Antrodia camphorata Supplementation during Early Life Alters Gut Microbiota and Inhibits Young-Onset Intestinal Tumorigenesis in APC1638N Mice Later in Life.

Young-onset colorectal cancer is an increasing concern worldwide due to the growing prevalence of Westernized lifestyles in childhood and adolescence. Environmental factors during early life, particularly early-life nutrition, significantly contribute to the increasing incidence. Recently, there have been reports of beneficial effects, including anti-inflammation and anti-cancer, of a unique fungus (Antrodia camphorate, AC) native to Taiwan. The objective of this study is to investigate the impact of AC supplementation in early life on the development of young-onset intestinal tumorigenesis. APC1638N mice were fed with a high-fat diet (HF) at 4-12 weeks of age, which is equivalent to human childhood/adolescence, before switching to a normal maintenance diet for an additional 12 weeks up to 24 weeks of age, which is equivalent to young to middle adulthood in humans. Our results showed that the body weight in the HF groups significantly increased after 8 weeks of feeding (p < 0.05). Following a switch to a normal maintenance diet, the change in body weight persisted. AC supplementation significantly suppressed tumor incidence and multiplicity in females (p < 0.05) and reduced IGF-1 and Wnt/ß-catenin signaling (p < 0.05). Moreover, it altered the gut microbiota, suppressed inflammatory responses, and created a microenvironment towards suppressing tumorigenesis later in life.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Detection of human enteric viruses in fresh produce of markets, farms and surface water used for irrigation in the Tehran, Iran.

Considering the major role of vegetables in the transmission of gastrointestinal diseases, investigation of the presence of gastrointestinal viruses is particularly important for public health. Additionally, monitoring and investigating potential points of contamination at various stages of cultivation, harvesting, and distribution can be important in identifying the sources of transmission. This study was conducted with the aim of identifying norovirus, adenovirus, hepatitis A virus, hepatitis E virus, rotaviruses, and astroviruses in vegetable samples from the fields and fruit and vegetable centers of Tehran City, and to investigate their presence in irrigation water by RT-qPCR. This study was carried out in two phases: initial and supplementary. During phase I, a total of 3 farms and 5 fruit and vegetable centers and a total of 35 samples from farms, 102 samples from fruit and vegetable centers and 8 agricultural water samples were collected. Zero, 16 and 1 samples were positive for at least one of the viruses from each of the sources, respectively. During phase II, 88 samples from 23 farms, 226 samples from 50 fruit and vegetable centers and 16 irrigation water samples were collected, with 23, 57 and 4 samples were positive for at least one virus, respectively. Rotavirus was the most frequently identified virus among the samples, followed by NoV GII, NoV GI, AstV, and AdV. HAV and HEV were not detected in any of the tested samples. The results of this study suggest that there may be a wide presence of viruses in vegetables, farms, and fruit and vegetable centers in Tehran City, which could have significant consequences considering the fact that many of these foods are consumed raw. Additionally, the detection of some of these viruses in irrigation water suggests that this may be a potential route for viral contamination of produce.

Turicibacter fermentation enhances the inhibitory effects of Antrodia camphorata supplementation on tumorigenic serotonin and Wnt pathways and promotes ROS-mediated apoptosis of Caco-2 cells.

Introduction: Diet-induced obesity has been shown to decrease the abundance of Turicibacter, a genus known to play a role in the serotonin signaling system, which is associated with colorectal tumorigenesis, making the presence of Turicibacter potentially influential in the protection of intestinal tumorigenesis. Recently, Antrodia camphorata (AC), a medicinal fungus native to Taiwan, has emerged as a promising candidate for complementary and alternative cancer therapy. Small molecules and polysaccharides derived from AC have been reported to possess health-promoting effects, including anti-cancer properties. Methods: Bacterial culture followed with cell culture were used in this study to determine the role of Turicibacter in colorectal tumorigenesis and to explore the anti-cancer mechanism of AC with Turicibacter fermentation. Results: Turicibacter fermentation and the addition of AC polysaccharide led to a significant increase in the production of nutrients and metabolites, including α-ketoglutaric acid and lactic acid (p < 0.05). Treatment of Turicibacter fermented AC polysaccharide was more effective in inhibiting serotonin signaling-related genes, including Tph1, Htr1d, Htr2a, Htr2b, and Htr2c (p < 0.05), and Wnt-signaling related protein and downstream gene expressions, such as phospho-GSK-3ß, active ß-catenin, c-Myc, Ccnd1, and Axin2 (p < 0.05). Additionally, it triggered the highest generation of reactive oxygen species (ROS), which activated PI3K/Akt and MAPK/Erk signaling and resulted in cleaved caspase-3 expression. In comparison, the treatment of AC polysaccharide without Turicibacter fermentation displayed a lesser effect. Discussion: Our findings suggest that AC polysaccharide effectively suppresses the tumorigenic serotonin and Wnt-signaling pathways, and promotes ROS-mediated apoptosis in Caco-2 cells. These processes are further enhanced by Turicibacter fermentation.

Improving Single-Molecule Antibody Detection Selectivity through Optimization of Peptide Epitope Presentation in OmpG Nanopore.

Outer membrane protein G (OmpG) is a monomeric porin found in Escherichia coli, which possesses seven flexible loops. OmpG has been engineered as a nanopore sensor, where its loops can host affinity epitopes for selective detection of biological molecules. In this study, we investigated various loop positions to incorporate a FLAG peptide antigen epitope in the most flexible loop 6 and tested the efficacy and sensitivity of these nanopore constructs in antibody detection. We observed an OmpG construct containing inserted FLAG sequence, which exhibited strong interaction with anti-FLAG antibodies in flow cytometry; however, it could not translate molecule interactions into a readable signal in current recordings. Further optimization of the peptide presentation strategy by replacing specific sections of loop 6 sequences with the FLAG tag created a construct capable of generating unique and distinct signals when interacting with various monoclonal or polyclonal anti-FLAG clones IgG antibodies in the mixture. The peptide display scheme demonstrated in this study can be generalized for the engineering of OmpG sensors, which can be used for screening and validating positive clones during antibody development, as well as for real-time quality control of cell cultures in monoclonal antibody production.

An Engineered OmpG Nanopore with Displayed Peptide Motifs for Single-Molecule Multiplex Protein Detection.

Molecular detection via nanopore, achieved by monitoring changes in ionic current arising from analyte interaction with the sensor pore, is a promising technology for multiplex sensing development. Outer Membrane Protein G (OmpG), a monomeric porin possessing seven functionalizable loops, has been reported as an effective sensing platform for selective protein detection. Using flow cytometry to screen unfavorable constructs, we identified two OmpG nanopores with unique peptide motifs displayed in either loop 3 or 6, which also exhibited distinct analyte signals in single-channel current recordings. We exploited these motif-displaying loops concurrently to facilitate single-molecule multiplex protein detection in a mixture. We additionally report a strategy to increase sensor sensitivity via avidity motif display. These sensing schemes may be expanded to more sophisticated designs utilizing additional loops to increase multiplicity and sensitivity.

Stigma, Opioids, and Public Health Messaging: The Need to Disentangle Behavior From Identity.

Stigma plays an important role in understanding successful interventions to control the opioid epidemic in the United States. Stigma has been described both as an agent to incentivize positive health behavior and as an agent of marginalization contributing to poorer health. Past scholarship has argued that stigma has positively motivated public health changes, for example, among tobacco users; it has also been associated with discrimination against vulnerable individuals, resulting in increasingly poorer health behaviors, for example in relation to HIV-prevention messaging.The discourse on stigma may conflate the denormalization of unhealthy behaviors with wholesale rejection of individual identities. More effective interventions would counter stigma against people who use opioids in general and specifically denormalize opioid misuse. These interventions might alter the effect of public health messaging and ultimately improve outcomes.We argue that public health educators and communication campaigns can contribute to positive social norm change and motivate healthy behaviors by incorporating strategies that attempt to disentangle unhealthy behaviors from identity.