TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency.

Introduction: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition. Methods: The study evaluated 93 pregnant women who had previously received two (n=21), three (n=55) or four (n=17) doses of COVID-19 vaccine. Also we evaluated maternal blood samples that were collected during childbirth. The levels of TRAIL, IP-10 and Nab inhibition were measured using enzyme-linked immunosorbent assays (ELISA). Results and discussion: Our study revealed four-dose group resulted in lower TRAIL levels when compared to the two-dose and three-dose groups (4.78 vs. 16.07 vs. 21.61 pg/ml, p = 0.014). The two-dose group had reduced IP-10 levels than the three-dose cohort (111.49 vs. 147.89 pg/ml, p=0.013), with no significant variation compared to the four-dose group. In addition, the four-dose group showed stronger Nab inhibition against specific strains (BA.2 and BA.5) than the three-dose group. A positive correlation was observed between TRAIL and IP-10 in the two-dose group, while this relationship was not found in other dose groups or between TRAIL/IP-10 and Nab inhibition. As the doses of the COVID-19 vaccine increase, the levels of TRAIL and IP-10 generally increase, only by the fourth dose, the group previously vaccinated with AZD1222 showed lower TRAIL but higher IP-10. Despite these changes, more doses of the vaccine consistently reinforced Nab inhibition, apparently without any relation to TRAIL and IP-10 levels. The variation may indicate the induction of immunological memory in vaccinated mothers, which justifies further research in the future.

Pilot Study on Evaluating the Impact of Tetanus, Diphtheria, and Pertussis (Tdap), Influenza, and COVID-19 Vaccinations on Antibody Responses in Pregnant Women.

This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully.

COVID-19 Vaccination in Pregnancy: Pilot Study for Maternal and Neonatal MicroRNA Profiles.

This pilot study explores alterations in miRNA profiles among pregnant women and their neonates upon receiving different doses of COVID-19 vaccines. Blood samples, including maternal blood (MB) and neonatal cord blood (CB), collected from five pregnant women were scrutinized using the miRNA PanelChip Analysis System, identifying nine distinct miRNAs, including miR-451a and miR-1972, which exhibited significant downregulation with two vaccine doses in both MB and CB. When compared with women vaccinated with four doses, miR-486-5p, miR-451a, and miR-1972 in the two-dose group also showed notable downregulation. Evaluating recipients of three and four doses, miR-423-5p and miR-1972 expression were significantly reduced in both MB and CB. Further comparative analysis highlighted a decline in miR-223-3p expression with increasing vaccine doses, while miR15a-5p, miR-16-5p, and miR-423-5p showed an upward trend. Notably, miR-451a, miR-1972, and miR-423-5p levels varied across doses and were associated with pathways such as "PI3K-Akt", "neurotrophin signaling", and "cortisol synthesis", suggesting the profound influence of vaccination on diverse molecular mechanisms. Our research has uncovered that escalating vaccine dosages impact miRNA profiles, which may be associated with the immunological response mechanisms in both the mother and fetus, thus indicating a substantial impact of vaccination on various molecular processes.

[Analyzing the Pollution Sources and Mechanisms of Urban Rivers Based on Identifying the Molecular Signature of Dissolved Organic Matter].

Dissolved organic matter (DOM) is an essential component of river pollutants. Under the new situation of black water treatment in urban areas of China, in view of the widespread problem of unclear sources of multiple pollutants, further analysis of DOM components in urban rivers from the molecular level is a key link to deeply explore the sources, causes, and mechanism of river pollution so as to achieve efficient management. In this study, the urban rivers in the central city were selected as the research object, and a total of five rivers were selected that were seriously affected by the discharge sewage of four combined and separated sewer systems, respectively. Using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), this study identified the molecular formulae and analyzed the elemental composition and compound groups of DOM in water and sediment samples at each site in dry and wet weather. The results showed that:①although CHO molecules and lignins were the main compounds in the urban river DOM, the high proportion of lipids, proteins, and heteroatomic compounds (especially CHOS molecules) revealed the anthropogenic pollution in rivers, which also led to the increase in DOC, TN, and NH+4-N. ②Surfactants such as C17H28O3S and C18H30O3S were ubiquitous in all urban rivers, which could be used as markers of domestic wastewater pollution. ③In wet weather, the rainfall inputs, storm runoffs, and hydraulic disturbance jointly led to the increase in the proportion of CHO molecules and lignin compounds; the decrease in proteins and lipids; the rise of DOC, TN, and NH+4-N concentrations in river water; and the decrease in DOC, TN, and NH+4-N concentrations and proteins and lipids in river sediments. ④The abundance of multi-heteroatomic compounds and condensed aromatics in the combined sewer system was higher than that in the separated sewer system, which may have been more severely polluted by domestic wastewater and storm runoff, especially kitchen wastewater. This study provides new insight for clarifying the critical causes of pollution in the new stage and provides an essential basis for further precision prevention and control of water pollution.

COVID-19 Bivalent Booster in Pregnancy: Maternal and Neonatal Antibody Response to Omicron BA.5, BQ.1, BF.7 and XBB.1.5 SARS-CoV-2.

Our study was to investigate the effects of bivalent COVID-19 booster vaccination during pregnancy on neutralizing antibody (Nab) levels in maternal blood (MB), transplacental transmission in umbilical cord blood (CB), and efficacy against Omicron SARS-CoV-2 subvariants including BA.5, BF.7, BQ.1, and XBB.1.5. We collected MB and CB from 11 pregnant participants during baby delivery and detected Nab inhibition by enzyme-linked immunosorbent assays (ELISA). Nab inhibition was 89-94% in MB and 82-89% in CB for Omicron subvariants. Those receiving AZD1222 vaccines in previous monovalent vaccination demonstrated poorer maternal Nab inhibition of BA.5, BQ.1, and XBB.1.5 than others. Poorer maternal Nab inhibition of BA.5, BF.7, and BQ.1 was found in those receiving two-dose AZD1222 vaccinations than with either one or no AZD1222 vaccination. MB from those with infants weighing < 3100 g demonstrated better Nab inhibition of BF.7 than those > 3100 g (97.99 vs. 95.20%, p = 0.048), and there were also similar trends for Nab inhibition of BA.5 and BQ.1. No significant differences were seen in CB samples. Although diminished maternal Nab inhibition was seen in those with previous monovalent AZD1222 vaccination and heavier newborns, neonatal Nab inhibition was still strong after bivalent COVID-19 booster vaccination.

Pilot Study for Immunogenicity of SARS-CoV-2 Vaccine with Seasonal Influenza and Pertussis Vaccines in Pregnant Women.

Background: It is well known that the implementation of routine immunizations to prevent vaccine-preventable diseases has a significant impact on the health and well-being of infants, children, and pregnant women. We aimed to evaluate the influence of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine on the immunogenicity of SARS-CoV-2 vaccine among pregnant women, the priority population recommended for vaccination. Methods: We conducted a prospective study among pregnant women without previous SARS-CoV-2 infection in Taiwan. Maternal and umbilical cord blood samples at delivery were analyzed for the percentage of inhibition of neutralizing antibodies (NAbs) against the original strain, Delta, and Omicron variants of SARS-CoV-2 as well as the total antibody to the SARS-CoV-2 spike protein. We examined the association between different doses of SARS-CoV-2 vaccine in combination with influenza and Tdap vaccination, and two-dose SARS-CoV-2 vaccination with or without influenza and Tdap vaccines via a two-sample t-test. Results of p < 0.05 were considered to be statistically significant. Results: 98 pregnant women were enrolled in our study, with 32 receiving two doses of SARS-CoV-2 mRNA-1273 vaccine, 60 receiving three-dose of mRNA-1273, and 6 receiving one-dose of ChAdOx1 and two-dose of mRNA-1273. Twenty-one participants were immunized with SARS-CoV-2, influenza, and Tdap vaccines. Of these 21 individuals, there were no significant NAbs levels in maternal and cord blood samples against the Omicron variant, regardless of doses or type of SARS-CoV-2 vaccine. However, antibody responses against the wild-type and Delta variant were significantly lower in all maternal sera in the two-dose SARS-CoV-2 vaccine group. Among 32 women receiving two-dose mRNA-1273, significantly lower levels of NAbs in maternal sera were observed against the Delta variant and total antibody both in maternal sera and cord blood were observed in individuals receiving SARS-CoV-2 and influenza vaccine. Conclusion: This is the pilot study to demonstrate the effects of influenza and the Tdap vaccine on the immunogenicity of the SARS-CoV-2 vaccine among pregnant women. These results suggest that combination vaccination during pregnancy may result in immunogenic interactions.

Haloperidol Instigates Endometrial Carcinogenesis and Cancer Progression by the NF-κB/CSF-1 Signaling Cascade.

Haloperidol is a routine drug for schizophrenia and palliative care of cancer; it also has antitumor effects in several types of cancer. However, the role of haloperidol in endometrial cancer (EC) development is still unclear. Here, we show that chronic haloperidol treatment in clinically relevant doses induced endometrial hyperplasia in normal mice and promoted tumor growth and malignancy in mice with orthotopic EC. The pharmacokinetic study indicated that haloperidol highly accumulated in the uterus of mice. In vitro studies revealed that haloperidol stimulated the cellular transformation of human endometrial epithelial cells (HECCs) and promoted the proliferation, migration, and invasion of human endometrial carcinoma cells (HECCs) by activating nuclear factor kappa B (NF-κB) and its downstream signaling target, colony-stimulating factor 1 (CSF-1). Gain of function of CSF-1 promotes the cellular transformation of HEECs and the malignant progression of HECCs. Moreover, blockade of CSF-1 inhibited haloperidol-promoted EC progression in vitro and in vivo. A population-based cohort study of EC patients further demonstrated that the use of haloperidol was associated with increased EC-specific mortality. Collectively, these findings indicate that clinical use of haloperidol could potentially be harmful to female patients with EC.