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UNC-authored articles published by MDPI
Works (441)
51. Postural Control Measurements to Predict Future Motor Impairment in Preterm Infants: A Systematic Review
- Title Tesim:
- Postural Control Measurements to Predict Future Motor Impairment in Preterm Infants: A Systematic Review
- Creator:
- McCarty, Dana B., LeBlond, Kristen D., Bosserman, Jennifer, Kelkar, Sonia, and Cassidy, Jessica
- Date of publication:
- 2023
- Abstract Tesim:
- Preterm infants are more likely to demonstrate developmental delays than fullterm infants. Postural measurement tools may be effective in measuring the center of pressure (COP) and asymmetry, as well as predicting future motor impairment. The objective of this systematic review was to evaluate existing evidence regarding use of pressure mats or force plates for measuring COP and asymmetry in preterm infants, to determine how measures differ between preterm and fullterm infants and if these tools appropriately predict future motor impairment. The consulted databases included PubMed, Embase, Scopus, and CINAHL. The quality of the literature and the risk of bias were assessed utilizing the ROB2: revised Cochrane risk-of bias tool. Nine manuscripts met the criteria for review. The postural control tools included were FSA UltraThin seat mat, Conformat Pressure-Sensitive mat, Play and Neuro-Developmental Assessment, and standard force plates. Studies demonstrated that all tools were capable of COP assessment in preterm infants and support the association between the observation of reduced postural complexity prior to the observation of midline head control as an indicator of future motor delay. Postural measurement tools provide quick and objective measures of postural control and asymmetry. Based on the degree of impairment, these tools may provide an alternative to standardized assessments that may be taxing to the preterm infant, inaccessible to therapists, or not sensitive enough to capture motor delays.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Health Sciences
- DOI:
- https://doi.org/10.17615/5yqy-m937
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3390/diagnostics13223473
- ISSN:
- 2075-4418
- Journal Issue:
- 22
- Journal Title:
- Diagnostics
- Journal Volume:
- 13
- Keyword:
- center of pressure, preterm infant, postural measurement, postural control, and force plate
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- , Duke Health, and Johns Hopkins Hospital
- Page Start:
- 3473
- Person:
- McCarty, Dana B., LeBlond, Kristen D., Bosserman, Jennifer, Kelkar, Sonia, and Cassidy, Jessica
- Publisher:
- MDPI
- Rights Statement Label:
- In Copyright
- Source:
- baa88845-d392-412f-91d8-70fc1c9ca1c7
52. Oleic Acid Exhibits Anti-Proliferative and Anti-Invasive Activities via the PTEN/AKT/mTOR Pathway in Endometrial Cancer
- Title Tesim:
- Oleic Acid Exhibits Anti-Proliferative and Anti-Invasive Activities via the PTEN/AKT/mTOR Pathway in Endometrial Cancer
- Creator:
- Newton, Meredith A., Shen, Xiaochang, John, Catherine, Deng, Boer, Hao, Tianran, Suo, Hongyan, Zhou, Chunxiao, Zhang, Xin, Kong, Weimin, Zhao, Ziyi, Burkett, Wesley C., Bae-Jump, Victoria L., Fan, Yali, and Sun, Wenchuan
- Date of publication:
- 2023
- Abstract Tesim:
- Reprogramming of fatty acid metabolism promotes cell growth and metastasis through a variety of processes that stimulate signaling molecules, energy storage, and membrane biosynthesis in endometrial cancer. Oleic acid is one of the most important monounsaturated fatty acids in the human body, which appears to have both pro- and anti-tumorigenic activities in various pre-clinical models. In this study, we evaluated the potential anti-tumor effects of oleic acid in endometrial cancer cells and the LKB1fl/flp53fl/fl mouse model of endometrial cancer. Oleic acid increased lipogenesis, inhibited cell proliferation, caused cell cycle G1 arrest, induced cellular stress and apoptosis, and suppressed invasion in endometrial cancer cells. Targeting of diacylglycerol acyltransferases 1 and 2 effectively increased the cytotoxicity of oleic acid. Moreover, oleic acid significantly increased the expression of wild-type PTEN, and knockdown of PTEN by shRNA partially reversed the anti-proliferative and anti-invasive effects of oleic acid. Inhibition of the AKT/mTOR pathway by ipatasertib effectively increased the anti-tumor activity of oleic acid in endometrial cancer cells. Oleic acid treatment (10 mg/kg, daily, oral) for four weeks significantly inhibited tumor growth by 52.1% in the LKB1fl/flp53fl/fl mice. Our findings demonstrated that oleic acid exhibited anti-tumorigenic activities, dependent on the PTEN/AKT/mTOR signaling pathway, in endometrial cancer.
- Resource type:
- Article
- Affiliation Label Tesim:
- University of North Carolina at Chapel Hill
- DOI:
- https://doi.org/10.17615/zsss-bh04
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3390/cancers15225407
- ISSN:
- 2072-6694
- Journal Issue:
- 22
- Journal Title:
- Cancers
- Journal Volume:
- 15
- Keyword:
- lipid droplets, PTEN/AKT pathway, endometrial cancer, invasion, cell proliferation, and oleic acid
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- and University of North Carolina at Chapel Hill
- Page Start:
- 5407
- Person:
- Newton, Meredith A., Shen, Xiaochang, John, Catherine, Deng, Boer, Hao, Tianran, Suo, Hongyan, Zhou, Chunxiao, Zhang, Xin, Kong, Weimin, Zhao, Ziyi, Burkett, Wesley C., Bae-Jump, Victoria L., Fan, Yali, and Sun, Wenchuan
- Publisher:
- MDPI
- Rights Statement Label:
- In Copyright
- Source:
- fa950164-9f1b-46b3-aff3-74ca45753810
53. High Fat Diet-Induced Obesity Dysregulates Splenic B Cell Mitochondrial Activity
- Title Tesim:
- High Fat Diet-Induced Obesity Dysregulates Splenic B Cell Mitochondrial Activity
- Creator:
- Benson, Emily, Lin, Chien-Te, Boykov, Ilya, Shaikh, Saame Raza, Neufer, P. Darrell, Kidd, Grahame, Pal, Anandita, and Fisher-Wellman, Kelsey H.
- Date of publication:
- 2023
- Abstract Tesim:
- Diet-induced obesity impairs mitochondrial respiratory responses in tissues that are highly metabolically active, such as the heart. However, less is known about the impact of obesity on the respiratory activity of specific cell types, such as splenic B cells. B cells are of relevance, as they play functional roles in obesity-induced insulin resistance, inflammation, and responses to infection. Here, we tested the hypothesis that high-fat-diet (HFD)-induced obesity could impair the mitochondrial respiration of intact and permeabilized splenic CD19+ B cells isolated from C57BL/6J mice and activated ex vivo with lipopolysaccharide (LPS). High-resolution respirometry was used with intact and permeabilized cells. To reveal potential mechanistic targets by which HFD-induced obesity dysregulates B cell mitochondria, we conducted proteomic analyses and 3D serial block face scanning electron microscopy (SBFEM). High-resolution respirometry revealed that intact LPS-stimulated B cells of obese mice, relative to controls, displayed lower ATP-linked, as well as maximal uncoupled, respiration. To directly investigate mitochondrial function, we used permeabilized LPS-stimulated B cells, which displayed increased H2O2 emission and production with obesity. We also examined oxidative phosphorylation efficiency simultaneously, which revealed that oxygen consumption and ATP production were decreased in LPS-stimulated B cells with obesity relative to controls. Despite minimal changes in total respiratory complex abundance, in LPS-stimulated B cells of obese mice, three of the top ten most downregulated proteins were all accessory subunits of respiratory complex I. SBFEM showed that B cells of obese mice, compared to controls, underwent no change in mitochondrial cristae integrity but displayed increased mitochondrial volume that was linked to bioenergetic function. Collectively, these results establish a proof of concept that HFD-induced obesity dysregulates the mitochondrial bioenergetic metabolism of activated splenic B cells.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Nutrition
- DOI:
- https://doi.org/10.17615/ws2r-qg85
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3390/nu15224807
- ISSN:
- 2072-6643
- Journal Issue:
- 22
- Journal Title:
- Nutrients
- Journal Volume:
- 15
- Keyword:
- high fat diet, obesity, proteome, mitochondria, and B cells
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- Cleveland Clinic, East Carolina University, and
- Page Start:
- 4807
- Person:
- Benson, Emily, Lin, Chien-Te, Boykov, Ilya, Shaikh, Saame Raza, Neufer, P. Darrell, Kidd, Grahame, Pal, Anandita, and Fisher-Wellman, Kelsey H.
- Publisher:
- MDPI
- Rights Statement Label:
- In Copyright
- Source:
- f577d5d6-1916-41a7-a8ea-9e574714806e
54. CK2 Chemical Probes: Past, Present, and Future
- Title Tesim:
- CK2 Chemical Probes: Past, Present, and Future
- Creator:
- Ong, Han Wee, Axtman, Alison D., and Drewry, David H.
- Date of publication:
- 2023
- Abstract Tesim:
- Protein kinase casein kinase 2 (CK2/CSNK2) is a pleiotropic kinase involved in many cellular processes and, accordingly, has been identified as a potential target for therapeutic intervention for multiple indications. Significant research effort has been invested into identifying CK2 inhibitors as potential drug candidates and potent and selective CK2 chemical probes to interrogate CK2 function. Here, we review the small molecule inhibitors reported for CK2 and discuss various orthosteric, allosteric, and bivalent inhibitors of CK2. We focus on the pyrazolo[1,5-a]pyrimidines and naphthyridines, two chemotypes that have been extensively explored for chemical probe development. We highlight the uptake and demonstrated utility of the pyrazolo[1,5-a]pyrimidine chemical probe SGC-CK2-1 by the scientific community in cellular studies. Finally, we propose criteria for an ideal in vivo chemical probe for investigating CK2 function in a living organism. While no compound currently meets these metrics, we discuss ongoing and future directions in the development of in vivo chemical probes for CK2.
- Resource type:
- Article
- Affiliation Label Tesim:
- Eshelman School of Pharmacy
- DOI:
- https://doi.org/10.17615/3pwm-nv66
- Edition:
- Publisher
- Identifier:
- https://doi.org/10.3390/kinasesphosphatases1040017
- ISSN:
- 2813-3757
- Journal Issue:
- 4
- Journal Title:
- Kinases and Phosphatases
- Journal Volume:
- 1
- Keyword:
- allosteric, CSNK2A2, naphthyridine, pyrazolopyrimidine, protein kinase CK2, CSNK2A1, chemical probe, bivalent, and orthosteric
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- Other Affiliation:
- Page End:
- 305
- Page Start:
- 288
- Person:
- Ong, Han Wee, Axtman, Alison D., and Drewry, David H.
- Publisher:
- MDPI
- Rights Statement Label:
- In Copyright
- Source:
- 26d8d291-62a7-4a9f-a07f-84277f38aedb
55. Vaping-Induced Proteolysis Causes Airway Surface Dehydration
- Title Tesim:
- Vaping-Induced Proteolysis Causes Airway Surface Dehydration
- Creator:
- Alexis, Neil E., Tarran, Robert, Coakley, Raymond D., and Ghosh, Arunava
- Date of publication:
- 2023
- Abstract Tesim:
- Proteases such as neutrophil elastase cleave and activate the epithelial sodium channel (ENaC), causing airway dehydration. Our current study explores the impact of increased protease levels in vapers’ airways on ENaC activity and airway dehydration. Human bronchial epithelial cultures (HBECs) were exposed to bronchoalveolar lavage fluid (BALF) from non-smokers, smokers and vapers. Airway surface liquid (ASL) height was measured by confocal microscopy as a marker of hydration. ENaC cleavage was measured by Western blotting. Human peripheral blood neutrophils were treated with a menthol-flavored e-liquid (Juul), and the resulting secretions were added to HBECs. BALF from smokers and vapers significantly and equally increased ENaC activity and decreased ASL height. The ASL height decrease was attenuated by protease inhibitors. Non-smokers’ BALF had no effect on ENaC or ASL height. BALF from smokers and vapers, but not non-smokers, induced ENaC cleavage. E-liquid-treated neutrophil secretions cleaved ENaC and decreased ASL height. Our study demonstrated that elevated protease levels in vapers’ airways have functional significance since they can activate ENaC, resulting in airway dehydration. Lung dehydration contributes to diseases like cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and asthma. Thus, our data predict that vaping, like smoking, will cause airway surface dehydration that likely leads to lung disease.
- Resource type:
- Article
- Affiliation Label Tesim:
- Center for Environmental Medicine, Asthma and Lung Biology, Marsico Lung Institute/UNC Cystic Fibrosis Center, and Department of Cell Biology and Physiology
- DOI:
- https://doi.org/10.17615/e0s0-7d45
- Edition:
- Publisher
- Identifier:
- https://dx.doi.org/10.3390/ijms242015348
- ISSN:
- 1422-0067
- Journal Issue:
- 20
- Journal Title:
- International Journal of Molecular Sciences
- Journal Volume:
- 24
- Keyword:
- ENaC, bronchoalveolar lavage fluid, airway surface liquid, e-cigarettes, menthol, and elastase
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- ORCID:
- Other Affiliation:
- and Kansas University Medical Center
- Page Start:
- 15348
- Person:
- Alexis, Neil E., Tarran, Robert, Coakley, Raymond D., and Ghosh, Arunava
- Publisher:
- MDPI
- Source:
- 9acf345c-27ae-4a4a-ac89-97411e4df613
56. The Performance of Flash Replenishment Contrast-Enhanced Ultrasound for the Qualitative Assessment of Kidney Lesions in Patients with Chronic Kidney Disease
- Title Tesim:
- The Performance of Flash Replenishment Contrast-Enhanced Ultrasound for the Qualitative Assessment of Kidney Lesions in Patients with Chronic Kidney Disease
- Creator:
- Kasoji, Sandeep K., Dayton, Paul A., Radhakrishna, Roshni, Chang, Emily H., Altun, Ersan, Qaqish, Bahjat, Sridharan, Anush, Rathmell, W. Kimryn, Walmer, Rachel W., Johnson, Kennita A., Wagner, Sean, Olinger, Kristen, Ritter, Victor S., and Lee, Ellie
- Date of publication:
- 2023
- Abstract Tesim:
- We investigated the accuracy of CEUS for characterizing cystic and solid kidney lesions in patients with chronic kidney disease (CKD). Cystic lesions are assessed using Bosniak criteria for computed tomography (CT) and magnetic resonance imaging (MRI); however, in patients with moderate to severe kidney disease, CT and MRI contrast agents may be contraindicated. Contrast-enhanced ultrasound (CEUS) is a safe alternative for characterizing these lesions, but data on its performance among CKD patients are limited. We performed flash replenishment CEUS in 60 CKD patients (73 lesions). Final analysis included 53 patients (63 lesions). Four readers, blinded to true diagnosis, interpreted each lesion. Reader evaluations were compared to true lesion classifications. Performance metrics were calculated to assess malignant and benign diagnoses. Reader agreement was evaluated using Bowker’s symmetry test. Combined reader sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing malignant lesions were 71%, 75%, 45%, and 90%, respectively. Sensitivity (81%) and specificity (83%) were highest in CKD IV/V patients when grouped by CKD stage. Combined reader sensitivity, specificity, PPV, and NPV for diagnosing benign lesions were 70%, 86%, 91%, and 61%, respectively. Again, in CKD IV/V patients, sensitivity (81%), specificity (95%), and PPV (98%) were highest. Inter-reader diagnostic agreement varied from 72% to 90%. In CKD patients, CEUS is a potential low-risk option for screening kidney lesions. CEUS may be particularly beneficial for CKD IV/V patients, where kidney preservation techniques are highly relevant.
- Resource type:
- Article
- Affiliation Label Tesim:
- Joint Department of Biomedical Engineering, Department of Medicine, Department of Radiology, and Department of Biostatistics
- DOI:
- https://doi.org/10.17615/pgsg-8v82
- Edition:
- Publisher
- Identifier:
- https://dx.doi.org/10.3390/jcm12206494
- ISSN:
- 2077-0383
- Journal Issue:
- 20
- Journal Title:
- Journal of Clinical Medicine
- Journal Volume:
- 12
- Keyword:
- kidney lesions, contrast-enhanced ultrasound, screening tool, performance metrics, and chronic kidney disease
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- ORCID:
- Other Affiliation:
- and Vanderbilt University
- Page Start:
- 6494
- Person:
- Kasoji, Sandeep K., Dayton, Paul A., Radhakrishna, Roshni, Chang, Emily H., Altun, Ersan, Qaqish, Bahjat, Sridharan, Anush, Rathmell, W. Kimryn, Walmer, Rachel W., Johnson, Kennita A., Wagner, Sean, Olinger, Kristen, Ritter, Victor S., and Lee, Ellie
- Publisher:
- MDPI
- Source:
- 7869ed3c-b94b-4cf2-9cfb-0abee35a4b99
57. Safety, Efficacy, and Ill Intent: Examining COVID-19 Vaccine Perceptions among the New Undervaccinated Moveable Middle in a U.S. Cohort, October 2022
- Title Tesim:
- Safety, Efficacy, and Ill Intent: Examining COVID-19 Vaccine Perceptions among the New Undervaccinated Moveable Middle in a U.S. Cohort, October 2022
- Creator:
- Fleary, Sasha A., Stanton, Eva, Parcesepe, Angela M., Piltch-Loeb, Rachael, Shen, Yanhan, Nash, Denis, and Penrose, Kate
- Date of publication:
- 2023
- Abstract Tesim:
- Individuals who received their primary vaccine series only (with no subsequent booster) may be a new type of “moveable middle” given their receipt of the original COVID-19 vaccination. One population within the moveable middle for whom tailored interventions may be needed is individuals with common mental disorders (CMD). The purpose of this paper is to understand the vaccine perceptions among this new moveable middle—the undervaccinated—and within the undervaccinated to examine the extent to which COVID-19 vaccine perceptions and motivations differ among those with and without symptoms of CMD. Using data from the CHASING COVID Cohort, we examine the relationship between vaccination status, CMD, and vaccine perceptions in the undervaccinated. Among 510 undervaccinated participants who had completed the primary vaccine series but were not boosted, the most common reasons for undervaccination focused on efficacy (not seeing a need for an additional dose, 42.4%; there not being enough evidence that a booster dose is effective, 26.5%; already having had COVID-19, 19.6%). Other concerns were related to safety (long-term side effects, 21.0%; short-term side effects, 17.6%) and logistics (plan to get a booster but haven’t had time yet, 18.8%). Overall, the greatest vaccine concerns (over 30%) for the undervaccinated focused on efficacy and safety issues. Symptoms of depression or anxiety were associated with lower levels of vaccine efficacy and greater safety concerns in adjusted models. The implications of our study are that campaigns that are hoping to maximize vaccination uptake should consider focusing on and emphasizing messaging on efficacy and safety issues.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Maternal and Child Health
- DOI:
- https://doi.org/10.17615/hrkm-gk35
- Edition:
- Publisher
- Identifier:
- https://dx.doi.org/10.3390/vaccines11111665
- ISSN:
- 2076-393X
- Journal Issue:
- 11
- Journal Title:
- Vaccines
- Journal Volume:
- 11
- Keyword:
- undervaccinated, safety, efficacy, COVID-19, and vaccine hesitancy
- Language Label:
- English
- License Label:
- Attribution-NonCommercial-NoDerivs 4.0 International
- ORCID:
- Other Affiliation:
- City University of New York, Harvard T.H. Chan School of Public Health, and
- Page Start:
- 1665
- Person:
- Fleary, Sasha A., Stanton, Eva, Parcesepe, Angela M., Piltch-Loeb, Rachael, Shen, Yanhan, Nash, Denis, and Penrose, Kate
- Publisher:
- MDPI
- Source:
- 1c89103d-8e6c-44dd-91c7-e76d261d02e0
58. Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age
- Title Tesim:
- Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age
- Creator:
- Roell K., O’Shea T.M., Engwall E., Mills C.A., Kuban K.C.K., Bulka C., Parsons P.J., Galusha A., Fry R.C., Freedman A.N., and Herring L.
- Date of publication:
- 2023
- Abstract Tesim:
- Prenatal exposure to toxic metals is associated with altered placental function and adverse infant and child health outcomes. Adverse outcomes include those that are observed at the time of birth, such as low birthweight, as well as those that arise later in life, such as neurological impairment. It is often the case that these adverse outcomes show sex-specific responses in relation to toxicant exposures. While the precise molecular mechanisms linking in utero toxic metal exposures with later-in-life health are unknown, placental inflammation is posited to play a critical role. Here, we sought to understand whether in utero metal exposure is associated with alterations in the expression of the placental proteome by identifying metal associated proteins (MAPs). Within the Extremely Low Gestational Age Newborns (ELGAN) cohort (n = 230), placental and umbilical cord tissue samples were collected at birth. Arsenic (As), cadmium (Cd), lead (Pb), selenium (Se), and manganese (Mn) concentrations were measured in umbilical cord tissue samples via ICP-MS/MS. Protein expression was examined in placental samples using an LC-MS/MS-based, global, untargeted proteomics analysis measuring more than 3400 proteins. MAPs were then evaluated for associations with pregnancy and neonatal outcomes, including placental weight and gestational age. We hypothesized that metal levels would be positively associated with the altered expression of inflammation/immune-associated pathways and that sex-specific patterns of metal-associated placental protein expression would be observed. Sex-specific analyses identified 89 unique MAPs expressed in female placentas and 41 unique MAPs expressed in male placentas. Notably, many of the female-associated MAPs are known to be involved in immune-related processes, while the male-associated MAPs are associated with intracellular transport and cell localization. Further, several MAPs were significantly associated with gestational age in males and females and placental weight in males. These data highlight the linkage between prenatal metal exposure and an altered placental proteome, with implications for altering the trajectory of fetal development.
- Resource type:
- Article
- Affiliation Label Tesim:
- Gillings School of Global Public Health, Department of Pediatrics, Department of Environmental Sciences and Engineering, and Department of Pharmacology
- DOI:
- https://doi.org/10.17615/10wc-6648
- Edition:
- Publisher
- Identifier:
- https://dx.doi.org/10.3390/ijms241914977
- ISSN:
- 1661-6596
- Journal Issue:
- 19
- Journal Title:
- International Journal of Molecular Sciences
- Journal Volume:
- 24
- Keyword:
- proteomics, sexual dimorphism, umbilical cord tissue, preterm birth, metals, and placenta
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- ORCID:
- Other Affiliation:
- , Boston Medical Center, University of South Florida, and University of Albany
- Person:
- Roell K., O’Shea T.M., Engwall E., Mills C.A., Kuban K.C.K., Bulka C., Parsons P.J., Galusha A., Fry R.C., Freedman A.N., and Herring L.
- Publisher:
- Multidisciplinary Digital Publishing Institute (MDPI)
- Source:
- 59280bac-f632-4800-8a3d-f13ea45edd37
59. Organotypic 3D Cell-Architecture Impacts the Expression Pattern of miRNAs–mRNAs Network in Breast Cancer SKBR3 Cells
- Title Tesim:
- Organotypic 3D Cell-Architecture Impacts the Expression Pattern of miRNAs–mRNAs Network in Breast Cancer SKBR3 Cells
- Creator:
- Aguilar-Medina, Maribel, López-Camarillo, César, Romero-Quintana, Geovanni, Avendaño-Felix, Mariana, Pérez-Plascencia, Carlos, Beltrán, Adriana S., Bermúdez, Mercedes, López-Gutiérrez, Jorge, Ramos-Payán, Rosalío, Gastélum-López, María de los Ángeles, and García Mata, Cristina
- Date of publication:
- 2023
- Abstract Tesim:
- Background. Currently, most of the research on breast cancer has been carried out in conventional two-dimensional (2D) cell cultures due to its practical benefits, however, the three-dimensional (3D) cell culture is becoming the model of choice in cancer research because it allows cell–cell and cell–extracellular matrix (ECM) interactions, mimicking the native microenvironment of tumors in vivo. Methods. In this work, we evaluated the effect of 3D cell organization on the expression pattern of miRNAs (by Small-RNAseq) and mRNAs (by microarrays) in the breast cancer SKBR3 cell line and analyzed the biological processes and signaling pathways regulated by the differentially expressed protein-coding genes (DE-mRNAs) and miRNAs (DE-microRNAs) found in the organoids. Results. We obtained well-defined cell-aggregated organoids with a grape cluster-like morphology with a size up to 9.2 × 105 μm3. The transcriptomic assays showed that cell growth in organoids significantly affected (all p < 0.01) the gene expression patterns of both miRNAs, and mRNAs, finding 20 upregulated and 19 downregulated DE-microRNAs, as well as 49 upregulated and 123 downregulated DE-mRNAs. In silico analysis showed that a subset of 11 upregulated DE-microRNAs target 70 downregulated DE-mRNAs. These genes are involved in 150 gene ontology (GO) biological processes such as regulation of cell morphogenesis, regulation of cell shape, regulation of canonical Wnt signaling pathway, morphogenesis of epithelium, regulation of cytoskeleton organization, as well as in the MAPK and AGE–RAGE signaling KEGG-pathways. Interestingly, hsa-mir-122-5p (Fold Change (FC) = 15.4), hsa-mir-369-3p (FC = 11.4), and hsa-mir-10b-5p (FC = 20.1) regulated up to 81% of the 70 downregulated DE-mRNAs. Conclusion. The organotypic 3D cell-organization architecture of breast cancer SKBR3 cells impacts the expression pattern of the miRNAs–mRNAs network mainly through overexpression of hsa-mir-122-5p, hsa-mir-369-3p, and hsa-mir-10b-5p. All these findings suggest that the interaction between cell–cell and cell–ECM as well as the change in the culture architecture impacts gene expression, and, therefore, support the pertinence of migrating breast cancer research from conventional cultures to 3D models.
- Resource type:
- Article
- Affiliation Label Tesim:
- University of North Carolina at Chapel Hill
- DOI:
- https://doi.org/10.17615/gcpw-4p60
- Edition:
- Publisher
- Identifier:
- https://dx.doi.org/10.3390/ncrna9060066
- ISSN:
- 2311-553X
- Journal Issue:
- 6
- Journal Title:
- Non-Coding RNA
- Journal Volume:
- 9
- Keyword:
- breast cancer, microRNAs, organotypic 3D cell culture, 2D cell culture, and 3D cell culture
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- ORCID:
- Other Affiliation:
- Autonomous University of Sinaloa, Autonomous University of Mexico City, National Autonomous University of Mexico, , and Autonomous University of Chihuahua
- Page Start:
- 66
- Person:
- Aguilar-Medina, Maribel, López-Camarillo, César, Romero-Quintana, Geovanni, Avendaño-Felix, Mariana, Pérez-Plascencia, Carlos, Beltrán, Adriana S., Bermúdez, Mercedes, López-Gutiérrez, Jorge, Ramos-Payán, Rosalío, Gastélum-López, María de los Ángeles, and García Mata, Cristina
- Publisher:
- MDPI
- Source:
- 7ec4a2d9-0e71-485d-a549-d5823250dbb3
60. NBL1 Reduces Corneal Fibrosis and Scar Formation after Wounding
- Title Tesim:
- NBL1 Reduces Corneal Fibrosis and Scar Formation after Wounding
- Creator:
- Mei, Hua, Liu, Emily, Tsai, Chi-Hao, Lu, Krystal Lynn, and Phan, Andrew
- Date of publication:
- 2023
- Abstract Tesim:
- Corneal scarring is a leading cause of blindness. Currently, there is no treatment to prevent and/or reduce corneal scar formation under pathological conditions. Our previous data showed that the NBL1 protein, also termed the DAN Family BMP (Bone morphogenetic protein) Antagonist, was highly expressed in corneal stromal cells upon wounding. Here, we examined the function of NBL1 in corneal wound healing. Mouse corneas were mechanically wounded, followed by a 2-week treatment using NBL1. Wounded corneas treated with vehicle or an Fc tag served as controls. Compared with the controls, NBL1 treatment facilitated wound re-epithelialization, partially restored the stromal thickness, and significantly reduced corneal scar formation. NBL1 treatment did not decrease immune cell infiltration, indicating that the anti-scarring effect was not dependent on immune suppression. We further examined the anti-fibrotic effect of NBL1 on human corneas. Pairs of human corneas were induced to form myofibroblasts (a key player in fibrosis and scarring) upon wounding and incubation in a medium containing TGF-β1. The OS corneas were treated with Fc as a control, and the OD corneas were treated with NBL1. Compared with the control, human corneas treated with NBL1 had significantly fewer myofibroblasts, which was consistent with these mouse data. A further study revealed that NBL1 treatment inhibited BMP canonical (phospho-Smad1/5) and no-canonical (phospho-p38) pathways in human corneas. Data show that NBL1 reduced corneal fibrosis and scar formation in mice and cultured human corneas. The underlying molecular mechanism is not certain because both anti-fibrotic Smad1/5 and pro-fibrotic p38 pathways were inhibited upon NBL1 treatment. Whether the p38 pathway dominates the Smad1/5 pathway during corneal fibrosis, leading to the anti-fibrotic effect of NBL1, needs further investigation.
- Resource type:
- Article
- Affiliation Label Tesim:
- Department of Ophthalmology and Department of Psychology and Neuroscience
- DOI:
- https://doi.org/10.17615/43aq-p493
- Edition:
- Publisher
- Identifier:
- https://dx.doi.org/10.3390/biom13111570
- ISSN:
- 2218-273X
- Journal Issue:
- 11
- Journal Title:
- Biomolecules
- Journal Volume:
- 13
- Keyword:
- NBL1, corneal scar, corneal wound, and fibrosis
- Language Label:
- English
- License Label:
- Attribution 4.0 International
- ORCID:
- Other Affiliation:
- Page Start:
- 1570
- Person:
- Mei, Hua, Liu, Emily, Tsai, Chi-Hao, Lu, Krystal Lynn, and Phan, Andrew
- Publisher:
- MDPI
- Source:
- fe3941b6-bcef-41b6-90f2-10b1a69573f9
Collection Details
- Total items
-
441
- Size
-
unknown
- Date created
-
May 26, 2022