Timed fetal inflammation and postnatal hypoxia cause cortical white matter injury, interneuron imbalances, and behavioral deficits in a double-hit rat model of encephalopathy of prematurity

Brain Behavior & Immunity - Health, Journal Year: 2024, Volume and Issue: 40, P. 100817 - 100817

Published: July 5, 2024

Extreme preterm birth-associated adversities are a major risk factor for aberrant brain development, known as encephalopathy of prematurity (EoP), which can lead to long-term neurodevelopmental impairments. Although progress in clinical care infants has markedly improved perinatal outcomes, there currently no curative treatment options available combat EoP. EoP multifactorial etiology, including but not limited pre- or postnatal immune activation and oxygen fluctuations. Elucidating the underlying mechanisms determining efficacy potential therapies relies on valid, clinically translatable experimental models that reflect pathophysiological hallmarks Here, we expand our double-hit rat model be used study disease therapeutic preclinical setting. Pregnant Wistar dams were intraperitoneally injected with 10 μg/kg LPS embryonic day (E)20 offspring was subjected hypoxia (140 min, 8% O

Language: Английский

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Computational approach for drug discovery against Gardnerella vaginalis in quest for safer and effective treatments for bacterial vaginosis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 29, 2024

Bacterial vaginosis (BV), primarily attributed to Gardnerella vaginalis, poses significant challenges due antibiotic resistance and suboptimal treatment outcomes. This study presents an integrated approach identify potential drug targets screen compounds against this bacterium by leveraging a computational methodology. Subtractive proteomics of the reference strain ASM286196v1/UMB0386 (assembly accession: GCA_002861965.1) facilitated prioritization proteins with essential bacterial functions pathways as targets. We selected 3-deoxy-7-phosphoheptulonate synthase (aroG gene product; also known DAHP synthase) for downstream analysis. Molecular docking was employed in PyRx (AutoDock Vina) predict binding affinities between aroG inhibitors from ZINC database synthase. dynamics simulations 100 ns, using GROMACS, validated stability drug-target interactions. Additionally, ADMET profiling aided selection favorable pharmacokinetic properties safety profile human hosts. PBPK showed that ZINC98088375 had highest bioavailability efficient systemic circulation. Conversely, ZINC5113880 demonstrated lowest absorption rate (39.661%). Moreover, cirrhosis, steatosis, renal impairment appeared influence blood concentration drug, impacting bioavailability. The integrative –omics utilized underscores computer-aided design offers rational strategy targeted inhibitor discovery G. vaginalis. is attempt address limitations current BV treatments, including resistance, pave way development safer more effective therapeutics.

Language: Английский

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Preterm birth; current prevention strategies and challenges

Global Reproductive Health, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 2, 2025

Preterm birth occurs when a baby is born alive before the full 37 weeks of pregnancy. delivery can occur spontaneously or be sign that doctor should schedule an early cesarean section induction labor. The purpose this review was to advance our understanding preterm and its preventive measures. This examined epidemiology, risk factors, clinical evaluation, management, strategies. primary maternal predisposing factors associated with were defects, infection, presence polymorphism genes, mothers rural residents, history prior abortions, hypertensive disorders during pregnancy, low weight, elementary education level, immigrants. To prevent birth, pregnant women receive counseling regarding balanced diet, social drug usage, follow-up visits medical facilities, relaxation techniques. Some evidence suggests low-dose aspirin other cyclooxygenase inhibitors help in cases where traditional treatments are ineffective. More research will necessary enhance outcomes care reproductive health.

Language: Английский

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Exploring the composition of placental microbiome and its potential origin in preterm birth

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 16, 2025

For years, the placenta was believed to be sterile, but recent studies reveal it hosts a unique microbiome. Despite these findings, significant questions remain about origins of placental microbiome and its effects on pregnancy fetal health. Some suggest may originate from vaginal tract, while others indicate that oral bacteria can enter maternal bloodstream seed placenta. However, research analyzing vaginal, oral, microbiomes within same cohort is lacking. Additionally, it's unclear whether differs between healthy pregnancies those with complications like preterm birth (PTB), which remains leading cause neonatal morbidity mortality worldwide. In this study, we performed 16S rRNA gene sequencing investigate composition in samples collected 18 women who experienced PTB 36 matched controls delivered at term (TB), all whom were part Molecular Signature Pregnancy (MSP) study. We leveraged multisite sampling MSP participants our previously published data potential assess varies complicated pregnancies. Our analysis revealed distinct profiles subjects compared term. Specifically, observed an increased abundance Treponema maltophilum, Bacteroides sp, Mollicutes, Prevotella buccae, Leptotrichia, Prevotella_sp_Alloprevotella, group. Importantly, maltophilum species showed higher group during second trimester, suggesting use as biomarkers. When assessed composition, found Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria most dominant phyla. Interestingly, microorganisms such Ureaplasma urealyticum more abundant samples. findings could or cavities, notable increase crosstalk sites cases PTB. cases, exhibited closer resemblance microbiome, whereas pregnancies, similar

Language: Английский

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Trichomonas vaginalis and female reproductive health

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 93 - 110

Published: Jan. 1, 2025

Language: Английский

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Global and population-specific association of MTHFR polymorphisms with preterm birth risk: a consolidated analysis of 44 studies

BMC Pregnancy and Childbirth, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 1, 2025

Abstract Background This study investigates the relationship between polymorphisms in MTHFR gene and risk of preterm birth (PTB). Methods A comprehensive literature review was conducted using databases such as PubMed, Web Science, CNKI, with search finalized on January 1, 2025. The specifically targeted studies published prior to this date, utilizing relevant keywords MeSH terms associated PTB genetic factors. Inclusion criteria encompassed original case-control, longitudinal, or cohort studies, no limitations language publication date. Associations were quantified odds ratios (ORs) 95% confidence intervals (CIs) via Comprehensive Meta-Analysis software. Results analysis included 44 case-control comprising 7,384 cases 51,449 controls, extracted from 28 publications both English Chinese. Among these 29 focused C677T polymorphism, while 15 examined A1298C variant. Pooled results demonstrated a significant association polymorphism under five models: allele (C vs. T; OR = 1.303, CI 1.151–1.475, p ≤ 0.001), homozygote (CC AA; 1.494, 1.212–1.842, heterozygote (CT 1.119–1.516, dominant + CT 1.341, 1.161–1.548, recessive 1.340, 1.119–1.604, 0.001). Subgroup analyses indicated associations Asian populations, particularly China India, correlations found Caucasian including those Austria. Moreover, did not demonstrate across studied ethnicities. Conclusions findings indicate risk, Indian identified groups. Conversely, appeared have negligible impact underscoring importance considering population-specific factors understanding epidemiology PTB.

Language: Английский

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The anti-inflammatory effects of vitamin D on offspring brain development during pregnancy: critical review

Published: March 8, 2025

Vitamin D (VD) plays a pivotal role in fetal brain development by regulating essential processes such as neuronal proliferation, differentiation, and apoptosis. Despite the critical of VD maternal health, studies have shown that almost 1 3 pregnant women UK may be vitamin D-deficient. Epidemiological demonstrated deficiency (VDD) during pregnancy can lead to adverse neurodevelopment, resulting postnatal cognitive deficits. Although mechanism which VDD affects function is unknown, there growing evidence showing an interaction with inflammatory markers. possesses well-documented anti-inflammatory properties, but has been associated increased chronic inflammation, adversely influence development. Animal suggest supplementation mitigate these effects, preventing or attenuating neurodevelopmental disorders offspring. no directly examined combined effects VDD, development, existing points creating heightened pro-inflammatory intrauterine environment. This abnormal overgrowth, structural changes. review aims explore interrelationship between highlighting need for further research evaluate how influences inflammation this process.

Language: Английский

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Assessment of Culture-Negative Neonatal Early-Onset Sepsis: Risk Factors and Utility of Currently Used Serum Biomarkers

Children, Journal Year: 2025, Volume and Issue: 12(3), P. 355 - 355

Published: March 13, 2025

Introduction: Neonatal sepsis is a severe and life-threatening condition caused by pathogens in the systemic circulation within first 28 days of life. The classical definition neonatal implies positive central cultures, but recent findings discuss culture-negative (clinical associated with laboratory findings). Since infected neonates initially express few non-specific clinical signs there are unreliable biochemical markers to identify early stages, it essential improve accuracy diagnosis reduce unnecessary antibiotic exposure. Objective: Our study aims assess influence risk factors utility currently used biomarkers early-onset (CN-EOS). Materials methods: We performed retrospective at Bucharest University Hospital, which included 131 preterm term newborns for EOS admitted Intensive Care Unit (NICU) over 12 months. were classified into two groups: confirmed negative-culture (CN-EOS) suspected (S-EOS). Patients from both groups received therapy day life; type duration different groups. For all patients, we measured C-reactive protein (CRP), procalcitonin (PCT) white blood count (WBC) birth after 72 h, tested culture 24 h life correlated results prenatal factors. Categorical variables presented as frequencies percentages, while continuous mean standard deviation. differences between variable determined Student’s t-test or Mann–Whitney U test, whereas categorical variables, Chi-square test (X2) was employed. performance (CRP PCT) diagnosing calculated. All tests statistically significant p-value < 0.05. Results: support significance low weight gestational age Apgar scores potential indicators EOS; PROM diagnosed chorioamnionitis smoking during pregnancy also important predictive Respiratory signs, such apnea respiratory distress syndrome, most encountered evaluation infants CN-EOS. Inflammatory inconsistent CN-EOS cases, proving that they not reliable enough initiating, continuing stopping therapy. Conclusions: Culture-negative remains challenge neonatologist, since time elapsed moment initiation empirical can make difference survival death. Continued efforts needed develop more effective diagnostic tools timely appropriate intervention.

Language: Английский

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Placental Molecular Expression of Different Pathogenic Vaginal Infections

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2863 - 2863

Published: March 21, 2025

This study evaluated the differential expression of four placental markers—vitamin D receptor (VDR), Cluster Differentiation 44 (CD44), osteopontin (OPN), and cyclooxygenase-2 (COX-2)—in response to pathogens, which may contribute our understanding pathogen-specific impacts on pregnancy outcomes. We immunohistochemically (IHC) analyzed tissues obtained from 70 healthy-term pregnant women in control group compared them 78 with above 24 weeks gestation, single-pathogen vaginal infection, premature rupture membranes/preterm membranes (PROM/PPROM). detected high these molecules cases Group B Streptococcus (GBS) Ureaplasma urealyticum infections, moderate Enterobacteriaceae except for Klebsiella; Klebsiella Candida species (spp.) vaginitis exhibited a lower healthy group. VDR, CD44, OPN had increased GBS infections; opportunistic pathogenicity both Escherichia coli spp. explains their low IHC positivity, tremendous ability Gram-negative bacteria elude host immunity is revealed by negative staining vaginitis. These findings suggest that alterations markers risk stratification complications mitigate risks adverse maternal fetal Interventions aiming modulate pathways might improve

Language: Английский

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Obstetric anesthesia and medicolegal/ethical issues

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 613 - 624

Published: Jan. 1, 2025

Language: Английский

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