Although polycyclic aromatic hydrocarbons (PAHs) are toxic pollutants for which some are known carcinogens, there is limited information on the cancer risk such substances pose to the population via ...marine sediments, despite a significant part of the world's food supply being derived from the coastal environment. This study was conducted in a heavily industrialized and urbanized coastal area, in Trinidad. PAHs were quantified in sediments during the dry and wet seasons and were observed to be significantly higher in the wet season compared to the dry season. Also emerging from this study is that PAH levels were lower, in the areas where natural gas is the dominant energy source for industries, compared with those areas where crude oil-based fossil fuel is predominantly used. Perylene levels were demonstrated to be of biogenic origin near the protected wetland area. It was observed that nearshore sediment PAHs concentrations were higher than offshore levels. The sources of PAHs, identified by Positive Matrix Factorization (PMF) in the marine sediments, were vehicular combustion of gasoline and diesel, biomass burning, industrial combustion and oil spills. The mean Incremental Lifetime Cancer Risks (ILCR) due to fish consumption from this region during the dry and wet seasons was >1 × 10−4, indicating a high cancer risk to the human population. The annual non-cancer risk (HQ) was high >1 at the 90th percentile level with an adverse risk to about 14% of the population. These results can be utilized for developing an effective environmental management policy for coastal areas in Trinidad and the wider Caribbean region, given that much of the islands' populations depend on the coastal regions for seafood. In addition, these results may assist in boosting current efforts of policymakers, towards phasing out crude oil-based fossil fuels for cleaner energy sources, such as compressed natural gas.
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•A dietary ingestion model was used to assess human cancer risk using sedimentary PAHs.•Gasoline and diesel fuel combustion are the major sources of PAHs found in sediment.•Seafood ingestion exposes 14% of the population to adverse health risk annually.•The population is exposed to high cancer risk (> 1 × 10−4) from fish consumption.•Measures to lower PAHs pollution in this area should focus on vehicular emissions.
This body of work demonstrated the levels of selected contaminants (as well as their potential sources), in mussels (Mytella guyanensis) - a known bio-indicator of pollution, along the west coast ...(Gulf-of-Paria) of Trinidad. The findings demonstrated that polyaromatic hydrocarbons levels in the mussels investigated were moderate to high (201.80–1200.08 μg/kg). Notably, benzo(a)pyrene levels (1.15–9.32 μg/kg) exceeded the European Union guidelines at various sites. The distribution of PAHs and trace elements in the Gulf of Paria are impacted by tidal currents and local source discharge. Significant risks were identified from toxic carcinogenic equivalent levels (3.01 to 22.37 μg/kg) and mutagenic equivalent levels (3.98 to 38.61 μg/kg). The concentration of trace elements, Zn (46.05–56.36 mg/kg) and Cd (0.46–1.17 mg/kg), exceeded both local and international guidelines at certain sites investigated. The analysis revealed a high bioavailability of the identified pollutants in the Gulf of Paria from industrial, urban and marine activities.
•The distribution of pollutants in the Gulf of Paria is affected by tidal currents and sources inputs.•The Gulf of Paria is moderate to highly contaminated by TPAH.•There is high bioavailability of TPAHs and trace elements in the Gulf of Paria.•Benzo(a)pyrene, Zn and Cd contaminations in mussels were above regulatory guidelines at some of the study sites.
Traditional medicine has traditionally appreciated the use of Podophyllum peltatum, a large herbaceous species with origins in eastern United States and southern Canada. This swiftly growing plant ...has recently sparked new interest due to its many uses. A true treasure of phytochemicals can be found there. This comprehensive review delves into the medicinal potential of Podophyllum peltatum, commonly known as mayapple, a rhizomatous perennial plant. Also, Dysosma pleianthum (bajiaolian), a species of May apple, is a traditional Chinese herbal medicine rich in podophyllotoxin. Mayapple has a long history of traditional use by indigenous peoples, and it has garnered significant attention from pharmacologists and medical researchers for its potential in treating various ailments, including cancer and viral infections.
The online databases including Google Scholar, and PubMed, were searched using different keywords: P. peltatum, antimicrobial activity, traditional uses, and antitumor activity. A total of 124 relevant papers out of 365 including the search terms were selected from the year 2000 to 2022.The purpose of this review was therefore to summarise the previously reported traditional uses and toxicity of the chosen plant species.
The results of our analysis showed that mayapple contains lignans with anti-cancer properties, leading to the development of FDA-approved cancer drugs such as etoposide. This review provided insights into the plant's morphology, taxonomy, traditional uses, agriculture, pharmacological investigation, chemical constituents, and analytical analysis.
Podophyllum peltatum is a useful medicinal plant but the highlighted toxicological aspects of mayapple, emphasize the need for caution in its use due to its potential for systemic toxicity when consumed in excessive doses.
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Surface rheology becomes important for droplets with adsorbed proteins, solid particulates, lipids, or polymers, and understanding how surface rheology alters basic droplet processes like coalescence ...provides insight into the processing of dispersions in industrial and biological systems. In this work, we model the approach of two equal-size deformable droplets under an axisymmetric, biaxial extensional flow in the Stokes flow limit. We explore how the viscosity contrast between the drop and suspending fluid alters the film drainage behaviour when interfacial viscosity is present. For a clean droplet at a fixed capillary number, the drainage time is observed to be independent of the viscosity ratio (λ) for λ≤O(1), while the drainage increases linearly with the viscosity ratio for λ≥O(1). Surface viscosity increases the drainage time by causing the thin film between the droplets to flatten and widen, and shifts the viscosity ratio at which the aforementioned scaling behaviour changes to larger values. The drainage time is increased more significantly at lower viscosity ratio values than higher values. In the second half of the paper, we examine how surface viscosity alters film drainage when the surfactant can be soluble. We examine the kinetically controlled adsorption/desorption limit. We find that surfactant solubility abolishes surface tension gradients and increases the prominence of surface viscosity effects, the effects of which are quantified for Boussinesq numbers Bq∼O(0.1).
The intestinal messenger RNA expression signature is affected by the presence and composition of the endogenous microbiota, with effects on host physiology. The intestine is also characterized by a ...distinctive micronome. However, it is not known if microbes also impact intestinal gene expression epigenetically. We investigated if the murine caecal microRNA expression signature depends on the presence of the microbiota, and the potential implications of this interaction on intestinal barrier function. Three hundred and thirty four microRNAs were detectable in the caecum of germ-free and conventional male mice and 16 were differentially expressed, with samples from the two groups clustering separately based on their expression patterns. Through a combination of computational and gene expression analyses, including the use of our curated list of 527 genes involved in intestinal barrier regulation, 2,755 putative targets of modulated microRNAs were identified, including 34 intestinal barrier-related genes encoding for junctional and mucus layer proteins and involved in immune regulation. This study shows that the endogenous microbiota influences the caecal microRNA expression signature, suggesting that microRNA modulation is another mechanism through which commensal bacteria impact the regulation of the barrier function and intestinal homeostasis. Through microRNAs, the gut microbiota may impinge a much larger number of genes than expected, particularly in diseases where its composition is altered. In this perspective, abnormally expressed microRNAs could be considered as novel therapeutic targets.
We previously reported that at term pregnancy, a decline in myometrial protein kinase A (PKA) activity leads to an exchange protein activated by cyclic AMP (Epac1)-dependent increase in oxytocin ...receptor (OTR) expression, promoting the onset of labour. Here, we studied the changes in the cyclic adenosine monophosphate (cAMP) effector system present in different phenotypes of preterm labour (PTL). Myometrial biopsies obtained from women with phenotypically distinct forms of PTL and the levels of PKA and OTR were examined. Although we found similar changes in the cAMP effector pathway in all forms of PTL, only in the case of twin PTL (T-PTL) was myometrial OTR levels increased in association with these results. Although there were several changes in the mRNA levels of components of the cAMP synthetic pathway, the total myometrial cAMP levels did not change with the onset of any subtype of PTL. With regards to the expression of cAMP-responsive genes, we found that the mRNA levels of 4 of the 5 cAMP-down-regulated genes were increased in T-PTL, similar to our findings in term labour. These data signify that although changes in the cAMP effector system were common to all forms of PTL, only in T-PTL were OTR levels increased. Similarly, the mRNA levels of cAMP-repressed genes were only increased in T-PTL supporting the concept that the decline in PKA levels influences myometrial function driving the onset of T-PTL.
Objective Uterine overdistention is thought to induce preterm labor in women with twin and multiple pregnancies, but the pathophysiology remains unclear. We investigated for the first time the ...pathogenesis of preterm birth associated with rapid uterine distention in a pregnant nonhuman primate model. Study Design A nonhuman primate model of uterine overdistention was created using preterm chronically catheterized pregnant pigtail macaques ( Macaca nemestrina ) by inflation of intraamniotic balloons (N = 6), which were compared to saline controls (N = 5). Cesarean delivery was performed due to preterm labor or at experimental end. Microarray, quantitative reverse transcriptase polymerase chain reaction, Luminex (Austin, TX), and enzyme-linked immunosorbent assay were used to measure messenger RNA (mRNA) and/or protein levels from monkey (amniotic fluid, myometrium, maternal plasma) and human (amniocytes, amnion, myometrium) tissues. Statistical analysis employed analysis of covariance and Wilcoxon rank sum. Biomechanical forces were calculated using the law of Laplace. Results Preterm labor occurred in 3 of 6 animals after balloon inflation and correlated with greater balloon volume and uterine wall stress. Significant elevations of inflammatory cytokines and prostaglandins occurred following uterine overdistention in an “inflammatory pulse” that correlated with preterm labor (interleukin IL-1β, tumor necrosis factor TNF-α, IL-6, IL-8, CCL2, prostaglandin E2, prostaglandin F2α, all P < .05). A similar inflammatory response was observed in amniocytes in vitro following mechanical stretch (IL1β, IL6, and IL8 mRNA multiple time points, P < .05), in amnion of women with polyhydramnios (IL6 and TNF mRNA, P < .05) and in amnion (TNF-α) and myometrium of women with twins in early labor (IL6, IL8, CCL2, all P < .05). Genes differentially expressed in the nonhuman primate after balloon inflation and in women with polyhydramnios and twins are involved in tissue remodeling and muscle growth. Conclusion Uterine overdistention by inflation of an intraamniotic balloon is associated with an inflammatory pulse that precedes and correlates with preterm labor. Our results indicate that inflammation is an early event after a mechanical stress on the uterus and leads to preterm labor when the stress is sufficiently great. Further, we find evidence of uterine tissue remodeling and muscle growth as a common, perhaps compensatory, response to uterine distension.
Oral microbes form a complex and dynamic biofilm community, which is subjected to daily host and environmental challenges. Dysbiosis of the oral biofilm is correlated with local and distal infections ...and postulating a baseline for the healthy core oral microbiota provides an opportunity to examine such shifts during the onset and recurrence of disease. Here we quantified the daily, weekly, and monthly variability of the oral microbiome by sequencing the largest oral microbiota time-series to date, covering multiple oral sites in ten healthy individuals. Temporal dynamics of salivary, dental, and tongue consortia were examined by high-throughput 16S rRNA gene sequencing over 90 days, with four individuals sampled additionally 1 year later. Distinct communities were observed between dental, tongue, and salivary samples, with high levels of similarity observed between the tongue and salivary communities. Twenty-six core OTUs that classified within
, and
genera were present in ≥95% samples and accounted for ~65% of the total sequence data. Phylogenetic diversity varied from person to person, but remained relatively stable within individuals over time compared to inter-individual variation. In contrast, the composition of rare microorganisms was highly variable over time, within most individuals. Using machine learning, an individual's oral microbial assemblage could be correctly assigned to them with 88-97% accuracy, depending on the sample site; 83% of samples taken a year after initial sampling could be confidently traced back to the source subject.
Inflammation is thought to play a pivotal role in the onset of term and some forms of preterm labour. Although, we recently found that myometrial inflammation is a consequence rather than a cause of ...term labour, there are several other reproductive tissues, including amnion, choriodecidua parietalis and decidua basalis, where the inflammatory stimulus to labour may occur. To investigate this, we have obtained amnion, choriodecidual parietalis and decidua basalis samples from women at various stages of pregnancy and spontaneous labour. The inflammatory cytokine profile in each tissue was determine by Bio-Plex Pro® cytokine multiplex assays and quantitative RT-PCR. Active motif assay was used to study transcription activation in the choriodecidua parietalis. Quantitative RT-PCR was use to study the pro-labour genes (PGHS-2, PGDH, OTR and CX43) in all of the tissues at the onset of labour and oxytocin (OT) mRNA expression in the choriodecidual parietalis and decidua basalis. Statistical significance was ascribed to a P value <0.05. In the amnion and choriodecidua parietalis, the mRNA levels of various cytokines decreased from preterm no labour to term no labour samples, but the protein levels were unchanged. The choriodecidua parietalis showed increase in the protein levels of IL-1beta and IL-6 in the term early labour samples. In the amnion and decidua basalis, the protein levels of several cytokines rose in term established labour. The multiples of the median derived from the 19-plex cytokine assay were greater in term early labour and term established labour samples from the choriodecidua parietalis, but only in term established labour for myometrium. These data suggest that the inflammatory stimulus to labour may begin in the choriodecidua parietalis, but the absence of any change in prolabour factor mRNA levels suggests that the cytokines may act on the myometrium where we observed changes in transcription factor activation and increases in prolabour gene expression in earlier studies.
With the onset of COVID-19, the development of ex vivo laboratory models became an urgent priority to study host-pathogen interactions in response to the pandemic. In this study, we aimed to ...establish an ex vivo mucosal tissue explant challenge model for studying SARS-CoV-2 infection and replication. Nasal or oral tissue samples were collected from eligible participants and explants generated from the tissue were infected with various SARS-CoV-2 strains, including IC19 (lineage B.1.13), Beta (lineage B.1.351) and Delta (lineage B.1.617.2). A qRT-PCR assay used to measure viral replication in the tissue explants over a 15-day period, demonstrated no replication for any viral strains tested. Based on this, the ex vivo challenge protocol was modified by reducing the viral infection time and duration of sampling. Despite these changes, viral infectivity of the nasal and oral mucosa was not improved. Since 67% of the enrolled participants were already vaccinated against SARS-CoV-2, it is possible that neutralizing antibodies in explant tissue may have prevented the establishment of infection. However, we were unable to optimize plaque assays aimed at titrating the virus in supernatants from both infected and uninfected tissue, due to limited volume of culture supernatant available at the various collection time points. Currently, the reasons for the inability of these mucosal tissue samples to support replication of SARS-CoV-2 ex vivo remains unclear and requires further investigation.
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