Recent Research Publications- September 2023
Well-being and stress vulnerability in ovarian cancer survivors during the COVID-19 pandemic.
Telles R, Zia S, Greteman B, Thaker P, Penedo F, Charlton M, Goodheart M, Armer J, Noble A, Sood A, Lutgendorf S.
J Psychosoc Oncol. 2023 Aug 17:1-16. doi: 10.1080/07347332.2023.2244474. Epub ahead of print. PMID: 37587850.
- This study was designed to examine (1) whether ovarian cancer (OC) survivors would have greater well-being vs. elevated distress compared to community members during a universal health stressor (COVID-19) and (2) how resources and risk factors at diagnosis predicted vulnerability to a subsequent health-related stressor.
Methods: One hundred seventeen OC survivors were recruited from two academic medical centers and compared to a community-based sample on COVID-related distress and disruption. Latent class analysis identified differentially impacted groups of survivors.
Results: Survivors reported lower distress than community members. Predictors of higher distress included shorter-term survivorship, greater disruption, and poorer emotional well--being (EWB) at diagnosis. Survivors were divided into high- and low-COVID-19-impact subgroups; high-impact individuals endorsed higher perceived stress and lower EWB at diagnosis.
Conclusion: Survivors reported lower COVID-related distress than community participants. While depression at diagnosis did not predict later distress, EWB was a strong predictor of response to a novel health-related stressor.
Ewald JT, Steinbrekera B, Bermick JR, Santillan DA, Colaizy TT, Santillan MK, Roghair RD.
Pediatr Rep. 2023 Aug 10;15(3):483-493. doi: 10.3390/pediatric15030044. PMID: 37606448; PMCID: PMC10443264.
Preterm delivery can be precipitated by preeclampsia or infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (clinical chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. Independent of gestational age, MCP-1 was significantly increased (p < 0.001) in association with maternal preeclampsia, but MCP-1 was decreased (p < 0.01), and CRP was increased (p < 0.01) in the presence of chorioamnionitis with funisitis. IL-6 and CRP were both increased in infants diagnosed with postnatal infection, with peak levels observed on days 2 and 3, respectively. In conclusion, suspected prenatal and postnatal infections and non-infectious complications of pregnancy are associated with unique biomarker profiles, independent of gestational age, including over a 2-fold increase in MCP-1 among newborns of mothers with preeclampsia. Further, in those clinically diagnosed with a postnatal infection in the absence of antenatal infection concerns, IL-6 increases before CRP, emphasizing a potential role for expanded biomarker screening if antibiotics are initially avoided in infants delivered for maternal indications.
Schrodt MV, Behan-Bush RM, Liszewski JN, Humpal-Pash ME, Boland LK, Scroggins SM, Santillan DA, Ankrum JA.
Stem Cell Res Ther. 2023 Aug 17;14(1):206. doi: 10.1186/s13287-023-03443-z. PMID: 37592321; PMCID: PMC10433682.
- Immunomodulation by mesenchymal stromal cells (MSCs) can occur through trophic factor mechanisms, however, intravenously infused MSCs are rapidly cleared from the body yet a potent immunotherapeutic response is still observed. Recent work suggests that monocytes contribute to the clearance of MSCs via efferocytosis, the body's natural mechanism for clearing dead and dying cells in a non-inflammatory manner. This begs the questions of how variations in MSC quality affect monocyte phenotype and if viable MSCs are even needed to elicit an immunosuppressive response.
- Herein, we sought to dissect MSC's trophic mechanism from their efferocytic mechanisms and determine if the viability of MSCs prior to efferocytosis influences the resultant phenotype of monocytes. We cultured viable or heat-inactivated human umbilical cord MSCs with human peripheral blood mononuclear cells for 24 h and observed changes in monocyte surface marker expression and secretion profile. To isolate the effect of efferocytosis from MSC trophic factors, we used cell separation techniques to remove non-efferocytosed MSCs before challenging monocytes to suppress T-cells or respond to inflammatory stimuli. For all experiments, viable and heat-inactivated efferocytic-licensing of monocytes were compared to non-efferocytic-licensing control.
- We found that monocytes efferocytose viable and heat-inactivated MSCs equally, but only viable MSC-licensed monocytes suppress activated T-cells and suppression occurred even after depletion of residual MSCs. This provides direct evidence that monocytes that efferocytose viable MSCs are immunosuppressive. Further characterization of monocytes after efferocytosis showed that uptake of viable-but not heat inactivated-MSC resulted in monocytes secreting IL-10 and producing kynurenine. When monocytes were challenged with LPS, IL-2, and IFN-γ to simulate sepsis, monocytes that had efferocytosed viable MSC had higher levels of IDO while monocytes that efferocytosed heat inactivated-MSCs produced the lowest levels of TNF-α.
- : Collectively, these studies show that the quality of MSCs efferocytosed by monocytes polarize monocytes toward distinctive immunosuppressive phenotypes and highlights the need to tailor MSC therapies for specific indications.
Synan L, Ghazvini S, Uthaman S, Cutshaw G, Lee CY, Waite J, Wen X, Sarkar S, Lin E, Santillan M, Santillan D, Bardhan R
ACS Appl Mater Interfaces. 2023 Aug 7. doi: 10.1021/acsami.3c04260. Epub ahead of print. PMID: 37549133.
Preterm birth (PTB) is the leading cause of infant deaths globally. Current clinical measures often fail to identify women who may deliver preterm. Therefore, accurate screening tools are imperative for early prediction of PTB. Here, we show that Raman spectroscopy is a promising tool for studying biological interfaces, and we examine differences in the maternal metabolome of the first trimester plasma of PTB patients and those that delivered at term (healthy). We identified fifteen statistically significant metabolites that are predictive of the onset of PTB. Mass spectrometry metabolomics validates the Raman findings identifying key metabolic pathways that are enriched in PTB. We also show that patient clinical information alone and protein quantification of standard inflammatory cytokines both fail to identify PTB patients. We show for the first time that synergistic integration of Raman and clinical data guided with machine learning results in an unprecedented 85.1% accuracy of risk stratification of PTB in the first trimester that is currently not possible clinically. Correlations between metabolites and clinical features highlight the body mass index and maternal age as contributors of metabolic rewiring. Our findings show that Raman spectral screening may complement current prenatal care for early prediction of PTB, and our approach can be translated to other patient-specific biological interfaces.
Breastfeeding Benefits both the Parent and the Baby.
Goodrich A.
Iowa Corridor Breastfeeding Coalition, 15 August 2023. BLOG
In preparing for the birth of your baby, you will hear about different ways that the baby can be fed. While formula is a suitable alternative for families who are not able or do not desire to breastfeed (or chest feed), it is important to acknowledge that breastfeeding benefits both the baby and the nursing person in ways that formula is not able to.
Ghazvini S, Uthaman S, Synan L, Lin EC, Sarkar S Santillan MK, Santillan DA, Bardhan R.
Bioeng Transl Med. 2023;e10595. doi:10.1002/btm2.10595.
Preeclampsia is a life-threatening pregnancy disorder. Current clinical assays cannot predict the onset of preeclampsia until the late 2nd trimester, which often leads to poor maternal and neonatal outcomes. Here we show that Raman spectroscopy combined with machine learning in pregnant patient plasma enables rapid, highly sensitive maternal metabolome screening that predicts preeclampsia as early as the 1st trimester with >82% accuracy. We identified 12, 15 and 17 statistically significant metabolites in the 1st, 2nd and 3rd trimesters, respectively. Metabolic pathway analysis shows multiple pathways corresponding to amino acids, fatty acids, retinol, and sugars are enriched in the preeclamptic cohort relative to a healthy pregnancy. Leveraging Pearson's correlation analysis, we show for the first time with Raman Spectroscopy that metabolites are associated with several clinical factors, including patients' body mass index, gestational age at delivery, history of preeclampsia, and severity of preeclampsia. We also show that protein quantification alone of proinflammatory cytokines and clinically relevant angiogenic markers are inadequate in identifying at-risk patients. Our findings demonstrate that Raman spectroscopy is a powerful tool that may complement current clinical assays in early diagnosis and in the prognosis of the severity of preeclampsia to ultimately enable comprehensive prenatal care for all patients.