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Journal of Translational Medicine Jun 2024Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV)...
BACKGROUND
Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown.
METHODS
A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA).
RESULTS
IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1β). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner.
CONCLUSION
Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.
Topics: Animals; Tight Junctions; Gastrointestinal Microbiome; Acetates; Humans; Lung Injury; Orthomyxoviridae Infections; Mice, Inbred C57BL; Influenza A virus; Fecal Microbiota Transplantation; Receptors, G-Protein-Coupled; Mice; Epithelial Cells; Dysbiosis; Fatty Acids, Volatile
PubMed: 38879538
DOI: 10.1186/s12967-024-05376-4 -
STAR Protocols Jun 2024The auxin-inducible degron (AID) system is a powerful tool to deplete proteins in vivo. Here, we present a protocol for AID-mediated depletion of two proteins...
The auxin-inducible degron (AID) system is a powerful tool to deplete proteins in vivo. Here, we present a protocol for AID-mediated depletion of two proteins (CFI-1/AT-rich interaction domain 3 [ARID3] and Y47D3A.21/density-regulated re-initiation and release factor [DENR]) in C. elegans tissues using different auxins and transport inhibitor response 1 (TIR1)-expressing strains. We describe steps for genetic crossing, sample preparation, fluorescent microscopy, and treatment with either natural (indole-3-acetic acid [IAA]) or synthetic (1-naphthaleneacetic acid, potassium salt [K-NAA]) auxins. We then detail procedures for comparing the degree of CFI-1 depletion in C. elegans neurons upon panneuronal or pansomatic TIR1 expression. For complete details on the use and execution of this protocol, please refer to Li et al..
PubMed: 38878287
DOI: 10.1016/j.xpro.2024.103133 -
Scientific Reports Jun 2024The aim of this study was to investigate the fertility of "Huajin 6" and the effect of exogenous methyl jasmonate on its fertility. In this study, "Huajin 6", "Huajin 6"...
The aim of this study was to investigate the fertility of "Huajin 6" and the effect of exogenous methyl jasmonate on its fertility. In this study, "Huajin 6", "Huajin 6" treated with methyl jasmonate and "Damaohua" were used as the research objects, the stamen phenotypes and the shape of pollen grains were observed, pollen viability and stigma receptivity were measured. The results showed that the pistil structure and function were normal, and although the stamen anthers did not dehisce, they were still capable of producing pollen with a certain amount of vigor. Methyl jasmonate could promote the opening of the flowers of "Huajin 6" and improve the development of pollen grains to a certain extent, but it could not promote anthers dehiscence of "Huajin 6". This study can provide theoretical guidance for the cultivation of new honeysuckle varieties using "Huajin 6".
Topics: Oxylipins; Flowers; Pollen; Fertility; Cyclopentanes; Acetates; Lonicera; Pollination
PubMed: 38877134
DOI: 10.1038/s41598-024-64435-4 -
PloS One 2024In this study, we aimed to compare the effectiveness of various chelating agents, ethilenediaminetetraacetic acid (EDTA), citric acid (CA), and etidronic acid (HEDP)...
INTRODUCTION
In this study, we aimed to compare the effectiveness of various chelating agents, ethilenediaminetetraacetic acid (EDTA), citric acid (CA), and etidronic acid (HEDP) mixed in two different forms, in removing the smear layer and promoting the penetration of an endodontic sealer into the dentinal tubules of extracted single-rooted teeth.
METHODS
The study used 75 teeth divided into five groups: 17% EDTA, 10% CA, 9% HEDP + NaOCl, 9% HEDP + distilled water (DW), and a control (DW) group. Scanning electron microscopy was used to assess smear layer removal and confocal laser microscopy was used to evaluate tubular sealer penetration at different depths from the apical tip.
RESULTS
Sealer penetration was highest with 17% EDTA and 10% CA as compared with the other agents (p<0.001). At the cervical third, the sealer penetration for EDTA, HEDP + NaOCl, and HEDP + DW groups were significantly different than those in DW (p = 0.020). For the middle third, EDTA, CA, and HEDP + NaOCl groups were significantly higher than those of the DW group (p<0.001). Cervical-level values were significantly higher than apical-level values for HEDP + NaOCl, HEDP + DW, and DW (p<0.001). Smear layer removal was lower with 9% HEDP + DW than with 17% EDTA and 10% CA at all depths (p<0.001). A significancy in smear layer removal was observed between 10% CA and control (p = 0.015) in middle depth.
CONCLUSION
Within the limitations of this study, highest values were seen in EDTA and CA in terms of sealer penetration and smear layer removal. In the light of these findings, the use of strong chelating agents highlights better clinical efficiency than dual-rinse or single HEDP irrigation.
Topics: Humans; Chelating Agents; Root Canal Filling Materials; Edetic Acid; Smear Layer; Citric Acid; Root Canal Irrigants; Microscopy, Electron, Scanning; Dentin
PubMed: 38875249
DOI: 10.1371/journal.pone.0303377 -
Food Science & Nutrition Jun 2024Rhamnan sulphate (RS) is a sulphated polysaccharide found in green algae such as that exhibits various biological functions, including anticoagulant, antitumour,...
Rhamnan sulphate (RS) is a sulphated polysaccharide found in green algae such as that exhibits various biological functions, including anticoagulant, antitumour, antiviral, and anti-obesity properties. In our previous clinical trial, we demonstrated that RS intake improves constipation. However, no specific bacteria showed a significant ( < .05) change. Notably, these results were obtained after a short RS inoculation period of only 2 weeks. In the present study, to evaluate the long-term effects of RS on the gut microbiota, we orally administered RS to BALB/c mice for 11 weeks, analyzed their blood biochemical data, and performed 16s rRNA-sequencing. Oral administration of RS increased body weight with increased food intake, whereas plasma total cholesterol and fasting plasma glucose levels decreased. RS-fed mice showed lower fasting insulin levels ( < .1) and decreased homeostatic model assessment for insulin resistance (HOMA-IR, < .0001), suggesting that RS improved insulin resistance. In the feces of mice, the amounts of acetic and propionic acids increased. In the gut microbiota, predictive metagenomic profiling using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) revealed functional alterations in Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways in RS-fed mice. Corresponding to the blood glucose-lowering effect, the glycolysis and tricarboxylic acid (TCA) cycle pathways were activated. In addition, the Firmicutes/Bacteroides (F/B) ratio, which may be associated with various health outcomes, was also reduced. These results suggest that the blood glucose-lowering effect, improvement in insulin resistance, and lipid-lowering effect of RS may be due to changes in the intestinal microbiota.
PubMed: 38873438
DOI: 10.1002/fsn3.4100 -
International Journal of Tryptophan... 2024The vital role of the maternal tryptophan (TRP) metabolism in maternal health and pregnancy is well established. However, non-medical maternal determinants influencing...
BACKGROUND
The vital role of the maternal tryptophan (TRP) metabolism in maternal health and pregnancy is well established. However, non-medical maternal determinants influencing the TRP metabolism have been poorly investigated. We hypothesise that periconceptional maternal non-medical determinants alter the TRP metabolism, affecting both kynurenine (KP) and serotonin pathway (SP) metabolite concentrations. Therefore, we investigated the influence of non-medical maternal determinants on the TRP metabolism during the periconception period.
METHODS
About 1916 pregnancies were included from the Rotterdam Periconceptional Cohort between November 2010 and December 2020. Data on periconceptional non-medical maternal determinants were collected through questionnaires. Serum samples were collected at 8.5 (SD = 1.6) weeks of gestation and TRP, kynurenine (KYN), 5-hydroxytryptophan (5-HTP), 5-HT (5-hydroxytryptamine) and 5-hydroxyindole acetic acid (5-HIAA) were determined using validated liquid chromatography (tandem) mass spectrometry. Mixed models were used to determine associations between periconceptional non-medical maternal determinants and these metabolites.
RESULTS
In total 11 periconceptional non-medical maternal determinants were identified. Protein intake was positively associated with TRP ( = .12, 95% CI = 0.07-0.17), while age, energy intake and body mass index (BMI) ( = -.24, 95% CI = -0.37 to -0.10) were negatively associated with TRP. Age, BMI and total homocysteine were associated with higher KYN, whereas non-western geographical origin was associated with lower KYN ( = -.09, 95% CI = -0.16 to -0.03). Protein intake and total homocysteine ( = .07, 95% CI = 0.03-0.11) had a positive association with 5-HTP, while a negative association was found for energy intake. A non-western geographical origin and drug use were associated with higher 5-HT, and BMI with lower 5-HT ( = -6.32, 95% CI = -10.26 to -2.38). Age was positively associated with 5-HIAA ( = .92, 95% CI = 0.29-1.56), and BMI negatively.
CONCLUSIONS
Periconceptional non-medical maternal determinants, including age, geographical origin, drug use, energy and protein intake, BMI and total homocysteine, influence KP and SP metabolite concentrations.
PubMed: 38873365
DOI: 10.1177/11786469241257816 -
Frontiers in Microbiology 2024is one of the most abundant bacteria in the gut microbiota of healthy adults, highly regarded as a next-generation probiotic. However, the functions of genomes from...
INTRODUCTION
is one of the most abundant bacteria in the gut microbiota of healthy adults, highly regarded as a next-generation probiotic. However, the functions of genomes from cultured strains and the distribution of different species in populations may differ among different sources.
METHODS
We here performed an extensive analysis of pan-genomes, functions, and safety evaluation of 136 genomes collected from 10 countries.
RESULTS
The genomes are clustered into 11 clusters, with only five of them were characterized and validly nomenclated. Over 80% of the accessory genes and unique genes of are found with unknown function, which reflects the importance of expanding the collection of strains. All the genomes have the potential to produce acetic acid and butyric acid. Nine clusters of are found significantly enriched in the healthy individuals compared with patients with type II diabetes..
DISCUSSION
This study provides a comprehensive view of genomic characteristic and functions and of culturable bacterium from human gut, and enables clinical advances in the future.
PubMed: 38873165
DOI: 10.3389/fmicb.2024.1379500 -
Frontiers in Microbiology 2024Kombucha fermentation yields a diverse range of beneficial macro and micronutrients. In our study, we examined the metabolites, antioxidant activity, organoleptic...
Kombucha fermentation yields a diverse range of beneficial macro and micronutrients. In our study, we examined the metabolites, antioxidant activity, organoleptic characteristics, and nutritional attributes of traditionally prepared kombucha tea, using black tea and sugar (control) as substrates, and compared them with tea made from tea dust and blackstrap molasses (test). Kombucha tea crafted from functional raw materials exhibited enhanced sensory qualities and improved health-promoting properties. The levels of tannins, flavonoids, and phenols play a crucial role in determining the antioxidant activity of kombucha tea. Using the DPPH and FRAP methods, we investigated the antioxidant activity throughout the fermentation period, ranging from day 0 to day 12, under optimized conditions. The results consistently demonstrated an initial increase in antioxidant activity from day 0 to 6, followed by a decline from day 6 to 12. Notably, statistical analysis revealed that the antioxidant activity of the test sample was significantly better ( > 0.001) compared to the control sample. The nutritional content of the kombucha from day 6 of the test sample is higher than the control sample provided sugars (fructose 0.4 ± 0.1, glucose 0.7 ± 0.1, sucrose 1.4 ± 0.1) g/100 mL, minerals (calcium, 19.4 ± 0.15, iron 23.1 ± 0.25, and potassium 28.3 ± 0.25) mg/100 mL, vitamins (B1 0.58 ± 0.01, B2 0.30 ± 0.02, B3 0.33 ± 0.02, B6 0.75 ± 0.02, B9 0.19 ± 0.03, B12 0.9 ± 0.03, and C 1.38 ± 0.06) mg/100 mL, sodium 4.35 ± 0.25 mg/100 mL, calories 14.85 ± 0.25 mg/100 mL, carbohydrates 3.135 ± 0.12, and acids (acetic acid 4.20 ± 0.02, glucuronic acid 1.78 ± 0.02) mg/100 mL on day 12. The predominant microbial species identified in both control and test samples included , and , each with varying dominance levels. These microorganisms play essential roles in metabolizing sugars, generating acids, and contributing to the distinctive flavor profile of kombucha. Sensory evaluations of the control and test samples were analyzed, and the overall preference was 88% for the test sample with tea dust and molasses. The sensory characteristics of the test sample included a fruity smell (41%), fizzy texture (66%), bright color (47%), and a fruity taste (67%), with overall acceptability (56%) rating it as excellent. Our research contributes to a deeper understanding of the interplay between raw materials, microbial composition, and the resulting composition of bioactive compounds.
PubMed: 38873151
DOI: 10.3389/fmicb.2024.1367697 -
Mathematical Biosciences and... May 2024We developed a mathematical model to simulate dynamics associated with the proliferation of Geobacter and ultimately optimize cellular operation by analyzing the...
We developed a mathematical model to simulate dynamics associated with the proliferation of Geobacter and ultimately optimize cellular operation by analyzing the interaction of its components. The model comprises two segments: an initial part comprising a logistic form and a subsequent segment that incorporates acetate oxidation as a saturation term for the microbial nutrient medium. Given that four parameters can be obtained by minimizing the square root of the mean square error between experimental Geobacter growth and the mathematical model, the model underscores the importance of incorporating nonlinear terms. The determined parameter values closely align with experimental data, providing insights into the mechanisms that govern Geobacter proliferation. Furthermore, the model has been transformed into a scaleless equation with only two parameters to simplify the exploration of qualitative properties. This allowed us to conduct stability analysis of the fixed point and construct a co-dimension two bifurcation diagram.
Topics: Geobacter; Acetates; Oxidation-Reduction; Models, Biological; Computer Simulation; Algorithms
PubMed: 38872566
DOI: 10.3934/mbe.2024263 -
Cancer Medicine Jun 2024Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other...
OBJECTIVES
Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment VIA performance.
DESIGN
Prospective study.
SETTING
Eight public health facilities in Zambia.
PARTICIPANTS
A total of 8204 women aged 25-55.
INTERVENTIONS
Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive.
MAIN OUTCOME MEASURES
Area under the receiver operating curve (AUC); sensitivity; specificity.
RESULTS
As a general population screening tool for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89-0.93), which translates to a sensitivity of 85% (95% CI = 81%-90%) and specificity of 86% (95% CI = 84%-88%) based on maximizing the Youden's index. This represents a considerable improvement over naked eye VIA, which as per a meta-analysis by the World Health Organization (WHO) has a sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88-0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83-0.91).
CONCLUSIONS
These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by nurses in a screening program, and support our ongoing efforts for moving to more broadly evaluate AVE for its clinical sensitivity, specificity, feasibility, and acceptability across a wider range of settings. Limitations of this study include potential inflation of performance estimates due to verification bias (as biopsies were only obtained from participants with visible aceto-white cervical lesions) and due to this being an internal validation (the test data, while independent from that used to develop the algorithm was drawn from the same study).
Topics: Humans; Female; Uterine Cervical Neoplasms; Smartphone; Zambia; Adult; Early Detection of Cancer; Prospective Studies; Middle Aged; Sensitivity and Specificity; Papillomavirus Infections; Algorithms; Uterine Cervical Dysplasia; Mass Screening; ROC Curve; Artificial Intelligence
PubMed: 38872398
DOI: 10.1002/cam4.7355