Abstract
The mammalian gut harbors a complex and dynamic microbial ecosystem: the microbiota. While emerging studies support that microbiota regulates brain function with a few molecular cues ...suggested, the overall biochemical landscape of the “microbiota-gut-brain axis” remains largely unclear. Here we use high-coverage metabolomics to comparatively profile feces, blood sera, and cerebral cortical brain tissues of germ-free C57BL/6 mice and their age-matched conventionally raised counterparts. Results revealed for all three matrices metabolomic signatures owing to microbiota, yielding hundreds of identified metabolites including 533 altered for feces, 231 for sera, and 58 for brain with numerous significantly enriched pathways involving aromatic amino acids and neurotransmitters. Multicompartmental comparative analyses single out microbiota-derived metabolites potentially implicated in interorgan transport and the gut-brain axis, as exemplified by indoxyl sulfate and trimethylamine-
N
-oxide. Gender-specific characteristics of these landscapes are discussed. Our findings may be valuable for future research probing microbial influences on host metabolism and gut-brain communication.
Genetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and ...interpretation of pathway alteration patterns of individual patients.
We sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Eligibility for targeted therapy was determined for each patient by a pathway-based approach. The analysis covered DNA repair, receptor tyrosine kinase, PI3K/AKT/MTOR, RAS/MAPK, cell cycle, and hedgehog pathways, and included 14 drug targets.
Postulated PARP, MTOR, and CDK4/6 inhibition sensitivity were most common. BRCA1/2 alterations, PTEN loss, and gain of PIK3CA and CCND1 were characteristic for high-grade serous carcinomas. Mutations of ARID1A, PIK3CA, and KRAS, and ERBB2 gain were enriched in the other histologies. PTEN mutations and high tumor mutational burden were characteristic for endometrioid carcinomas. Drug target downstream alterations impaired actionability in all histologies, and many alterations would not have been discovered by key gene mutational analysis. Individual patients often had more than one actionable drug target.
Genetic alterations in ovarian carcinomas are complex and differ among histologies. Our results aid the personalization of therapy and biomarker analysis for clinical studies, and indicate a high potential for combinations of targeted therapies.
This study aims to explore the influential factors that reduce risk perception and encourage travel amongst senior citizens. Self-efficacy and social influence are suggested as two antecedents. The ...moderating roles of destination image and perceived value are also discussed. The results of this study show that self-efficacy has a negative effect on financial risk and socio-psychological risk, whereas social influence has a positive effect on financial risk. In addition, self-efficacy and social influence are important factors that increase seniors’ revisit intentions. Seniors’ environmental risk perception has a significant impact on revisit intention, while socio-psychological risk increases revisit intention. The moderating roles of destination image and perceived value can facilitate the positive effects of self-efficacy and social influence on revisit intention. Furthermore, destination image is also an important moderator that makes seniors neglect the threat of financial loss and travel again in the future.
•Participants expressed lower fatigue and depression after viewing nature scenes.•Virtual nature scenes rated higher in perceived restorativeness.•Virtual natural environments were described as ...appeasing and relaxing.•VR natural settings can be a restorative experience for middle-aged and elderly group.
Previous studies have demonstrated health benefits result from exposure to natural environments. Virtual reality (VR) may offer an alternative to actual outdoor immersion by generating a simulated health-promoting environment. Given that health issues are more prevalent in older adults, this study investigated the restorative effects of virtual natural settings on middle-aged and elderly adults. A cross-over pretest-posttest design was used to measure changes in participants’ mood levels, physiological and psychological responses, and attentional measures of cognitive functioning (N = 34). Semi-structured interviews after the VR experiences were conducted to evaluate participants’ experiences. Physiological responses to VR did not differ between virtual natural and urban settings. In contrast, participants expressed more positive feelings and lower levels of fatigue and depression after viewing virtual nature settings than after viewing virtual urban settings. Virtual nature settings were also rated as more restorative than virtual urban settings. Further, participants described virtual natural settings as appeasing and relaxing, so much so that they were motivated to travel outdoors to experience the settings shown in VR. Our findings provide additional evidence that viewing simulated natural settings in VR can be beneficial for this population. Perhaps the most promising finding is that VR may motivate older adults to experience nature outdoors, thus promoting synergistic benefits first during virtual exposure and then during actual exposure.
The aim of this study was to investigate the ameliorative effects of fish oil on hepatic injury in ethanol-fed rats based on the intestinal permeability and microbiota. Rats were assigned to 6 groups ...and fed either a control diet or an ethanol diet such as C (control), CF25 (control with 25% fish oil), CF57 (control with 57% fish oil), E (ethanol), EF25 (ethanol with 25% fish oil), and EF57 (ethanol with 57% fish oil) groups. Rats were sacrificed at the end of 8 weeks. Plasma aspartate aminotransferase (AST) and aminotransferase (ALT) activities, hepatic cytokines, and plasma endotoxin levels were significantly higher in the E group. In addition, hepatic histopathological analysis scores in the E group were significantly elevated. Rats in the E group also showed increased intestinal permeability and decreased numbers of fecal Bifidobacterium. However, plasma AST and ALT activities and hepatic cytokine levels were significantly lower in the EF25 and EF57 groups. Histological changes and intestinal permeability were also improved in the EF25 and EF57 groups. The fecal Escherichia coli numbers were significantly lower, but fecal Bifidobacterium numbers were significantly higher in the EF25 and EF57 groups.
Aims and objectives
This study reviewed existing literature to investigate how frequently nurses include complementary and alternative forms of medicine in their clinical practice. In so doing, we ...investigated nurses' knowledge of and attitudes towards complementary and alternative medicine as well as their ability to communicate the risks and benefits of these therapies with patients.
Background
Little information is available concerning nurses' knowledge and attitudes towards complementary and alternative medicine or how they incorporate these therapies into their practice. In addition, little is known about the ability of nurses to communicate the risks and benefits of complementary and alternative medicine to their patients.
Study design
This study used a scoping review method to map and synthesise existing literature.
Data sources
Both electronic and manual searches were used to identify relevant studies published between January 2007 and January 2014.
Review methods
The review was conducted in five stages: (1) identification of research question(s), (2) locate studies, (3) selection of studies, (4) charting of data, and (5) collating, summarising, and reporting of results.
Results
Fifteen papers met the inclusion criteria for this review, among which 53·7% referenced how frequently nurses include complementary and alternative medicine in their practice. We found that 66·4% of nurses had positive attitudes towards complementary and alternative medicine; however, 77·4% did not possess a comprehensive understanding of the associated risks and benefits. In addition, nearly half of the respondents (47·3–67·7%) reported feeling uncomfortable discussing complementary and alternative medicine therapies with their patients.
Conclusion
The lack of knowledge about complementary and alternative medicine among nurses is a cause for concern, particularly in light of its widespread application.
Relevance to clinical practice
Findings from this study suggest that health care professionals need to promote evidence informed decision‐making in complementary and alternative medicine practice and be knowledgeable enough to discuss complementary and alternative medicine therapies. Without involvement of complementary and alternative medicine communication on the part of our profession, we may put our patients at risk of uninformed and without medical guidance.
Arsenic exposure can perturb gut microbiota and their metabolic functions. We exposed C57BL/6 mice to 1 ppm arsenic in drinking water and investigated whether arsenic exposure affects the homeostasis ...of bile acids, a group of key microbiome-regulated signaling molecules of microbiome–host interactions. We found that arsenic exposure differentially changed major unconjugated primary bile acids and consistently decreased secondary bile acids in the serum and liver. The relative abundance of Bacteroidetes and Firmicutes was associated with the bile acid level in serum. This study demonstrates that arsenic-induced gut microbiota dysbiosis may play a role in arsenic-perturbed bile acid homeostasis.
Single-cell nanopore sequencing of full-length mRNAs transforms single-cell multi-omics studies. However, challenges include high sequencing errors and dependence on short-reads and/or barcode ...whitelists. To address these, we develop scNanoGPS to calculate same-cell genotypes (mutations) and phenotypes (gene/isoform expressions) without short-read nor whitelist guidance. We apply scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell-lines. Standalone, scNanoGPS deconvolutes error-prone long-reads into single-cells and single-molecules, and simultaneously accesses both phenotypes and genotypes of individual cells. Our analyses reveal that tumor and stroma/immune cells express distinct combination of isoforms (DCIs). In a kidney tumor, we identify 924 DCI genes involved in cell-type-specific functions such as PDE10A in tumor cells and CCL3 in lymphocytes. Transcriptome-wide mutation analyses identify many cell-type-specific mutations including VEGFA mutations in tumor cells and HLA-A mutations in immune cells, highlighting the critical roles of different mutant populations in tumors. Together, scNanoGPS facilitates applications of single-cell long-read sequencing technologies.
Formation of DNA adducts is a key event during carcinogenesis. DNA adducts, if not repaired properly, can lead to mutations and cancer. DNA adducts have been frequently used as biomarkers to evaluate ...chemical exposure. Vinyl acetate monomer (VAM) is widely used in the manufacture of various industrial polymers. Previous studies have documented that VAM induced nasal tumors in rodents exposed to high exposure levels of VAM. VAM is metabolized by carboxylesterase to acetaldehyde (AA), which subsequently results in DNA adducts. However, AA is also an endogenous metabolite in living cells, which impedes accurate assessment of the contribution of VAM exposure under the substantial endogenous background. To address this challenge, we exposed rats to stable isotope labeled 13C2-VAM at 50, 200, and 400 ppm through inhalation for 6 h, followed by DNA adduct analysis in nasal respiratory and olfactory epithelia with highly sensitive mass spectrometry. Our results show that exogenous N 2-ethyl-dG adducts were present in all rats exposed to 13C2-VAM, with over 2-fold higher DNA adducts in nasal respiratory epithelium than olfactory epithelium. Our data also show that N 2-ethyl-dG is a more sensitive biomarker to assess VAM exposure than 1,N 2-propano-dG adducts. Moreover, a very low amount of exogenous N 2-ethyl-dG adducts were detected in peripheral blood mononuclear cell samples of exposed rats, suggesting that only an extremely small percentage of 13C2-VAM or its metabolite may enter into systemic circulation to potentially damage tissues beyond nasal epithelium. Furthermore, exogenous N 2-ethyl-dG DNA adducts undergo rapid repair or spontaneous loss in nasal epithelium of exposed rats. Taken together, the results presented herein provide novel quantitative data and lay the foundation for future studies to improve risk assessment of VAM.
Inhibition of microglial over-activation is an important strategy to counter balance neurodegenerative progression. We previously demonstrated that the adenosine monophosphate-activated protein ...kinase (AMPK) may be a therapeutic target in mediating anti-neuroinflammatory responses in microglia. Brain-derived neurotrophic factor (BDNF) is one of the major neurotrophic factors produced by astrocytes to maintain the development and survival of neurons in the brain, and have recently been shown to modulate homeostasis of neuroinflammation. Therefore, the present study focused on BDNF-mediated neuroinflammatory responses and may provide an endogenous regulation of neuroinflammation. Among the tested neuroinflammation, epigallocatechin gallate (EGCG) and minocycline exerted BDNF upregulation to inhibit COX-2 and proinflammatory mediator expressions. Furthermore, both EGCG and minocycline upregulated BDNF expression in microglia through AMPK signaling. In addition, minocycline and EGCG also increased expressions of erythropoietin (EPO) and sonic hedgehog (Shh). In the endogenous modulation of neuroinflammation, astrocyte-conditioned medium (AgCM) also decreased the expression of COX-2 and upregulated BDNF expression in microglia. The anti-inflammatory effects of BDNF were mediated through EPO/Shh in microglia. Our results indicated that the BDNF-EPO-Shh novel-signaling pathway underlies the regulation of inflammatory responses and may be regarded as a potential therapeutic target in neurodegenerative diseases. This study also reveals a better understanding of an endogenous crosstalk between astrocytes and microglia to regulate anti-inflammatory actions, which could provide a novel strategy for the treatment of neuroinflammation and neurodegenerative diseases.
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