DNA methylation is the most well studied of the epigenetic regulators in relation to environmental exposures. To date, numerous studies have detailed the manner by which DNA methylation is influenced ...by the environment, resulting in altered global and gene-specific DNA methylation. These studies have focused on prenatal, early-life, and adult exposure scenarios. The present review summarizes currently available literature that demonstrates a relationship between DNA methylation and environmental exposures. It includes studies on aflatoxin B
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, air pollution, arsenic, bisphenol A, cadmium, chromium, lead, mercury, polycyclic aromatic hydrocarbons, persistent organic pollutants, tobacco smoke, and nutritional factors. It also addresses gaps in the literature and future directions for research. These gaps include studies of mixtures, sexual dimorphisms with respect to environmentally associated methylation changes, tissue specificity, and temporal stability of the methylation marks.
After the initial shock of the early months of the global COVID-19 pandemic, international collaboration in COVID-19 research continues to show aberrant patterns compared to coronavirus research in ...pre-COVID times. The most affected nations tend to produce the greatest number of coronavirus articles, with output closely coupled to the rate of infection. COVID-19 research has fewer nations and smaller teams than pre-COVID research, a trend which intensifies throughout the pandemic. The United States remains the single largest contributor to the global publication output, but contrary to China’s dominance in the initial months of the pandemic, China’s contribution falls as the national COVID-19 caseload drops. China-USA collaborations drop as the pandemic continues, perhaps due to China’s reduced rate of publication on the topic, and perhaps due to political obstacles, or a combination of these factors.
Per- and polyfluoroalkyl substances (PFAS), a class of environmental contaminants, have been detected in human placenta and cord blood. The mechanisms driving PFAS-induced effects on the placenta and ...adverse pregnancy outcomes are not well understood. This study investigated the impact of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and a replacement PFAS known as hexafluoropropylene oxide dimer acid (HFPO-DA, tradename GenX) on placental trophoblasts in vitro. Several key factors were addressed. First, PFAS levels in cell culture reagents at baseline were quantified. Second, the role of supplemental media serum in intracellular accumulation of PFAS in a human trophoblast (JEG3) cell line was established. Finally, the impact of PFAS on the expression of 96 genes involved in proper placental function in JEG3 cells was evaluated. The results revealed that serum-free media (SFM) contained no detectable PFAS. In contrast, fetal bovine serum-supplemented media (SSM) contained PFNA, PFUdA, PFTrDA, and 6:2 FTS, but these PFAS were not detected internally in cells. Intracellular accumulation following 24 hr treatments was significantly higher when cultured in SFM compared to SSM for PFOS and PFOA, but not HFPO-DA. Treatment with PFAS was associated with gene expression changes (n = 32) in pathways vital to placental function, including viability, syncytialization, inflammation, transport, and invasion/mesenchymal transition. Among the most robust PFAS-associated changes were those observed in the known apoptosis-related genes, BAD and BAX. These results suggest a complex relationship between PFAS, in vitro culture conditions, and altered expression of key genes necessary for proper placentation.
Numerous examples have been presented of enzyme activities, assayed in vitro, that appear relevant to the synthesis of structural polysaccharides, and to their assembly and subsequent degradation in ...the primary cell walls (PCWs) of higher plants. The accumulation of the corresponding mRNAs, and of the (immunologically recognized) proteins, has often also (or instead) been reported. However, the presence of these mRNAs, antigens and enzymic activities has rarely been shown to correspond to enzyme action in the living plant cell. In some cases, apparent enzymic action is observed in vivo for which no enzyme activity can be detected in in-vitro assays; the converse also occurs. Methods are reviewed by which reactions involving structural wall polysaccharides can be tracked in vivo. Special attention is given to xyloglucan endotransglucosylase (XET), one of the two enzymic activities exhibited in vitro by xyloglucan endotransglucosylase/hydrolase (XTH) proteins, because of its probable importance in the construction and restructuring of the PCW's major hemicellulose. Attention is also given to the possibility that some reactions observed in the PCW in vivo are not directly enzymic, possibly involving the action of hydroxyl radicals. It is concluded that some proposed wall enzymes, for example XTHs, do act in vivo, but that for other enzymes this is not proven.
Preeclampsia (PE), a condition during pregnancy that involves high blood pressure and proteinuria, is potentially fatal to both mother and child. PE currently has no known etiology or cure but has ...been tied to poor placental trophoblast cell migration. Increased levels of the toxic metal cadmium (Cd) have been associated with increased risk of developing PE, as well as miRNA-associated regulation of the transforming growth factorbeta (TGF-β) pathway. Signal reprogramming of the TGF-β pathway via epigenetic mechanisms is hypothesized to modify placental trophoblast function. In the present study we investigated the role of increased and decreased signaling of the TGF-β pathway in relation to Cd-induced reduction in cellular migration in JEG3 trophoblast cells. Furthermore, the role of a miR-26a as a molecular mediator of placental trophoblast migration was confirmed. The results demonstrate that increased expression of miR-26a and decreased signaling of the TGF-β pathway increase placental cell migration. These findings have relevance for mechanistic understanding of the underpinnings of poor placentation associated with PE.
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•Cadmium treatment decreases placental trophoblast migration.•Increased TGF-β pathway signaling results in diminished trophoblast migration.•TGF-β pathway-targeting miRNAs are critical in regulating trophoblast migration.•miRNAs have the potential as therapeutic targets for cadmium-associated PE.
Exposure to cigarette smoke is known to result in impaired host defense responses and immune suppressive effects. However, the effects of new and emerging tobacco products, such as e-cigarettes, on ...the immune status of the respiratory epithelium are largely unknown. We conducted a clinical study collecting superficial nasal scrape biopsies, nasal lavage, urine, and serum from nonsmokers, cigarette smokers, and e-cigarette users and assessed them for changes in immune gene expression profiles. Smoking status was determined based on a smoking history and a 3- to 4-wk smoking diary and confirmed using serum cotinine and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels. Total RNA from nasal scrape biopsies was analyzed using the nCounter Human Immunology v2 Expression panel. Smoking cigarettes or vaping e-cigarettes resulted in decreased expression of immune-related genes. All genes with decreased expression in cigarette smokers (n = 53) were also decreased in e-cigarette smokers. Additionally, vaping e-cigarettes was associated with suppression of a large number of unique genes (n = 305). Furthermore, the e-cigarette users showed a greater suppression of genes common with those changed in cigarette smokers. This was particularly apparent for suppressed expression of transcription factors, such as EGR1, which was functionally associated with decreased expression of 5 target genes in cigarette smokers and 18 target genes in e-cigarette users. Taken together, these data indicate that vaping e-cigarettes is associated with decreased expression of a large number of immune-related genes, which are consistent with immune suppression at the level of the nasal mucosa.
Basketball is a sport that is characterized by various physical performance parameters and motor abilities such as speed, strength, and endurance, which are all underpinned by an athlete’s efficient ...use of the stretch-shortening cycle (SSC). A common assessment to measure SSC efficiency is the countermovement jump (CMJ). When performed on a force plate, a plethora of different force-time metrics may be gleaned from the jump task, reflecting neuromuscular performance characteristics. The aim of this study was to investigate how different CMJ force-time characteristics change across different parts of the athletic year, within a sample of elite collegiate male basketball players. Twelve basketball players performed CMJ’s on near-weekly basis, combining for a total of 219 screenings. The span of testing was broken down into four periods: pre-season, non-conference competitive period, conference competitive period, and post-season competitive period. Results suggest that basketball players were able to experience improvements and maintenance of performance with regards to various force-time metrics, transitioning from the pre-season period into respective later phases of the in-season period. A common theme was a significant improvement between the pre-season period and the non-conference period. Various force-time metrics were subject to change, while outcome metrics such as jump height remained unchanged, suggesting that practitioners are encouraged to more closely monitor how different force-time characteristics change over extended periods of time.
Background
Enhanced recovery programmes (ERPs) have been shown to reduce length of hospital stay (LOS) and complications in colorectal surgery. Whether ERPs have the same benefits in open liver ...resection surgery is unclear, and randomized clinical trials are lacking.
Methods
Consecutive patients scheduled for open liver resection were randomized to an ERP group or standard care. Primary endpoints were time until medically fit for discharge (MFD) and LOS. Secondary endpoints were postoperative morbidity, pain scores, readmission rate, mortality, quality of life (QoL) and patient satisfaction. ERP elements included greater preoperative education, preoperative oral carbohydrate loading, postoperative goal‐directed fluid therapy, early mobilization and physiotherapy. Both groups received standardized anaesthesia with epidural analgesia.
Results
The analysis included 46 patients in the ERP group and 45 in the standard care group. Median MFD time was reduced in the ERP group (3 days versus 6 days with standard care; P < 0·001), as was LOS (4 days versus 7 days; P < 0·001). The ERP significantly reduced the rate of medical complications (7 versus 27 per cent; P = 0·020), but not surgical complications (15 versus 11 per cent; P = 0·612), readmissions (4 versus 0 per cent; P = 0·153) or mortality (both 2 per cent; P = 0·987). QoL over 28 days was significantly better in the ERP group (P = 0·002). There was no difference in patient satisfaction.
Conclusion
ERPs for open liver resection surgery are safe and effective. Patients treated in the ERP recovered faster, were discharged sooner, and had fewer medical‐related complications and improved QoL. Registration number: ISRCTN03274575 (http://www.controlled‐trials.com).
Faster recovery and discharge