Browsing by Author "Panaitescu, Bogdan"

Now showing 1 - 11 of 11
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    A Protocol for Evaluating Vital Signs and Maternal-Fetal Parameters Using High-Resolution Ultrasound in Pregnant Mice
    (2020) Galaz, Jose; Romero, Roberto; Arenas-Hernandez, Marcia; Panaitescu, Bogdan; Garcia-Flores, Valeria; Gomez-Lopez, Nardhy
    Pregnancy is a unique physiological state in which two individuals coexist: the mother and the fetus. Disruption of maternal-fetal crosstalk leads to pregnancy and neonatal pathologies. Therefore, assessing maternal-fetal well-being is essential for understanding the physiological and pathological processes occurring during pregnancy. Herein, we provide a protocol that allows for the determination of body temperature, blood pressure, and the evaluation of uterine and umbilical arteries as well as maternal and fetal heart rate using high-resolution ultrasound in pregnant mice. For complete details on the use and execution of this protocol, please refer to Gomez-Lopez et al. (2020).
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    A single-cell atlas of murine reproductive tissues during preterm labor
    (2023) Garcia-Flores, Valeria; Romero, Roberto; Peyvandipour, Azam; Galaz, Jose; Pusod, Errile; Panaitescu, Bogdan; Miller, Derek; Xu, Yi; Tao, Li; Liu, Zhenjie; Tarca, Adi L.; Pique-Regi, Roger; Gomez-Lopez, Nardhy
    Preterm birth, the leading cause of perinatal morbidity and mortality worldwide, frequently results from the syndrome of preterm labor. The best-established causal link to preterm labor is intra-amniotic infection, which involves premature activation of the parturition cascade in the reproductive tissues. Herein, we utilize single-cell RNA sequencing (scRNA-seq) to generate a single-cell atlas of the murine uterus, decidua, and cervix in a model of infection-induced preterm labor. We show that preterm labor affects the transcriptomic profiles of specific immune and non-immune cell subsets. Shared and tissue-specific gene expression sig-natures are identified among affected cells. Determination of intercellular communications implicates spe-cific cell types in preterm labor-associated signaling pathways across tissues. In silico comparison of murine and human uterine cell-cell interactions reveals conserved signaling pathways implicated in labor. Thus, our scRNA-seq data provide insights into the preterm labor-driven cellular landscape and communications in reproductive tissues.
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    Betamethasone as a potential treatment for preterm birth associated with sterile intra-amniotic inflammation: a murine study
    (2021) Galaz, Jose; Romero, Roberto; Arenas-Hernandez, Marcia; Panaitescu, Bogdan; Para, Robert; Gomez-Lopez, Nardhy
    Objectives: Preterm birth remains the leading cause of perinatal morbidity and mortality worldwide. Preterm birth is preceded by spontaneous preterm labor, which is commonly associated with sterile intra-amniotic inflammation; yet, no approved treatment exists for this clinical condition. Corticosteroids are the standard of care to improve neonatal outcomes in women at risk of preterm birth. Herein, we first validated our model of alarmininduced preterm birth. Next, we investigated whether treatment with betamethasone could prevent preterm birth resulting from sterile intra-amniotic inflammation in mice.
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    Blockade of IL-6R prevents preterm birth and adverse neonatal outcomes
    (2023) Farias-Jofre, Marcelo; Romero, Roberto; Galaz, Jose; Xu, Yi; Miller, Derek; Garcia-Flores, Valeria; Arenas-Hernandez, Marcia; Winters, Andrew D.; Berkowitz, Bruce A.; Podolsky, Robert H.; Shen, Yimin; Kanninen, Tomi; Panaitescu, Bogdan; Glazier, Catherine R.; Pique-Regi, Roger; Theis, Kevin R.; Gomez-Lopez, Nardhy
    Background Preterm birth preceded by spontaneous preterm labour often occurs in the clinical setting of sterile intra-amniotic inflammation (SIAI), a condition that currently lacks treatment.Methods Proteomic and scRNA-seq human data were analysed to evaluate the role of IL-6 and IL-1 alpha in SIAI. A C57BL/6 murine model of SIAI-induced preterm birth was developed by the ultrasound-guided intra-amniotic injection of IL-1 alpha. The blockade of IL-6R by using an aIL-6R was tested as prenatal treatment for preterm birth and adverse neonatal outcomes. QUEST-MRI evaluated brain oxidative stress in utero. Targeted transcriptomic profiling assessed maternal, foetal, and neonatal inflammation. Neonatal biometrics and neurodevelopment were tested. The neonatal gut immune-microbiome was evaluated using metagenomic sequencing and immunophenotyping.Findings IL-6 plays a critical role in the human intra-amniotic inflammatory response, which is associated with elevated concentrations of the alarmin IL-1 alpha. Intra-amniotic injection of IL-1 alpha resembles SIAI, inducing preterm birth (7% vs. 50%, p = 0.03, Fisher's exact test) and neonatal mortality (18% vs. 56%, p = 0.02, Mann-Whitney U-test). QUEST-MRI revealed no foetal brain oxidative stress upon in utero IL-1 alpha exposure (p > 0.05, mixed linear model). Prenatal treatment with aIL-6R abrogated IL-1 alpha-induced preterm birth (50% vs. 7%, p = 0.03, Fisher's exact test) by dampening inflammatory processes associated with the common pathway of labour. Importantly, aIL-6R reduces neonatal mortality (56% vs. 22%, p = 0.03, Mann-Whitney U-test) by crossing from the mother to the amniotic cavity, dampening foetal organ inflammation and improving growth. Beneficial effects of prenatal IL -6R blockade carried over to neonatal life, improving survival, growth, neurodevelopment, and gut immune homeostasis.Interpretation IL-6R blockade can serve as a strategy to treat SIAI, preventing preterm birth and adverse neonatal outcomes.
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    Cellular immune responses in amniotic fluid of women with preterm prelabor rupture of membranes
    (WALTER DE GRUYTER GMBH, 2020) Galaz, Jose; Romero, Roberto; Slutsky, Rebecca; Xu, Yi; Motomura, Kenichiro; Para, Robert; Pacora, Percy; Panaitescu, Bogdan; Hsu, Chaur Dong; Kacerovsky, Marian; Gomez Lopez, Nardhy
    Background: Preterm birth is the leading cause of perinatal morbidity and mortality. Preterm prelabor rupture of membranes (pPROM) occurs in 30% of preterm births; thus, this complication is a major contributor to maternal and neonatal morbidity. However, the cellular immune responses in amniotic fluid of women with pPROM have not been investigated.
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    Clarithromycin prevents preterm birth and neonatal mortality by dampening alarmin-induced maternal–fetal infammation in mice
    (2022) Galaz, José; Romero, Roberto; Arenas-Hernandez, Marcia; Farías Jofré, Marcelo Enrique; Motomura, Kenichiro; Liu, Zhenjie; Kawahara, Naoki; Demery-Poulos, Catherine; Liu, Tzu N.; Padron, Justin; Panaitescu, Bogdan; Gomez-Lopez, Nardhy
    Background: One of every four preterm neonates is born to a woman with sterile intra-amniotic inflammation (inflammatory process induced by alarmins); yet, this clinical condition still lacks treatment. Herein, we utilized an established murine model of sterile intra-amniotic inflammation induced by the alarmin high-mobility group box-1 (HMGB1) to evaluate whether treatment with clarithromycin prevents preterm birth and adverse neonatal outcomes by dampening maternal and fetal inflammatory responses. Methods: Pregnant mice were intra-amniotically injected with HMGB1 under ultrasound guidance and treated with clarithromycin or vehicle control, and pregnancy and neonatal outcomes were recorded (n = 15 dams each). Additionally, amniotic fluid, placenta, uterine decidua, cervix, and fetal tissues were collected prior to preterm birth for determination of the inflammatory status (n = 7–8 dams each). Results: Clarithromycin extended the gestational length, reduced the rate of preterm birth, and improved neonatal mortality induced by HMGB1. Clarithromycin prevented preterm birth by interfering with the common cascade of parturition as evidenced by dysregulated expression of contractility-associated proteins and inflammatory mediators in the intra-uterine tissues. Notably, clarithromycin improved neonatal survival by dampening inflammation in the placenta as well as in the fetal lung, intestine, liver, and spleen. Conclusions: Clarithromycin prevents preterm birth and improves neonatal survival in an animal model of sterile intra-amniotic inflammation, demonstrating the potential utility of this macrolide for treating women with this clinical condition, which currently lacks a therapeutic intervention.
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    Clinical chorioamnionitis at term IX : in vivo evidence of intra-amniotic inflammasome activation
    (2019) Gomez-López, Nardhy; Romero, Roberto; Maymon, Ely; Kusanovic, Juan Pedro; Panaitescu, Bogdan; Miller, Derek; Pacora, Percy; Tarca, Adi L.; Motomura, Kenichiro; Erez, Offer; Jung, Eunjung J.; Hassan, Sonia S.; Hsu, Chaur Dong
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    Clinical chorioamnionitis at term X: microbiology, clinical signs, placental pathology, and neonatal bacteremia implications for clinical care
    (2021) Romero, Roberto; Pacora, Percy; Kusanovic, Juan Pedro; Jung, Eunjung; Panaitescu, Bogdan; Maymon, Eli; Erez, Offer; Berman, Susan; Bryant, David R.; Gomez-Lopez, Nardhy; Theis, Kevin R.; Bhatti, Gaurav; Kim, Chong Jai; Yoon, Bo Hyun; Hassan, Sonia S.; Hsu, Chaur-Dong; Yeo, Lami; Diaz-Primera, Ramiro; Marin-Concha, Julio; Lannaman, Kia; Alhousseini, Ali; Gomez-Roberts, Hunter; Varrey, Aneesha; Garcia-Sanchez, Angel; Gervasi, Maria Teresa
    Objectives: Clinical chorioamnionitis at term is considered the most common infection-related diagnosis in labor and delivery units worldwide. The syndrome affects 5-12% of all term pregnancies and is a leading cause of maternal morbidity and mortality as well as neonatal death and sepsis. The objectives of this study were to determine the (1) amniotic fluid microbiology using cultivation and molecular microbiologic techniques; (2) diagnostic accuracy of the clinical criteria used to identify patients with intraamniotic infection; (3) relationship between acute inflammatory lesions of the placenta (maternal and fetal inflammatory responses) and amniotic fluid microbiology and inflammatory markers; and (4) frequency of neonatal bacteremia.
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    Innate lymphoid cells at the human maternal-fetal interface in spontaneous preterm labor
    (WILEY, 2018) Xu, Yi; Romero, Roberto; Miller, Derek; Silva, Pablo; Panaitescu, Bogdan; Theis, Kevin R.; Arif, Afrah; Hassan, Sonia S.; Gomez Lopez, Nardhy
    Problem: Pathological inflammation is causally linked to preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Our aims were to investigate whether (i) the newly described family of innate lymphoid cells (ILCs) was present at the human maternal-fetal interface and (ii) ILC inflammatory subsets were associated with the pathological process of preterm labor.
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    The diagnostic performance of the beta-glucan assay in the detection of intra-amniotic infection with Candida species
    (2019) Pacora, Percy; Romero, Roberto; Erez, Offer; Maymon, Eli; Panaitescu, Bogdan; Ivelic Kusanovic, Radoslav; Tarca, A. L.; Hsu, C. D.; Hassan, S. E.
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    The immunophenotype of amniotic fluid leukocytes in normal and complicated pregnancies
    (WILEY, 2018) Gomez Lopez, Nardhy; Romero, Roberto; Xu, Yi; Miller, Derek; Leng, Yaozhu; Panaitescu, Bogdan; Silva, Pablo; Faro, Jonathan; Alhousseini, Ali; Gill, Navleen; Hassan, Sonia S.; Hsu, Chaur Dong
    ProblemThe immune cellular composition of amniotic fluid is poorly understood. Herein, we determined: 1) the immunophenotype of amniotic fluid immune cells during the second and third trimester in the absence of intra-amniotic infection/inflammation; 2) whether amniotic fluid T cells and ILCs display different phenotypical characteristics to that of peripheral cells; and 3) whether the amniotic fluid immune cells are altered in women with intra-amniotic infection/inflammation.