Parajuli, A*
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ETHNOPHARMACOLOGICAL RELEVANCE: Neopicrorhiza scrophulariiflora (Pennell) Hong is important medicinal plant that is native to the eastern Himalayas and Hengduan mountains in China. It is also distributed in Nepal, north east India, Bhutan and northern Myanmar. Plant parts are traditionally used against different kinds of diseases and various compounds present in different plant parts are also effective against many diseases. Thus, N. scrophulariiflora has a high potential to maintain human health. AIM OF THE REVIEW: Although N. scrophulariiflora is very important and widely studied plant species but there is no comprehensive up-to-date review of published and unpublished literature. So, in the present article we have compiled and critically commented on the botanical characteristics, traditional uses, plant growth and cultivation, micropropagation, conservation status, secondary metabolites, pharmacology and toxicity of the plant. MATERIALS AND METHODS: Extensive literature searches both electronic online databases (Google Scholar, Scopus, Springer Link, Web of Science, ScienceDirect, ResearchGate, PubMed, ChemSpider, USPTO, Google patents and Espacenet) and library visits in Nepal were carried out to collect the literature on information published prior to April 2019. RESULTS: N. scrophulariiflora was traditionally used for 82 ailments/diseases. There are 124 major phytochemicals extracted from the plant. Several compounds are effective in bioactivity. Pharmacologically, the plant is proved to be anti-atherosclerotic, antidiabetic and anti-inflammatory in-vivo studies, and antimicrobial, antimalarial, antioxidative, hepatoprotective, immunomodulatory and nerve growth factor potentiating from in-vitro studies. Renal improvement activities were confirmed from both in-vivo and in-vitro studies. Toxicological tests and a single clinical trial in human beings have supported the notion that the plant is not poisonous but beneficial for curing wide ranges of diseases. CONCLUSION: N. scrophulariiflora is valuable medicinal plant that can serve as promising source of non-harmful and potential medicinal herbal remedies for human beings.
- MeSH
- etnofarmakologie * MeSH
- jitrocelovité chemie MeSH
- lidé MeSH
- rostlinné extrakty farmakologie terapeutické užití MeSH
- tradiční lékařství metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Bhútán MeSH
- Čína MeSH
- Indie MeSH
- Myanmar MeSH
- Nepál MeSH
A resilient immune system is characterized by its capacity to respond appropriately to challenges, such as infections, and it is crucial in vaccine response. Here we report a paired randomized intervention-control trial in which we evaluated the effect of microbially rich soil on immune resilience and pneumococcal vaccine response. Twenty-five age and sex matched pairs of volunteers were randomized to intervention and control groups. The intervention group rubbed hands three times a day in microbially rich soil until participants received a pneumococcal vaccine on day 14. Vaccine response, skin and gut bacteriome and blood cytokine levels were analyzed on days 0, 14 and 35. Peripheral blood mononuclear cells (PBMCs) were stimulated with vaccine components and autoclaved soil for cytokine production. Commensal bacterial community shifted only in the intervention group during the 14-day intervention period. When PBMCs collected on day 14 before the vaccination were stimulated with the vaccine components, IFN-y production increased in the intervention but not in the control group. On day 35, vaccination induced a robust antibody response in both groups. In parallel, gut bacterial community was associated with TGF-β plasma levels and TGF-β decrease in plasma was lower in the intervention group. The results indicate that exposure to microbially rich soil can modulate the cell-mediated immunity to components in pneumococcal vaccine.
- MeSH
- buněčná imunita * MeSH
- cytokiny metabolismus krev MeSH
- dospělí MeSH
- kůže * imunologie mikrobiologie MeSH
- leukocyty mononukleární * imunologie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrobiota imunologie MeSH
- pneumokokové infekce prevence a kontrola imunologie MeSH
- pneumokokové vakcíny * imunologie aplikace a dávkování MeSH
- půdní mikrobiologie MeSH
- střevní mikroflóra imunologie MeSH
- vakcinace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
According to the hygiene and biodiversity hypotheses, increased hygiene levels and reduced contact with biodiversity can partially explain the high prevalence of immune-mediated diseases in developed countries. A disturbed commensal microbiota, especially in the gut, has been linked to multiple immune-mediated diseases. Previous studies imply that gut microbiota composition is associated with the everyday living environment and can be modified by increasing direct physical exposure to biodiverse materials. In this pilot study, the effects of rural-second-home tourism were investigated on the gut microbiota for the first time. Rural-second-home tourism, a popular form of outdoor recreation in Northern Europe, North America, and Russia, has the potential to alter the human microbiota by increasing exposure to nature and environmental microbes. The hypotheses were that the use of rural second homes is associated with differences in the gut microbiota and that the microbiota related to health benefits are more diverse or common among the rural-second-home users. Based on 16S rRNA Illumina MiSeq sequencing of stool samples from 10 urban elderly having access and 15 lacking access to a rural second home, the first hypothesis was supported: the use of rural second homes was found to be associated with lower gut microbiota diversity and RIG-I-like receptor signaling pathway levels. The second hypothesis was not supported: health-related microbiota were not more diverse or common among the second-home users. The current study encourages further research on the possible health outcomes or causes of the observed microbiological differences. Activities and diet during second-home visits, standard of equipment, surrounding environment, and length of the visits are all postulated to play a role in determining the effects of rural-second-home tourism on the gut microbiota.
- MeSH
- lidé MeSH
- mikrobiota * MeSH
- pilotní projekty MeSH
- RNA ribozomální 16S genetika MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- Finsko MeSH
- Rusko MeSH
- Severní Amerika MeSH
AIM: Current attempts to modulate the human microbiota and immune responses are based on probiotics or human-derived bacterial transplants. We investigated microbial modulation by soil and plant-based material. MATERIALS & METHODS: We performed a pilot study in which healthy adults were exposed to the varied microbial community of a soil- and plant-based material. RESULTS: The method was safe and feasible; exposure was associated with an increase in gut microbial diversity. CONCLUSION: If these findings are reproduced in larger studies nature-derived microbial exposure strategies could be further developed for testing their efficacy in the treatment and prevention of immune-mediated diseases.
- MeSH
- Bacteria klasifikace genetika izolace a purifikace MeSH
- biodiverzita MeSH
- dospělí MeSH
- feces mikrobiologie MeSH
- gastrointestinální trakt imunologie mikrobiologie MeSH
- imunita * MeSH
- imunomodulace MeSH
- kůže imunologie mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- pilotní projekty MeSH
- půda chemie MeSH
- půdní mikrobiologie * MeSH
- rostliny mikrobiologie MeSH
- střevní mikroflóra * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
Recent COVID-19 vaccines unleashed the potential of mRNA-based therapeutics. A common bottleneck across mRNA-based therapeutic approaches is the rapid design of mRNA sequences that are translationally efficient, long-lived and non-immunogenic. Currently, an accessible software tool to aid in the design of such high-quality mRNA is lacking. Here, we present mRNAid, an open-source platform for therapeutic mRNA optimization, design and visualization that offers a variety of optimization strategies for sequence and structural features, allowing one to customize desired properties into their mRNA sequence. We experimentally demonstrate that transcripts optimized by mRNAid have characteristics comparable with commercially available sequences. To encompass additional aspects of mRNA design, we experimentally show that incorporation of certain uridine analogs and untranslated regions can further enhance stability, boost protein output and mitigate undesired immunogenicity effects. Finally, this study provides a roadmap for rational design of therapeutic mRNA transcripts.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: According to the biodiversity hypothesis of immune-mediated diseases, lack of microbiological diversity in the everyday living environment is a core reason for dysregulation of immune tolerance and - eventually - the epidemic of immune-mediated diseases in western urban populations. Despite years of intense research, the hypothesis was never tested in a double-blinded and placebo-controlled intervention trial. OBJECTIVE: We aimed to perform the first placebo-controlled double-blinded test that investigates the effect of biodiversity on immune tolerance. METHODS: In the intervention group, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil, or in the placebo group, visually similar, but microbially poor sand colored with peat (13 participants per treatment group). Children played twice a day for 20 min in the sandbox for 14 days. Sand, skin and gut bacterial, and blood samples were taken at baseline and after 14 days. Bacterial changes were followed for 28 days. Sand, skin and gut metagenome was determined by high throughput sequencing of bacterial 16 S rRNA gene. Cytokines were measured from plasma and the frequency of blood regulatory T cells was defined as a percentage of total CD3 +CD4 + T cells. RESULTS: Bacterial richness (P < 0.001) and diversity (P < 0.05) were higher in the intervention than placebo sand. Skin bacterial community, including Gammaproteobacteria, shifted only in the intervention treatment to resemble the bacterial community in the enriched sand (P < 0.01). Mean change in plasma interleukin-10 (IL-10) concentration and IL-10 to IL-17A ratio supported immunoregulation in the intervention treatment compared to the placebo treatment (P = 0.02). IL-10 levels (P = 0.001) and IL-10 to IL-17A ratio (P = 0.02) were associated with Gammaproteobacterial community on the skin. The change in Treg frequencies was associated with the relative abundance of skin Thermoactinomycetaceae 1 (P = 0.002) and unclassified Alphaproteobacteria (P < 0.001). After 28 days, skin bacterial community still differed in the intervention treatment compared to baseline (P < 0.02). CONCLUSIONS: This is the first double-blinded placebo-controlled study to show that daily exposure to microbial biodiversity is associated with immune modulation in humans. The findings support the biodiversity hypothesis of immune-mediated diseases. We conclude that environmental microbiota may contribute to child health, and that adding microbiological diversity to everyday living environment may support immunoregulation.
- MeSH
- Bacteria genetika MeSH
- biodiverzita MeSH
- cytokiny MeSH
- dvojitá slepá metoda MeSH
- interleukin-10 * MeSH
- interleukin-17 * MeSH
- lidé MeSH
- písek MeSH
- předškolní dítě MeSH
- regulační T-lymfocyty MeSH
- Check Tag
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
As the incidence of immune-mediated diseases has increased rapidly in developed societies, there is an unmet need for novel prophylactic practices to fight against these maladies. This study is the first human intervention trial in which urban environmental biodiversity was manipulated to examine its effects on the commensal microbiome and immunoregulation in children. We analyzed changes in the skin and gut microbiota and blood immune markers of children during a 28-day biodiversity intervention. Children in standard urban and nature-oriented daycare centers were analyzed for comparison. The intervention diversified both the environmental and skin Gammaproteobacterial communities, which, in turn, were associated with increases in plasma TGF-β1 levels and the proportion of regulatory T cells. The plasma IL-10:IL-17A ratio increased among intervention children during the trial. Our findings suggest that biodiversity intervention enhances immunoregulatory pathways and provide an incentive for future prophylactic approaches to reduce the risk of immune-mediated diseases in urban societies.
- MeSH
- biodiverzita MeSH
- dítě MeSH
- kůže MeSH
- lidé MeSH
- mikrobiota * MeSH
- střevní mikroflóra * MeSH
- zařízení denní péče pro děti MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- MeSH
- autofagie * fyziologie MeSH
- biotest metody normy MeSH
- lidé MeSH
- počítačová simulace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
- směrnice MeSH
