Embryonic exposure to butylparaben and propylparaben induced developmental toxicity and triggered anxiety-like neurobehavioral response associated with oxidative stress and apoptosis in the head of zebrafish larvae.

Parabens are synthetic antimicrobial compounds used as a preservative for extending the shelf life of food, pharmaceutical and cosmetic products. The alkyl chain length of the paraben esters positively correlates with their antimicrobial property. Hence, long-chain paraben esters, namely butylparaben and propylparaben, are used in combination as they have better solubility and antimicrobial efficacy. Extensive use of parabens has now resulted in the ubiquitous presence of these compounds in various human and environmental matrices. During early life, exposure to environmental contaminants is known to cause oxidative-stress mediated apoptosis in developing organs. The brain being one of the high oxygen-consuming, metabolically active and lipid-rich organ, it is primarily susceptible to reactive oxygen species (ROS) and lipid peroxidation (LP) induced neuronal cell death. The primary cause for the impairment in cognitive and emotional neurobehvioural outcomes in neurodegenerative disease was found to be associated with neuronal apoptosis. The present study aimed to study butylparaben and propylparaben's effect on zebrafish during early embryonic stages. Besides this, the association between alteration in anxiety-like neurobehavioral response with oxidative stress and antioxidant status in head region was also studied. The study results showed variation in the toxic signature left by butylparaben and propylparaben on developmental parameters such as hatching rate, survival and non-lethal malformations in a time-dependent manner. Data from the light-dark preference test showed embryonic exposure to butylparaben and propylparaben to trigger anxiety-like behavior in zebrafish larvae. In addition, a significant increase in intracellular ROS and LP levels correlated with suppressed antioxidant enzymes: superoxide dismutases (SOD), catalases (CAT), Glutathione peroxidase (GPx), glutathione S-transferase (GST), and Glutathione (GSH) activity in the head region of the zebrafish larvae. Acetylcholinesterase (AChE) activity was also suppressed in the exposed groups, along with increased nitric oxide production. The overall observations show increased oxidative stress indices correlating with upregulated expression of apoptotic cells in a dose-dependent manner. Collectively, our findings reveal butylparaben and propylparaben as an anxiogenic neuroactive compound capable of inducing anxiety-like behavior through a mechanism involving oxidative-stress-induced apoptosis in the head of zebrafish larvae, which suggests a potential hazard to the early life of zebrafish and this can be extrapolated to human health as well.

Evaluating Morphology of the Pterygomaxillary Junction and Its Association With the Orbit in Different Facial Skeletal Relationships.

PURPOSE: The etiology for blindness after Le Fort I osteotomy is poorly understood. The authors propose that a study of the morphology and anatomical relationship of the pterygomaxillary junction to orbital vital structures may be crucial for understanding the possible etiology. MATERIALS AND METHODS: This retrospective observational study involved analysis of data procured from computed tomography scans of individuals who were categorized into 4 groups based on their skeletal characteristics: skeletal Class I, II, and III and cleft lip and palate (CLP). The outcome variables included i) the height, width, and thickness of the pterygomaxillary junction (PTMJ) which represent its morphology and ii) distance of the PTMJ to the superior orbital fissure and optic canal, to demonstrate its proximity to orbital vital structures. Primary outcome measures were to i) compare variance of the outcome variables across groups, ii) determine association between PTMJ morphology and its proximity to the orbit, and iii) determine association between skeletal morphology and the outcome variables. Data were analyzed using descriptive and inferential statistics to study variance and association. RESULTS: Forty patients (80 sides) were divided into 4 groups. The CLP group demonstrated maximum height and thickness of the PTMJ, whereas the Class II group demonstrated the minimum (P < .001 and P = .001, respectively). The CLP group demonstrated the closest proximity of the PTMJ to orbital vital structures (P < .001), with Class II being the farthest (P < .001). There was a weak positive correlation between the PTMJ height and its thickness and width, whereas a moderate negative correlation was seen between the PTMJ height and its distance from the optic canal and superior orbital fissures (P < .001). CONCLUSIONS: Morphology of the PTMJ varies with facial skeletal relationship and also influences the relationship of the PTMJ with the orbital vital structures. This may be critical in understanding the pathophysiology of blindness after Le Fort I osteotomies.

In utero exposure to endocrine-disrupting chemicals, maternal factors and alterations in the epigenetic landscape underlying later-life health effects.

Widespread persistence of endocrine-disrupting chemicals (EDCs) in the environment has mandated the need to study their potential effects on an individual's long-term health after both acute and chronic exposure periods. In this review article a particular focus is given on in utero exposure to EDCs in rodent models which resulted in altered epigenetic programming and transgenerational effects in the offspring causing disrupted reproductive and metabolic phenotypes. The literature to date establishes the impact of transgenerational effects of EDCs potentially associated with epigenetic mediated mechanisms. Therefore, this review aims to provide a comprehensive overview of epigenetic programming and it's regulation in mammals, primarily focusing on the epigenetic plasticity and susceptibility to exogenous hormone active chemicals during the early developmental period. Further, we have also in depth discussed the epigenetic alterations associated with the exposure to selected EDCs such as Bisphenol A (BPA), di-2-ethylhexyl phthalate (DEHP) and vinclozlin upon in utero exposure especially in rodent models.

SARS-CoV-2/human interactome reveals ACE2 locus crosstalk with the immune regulatory network in the host.

Severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), remains to be a threat across the globe. SARS-CoV-2 entry into the host is mediated by binding of viral spike protein to the Human angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is an essential member of the Renin-Angiotensin system (RAS) involved in maintaining the blood pressure and vascular remodelling. Although ACE2 receptor is the entry point to the host, recent studies show activation of ACE2 to modulate the host to develop a suitable environment for its replication. However, the ACE2 activating the immune signals on SARS-CoV-2 attachment is still under investigation. We have used systems biological approach to construct the host regulatory network upon SARS-CoV-2 attachment to the ACE2 receptor. Since lungs are the primary infection site, we integrate human lung gene expression profile along with the host regulatory network to demonstrate the altered host signalling mechanism in viral infection. Further, the network was functionally enriched to determine immune modulation in the network. We also used the proteomic database to assess the occurrence of similar signalling events in other human tissues that exhibit lineage of infection across different organs. The constructed network contains 133 host proteins with 298 interactions that directly or indirectly connect to the ACE2 receptor. Among 133 proteins, 29 were found to be differentially regulated in the host lungs on SARS-CoV-2 infection. Altered proteins connect multiple proteins in a network that modulates kinase, carboxypeptidase and cytokine activity, leading to changes in the host immune system, cell cycle and signal transduction mechanisms. Further investigation showed the presence of similar signalling events in the kidneys, placenta, pancreas, testis, small intestine and adrenal gland as well. Overall, our results will help in understanding the immune molecular regulatory networks influenced by the ACE2 mediated interaction in other body tissues, which may aid in identifying the secondary health complications associated with SARS-CoV-2 infection.