Teratogenic Research Articles

Absence of developmental and reproductive toxicity in rats, rabbits, and zebrafish embryos exposed to antimalarial drug cabamiquine.

When developing new antimalarial drugs, considering their potential use during pregnancy as preventive or curative therapy is crucial. This prevents the parasite from affecting embryonic development and reduces maternal and fetal death risks. Consequently, understanding the exposure and safety of antimalarial drugs during pregnancy is crucial, with well-designed animal studies playing a key role in this assessment. As part of the drug development program for cabamiquine, a series of developmental and reproductive toxicity studies were conducted in rats and rabbits. Additionally, the zebrafish embryo model was used to further improve embryo exposure, minimize confounding factors related to maternal toxicity, and assess developmental risks of cabamiquine. In these studies, although maternal toxicity was observed, there were no cabamiquine-related adverse effects on fertility, embryonic, or fetal development at maternal exposures representing significant multiples (up to five and 10 times higher in rabbit and rats, respectively) than the exposure at the anticipated efficacious human dose. Similarly, no adverse effects were observed on ZF embryonic development, even though cabamiquine concentrations in the embryos were 10-fold higher than nominal concentrations. The results obtained in a full set of reproductive toxicity studies did not provide evidence of detrimental effects on the conceptuses and progeny at maternally nontoxic doses and exposures, still representing a multiple of the anticipated systemic exposures in women of childbearing potential (WOCBP). Cabamiquine can therefore be considered a suitable therapeutic option for WOCBP and pregnant women living in malaria-endemic regions by significantly reducing maternal and infant malaria death rates.

Investigating the mechanism of Bacillus amyloliquefaciens YUAD7 degrading aflatoxin B1 in alfalfa silage using isotope tracing and nuclear magnetic resonance methods

BackgroundFungal toxins are highly toxic and widely distributed, presenting a considerable threat to global agricultural development. Addressing the issue of aflatoxin B1 (AFB1) contamination in feed, it is crucial to ascertain the effectiveness and mechanisms of microbial strains in degradation.ResultsThis study used isotope tracing and nuclear magnetic resonance (NMR) to investigate the degradation products of Bacillus amyloliquefaciens YUAD7 in complex substrates. By tracing 14C34-AFB1 and utilizing NMR, ultra-performance liquid chromatography–quadrupole time-of-flight/mass spectrometry (UPLC–Q-TOF/MS) purification and identification techniques, it was confirmed that AFB1 was degraded by YUAD7 into C12H14O4, C5H12N2O2, C10H14O2, and C4H12N2O, effectively removing 99.7% of AFB1 (100 μg/kg) from alfalfa silage. YUAD7 targeted the ester bond in the vanillin lactone ring structure, the ether bond in the furan ring structure, and the unsaturated carbon–carbon double bond in the furan ring structure during AFB1 degradation, disrupting the toxic sites responsible for AFB1's carcinogenic, teratogenic, and mutagenic effects and achieving biodegradation. Moreover, B. amyloliquefaciens YUAD7 transformed AFB1 through processes like hydrogenation, enzyme modification, and the loss of the -CO group while also being associated with metabolic pathways such as alanine, aspartate, glutamate metabolism, glutathione metabolism, cysteine and methionine metabolism, and pentose and glucuronate interconversions.ConclusionsThe utilization of isotope tracing allowed for rapid identification of degradation products in complex substrates, while NMR elucidated the structures of these products. This deepens our understanding of AFB1 biodegradation mechanisms, providing technical support for the practical application of these bacteria in degradation, and new insights into studying the biological degradation mechanism. B. amyloliquefaciens YUAD7 can be used as a potential strain for degrading AFB1 in large-scale silage.Graphical

Integrase inhibitor drugs during pregnancy and congenital anomalies: A case/non-case study from the global pharmacovigilance database VigiBase®.

In 2018, a significant neural tube defects (NTD) signal was reported after pre-conceptional exposure to dolutegravir, but was not confirmed in further analysis. Since 2019, dolutegravir-based regimen, an integrase inhibitor (INI), is recommended by WHO as the most-effective first-line therapy in all patients living with HIV. To explore the potential INI-related teratogenic effect, we searched disproportionate signals between exposure to INI-class drugs and congenital anomalies, compared to non-INI drugs, using the international pharmacovigilance database, VigiBase®. We selected all the reports registered in VigiBase® between 01/01/2007 and 30/03/2021 on any antiretroviral drug-related fetal or neonatal adverse drug reactions, declared either in children (<2 years) exposed in utero or in pregnant women (12-50 years). A case/non-case study was conducted to detected signals between congenital anomalies and prenatal exposure to any INI-class drug, compared to non-INI drugs, by estimating adjusted reporting odds ratios (aROR) with 95% confidence intervals (95%CI). We identified 2521 unique reports, among which 664 (26.3%) were related to INI-class use. Overall, 520 congenital anomalies were cited from 327 unique reports, of whom 31.0% were INI-related. Compared to non-INI drugs, no significant disproportionate reporting signal between prenatal exposure to INI-class drugs and congenital anomalies was found (aROR 1.13; 95% CI:0.85-1.51). However, specific significant signals were reported for raltegravir/elvitegravir/dolutegravir drug exposure and urinary malformations (aROR 2.43; 95%CI:1.08-5.43), digestive malformations (aROR 3.09; 95%CI:1.22-7.84), and NTDs (aROR 3.02; 95%CI:1.09-8.37). Although specific congenital anomalies signals associated with raltegravir/elvitegravir/dolutegravir exposure were notified, causal relationship needs to be further investigated in prospective studies.

Exploration of thiosemicarbazone-quinolone hybrids over in-silico, antioxidant, and zebrafish embryo toxicity studies

In this study, we successfully synthesized a series of acetyl quinolone thiosemicarbazones (5a-d, 6a-d) using a simple work-up procedure yielding column-free products. The structures of the synthesized compounds were confirmed by various spectroscopic techniques, including 1H, 13C, and 2D NMR, along with FT-IR. Detailed 2D NMR analyses such as COSY, HSQC, and HMBC were also performed. The biological activities were evaluated through in-vitro, in-vivo, and in-silico studies. In-vitro antioxidant properties were assessed using radical scavenging assays, revealing significant activity for compounds 5b and 6b, likely due to the aromatic ring substitution in the thiosemicarbazide side chain. In-vivo zebrafish embryo toxicity studies indicated minimal toxicity for these compounds. Additionally, in-silico studies showed that compounds 5b and 6b have good binding energies for proteins 2C0U, 3NM8 and 2X08. Further the DFT study of HOMO and LUMO energy gap is small for 5b and 6b. These findings suggest that acetyl quinolone thiosemicarbazones are promising candidates for various biological applications due to their potent antioxidant activity and low toxicity.

Prenatal olanzapine exposure and congenital talipes equinovarus (clubfoot): a case report and review of emerging evidence

Recently, concerns have emerged about the potential teratogenic effects of olanzapine, particularly its association with congenital malformations such as congenital talipes equinovarus (clubfoot). Evidence from a large Finnish study, which reported a 2.5-fold increase in musculoskeletal anomalies, as well as various case reports, suggests a significant link between in-utero exposure to olanzapine and these anomalies. This case report aims to add to the growing body of evidence by detailing a new instance of clubfoot following prenatal olanzapine exposure. A 25-year-old woman suffering from bipolar I disorder with psychotic features was treated with olanzapine during pregnancy, resulting in the birth of a male infant with clubfoot but no other malformations. This case underscores the importance of careful risk assessment and monitoring for pregnant women undergoing psychiatric treatment with olanzapine. Potential mechanisms, such as disrupted fetal musculoskeletal development due to olanzapine’s pharmacological effects, warrant further investigation. Comparative analysis with other cases highlights consistent patterns, emphasizing the need for further research to elucidate the mechanisms and risk factors involved.

Hydroethanolic extracts from Bauhinia guianensis: a study on acute toxicity in Zebrafish embryos and adults

Context The botanical species Bauhinia guianensis Aublet (Leguminosae-Cercidoideae) is traditionally used in the Amazon for medicinal purposes. Objective The acute toxicity of the hydroethanolic extracts from B. guianensis leaves and stems (HELBg and HESBg) was evaluated in zebrafish (Danio rerio), with emphasis on the embryonic developmental stage and adult alterations. Materials and methods Extracts were analyzed on LC-DAD-MS/MS. Zebrafish eggs were inoculated individually with concentrations of HELBg and HESBg (0.25, 0.5, 0.75, 1.0, and 1.5 µg/mL), observed for 96 h. Adult zebrafish were treated with a single oral dose (100, 200, 500, 1000, and 2000 mg/kg) of HELBg and HESBg, observed for 48 h. Results HELBg and HESBg analysis detected 55 compounds. Both extracts exhibited toxicity, including embryo coagulation at higher doses of HELBg and absence of heartbeats in embryos at all doses of HESBg. Behavioral variations were observed; tissue alterations in adult zebrafish were found at the highest doses, primarily in the liver, intestine, and kidneys because of HELBg and HESBg effects. The LD50 of HESBg was 1717 mg/kg, while HELBg exceeded the limit dose of 2000 mg/kg. Conclusions The study on acute toxicity of B. guianensis extracts exhibits significant toxic potential, emphasizing effects on embryonic and adult zebrafish. The results suggest relative safety of the species preparations, encouraging further clinical trials on potential biological activities.

Embryo-fetal developmental toxicity of carbamazepine administered orally in wistar rat

Carbamazepine is an anticonvulsant medication commonly used to treat epilepsy and other neurological disorders. The purpose of this study was to assess the impact of carbamazepine on prenatal development, including maternal-fetal, external, visceral, and skeletal toxicity. Additionally, the study aimed to investigate the effects of orally administered Carbamazepine at a lower dose range in Wistar rats. Pregnant female rats were randomly distributed into control (G1) group administered with distilled water orally (n=8), low dose (G2) group administered at 25 mg/kg, intermediate dose (G3) group at 50 mg/kg, and high dose (G4) group at 100 mg/kg through oral gavage from gestation day (GD) 5–19. Pregnant female rats were scheduled to necropsy on gestation day (GD) 20. During the evaluation, the uterus was observed for number of live or viable fetuses, dead fetuses, early resorptions, late resorptions, number of corpora lutea and the sex ratio (m/f) per litter. Further, fetuses were subjected to materno-fetal examination which included observation for placenta, amniotic fluid, and umbilical cord followed by external evaluation. Additionally, half of the fetuses were subjected to visceral, craniofacial evaluation and other half of the fetuses were subjected to skeletal evaluation by double staining method using Alcian Blue for cartilages and Alizarin Red S for bones. It was observed that there was a significant decrease in the rate of pregnancy in the intermediate dose (G3) group and in high dose (G4) group when compared with the control group. Moreover, treatment with the Carbamazepine caused significant increase in fetal malformations such as dilation of lateral and third ventricle in brain, in intermediate dose (G3) group and high dose (G4) group when compared with the control (G1) group, dilation of ureters in high dose (G4) group. Fetal skeletal malformations like bent and nodulated ribs were also observed in intermediate dose (G3) group. Existing research substantially supports the claim that carbamazepine can cause teratogenic effects and prenatal development toxicity even at a lower dose range.

Toxicity and related molecular mechanisms of Sb(III) in the embryos and larvae of zebrafish (Danio rerio)

Antimony (Sb) pollution poses a severe threat to humans and ecosystems due to the extensive use of Sb in various fields. However, little is known about the toxic effects of Sb and its aquatic ecotoxicological mechanism. This study aimed to reveal the toxicity and related molecular mechanisms of trivalent Sb (Sb(III)) in zebrafish embryos/larvae. Sb(III) accumulated in larvae, which correlated with the exposure concentration. Although no significant lethal or teratogenic effects were observed, normal growth and development were affected. Exposure to 10 or 20 mg/L Sb(III) increased the levels of reactive oxygen species in the larvae while enhancing catalase activity and increasing cell apoptosis. Transcriptomic analysis revealed that Sb(III) promoted glutathione metabolism and the ferroptosis pathway. In addition, symptoms associated with ferroptosis, including mitochondrial damage, biochemical levels of related molecules and increased tissue iron content, were detected. Quantitative polymerase chain reaction (qPCR) analyses further confirmed that Sb(III) significantly altered the transcription levels of genes related to the ferroptosis pathway by disrupting iron homeostasis. Furthermore, ferrostatin-1 (Fer-1) mitigated the toxic effects induced by Sb(III) in zebrafish. Our research fills the gap in the literature on the toxicity and mechanism of Sb(III) in aquatic organisms, which is highly important for understanding the ecological risks associated with Sb.

A comparative study of in vivo toxicity in zebrafish embryos synthesized CuO nanoparticles characterized from Salacia reticulata.

The Salacia reticulata, a medicinal woody climbing shrub, was utilized for our study, the green synthesis of CuO nanoparticles, which were analyzed through SEM, EDX, FTIR, XRD, and UV‒Vis spectroscopy. This study assessed the toxicity to zebrafish embryos and explored the antibacterial, cytotoxic, antidiabetic, and anti-inflammatory properties of the synthesized nanoparticles. In results, the UV absorption of the CuO NPs showed that the intensity of nanoparticle green colloidal suspension changed from blue to green, which also confirmed that the spectrum of the green CuO NPs changed from colorless to black. in FT-IR and XRD spectral analysis to identify functional groups and determine the particle size of CuO NPs prepared by green and chemical methods. Its showed that CuO NPs (green) had a size of approximately 42.2nm, while CuO NPs (chemical) had a size of approximately 84nm. The morphology of these NPs was analyzed using SEM-EDX. Compared with their chemically prepared counterparts, the green-synthesized CuO nanoparticles demonstrated superior dispersion. Additionally, both green and chemical CuO nanoparticles at a concentration of 200 µL/mL caused developmental anomalies and increased mortality in zebrafish embryos and larvae. The green and chemical CuO NPs inhibited α-glucosidase enzyme activity at concentrations between 10 and 50 µL/mL, with IC50 values of 22 µL/mL and 26 µL/mL, respectively. The extract exhibited anti-inflammatory activity, with IC50 values of 274 and 109 µL/mL. The authors concluded that this green nanoparticle method has potential as a more eco-friendly and cost-effective alternative to traditional synthetic methods. NPs are widely used in human contact fields (medicine and agriculture), hence synthesis methods that do not involve toxic substances are becoming increasingly important.

Application of whole exome sequencing technology in the diagnosis of hereditary eye diseases

Objective: To evaluate the application of whole exome sequencing (WES) in the diagnosis of hereditary eye diseases. Methods: A total of 24 patients who came to the Obstetrics and Gynecology Hospital of Fudan University for reproductive genetic counseling from December 2020 to December 2023 with the main complaint of congenital eye disorders were included in this study. All cases had no known infections or exposure to known teratogenic drugs, karyotype and chromosome microarray analysis (CMA) abnormalities. Genomic DNA was extracted from the peripheral blood of the probands and their family members and tested for WES. Among them, three individual WES and 21 Trio WES were performed. Potential pathogenic sites were screened and analyzed by Sanger sequencing. For RPGRIP1:c.1611+26G>A site, minigene vector was constructed and RT-qPCR was performed to detect the effect of mRNA splicing. Results: A total of 24 families were collected in this study, of which 20 yielded positive results, achieving a diagnosis rate of 83.3% (20/24). The results involved 21 genes and identified 30 distinct variants, 19 of which were new variants reported. Prenatal diagnostic analysis of family 3 revealed that the fetus carried a c.6970G>T heterozygous nonsense mutation in the PRPF8 gene. The results of RT-PCR with the minigene vector at the non-classical splice site in family 24 indicated that the transcription product of the mutant plasmid was partially retained 104 bp in intron 12, resulting in a p.Glu538Valfs*12 alteration of the protein. Conclusions: The high detection rate of WES in the diagnosis of hereditary eye diseases further supports the advantages of its application as an important molecular detection tool for determining the etiology of hereditary eye diseases.

Comparative Evaluation of Cytotoxicity of Zinc Oxide Nanoparticles Mixed With Herbal Extract as an Intracanal Medicament: A Zebrafish Model Study.

Objective In this study, zebrafish embryos are used to study the cytotoxic effects of a novel intracanal medication (ICM) based on zinc oxide nanoparticles (ZnO NPs) loaded with polyherbal extracts (Azadirachta indica and Solanum xanthocarpum). Material and methods In the present study, a green and sustainable method was employed for the synthesis of ZnO NPs mixed with bark and seed extracts of Azadirachta indica and Solanum xanthocarpum to be used as a polyherbal ICM. Formulation of ZnO NPs was confirmed with color change in mixture produced upon dissolving zinc acetate dihydrate in distilled water followed by slow addition of sodium hydroxide solution and herbal extracts. The effects of these green synthesized ZnO NPs were evaluated through a zebrafish embryo toxicity test. Embryos were exposed to different concentrations (25, 50, and 100 µg/mL) of synthesized experimental doses of ZnO NP and compared with the control embryos. Toxicological endpoints, such as the zebrafish embryo's survival rate, hatching rate, and heart rate, were noted and described. Results A concentration-dependent increase in mortality rate and hatching delay followed by declined heart rate was observed in green synthesized ZnO NP-treated embryos. The maximum toxicity was observed with an increase in the concentration of 100 µg/mL of the experimental dose, and at a low concentration of 25 µg/mL, it does not effectively show any developmental alteration in zebrafish embryos. Conclusion A novel polyherbal ICM loaded with ZnO NPs exhibited a dose-dependent effect on the heart rate, hatching, and mortality rate of the embryos. At optimal concentrations, the medication demonstrated minimal developmental malformations and cytotoxic effects, indicating its safety for use. However, increasing concentrations of the medication resulted in severe developmental malformations.

Ecotoxicity and environmental safety assessment of two-dimensional niobium carbides (MXenes)

Two-dimensional (2D) MXenes have gained great interest in water treatment, biomedical, and environmental applications. The antimicrobial activity and cell toxicity of several MXenes including Nb4C3Tx and Nb2CTx have already been explored. However, potential side effects related to Nb-MXene toxicity, especially on aquatic pneuma, have rarely been studied. Using zebrafish embryos, we investigated and compared the potential acute toxicity between two forms of Nb-MXene: the multilayer (ML-Nb4C3Tx, ML-Nb2CTx) and the delaminated (DL-Nb2CTx, and DL-Nb4C3Tx) Nb-MXene. The LC50 of ML-Nb4C3Tx, ML-Nb2CTx, DL-Nb2CTx, and DL-Nb4C3Tx were estimated to be 220, 215, 225, and 128 mg/L, respectively. Although DL-Nb2CTx, and DL-Nb4C3Tx derivatives have similar sizes, DL-Nb4C3Tx not only shows the higher mortality (LC50 = 128 mg/L Vs 225 mg/L), but also the highest teratogenic effect (NOEC = 100 mg/L Vs 200 mg/L). LDH release assay suggested more cell membrane damage and a higher superoxide anion production in DL-Nb4C3Tx than DL-Nb2CTx,. Interestingly, both DL-Nb-MXene nanosheets showed insignificant cardiac, hepatic, or behavioral toxic effects compared to the negative control. Embryos treated with the NOEC of DL-Nb2CTx presented hyperlocomotion, while embryos treated with the NOEC of DL-Nb4C3Tx presented hyperlocomotion, suggesting developmental neurotoxic effect and muscle impairment induced by both DL-Nb-MXene. According to the Fish and Wildlife Service (FSW) Acute Toxicity Rating Scale, all tested Nb-MXene nanosheets were classified as “Practically not toxic”. However, DL-Nb4C3Tx should be treated with caution as it might cause a neurotoxic effect on fauna when it ends up in wastewater in high concentrations.

Fetal Alcohol Syndrome: a complex case of teratogenic effects of maternal alcohol consumption and clinical managment

Fetal Alcohol Syndrome: a complex case of teratogenic effects of maternal alcohol consumption and clinical managment

Sodium valproate effects on the morphological and neurobehavioral phenotype of zebrafish

The anticonvulsant sodium valproate (SV) is frequently administered as a medicament but bears several negative effects in case of exposure during development. We analyzed extensively these early development effects of using the zebrafish model. Zebrafish embryos were exposed as eggs to two sublethal concentrations of SV, 10 and 25 mg/L. A general embryo toxicity analysis revealed extended anomalies in the cardiovascular system, and in the craniofacial and the spinal skeleton, as well as high mortality, in the embryos exposed to SV. The teratogenic potential of SV was confirmed in hacthed larvae by morphometric and cartilage profile analysis. Last, neurobehavioral impairments due to SV were highlighted in subjects’ activity, anxiety, response to stimulations, habituation learning, and daily synchronization of locomotor activity, overall mirroring typical phenotypes associated with autistic spectrum disorders. In conclusion, our results confirmed the presence of extended and multifaced impacts of exposure to SV during development.

Enhanced biodegradation of benzo[a]pyrene with Trametes versicolor stimulated by citric acid.

Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants with carcinogenic, mutagenic and teratogenic effects. The white-rot fungi in the fungal group have significant degradation ability for high molecular weight organic pollutants. However, exogenous fungi are easily antagonized by indigenous microorganisms. Low molecular weight organic acids, a small molecular organic matter secreted by plants, can provide carbon sources for soil microorganisms. Combining organic acids with white rot fungi may improve the nutritional environment of fungi. In this study, immobilized Trametes versicolor was used to degrade benzo[a]pyrene in soil, and its effect on removing benzo[a]pyrene in soil mediated by different low molecular weight organic acids was investigated. The results showed that when the degradation was 35days, the removal effect of the experimental group with citric acid was the best, reaching 43.7%. The degradation effect of Trametes versicolor on benzo[a]pyrene was further investigated in the liquid medium when citric acid was added, and the effects of citric acid on the biomass, extracellular protein concentration and laccase activity of Trametes versicolor were investigated by controlling different concentrations of citric acid. In general, citric acid can act as a carbon source for Trametes versicolor and promote its extracellular protein secretion and laccase activity, thereby accelerating the mineralization of benzo[a]pyrene by Trametes versicolor. Therefore, citric acid can be used as a biostimulant in the remediation of PAHs contaminated soil with Trametes versicolor.

Bio-inspired magnetic chitosan/Iron oxide macromolecules for multiple anionic dyes adsorption from aqueous media

Organic anionic dyes are major water pollutants due to their low degradability caused by complex aromatic structures. Not only do they exert toxic, mutagenic, teratogenic, tumorigenic, and genotoxic effects, but they also decrease fertility and cause irritation to the skin and respiratory system in humans. This long-term toxicity has detrimental effects on aquatic organisms and their surroundings, resulting in an imbalanced ecosystem. In this study, a Cs@Fe3O4 magnetic biosorbent was synthesised to uptake three anionic dyes and characterised for FTIR, BET/BJH, XRD, TGA, VSM, and FESEM analyses. The biosorbent average surface area was confirmed to be 52.6524 m2/g, with average pore sizes of 7.3606 nm and 6.9823 nm for adsorption-desorption processes, respectively. Batch adsorption studies pH values, contact times, temperature, initial dye concentrations, and adsorbent dosages were examined. Several isotherm and kinetic models were studied to determine the adsorption mechanism. The adsorption data of these dyes at equilibrium was observed to match Langmuir's isotherm and pseudo-second-order kinetic models. The thermodynamic study revealed that the adsorption process for these dyes was an exothermic reaction. Maximum adsorption capacities for congo red, methyl orange, and metanil yellow were 117.77 mg/g, 137.77 mg/g, and 155.57 mg/g, respectively. The reusability of recovered Cs@Fe3O4 after dye adsorption was evaluated up to five continuous adsorption-desorption cycles for its possible industrial applications.

Effects of valproic acid on transcript levels in neurotrophin signaling pathway in mice hippocampus according to the implementation period

Abstract Background/Aim Valproic acid (VPA), is an antiepileptic drug and it has been known for a long time that exposure to VPA in the fetal period causes many behavioral, cognitive, and structural disorders. In this study, we aimed to evaluate the effects of the implementation period of VPA during pregnancy on both behavioral tests and the expression of 45 key genes belonging to the neurotrophin signaling pathway. Methods The study was designed to form four different groups of five female mice in each group. The experimental and control groups were divided into mature (n = 5) and immature (n = 5) subgroups, respectively. VPA (500 mg/kg dose) was subcutaneously administered to the experimental groups. All mice were first tested for behavioral changes, and then the hippo-campal tissues were used for RNA isolation. The expression levels of 45 transcripts associated with the neurotrophin signaling pathway were determined by real-time RT-PCR in the hippocampus. Results No differences were found between the groups in any of the behavioral tests. When gene expression was examined, there was a difference between the groups in the transcript levels of Ngf(neurotrophic growth factor), Ntrk2 (neurotrophic receptor tyrosine kinase 2), Shc1 (SHC adaptor protein 1), Chka (choline kinase alpha), and Mapk1 (mitogen-activated protein kinase 1) genes. Conclusions This study demonstrated the effects of VPA on transcript levels at different maturation stages. We believe that it is important to explain the structural and cognitive teratogenic side effects caused by VPA in human fetuses using genes whose expression changes.

The Pathognomonic ultrasonographic findings in fetus with COVID-19 infection

Aim: The main goal is to identify the pathognomonic sonographic signs for foetal SARS-CoV-2 infection and to determine whether or not transplacental SARS-CoV-2 transmission is possible. Patients and Methods: In total, 105 pregnant women with positive SARS-CoV-2 PCR swabs during the first trimester with mild or moderate infection without hospitalisation and/or oxygen support were included in this prospective comparative study, which was carried out at the ultrasound and foetal medicine unit of Ain Shams University Maternity Hospital from January 2021 to June 2023. The SARS-CoV-2 positive group was compared to the control group with inclusion and exclusion criteria. Results: In the COVID-19 group, pathognomonic ultrasonographic results were considerably more common. The COVID-19 group had a considerably higher frequency of placental calcifications and oligohydramnios. In the COVID-19 cohort, patients with positive pathognomonic ultrasonographic results had considerably higher BMIs. In the COVID-19 cohort, gestational age at infection, and BMI ≥30.0 kg/m2 were significant independent risk factors for the development of pathognomonic ultrasonographic abnormalities. Those in the control group who had positive pathognomonic ultrasonographic results were older and had higher rates of hypertension. Significant independent risk variables for the incidence of pathognomonic ultrasonographic findings in the control group included age ≥34.0 years and hypertension. Conclusion: There is no evidence of a teratogenic effect linked to maternal SARS-CoV-2 infection during the first few months of pregnancy. However, early pregnancy infection with COVID-19 is linked to pathognomonic ultrasonography findings of placental calcifications and oligohydramnios.

Assessing the Efficiency of Microalgae in the Removal of Salicylic Acid from Contaminated Water: Insights from Zebrafish Embryo Toxicity Tests

Microalgae-based water treatments for the removal of different types of pollution have been gaining considerable attention during the last few decades. However, information about microalgae potential in the removal of pharmaceuticals and personal care products (PPCPs) and the ecotoxicological outcomes is still limited. Therefore, in this work, we aimed at investigating salicylic acid removal from water by three different microalgae strains, namely Chlorella sorokiniana, Chlorella vulgaris and Scenedesmus obliquus. For such a purpose, photobioreactors were operated under batch and semi-continuous mode. Apart from determining the reduction in the concentration of salicylic acid attained by each strain, we used zebrafish embryo bioassays to assess the efficiency of microalgae to reduce its toxicity effects. S. obliquus was the strain that achieved the most significant decrease in the concentration and toxic effects of salicylic acid. Indeed, S. obliquus was able to rescue mortality and reduce abnormalities at practically 100%. The efficiency of C. sorokiniana and, especially, that of C. vulgaris were not so remarkable, indicating that the removal of SA and its toxic effects from water by microalgae is markedly strain dependent. The obtained results proved the importance of considering toxic effects for a more comprehensive evaluation of microalgae efficiency in the removal of PPCPs in view of an adequate selection for water treatment.

The Search for Drugs Derived from Natural Products for Toxoplasma gondii Infection Treatment in the Last 20 Years - A Systematic Review.

Toxoplasmosis is a worldwide distributed zoonosis caused by Toxoplasma gondii (T. gondii), an obligate intracellular protozoan. The infection in immunocompetent hosts usually progresses with mild or no symptoms. However, in immunocompromised individuals, this disease can cause severe or fatal symptoms. Sulfadiazine and pyrimethamine are two drugs used as standard therapies for human toxoplasmosis. Although they do not cause chronic infection, they may cause hematological toxicity, hypersensitivity, intolerance, teratogenic effects, gastrointestinal disorders, and bone marrow suppression. The limited effect, significant toxicity, and emerging resistance to current drugs available to treat T. gondii infections require investigating other effective, nontoxic, and well-tolerated alternatives. Medicinal plants are, traditionally, the most promising sources used to treat infectious diseases Conclusion: This review provides data on new therapeutic and prophylactic methods for T. gondii infection based on the use of extracts and/or compounds derived from natural products, which have been reported to be useful as alternative treatment options in the last 20 years.