Recent Research Articles from UNTHSC

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

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
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A Novel Syndrome With Short Stature, Mandibular Hypoplasia, and Osteoporosis May Be Associated With a PRRT3 Variant.

Tue, 08/18/2020 - 06:09

A Novel Syndrome With Short Stature, Mandibular Hypoplasia, and Osteoporosis May Be Associated With a PRRT3 Variant.

J Endocr Soc. 2020 Aug 01;4(8):bvaa088

Authors: Garg A, El-Shanti H, Xing C, Zhou Z, Abujbara M, Al-Rashed K, El-Khateeb M, Ajlouni K, Agarwal AK

Abstract
Context: Despite considerable progress in elucidating the molecular basis of various progeroid syndromes, some rare patients remain unexplained.
Objective: To elucidate molecular genetic basis of a novel autosomal recessive progeroid syndrome.
Participants: A 24-year-old male and his 18-year-old sister with short stature, mandibular hypoplasia, pointed nose, shrill voice, severe osteoporosis, and short eyebrows and their unaffected siblings and parents belonging to a consanguineous Arab family.
Results: Using exome and Sanger sequencing, we report a novel homozygous p.Glu394Lys disease-causing variant in proline-rich transmembrane protein 3 (PRRT3). PRRT3 belongs to the family of proline-rich proteins containing several repeats of a short proline-rich sequence, but its function remains to be determined. Preliminary observations showing colocalization of Prrt3 and synaptophysin support its role in vesicle exocytosis. Consistent with the highest messenger ribonucleic acid expression of PRRT3 in the pituitary, both the patients had mild growth hormone deficiency but had near normal reproductive development.
Conclusions: We conclude that the homozygous p.Glu394Lys variant in PRRT3 may be associated with a novel autosomal recessive, progeroid syndrome with short stature, mandibular hypoplasia, osteoporosis, short eyebrows, and mild growth hormone (GH) deficiency. Our findings extend the spectrum of progeroid syndromes and elucidate important functions of PRRT3 in human biology, including secretion of GH from the pituitary.

PMID: 32803092 [PubMed - as supplied by publisher]

Uterine perivascular adipose tissue is a novel mediator of uterine artery blood flow and reactivity in rat pregnancy.

Tue, 08/18/2020 - 06:09
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Uterine perivascular adipose tissue is a novel mediator of uterine artery blood flow and reactivity in rat pregnancy.

J Physiol. 2019 08;597(15):3833-3852

Authors: Osikoya O, Ahmed H, Panahi S, Bourque SL, Goulopoulou S

Abstract
KEY POINTS: In vivo, uterine perivascular adipose tissue (PVAT) potentiates uterine artery blood flow in pregnant rats, although not in non-pregnant rats. In isolated preparations, uterine PVAT has pro-contractile and anti-dilatory effects on uterine arteries. Pregnancy induces changes in uterine arteries that makes them responsive to uterine PVAT signalling.
ABSTRACT: An increase in uterine artery blood flow (UtBF) is a common and necessary feature of a healthy pregnancy. In the present study, we tested the hypothesis that adipose tissue surrounding uterine arteries (uterine perivascular adipose tissue; PVAT) is a novel local mediator of UtBF and uterine artery tone during pregnancy. In vivo experiments in anaesthetized Sprague-Dawley rats showed that pregnant animals (gestational day 16, term = 22--23 days) had a three-fold higher UtBF compared to non-pregnant animals. Surgical removal of uterine PVAT reduced UtBF only in pregnant rats. In a series of ex vivo bioassays, we demonstrated that uterine PVAT had pro-contractile and anti-dilatory effects on rat uterine arteries. In the presence of PVAT-conditioned media, isolated uterine arteries from both pregnant and non-pregnant rats had reduced vasodilatory responses. In non-pregnant rats, these responses were mediated at the level of uterine vascular smooth muscle, whereas, in pregnant rats, PVAT-media reduced endothelium-dependent relaxation. Pregnancy increased adipocyte size in ovarian adipose tissue but had no effect on uterine PVAT adipocyte morphology. In addition, pregnancy down-regulated the gene expression of metabolic adipokines in uterine but not in aortic PVAT. In conclusion, this is the first study to demonstrate that uterine PVAT plays a regulatory role in UtBF, at least in part, as a result of its actions on uterine artery tone. We propose that the interaction between the uterine vascular wall and its adjacent adipose tissue may provide new insights for interventions in pregnancies with adipose tissue dysfunction and abnormal UtBF.

PMID: 31165480 [PubMed - indexed for MEDLINE]

What happens to agreement over time? A longitudinal study of self-reported substance use compared to saliva toxicological testing among subsidized housing residents.

Sat, 08/15/2020 - 06:36
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What happens to agreement over time? A longitudinal study of self-reported substance use compared to saliva toxicological testing among subsidized housing residents.

J Subst Abuse Treat. 2019 06;101:12-17

Authors: Rendon A, Mun EY, Spence-Almaguer E, Walters ST

Abstract
The agreement between self-reported and toxicologically verified substance use provides important information about the validity of self-reported use. While some studies report aggregate agreement across follow-up points, only a few have examined the agreement at each time point separately. An overall rate of agreement across time may miss changes that occur as people progress through a research study. In this study, a sample of 644 adults (43.8% male, 32.6% White, 57.0% Black, 90.2% ages 36+) residing in subsidized housing was used to determine the agreement between self-reported use and saliva toxicological testing for marijuana, cocaine, PCP, amphetamine, and methamphetamine at three different time points. Agreement between saliva toxicological testing and self-report ranged between 84.2% and 94.3% for different substances over time. Higher rates of agreement were found for cocaine than had been reported by previous studies. Statistically significant differences in the odds ratios of concordance over time (baseline, 6-month, and 12-month follow-up) were found for marijuana and the combined category for PCP, amphetamine, and methamphetamine. Our findings suggest that oral fluid drug tests generally withstand community field assessments and result in relatively high levels of agreement for marijuana, cocaine, PCP, amphetamine, and methamphetamine use, when compared to self-report. Because of the ease of sample collection and low chance of adulteration, we conclude that saliva testing is a viable method for toxicological confirmation of substance use behavior in this setting.

PMID: 31174709 [PubMed - indexed for MEDLINE]

How many familial relationship testing results could be wrong?

Fri, 08/14/2020 - 06:06

How many familial relationship testing results could be wrong?

PLoS Genet. 2020 Aug;16(8):e1008929

Authors: Ge J, Budowle B

PMID: 32790673 [PubMed - as supplied by publisher]

Thymic rejuvenation via FOXN1-reprogrammed embryonic fibroblast (FREF) to counteract age-related inflammation.

Fri, 08/14/2020 - 06:06

Thymic rejuvenation via FOXN1-reprogrammed embryonic fibroblast (FREF) to counteract age-related inflammation.

JCI Insight. 2020 Aug 13;:

Authors: Oh J, Wang W, Thomas R, Su DM

Abstract
Age-associated systemic, chronic inflammation is partially attributed to increased self (auto)-reactivity, resulting from disruption of central tolerance in the aged, involuted thymus. This involution causally results from gradually decreased expression of the transcription factor FOXN1 in thymic epithelial cells (TECs), while exogenous FOXN1 in TECs can partially rescue age-related thymic involution. Given the findings that TECs induced from FOXN1-overexpressing embryonic fibroblasts can generate an ectopic de novo thymus under the kidney capsule and intra-thymically injected naturally young TECs can lead to middle-aged thymus regrowth, we attempted to extend these two findings by combining them as a novel thymic rejuvenation strategy with two types of promoter-driven (Rosa26CreERT and FoxN1Cre) Cre-mediated FOXN1-reprogrammed embryonic fibroblasts (FREFs). We engrafted these two-types of FREFs directly into the aged murine thymus. We found significant regrowth of the native aged thymus with rejuvenated architecture and function in both males and females, exhibiting increased thymopoiesis and reinforced thymocyte negative selection, along with reduced senescent T cells and auto-reactive T cell-mediated inflammation in old mice. Therefore, this strategy has preclinical significance and presents a strategy to potentially rescue decreased thymopoiesis and perturbed negative selection to significantly, albeit partially, restore defective central tolerance and reduce subclinical autoimmune symptoms in the elderly.

PMID: 32790650 [PubMed - as supplied by publisher]

Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF-7 breast cancer cells.

Thu, 08/13/2020 - 07:58
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Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF-7 breast cancer cells.

Oncol Lett. 2020 Sep;20(3):2291-2301

Authors: de Mascena Costa LA, Debnath D, Harmon AC, de Sousa Araújo S, da Silva Souza HD, de Athayde Filho PF, Wischral A, Adrião Gomes Filho M, Mathis JM

Abstract
In the present study, the cytotoxic effects of a 1,3-thiazolium-5-thiolate derivative of a mesoionic compound, MIH 2.4Bl, were assessed in the MCF-7 breast cancer cell line. The cytotoxic effects of MIH 2.4Bl were determined using a crystal violet assay. Using a dose-response curve, the IC50 value of MIH 2.4Bl was determined to be 45.8±0.8 µM. Additionally, the effects of MIH 2.4Bl on mitochondrial respiration were characterized using oxygen consumption rate analysis. Treating MCF-7 cells with increasing concentrations of MIH 2.4Bl resulted in a significant reduction in all mitochondrial respiratory parameters compared with the control cells, indicative of an overall decrease in mitochondrial membrane potential. The induction of autophagy by MIH 2.4Bl was also examined by measuring changes in the expression of protein markers of autophagy. As shown by western blot analysis, treatment of MCF-7 cells with MIH 2.4Bl resulted in increased protein expression levels of Beclin-1 and ATG5, as well as an increase in the microtubule-associated protein 1A/1B light chain 3B (LC3B)-II to LC3B-I ratio compared with the control cells. Microarray analysis of changes in gene expression following MIH 2.4Bl treatment demonstrated 3,659 genes exhibited a fold-change ≥2. Among these genes, 779 were up-regulated, and 2,880 were down-regulated in cells treated with MIH 2.4Bl compared with the control cells. Based on the identity of the transcripts and fold-change of expression, six genes were selected for verification by reverse transcription-quantitative (RT-q)PCR; activating transcription factor 3, acidic repeat-containing protein, heparin-binding EGF-like growth factor, regulator of G-protein signaling 2, Dickkopf WNT signaling pathway inhibitor 1 and adhesion molecule with Ig like domain 2. The results of RT-qPCR analysis of RNA isolated from control and MIH 2.4Bl treated cells were consistent with the expression changes identified by microarray analysis. Together, these results suggest that MIH 2.4Bl may be a promising candidate for treating breast cancer and warrants further in vitro and in vivo investigation.

PMID: 32782546 [PubMed]

The effect of intermittent hypoxia training on migraine: a randomized controlled trial.

Tue, 08/11/2020 - 06:09

The effect of intermittent hypoxia training on migraine: a randomized controlled trial.

Am J Transl Res. 2020;12(7):4059-4065

Authors: Bao X, Liu H, Liu HY, Long Y, Tan JW, Zhu ZM

Abstract
OBJECTIVE: To study the effect of intermittent hypoxia training (IHT) for migraine.
DESIGN: A single-blind, randomized controlled trial. All participants were recruited from a rehabilitation department in an acute university-affiliated hospital.
METHODS: Participants with migraines were randomly assigned to two groups (IHT group and control group). The Migraine Disability Assessment (MIDAS), Visual Analog Scale (VAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and cerebrovascular hemodynamic parameters were collected at baseline and end of the 8th week. The attack frequencies of migraines were evaluated at 3 months.
RESULTS: Among the 48 subjects, five males and forty-three females, the ages ranged from 19 to 53 years old (mean ± SD = 31.3±7.78). MIDAS, SF-36, VAS, BAI, BDI, VEGF, CGRP and cerebrovascular hemodynamic parameters were improved after IHT intervention. There were significant differences between IHT group and the control group in MIDAS, SF-36, VAS, BAI, BDI, VEGF, CGRP and cerebrovascular hemodynamic parameters at the end of the 8th weeks (P<0.05). Attack frequencies were improved within 3 months after IH training intervention (P<0.01), but not in the control group (P>0.05). No adverse events occurred during the study.
CONCLUSION: IHT could improve migraines after intervention up to three months. IHT could be an effective method for relieving a migraine.

PMID: 32774759 [PubMed - as supplied by publisher]

Comment on: Curative-intent radiotherapy for pediatric osteosarcoma: The St. Jude experience.

Tue, 08/11/2020 - 06:09
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Comment on: Curative-intent radiotherapy for pediatric osteosarcoma: The St. Jude experience.

Pediatr Blood Cancer. 2020 06;67(6):e28287

Authors: Vicenzi P, Johnnidis M, Hamby T, Ray A

PMID: 32293779 [PubMed - indexed for MEDLINE]

New Measures for the Coronavirus Disease 2019 Response: A Lesson From the Wenzhou Experience.

Tue, 08/11/2020 - 06:09
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New Measures for the Coronavirus Disease 2019 Response: A Lesson From the Wenzhou Experience.

Clin Infect Dis. 2020 07 28;71(15):866-869

Authors: Ruan L, Wen M, Zeng Q, Chen C, Huang S, Yang S, Yang J, Wang J, Hu Y, Ding S, Zhang Y, Zhang H, Feng Y, Jin K, Zhuge Q

Abstract
As the outbreak of coronavirus disease 2019 (COVID-19) has spread globally, determining how to prevent the spread is of paramount importance. We reported the effectiveness of different responses of 4 affected cities in preventing the COVID-19 spread. We expect the Wenzhou anti-COVID-19 measures may provide information for cities around the world that are experiencing this epidemic.

PMID: 32246149 [PubMed - indexed for MEDLINE]

The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?

Tue, 08/11/2020 - 06:09
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The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?

Int J Epidemiol. 2020 06 01;49(3):717-726

Authors: Peeri NC, Shrestha N, Rahman MS, Zaki R, Tan Z, Bibi S, Baghbanzadeh M, Aghamohammadi N, Zhang W, Haque U

Abstract
OBJECTIVES: To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China.
METHODS: Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS) and COVID-19. Comparisons between the viruses were made.
RESULTS: Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally.
CONCLUSIONS: We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.

PMID: 32086938 [PubMed - indexed for MEDLINE]

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