Recent Research Articles from UNTHSC
Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.
Cerebral ischemia induces angiogenesis in the peri-infarct regions via Notch1 signaling activation.
Exp Neurol. 2018 06;304:30-40
Authors: Ren C, Yao Y, Han R, Huang Q, Li H, Wang B, Li S, Li M, Mao Y, Mao X, Xie L, Zhou L, Hu J, Ji X, Jin K
The Notch1 signaling pathway is considered as one of important regulators of angiogenesis during development, but its role in cerebral ischemia-induced angiogenesis is less well understood. Here, we used human and rodent brains to explore whether Notch1 signaling was involved in the angiogenesis after focal cerebral ischemia. Using immunohistochemistry on surgically resected ischemic stroke brain tissue, we found that the area, volume, and length of the blood vessels in the peri-infarct regions were significantly increased after ischemic stroke in humans, compared with non-ischemic stroke specimens. In addition, the expression of the activated form of Notch1 (Notch intracellular domain; NICD) was increased in endothelial cells of the peri-infarct region. The Notch1 ligand, Jagged1, also increased in abundance in the peri-infarct regions in human. We further confirmed that Notch1 signaling was activated in the peri-infarct regions in a mouse distal middle cerebral artery occlusion (dMCAO) model. Lentivirus-mediated Notch1 knockdown reduced ischemia-induced angiogenesis in the peri-infarct regions of the brain. Our findings suggest that ischemic stroke in human can also induce angiogenesis in the peri-infarct regions as does in animal models of focal ischemia and that Notch1 signaling plays a critical role in mediating this process, which may provide fundamental knowledge regarding the potential mechanisms underlying angiogenesis after ischemic stroke.
PMID: 29481785 [PubMed - indexed for MEDLINE]
Clotam enhances anti-proliferative effect of vincristine in Ewing sarcoma cells.
Apoptosis. 2019 Jan 04;:
Authors: Shelake S, Sankpal UT, Eslin D, Bowman WP, Simecka JW, Raut S, Ray A, Basha R
Current therapeutic strategies used in Ewing sarcoma (ES) especially for relapsed patients have resulted in modest improvements in survival over the past 20 years. Combination therapeutic approach presents as an alternative to overcoming drug resistance in metastatic ES. This study evaluated the effect of Clotam (tolfenamic acid or TA), a small molecule and inhibitor of Specificity protein1 (Sp1) and survivin for sensitizing ES cell lines to chemotherapeutic agent, vincristine (VCR). ES cells (CHLA-9 and TC-32) were treated with TA or VCR or TA + VCR (combination), and cell viability was assessed after 24/48/72 h. Effect of TA or VCR or TA + VCR treatment on cell cycle arrest and apoptosis were evaluated using propidium iodide, cell cycle assay and Annexin V flow cytometry respectively. The apoptosis markers, caspase 3/7 (activity levels) and cleaved-PARP (protein expression) were measured. Cardiomyocytes, H9C2 were used as non-malignant cells. While, all treatments caused time- and dose-dependent inhibition of cell viability, interestingly, combination treatment caused significantly higher response (~ 80% inhibition, p < 0.05). Cell viability inhibition was accompanied by inhibition of Sp1 and Survivin. TA + VCR treatment significantly (p < 0.05) increased caspase 3/7 activity which strongly correlated with upregulated c-PARP level and Annexin V staining. Cell cycle arrest was observed at G0/G1 (TA) or G2/M (VCR and TA + VCR). All treatments did not cause cytotoxicity in H9C2 cells. These results suggest that TA could enhance the anti-cancer activity of VCR in ES cells. Therefore, TA + VCR combination could be further tested to develop as safe/effective therapeutic strategy for treating ES.
PMID: 30610505 [PubMed - as supplied by publisher]
Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes⁻4.
Molecules. 2018 Dec 31;24(1):
Authors: Mangoni AA, Guillou C, Vanden Eynde JJ, Hulme C, Jampilek J, Li W, Prokai-Tatrai K, Rautio J, Collina S, Tuccinardi T, Sousa ME, Sabatier JM, Galdiero S, Karaman R, Kokotos G, Torri G, Luque FJ, Vasconcelos MH, Hadjipavlou-Litina D, Siciliano C, Gütschow M, Ragno R, Gomes PAC, Agrofoglio LA, Muñoz-Torrero D
Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules. [...].
PMID: 30602690 [PubMed - in process]
Applying Organizational Health Literacy to Maternal and Child Health.
Matern Child Health J. 2019 Jan 02;:
Authors: Vamos CA, Thompson EL, Griner SB, Liggett LG, Daley EM
Purpose Describe the development of an innovative teaching activity that applies organizational health literacy to maternal and child health (MCH). Description Health literacy is a strong predictor of health behavior and outcomes. While the study of health literacy has traditionally been confined to skills and capacities of individuals, the significant role of the social and physical environmental contexts in facilitating or hindering one's ability to obtain, understand, and make informed decision about their health has been recognized. MCH organizations play a critical role in influencing health literacy across system levels. This teaching activity aims to equip students with knowledge and skills needed to foster organizational health literacy. Assessment The teaching activity is assembled within a toolkit which includes the following: (1) instructor lesson plan; (2) interactive PowerPoint presentation with instructor notes; (3) field assignment description; (4) health literacy attribute assessment worksheets; and (5) grading rubric. The teaching tool was pilot tested by a student research team member to assess the educational value and assignment logistics, resulting in minor edits (i.e., addition of interviewer probes, and option of a group project-format to permit triangulation of multiple organizational interviews). Conclusion The field of MCH is expanding in complexity, and the demands of health systems on women, children, and families must be mediated by conscious efforts within organizations. Through teaching the importance and function of organizational health literacy to students in MCH, educators can prepare an emerging workforce to improve health literacy, and ultimately the quality of healthcare for women, children, and families.
PMID: 30600522 [PubMed - as supplied by publisher]
NIST interlaboratory studies involving DNA mixtures (MIX13): A modern analysis.
Forensic Sci Int Genet. 2018 11;37:172-179
Authors: Buckleton JS, Bright JA, Cheng K, Budowle B, Coble MD
MIX13 was an interlaboratory exercise directed by NIST in 2013. The goal of the exercise was to evaluate the general state of interpretation methods in use at the time across the forensic community within the US and Canada and to measure the consistency in mixture interpretation. The findings were that there was a large variation in analysts' interpretations between and within laboratories. Within this work, we sought to evaluate the same mock mixture cases analyzed in MIX13 but with a more current view of the state-of-the-science. Each of the five cases were analyzed using the Identifiler™ multiplex and interpreted with the combined probability of inclusion, CPI, and four different modern probabilistic genotyping systems. Cases 1-4 can be interpreted without difficulty by any of the four PG systems examined. Cases 1 and 4 could also be interpreted successfully with the CPI by assuming two donors. Cases 2 and 3 cannot be interpreted successfully with the CPI because of potential of allele dropout. Case 3 demonstrated the need to consider relevant background information before interpretation of the profile. This case does not show that there is some barrier to interpretation caused by relatedness beyond the increased allelic overlap that can occur. Had this profile been of better template it might have been interpreted using the CPI despite the (potential) relatedness of contributors. Case 5 suffers from over-engineering. It is unclear whether reference 5C, a non-donor, can be excluded by manual methods. Inclusion of reference 5C should be termed an adventitious match not a false inclusion. Beyond this statement this case does not contribute to the interlaboratory study of analyst/laboratory interpretation method performance, instead, it explores the limits of DNA analysis. Taken collectively the analysis of these five cases demonstrates the benefits of changing from CPI to a PG system.
PMID: 30176439 [PubMed - indexed for MEDLINE]
Potential highly polymorphic short tandem repeat markers for enhanced forensic identity testing.
Forensic Sci Int Genet. 2018 11;37:162-171
Authors: Novroski NMM, Woerner AE, Budowle B
Due to their polymorphic nature, short tandem repeats (STRs) are well-studied and routinely used genetic markers for forensic DNA typing. However, even the largest STR multiplexes are limited in their ability to parse out individuals in a DNA mixture sample, due to alleles shared by size detected by capillary electrophoresis and challenges in resolving minor alleles from stutter, and inherent heterozygote imbalance. In this study, STRs were explored in public datasets that displayed sequence variation and may have limited allele length spread. STRs were first selected using fundamental criteria of high heterozygosity, tetra-, penta-, or hexanucleotide repeat length, and overall relative narrow allele spread (based on length). All candidates were further scrutinized for chemistry compatibility. The resulting STRs were multiplexed and sequenced by massively parallel sequencing in a limited sample population set. Each candidate STR was evaluated for analytical performance and desired biological properties. The findings presented describe a refined set of 53 potential highly polymorphic STR markers (high sequence diversity and heterozygosity; reduced allele spread) that may be suitable to supplement the current core marker set(s) for possible enhanced characterization of complex DNA profiles.
PMID: 30176438 [PubMed - indexed for MEDLINE]
Ischemic and hypoxic conditioning: Potential for protection of vital organs.
Exp Physiol. 2018 Dec 31;:
Authors: Sprick JD, Mallet RT, Przyklenk K, Rickards CA
NEW FINDINGS: What is the topic of this review? Paradoxically, ischemic and hypoxic conditioning paradigms protect vital organs from ischemic and hypoxic injury. In this Symposium Report, we focus on remote ischemic preconditioning (RIPC) and hypoxic preconditioning as novel therapeutic approaches for cardiac- and neuro-protection. What advances does it highlight? Growing interest in ischemic and hypoxic preconditioning has facilitated improved understanding of associated mechanisms and signaling pathways, and identified potential pitfalls with application of these therapies to clinical trials. Novel adaptations of preconditioning paradigms have also been developed, including intermittent hypoxia training, RIPC training, and RIPC-exercise, extending their utility to chronic settings.
ABSTRACT: Myocardial infarction and stroke remain leading causes of death worldwide, despite extensive resources directed towards developing effective treatments. In this Symposium Report we highlight the potential applications of intermittent ischemic and hypoxic conditioning protocols to combat the deleterious consequences of heart and brain ischemia. Insights into mechanisms underlying the protective effects of intermittent hypoxia training (IHT) are discussed, including the activation of hypoxia-inducible factor-1 and Nrf2 transcription factors, synthesis of antioxidant and ATP-generating enzymes, and a shift in microglia from pro- to anti-inflammatory phenotypes. Although there is little argument regarding the efficacy of remote ischemic preconditioning (RIPC) in pre-clinical models, this strategy has not consistently translated into the clinical arena. This lack of translation may be related to the patient populations targeted thus far, and the anesthetic regimen used in two of the major RIPC clinical trials. Additionally, we do not fully understand the mechanism through which RIPC protects the vital organs, and co-morbidities (e.g., hypercholesterolemia, diabetes) may interfere with its efficacy. Finally, novel adaptations have been made to extend RIPC to more chronic settings. One adaptation is RIPC-exercise (RIPC-X), an innovative paradigm that applies cyclical RIPC to blood flow restriction exercise (BFRE). Recent findings suggest that this novel exercise modality attenuates the exaggerated hemodynamic responses that may limit the use of conventional BFRE in some clinical settings. Collectively, intermittent ischemic and hypoxic conditioning paradigms remain an exciting frontier for the protection against ischemic injuries. This article is protected by copyright. All rights reserved.
PMID: 30597638 [PubMed - as supplied by publisher]
Failed Early Intervention of Pyomyositis in an Immunocompetent Individual.
Case Rep Infect Dis. 2018;2018:4296976
Authors: Al-Dossari R, Zekri S
Pyomyositis is a purulent infection of striated muscle tissue that usually leads to an abscess, commonly due to S. aureus. Pyomyositis is typically found in tropic regions, but it is increasingly being recognized in temperate climates, especially in immunocompromised individuals. Patient presentation ranges from afebrile with mildly elevated WBC to frank sepsis. In many reported cases, patients may develop multiple abscesses at different sites. We report a case of a 54-year-old male with a history of chronic obstructive pulmonary disease (COPD) presenting with right pectoral infection. This case demonstrates the possibility that antibiotic therapy in early presentations may not effectively prevent abscess formation, contrary to treatment suggestions found in the literature.
PMID: 30595930 [PubMed]
Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice.
Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice.
Sci Rep. 2017 06 23;7(1):4145
Authors: Li W, Ding Y, Smedley C, Wang Y, Chaudhari S, Birnbaumer L, Ma R
The present study was conducted to determine if TRPC6 regulates glomerular filtration rate (GFR) and the contractile function of glomerular mesangial cells (MCs). GFR was assessed in conscious TRPC6 wild type and knockout mice, and in anesthetized rats with and without in vivo knockdown of TRPC6 in kidneys. We found that GFR was significantly greater, and serum creatinine level was significantly lower in TRPC6 deficient mice. Consistently, local knockdown of TRPC6 in kidney using TRPC6 specific shRNA construct significantly attenuated Ang II-induced GFR decline in rats. Furthermore, Ang II-stimulated contraction and Ca2+ entry were significantly suppressed in primary MCs isolated from TRPC6 deficient mice, and the Ca2+ response could be rescued by re-introducing TRPC6. Moreover, inhibition of reverse mode of Na+-Ca2+ exchange by KB-R7943 significantly reduced Ca2+ entry response in TRPC6-expressing, but not in TRPC6-knocked down MCs. Ca2+ entry response was also significantly attenuated in Na+ free solution. Single knockdown of TRPC6 and TRPC1 resulted in a comparable suppression on Ca2+ entry with double knockdown of both. These results suggest that TRPC6 may regulate GFR by modulating MC contractile function through multiple Ca2+ signaling pathways.
PMID: 28646178 [PubMed - indexed for MEDLINE]