammatory role in activated human astrocytes during neuroinflammatory pathologies, such as HAND.

PMID: 33171974 [PubMed]

3D Spheroids Derived from Human Lipedema ASCs Demonstrated Similar Adipogenic Differentiation Potential and ECM Remodeling to Non-Lipedema ASCs In Vitro.

Thu, 11/12/2020 - 14:59
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3D Spheroids Derived from Human Lipedema ASCs Demonstrated Similar Adipogenic Differentiation Potential and ECM Remodeling to Non-Lipedema ASCs In Vitro.

Int J Mol Sci. 2020 Nov 07;21(21):

Authors: Al-Ghadban S, Pursell IA, Diaz ZT, Herbst KL, Bunnell BA

Abstract
The growth and differentiation of adipose tissue-derived stem cells (ASCs) is stimulated and regulated by the adipose tissue (AT) microenvironment. In lipedema, both inflammation and hypoxia influence the expansion and differentiation of ASCs, resulting in hypertrophic adipocytes and deposition of collagen, a primary component of the extracellular matrix (ECM). The goal of this study was to characterize the adipogenic differentiation potential and assess the levels of expression of ECM-remodeling markers in 3D spheroids derived from ASCs isolated from both lipedema and healthy individuals. The data showed an increase in the expression of the adipogenic genes (ADIPOQ, LPL, PPAR-γ and Glut4), a decrease in matrix metalloproteinases (MMP2, 9 and 11), with no significant changes in the expression of ECM markers (collagen and fibronectin), or integrin A5 in 3D differentiated lipedema spheroids as compared to healthy spheroids. In addition, no statistically significant changes in the levels of expression of inflammatory genes were detected in any of the samples. However, immunofluorescence staining showed a decrease in fibronectin and increase in laminin and Collagen VI expression in the 3D differentiated spheroids in both groups. The use of 3D ASC spheroids provide a functional model to study the cellular and molecular characteristics of lipedema AT.

PMID: 33171717 [PubMed - in process]

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