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  • Frontiers Media SA  (12)
  • 1
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-7-7)
    Abstract: Group A streptococcus (GAS, Streptococcus pyogenes ) is a common pathogen that can cause a variety of human diseases. Streptolysin O (SLO) is an exotoxin produced by GAS. It is a pore-forming toxin (PFT) that exhibits high in vivo toxicity. SLO enables GAS to evade phagocytosis and clearance by neutrophils, induces eukaryotic cell lysis, and activates inflammatory bodies. Luteolin is a natural compound that is produced by a wide range of plant species, and recent studies have shown that luteolin can inhibit the growth and alter the morphological of GAS. Here, we reported that luteolin can weaken the cytotoxicity and hemolytic activity of SLO in vitro . Briefly, luteolin bound SLO with high affinity, inhibited its dissolution of erythrocytes, affected its conformational stability and inhibited the formation of oligomers. To further verify the protective effect of luteolin, we used an in vitro SLO-induced human laryngeal carcinoma epithelial type-2 cells (HEp-2) model. Notably, our results showed luteolin protected HEp-2 cells from SLO induced cytotoxicity and changed in cell membrane permeability. In addition, we explored the role of luteolin in protecting mice from GAS-mediated injury using an aerosolized lung delivery model, and our results indicate that luteolin increases murine survival rate following inoculation with a lethal dose of GAS, and that survival was also associated with decreased pathological damage to lung tissue. Our results suggest that luteolin may be a novel drug candidate for the treatment of GAS infection.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 2
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 10 ( 2023-3-17)
    Abstract: Syncope is a common emergency with diverse etiologies in children. Among these, cardiac syncope (CS) is associated with high mortality and is usually difficult to diagnose. However, there is still no validated clinical prediction model to distinguish CS from other forms of pediatric syncope. The Evaluation of Guidelines in Syncope Study (EGSYS) score was designed to identify CS in adults and has been validated in several studies. In this study, we aimed to assess the ability of the EGSYS score in predicting CS in children. Methods In this retrospective study, we calculated and analyzed the EGSYS scores of 332 children hospitalized for syncope between January 2009 and December 2021. Among them, 281 were diagnosed with neurally mediated syncope (NMS) through the head-up tilt test, and 51 were diagnosed with CS using electrocardiography (ECG), echocardiography (ECHO), coronary computed tomography angiography (CTA), myocardial enzymes and genetic screening. The receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test were used to evaluate the predictive value of the EGSYS score system. Results The median scores of 51 children with CS and 281 children with NMS were 4 [interquartile range (IQR): 3-5] and −1 (IQR: -2-1), respectively. The area under the ROC curve (AUC) was 0.922 [95% confidence interval (CI): 0.892-0.952; P  & lt; 0.001], indicating that the EGSYS score system has good discrimination. The best cutoff point was ≥3, with a sensitivity and specificity of 84.3% and 87.9%, respectively. The Hosmer-Lemeshow test demonstrated satisfactory calibration ( χ ²=1.468, P  & gt; 0.05) of the score, indicating a good fit of the model. Conclusion The EGSYS score appeared to be sensitive for differentiating CS from NMS in children. It might be used as an additional diagnostic tool to aid pediatricians in accurately identifying children with CS in the clinical practice.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2781496-8
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-1-27)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-1-27)
    Abstract: The life-threatening disease streptococcal toxic shock-like syndrome (STSLS), caused by the bacterial pathogen Streptococcus suis ( S. suis ). Proinflammatory markers, bacterial load, granulocyte recruitment, and neutrophil extracellular traps (NETs) levels were monitored in wild-type (WT) and Fpr2 -/- mice suffering from STSLS. LXA4 and AnxA1, anti-inflammatory mediators related to Fpr2, were used to identity a potential role of the Fpr2 in STSLS development. We also elucidated the function of Fpr2 at different infection sites by comparing the STSLS model with the S. suis -meningitis model. Compared with the WT mice, Fpr2 -/- mice exhibited a reduced inflammatory response and bacterial load, and increased neutrophil recruitment. Pretreatment with AnxA1 or LXA4 impaired leukocyte recruitment and increased both bacterial load and inflammatory reactions in WT but not Fpr2 -/- mice experiencing STSLS. These results indicated that Fpr2 impairs neutrophil recruitment during STSLS, and this impairment is enhanced by AnxA1 or LXA4. By comparing the functions of Fpr2 in different S. suis infection models, inflammation and NETs was found to hinder bacterial clearance in S. suis meningitis, and conversely accelerate bacterial clearance in STSLS. Therefore, interference with neutrophil recruitment could potentially be harnessed to develop new treatments for this infectious disease.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Microbiology Vol. 13 ( 2022-5-17)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-5-17)
    Abstract: Urinary tract infections (UTIs) are among the most common acquired bacterial infections in humans. The current gold standard method for identification of uropathogens in clinical laboratories is cultivation. However, culture-based assays have substantial drawbacks, including long turnaround time and limited culturability of many potential pathogens. Nanopore sequencing technology can overcome these limitations and detect pathogens while also providing reliable predictions of drug susceptibility in clinical samples. Here, we optimized a metagenomic nanopore sequencing (mNPS) test for pathogen detection and identification in urine samples of 76 patients with acute uncomplicated UTIs. We first used twenty of these samples to show that library preparation by the PCR Barcoding Kit (PBK) led to the highest agreement of positive results with gold standard clinical culture tests, and enabled antibiotic resistance detection in downstream analyses. We then compared the detection results of mNPS with those of culture-based diagnostics and found that mNPS sensitivity and specificity of detection were 86.7% [95% confidence interval (CI), 73.5–94.1%] and 96.8% (95% CI, 82.4–99.9%), respectively, indicating that the mNPS method is a valid approach for rapid and specific detection of UTI pathogens. The mNPS results also performed well at predicting antibiotic susceptibility phenotypes. These results demonstrate that our workflow can accurately diagnose UTI-causative pathogens and enable successful prediction of drug-resistant phenotypes within 6 h of sample receipt. Rapid mNPS testing is thus a promising clinical diagnostic tool for infectious diseases, based on clinical urine samples from UTI patients, and shows considerable potential for application in other clinical infections.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-11-24)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-11-24)
    Abstract: Streptococcus agalactiae , also known as group B streptococcus (GBS), can cause pneumonia, meningitis, and bacteremia, making it a pathogen that can increase the risk of death in newborns and immunodeficient individuals. Neutrophils are the first barrier to a host’s innate immune defense against these infections. Fpr2(Formyl peptide receptor 2) is an important chemotactic receptor of neutrophils, though its activation would cause pro- and anti-inflammatory effects. In this study, we found that mice without Fpr2 receptor were highly susceptible to GBS infections. These mice demonstrated decreased chemotaxis to neutrophils, decreased bactericidal ability of neutrophils, and high mortality. RNA-seq and Luminex assay indicated that Fpr2 activates key signal molecules downstream and produces chemokines CXCL1/2 to chemotaxis neutrophils. Like Fpr2 -/- , CXCL1/2 or neutrophil depletion impairs host’s ability to defend against GBS infection. Altogether, these data indicate that Fpr2 contributes to a host’s ability to control GBS infection and that a lack of Fpr2 was associated with selective impairment during the production of chemokines CXCL1 and CXCL2 as well as neutrophil recruitment. Here, We clarified that Fpr2, as a chemotactic receptor, could not only directly chemotactic neutrophils, but also regulate the production of chemokines to control infection by chemotactic neutrophils.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 6
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 11 ( 2023-8-29)
    Abstract: Orthostatic intolerance (OI) is usually mediated by the autonomic nerve and most often happens in the upright position. However, it can also occur in other positions and can be relieved by lying down while likely to have another attack after relief. In the current study, we aim to evaluate the predictive effect of catecholamines and electrolytes on the recurrence of OI in children. Materials and methods Children who were diagnosed with vasovagal syncope (VVS), postural tachycardia syndrome (POTS), and VVS combined with POTS were enrolled in this retrospective study and were followed up after 1-year physical treatment. Catecholamines in urine collected within 24 h, renin, angiotensin II, aldosterone in plasma, and electrolytes in both blood and urine collected in the morning were tested. A multivariate analysis and a receiver operating characteristic curve were used to validate the prediction effect. Results In the VVS cohort, the 24 h urine adrenaline (AD) and norepinephrine (NE) levels of the non-recurrence group were lower than the 24 h urine AD and NE levels of the recurrence group, with a significant difference of P   & lt; 0.05. A different content can also be witnessed in the POTS cohort that the urine of the non-recurrence group contained lower sodium and chlorine. As for the VVS + POTS cohort, the non-recurrence group has lower AD and NE levels and higher potassium and phosphorus levels in urine, the difference of which proved prominent as well. Conclusion The study provides further evidence that AD, NE, and electrolytes in urine are promising factors that are closely related to the recurrence of OI in children. The integrated evaluation system merging AD and NE may have better predictive ability.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711999-3
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Public Health Vol. 10 ( 2022-10-20)
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 10 ( 2022-10-20)
    Abstract: Botulinum toxin A(BoNT/A) is a neurotoxin produced by the bacteria Clostridium botulinum , which can cause serious food poisoning and is recognized as a potential biological warfare agent. BoNT/A is does not degrade easily and can remain in the complex matrix for a long time. Meanwhile, the poisonous dose of botulinum toxin exceptionally low and intravenous human lethal doses estimated at 1-3 ng/kg. Therefore, sensitive and accurate detection methods suitable for testing a wide range of complex samples are urgently needed. To this end, the “amplified luminescent proximity homogeneous assay linked immunosorbent assay” (AlphaLISA) was established for the detection of BoNT/A and its detection efficacy in plasma, beverage, food, and other complex samples was evaluated. The results showed that this method can very effectively resist matrix interference. The detection time is rapid, reaching a detection limit for all samples of up to 0.1 ng/mL in only 30 min. BoNT/A can also be accurately detected in vomit samples of patients with clinical food poisoning. This study demonstrates that AlphaLISA is an effective tool for the detection of BoNT/A in complex samples and can potentially be developed for commercial use in the future.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711781-9
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Public Health Vol. 11 ( 2023-8-4)
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 11 ( 2023-8-4)
    Abstract: To assess the disease burden and changing trend of cardiomyopathy in children aged 0–14 years in China from 1990 to 2019. Methods This study was based on the Global Burden of Disease Study 2019; the age-specific prevalence rate, mortality rate and disability-adjusted life year (DALY) rate were used for analysis. Estimated annual percentage change (EAPC) in burden rate and its 95% confidence interval were calculated. The data of China were compared with the global average level. Results In 2019, the numbers of prevalence, deaths, and DALYs of cardiomyopathy in children aged 0–14 years in China were 4,493 [95% uncertainty interval ( UI ): 2687 ~ 6,838], 434 (95% UI : 337 ~ 565) and 37,522 (95% UI : 29,321 ~ 48,891), with declining amplitudes of 16.32, 70.56, and 70.74%, compared with 1990, respectively. In 2019, the prevalence rate of cardiomyopathy in Chinese children aged 0–14 years was 2.00/100,000 (95% UI : 1.2/100,000 ~ 3.04/100,000), higher than 1990 [1.66/100,000 (95% UI :1.00/100,000 ~ 2.53/100,000)]; mortality rate was 0.19/100,000 (95% UI : 0.15/100,000 ~ 0.25/100,000), significantly lower than 1990 [0.46/100,000 (95% UI : 0.25/100,000 ~ 0.95/100,000)]; DALY rate was 16.69/100,000 (95% U I: 13.04/100,000 ~ 21.75/100,000), also significantly lower than 1990 [39.71/100,000 (95% UI : 22.06/100,000 ~ 82.8/100,000)]. All burden rates of cardiomyopathy in Chinese children aged 0–14 years old were all lower than the global averages of 2019; the burden rates of male children were higher than female children. In all calendar years from 1990 to 2019, the mortality and DALY rates of children younger than 1-year-old were significantly higher than in the other age groups of 0–14 years old. From 1990 to 2019, the prevalence rate of cardiomyopathy aged 0–14 years old gradually increased, with EAPC of 0.82 (95% CI : 0.71–0.93); mortality rate and DALY rate decreased [EAPC = −2.32 (95% CI : −2.59 to −2.05)]. Conclusion From 1990 to 2019, the disease burden of cardiomyopathy in children of China aged 0–14 years was heterogeneous; the burden of male children was higher than females; and the burden of cardiomyopathy in children younger than 1 year old needs more attention.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711781-9
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  • 9
    In: Frontiers in Earth Science, Frontiers Media SA, Vol. 10 ( 2022-3-11)
    Abstract: With the latest uplift episode of Tian Shan occurring since early Miocene, a series of thrust–fold belts were formed in front of Tian Shan. The Kashi foreland thrust–fold belt (KFTB) provided a unique case to understand the ongoing intracontinental deformation within the Pamir–Tian Shan convergence zone (PTCZ). Previous cosmogenic nuclide chronological studies on growth folds suggested that the young thrust–fold belt in front of Pamir formed during 6–1.07 Ma. However, the age constraints of late Cenozoic deformation in front of southwestern Tian Shan are still debated. In this study, we attempt to constrain the initial deformation time of the NEE-striking Atushi anticline (ATA) in the KFTB through the cosmogenic nuclide burial dating data of growth strata near the boundary between Pliocene–Pleistocene Atushi Formation and Xiyu Formation (Xiyu Conglomerate), which are exposed in the southern limb of ATA. Moreover, detailed geological interpretations of multiple remote sensing images and field investigations are also carried out to document the late Cenozoic structural deformation and geomorphologic features of ATA. The 26 Al/ 10 Be burial dating data of four fine-grained samples reveal that the syntectonic deposit of ATA initiated at 1.79 ± 0.16 Ma, and the deposit of Xiyu Conglomerate started since 1.67 ± 0.18 Ma. Thus, we suggest that the thrust–folding of ATA began at ca.1.79 Ma and is currently still active.
    Type of Medium: Online Resource
    ISSN: 2296-6463
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2741235-0
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular and Infection Microbiology Vol. 12 ( 2022-6-28)
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 12 ( 2022-6-28)
    Abstract: Metagenomic next-generation sequencing (mNGS) is a novel useful strategy that is increasingly used for pathogens detection in clinic. Some emerging mNGS technologies with long-read ability are useful to decrease sequencing time and increase diagnosed accuracy, which is of great significance in rapid pathogen diagnosis. Reliable DNA extraction is considered critical for the success of sequencing; hence, there is thus an urgent need of gentle DNA extraction method to get unbiased and more integrate DNA from all kinds of pathogens. In this study, we systematically compared three DNA extraction methods (enzymatic cell lysis based on MetaPolyzyme, mechanical cell lysis based on bead beating, and the control method without pre–cell lysis, respectively) by assessing DNA yield, integrity, and the microbial diversity based on long-read nanopore sequencing of urine samples with microbial infections. Compared with the control method, the enzymatic-based method increased the average length of microbial reads by a median of 2.1-fold [Inter Quartile Range (IQR), 1.7–2.5; maximum, 4.8) in 18 of the 20 samples and the mapped reads proportion of specific species by a median of 11.8-fold (Inter Quartile Range (IQR), 6.9–32.2; maximum, 79.27]. Moreover, it provided fully (20 of 20) consistent diagnosed results to the clinical culture and more representative microbial profiles ( P & lt; 0.05), which all strongly proves the excellent performance of enzymatic-based method in long-read mNGS–based pathogen identification and potential diseases diagnosis of microbiome related.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2619676-1
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