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AIMS: To explore the therapeutic potential of Forsythoside B in treating Streptococcus pneumoniae (S. pneumoniae) infections, focusing on its ability to inhibit pneumolysin activity and protect cells from damage. METHODS AND RESULTS: Hemolysis tests were used to evaluate Forsythoside B's inhibitory effect on pneumolysin activity, while growth curve analysis assessed its impact on S. pneumoniae growth. Western blotting and oligomerization analysis were conducted to examine its influence on pneumolysin oligomerization. Cytotoxicity assays, including LDH release and live/dead cell staining, evaluated the protective effects of Forsythoside B against pneumolysin-induced damage in A549 cells. Additionally, a mouse model was employed to test the effects on survival rates, lung bacterial load, and inflammation. The results showed that Forsythoside B significantly inhibited pneumolysin activity, reduced its oligomerization, and protected A549 cells from damage without affecting bacterial growth. In the mouse model, it improved survival rates and reduced lung inflammation, indicating its potential as a therapeutic agent against S. pneumoniae infections. CONCLUSIONS: Forsythoside B shows potential as a therapeutic agent for treating pneumonia, particularly in infections caused by S. pneumoniae.
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Ácidos Cafeicos , Extractos Vegetales , Streptococcus pneumoniae , Animales , Humanos , Ratones , Células A549 , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Modelos Animales de Enfermedad , Glucósidos/farmacología , Extractos Vegetales/farmacología , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Estreptolisinas , Virulencia/efectos de los fármacos , Ácidos Cafeicos/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Xiao-er-kang-du (XEKD) capsule is a Chinese herbal formula used for treatment of upper respiratory tract infection caused by various viruses in pediatric patients in China. XEKD is used clinically for the treatment of influenza-like symptoms, including fever, chills, cough, stuffy and runny nose, headache, and sore throat, with remarkable efficacy. However, the pharmacologic mechanism of XEKD against influenza B virus (IBV) infection is unclear. AIM OF THE STUDY: The main purpose of the present work is to explore the curative effect as well as possible mechanisms of XEKD against influenza B virus (IBV) (Victoria strain). MATERIALS AND METHODS: Both in vivo and in vitro experiments were performed to confirm the antiviral properties of XEKD. High-performance liquid chromatography was used to analyze the active components and assess the stability of XEKD. In addition, the mechanism of action of XEKD against IBV (Victoria) was investigated by western blot, immunofluorescence, and immunohistochemical analyses, in addition to confocal fluorescence microscopy. RESULTS: The findings revealed that XEKD demonstrated antiviral effects against IBV infection in both in vivo and in vitro via the mTOR/ULK1/Beclin1/VPS34 pathway and promote cellular autophagy to mitigate IBV-induced lung tissue damage. The results of this work are expected to lead to a deeper understanding of the mechanism underlying the effect of the XEKD capsule against IBV infections. CONCLUSIONS: IBV infection was found to inhibit autophagy, which exacerbated inflammatory damage. XEKD regulates autophagy through the mTOR/ULK1/Beclin1/VPS34 pathway and exerts antiviral effects, thereby laying a foundation for further development of XEKD as a potential therapeutic against IBV infection.
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Childhood asthma is a chronic inflammatory disease of the airways, the pathogenesis of which involves multiple factors including genetic predisposition, environmental exposure, and immune system regulation. To date, the causal relationships between immune cells, plasma metabolites, and childhood asthma remain undetermined. Therefore, we aim to utilize the Mendelian randomization approach to assess the causal relationships among immune cells, plasma metabolites, and childhood asthma. This study employed the Mendelian randomization approach to investigate how immune cells influenced the risk of childhood asthma by modulating the levels of plasma metabolites. Five Mendelian randomization methods-inverse variance weighted, weighted median, Mendelian randomization-Egger, simple mode, and weighted mode-were utilized to explore the causal relationships among 731 types of immune cells, 1400 plasma metabolites, and childhood asthma. The instrumental variables for the 731 immune cells and 1400 plasma metabolites were derived from a genome-wide association study meta-analysis. Additionally, sensitivity analyses were conducted to examine the robustness of the results, potential heterogeneity, and pleiotropy. The inverse variance weighted results indicated that HLA DR on dendritic cells (DC) is a risk factor for childhood asthma (OR: 1.08, 95% CI: 1.02-1.14). In contrast, HLA DR on DC acts as a protective factor against elevated catechol glucuronide levels (OR: 0.94, 95% CI: 0.91-0.98), while catechol glucuronide levels themselves serve as a protective factor for childhood asthma (OR: 0.73, 95% CI: 0.60-0.89). Thus, HLA DR on DC can exert a detrimental effect on childhood asthma through the negative regulation of catechol glucuronide levels. The mediating effect was 0.018, accounting for a mediation effect proportion of 23.4%. This study found that HLA DR on DC can exert a risk effect on childhood asthma through the negative regulation of catechol glucuronide levels, providing new strategies for the prevention and treatment of childhood asthma and guiding future research and clinical practice.
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Asma , Análisis de la Aleatorización Mendeliana , Humanos , Asma/inmunología , Asma/sangre , Asma/genética , Niño , Estudio de Asociación del Genoma Completo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Factores de Riesgo , Antígenos HLA-DR/sangre , Antígenos HLA-DR/genética , Predisposición Genética a la EnfermedadRESUMEN
BACKGROUND: We aim to investigate the effect of YiQi GuBen formula (YQGB) on airway inflammation and airway remodeling in the ovalbumin (OVA)-induced asthma model to further explore the potential mechanisms of YQGB in treating allergic asthma. METHODS: Mice were divided into five groups randomly (n = 10): the control group, OVA group, OVA + Dex (0.1 mg/kg) group, OVA + low-dose (1.1 g/kg) YQGB group, and OVA + high-dose (2.2 g/kg) YQGB group. Inflammatory cell count and IgE were detected in bronchoalveolar lavage fluid (BALF). Lung tissue histopathology was observed by using H&E, PAS, Masson, and immunohistochemistry staining. qRT-PCR and western blot were applied to analyze key genes and proteins associated with TLR4 and NF-κB signaling pathways. RESULTS: In OVA-induced asthma mice, YQGB decreased eosinophils and IgE in BALF. YQGB alleviated the OVA-induced inflammatory infiltration and declined IL-4, IL-5, IL-13, Eotaxin, ECP, GM-CSF, LTC4, and LTD4. YQGB attenuated the OVA-induced goblet cell metaplasia and mucus hypersecretion. YQGB mitigated the OVA-induced subepithelial fibrosis and lowered TGF-ß1, E-Cadherin, Vimentin, and Fibronectin. YQGB ameliorated the OVA-induced airway smooth muscle thickening and lessened α-SMA and PDGF levels. YQGB reduced the expression of TLR4, MyD88, TRAF6, IκBα, and p65 mRNAs, and IκBα and p-p65 protein levels were also reduced. CONCLUSION: YQGB exhibits the anti-asthma effect by reducing airway inflammation and airway remodeling through suppressing TLR4/NF-κB signaling pathway, and is worth promoting clinically.
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Remodelación de las Vías Aéreas (Respiratorias) , Asma , Líquido del Lavado Bronquioalveolar , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Ratones Endogámicos BALB C , FN-kappa B , Ovalbúmina , Transducción de Señal , Receptor Toll-Like 4 , Animales , Asma/tratamiento farmacológico , Asma/inducido químicamente , Receptor Toll-Like 4/metabolismo , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , FN-kappa B/metabolismo , Medicamentos Herbarios Chinos/farmacología , Ratones , Inmunoglobulina E/sangre , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Femenino , Inflamación/tratamiento farmacológico , Eosinófilos/efectos de los fármacos , Eosinófilos/metabolismo , Antiasmáticos/farmacología , Citocinas/metabolismoRESUMEN
Objective: This study aims to explore the effect of YiQi GuBen capsule on improving mitochondrial dysfunction in an animal model of asthma.Methods: The mice (n = 8) were divided into four groups including control (NC), ovalbumin (OVA), dexamethasone (OVA + DEX), and YiQi GuBen (OVA + YQGB) groups. Firstly, we established an OVA-induced mouse asthma model except for the NC group, which then were treated with dexamethasone and YiQi GuBen capsule. Subsequently, HE staining and Masson staining were used for pathological analysis of mice lung tissues. Next, we used transmission electron microscopy (TEM) to observe the effect of the Yiqi Guben capsule on the ultrastructure of mitochondria. Flow cytometry was used to analyze the ROS level, membrane potential, and the number of mitochondria in lung tissue. Moreover, we analyzed the copy number of mitochondrial DNA (mtDNA) and the expression levels of activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM).Results: The results of the pathological analysis showed that after treatment with the YiQi GuBen capsule, the lung tissue damage was significantly reduced. In addition, we observed that the ultrastructural damage of mitochondria was improved. Flow cytometry proved that after treatment with the YiQi GuBen capsule, the level of ROS in the mitochondria was effectively reduced, while the mitochondrial membrane potential decreased and the number increased significantly. Moreover, we found that the copy number of mtDNA was significantly increased and the expression levels of PGC-1α and TFAM were significantly upgraded.Conclusion: This study suggests YiQi GuBen capsule can effectively improve mitochondrial dysfunction in the OVA-induced mouse model.
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Asma , ADN Mitocondrial , Medicamentos Herbarios Chinos , Pulmón , Mitocondrias , Ovalbúmina , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Especies Reactivas de Oxígeno , Animales , Asma/tratamiento farmacológico , Asma/patología , Medicamentos Herbarios Chinos/farmacología , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Pulmón/efectos de los fármacos , Pulmón/patología , Especies Reactivas de Oxígeno/metabolismo , ADN Mitocondrial/efectos de los fármacos , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Femenino , Dexametasona/farmacología , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Cápsulas , Proteínas del Grupo de Alta MovilidadRESUMEN
BACKGROUND: At present, the need for vitamin C supplementation for pregnant smokers has not been fully studied. This study is aimed at investigating whether vitamin C supplementation for pregnant smoking women can improve the pulmonary function of their offspring. METHODS: Four databases were searched from inception to April 1, 2023 for studies on the effect of vitamin C supplementation to pregnant smokers on the pulmonary function of their offspring. Meanwhile, the reference lists of relevant studies were manually searched. The risk of bias in the included studies was assessed using the Cochrane Collaboration tool, and the data was analyzed using STATA/SE 17.0. RESULTS: Four randomized controlled trials (RCTs), all of high quality, were enrolled in this meta-analysis, including 787 pregnant women. The offspring of pregnant smokers who received vitamin C supplementation exhibited improved Forced Expiratory Flow between 25 and 75% (FEF25-75), FEF50, FEF75, and Forced Vital Capacity (FVC) compared to those who did not receive vitamin C supplementation. However, there was no statistically significant difference in Forced Expiratory Volume at 0.5 s (FEV0.5) and the ratio of FEV0.5 to FVC between the offspring of pregnant smokers who received vitamin C and the control group. CONCLUSION: Vitamin C supplementation for smoking pregnant women may enhance the pulmonary function of their offspring, particularly in FEF25-75, FEF50, FEF75, and FVC. Nevertheless, there are no significant differences in FEV0.5 and the FEV0.5/FVC ratio. These findings suggest that vitamin C supplementation has potential benefits for specific pulmonary function. Further studies are needed to comprehensively assess the effects of vitamin C on pulmonary function in the context of maternal smoking during pregnancy.
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Fumadores , Vitaminas , Embarazo , Femenino , Humanos , Vitaminas/uso terapéutico , Pulmón , Ácido Ascórbico , Suplementos DietéticosRESUMEN
BACKGROUND: Tic disorder is a common neurodevelopmental disorder in childhood, characterized primarily by motor or vocal tics. However, there is no systematic evaluation of pediatric massage therapy for children with Tic disorder. This study aims to evaluate the effectiveness and safety of massage therapy for children with tic disorder through a comprehensive meta-analysis and systematic review. METHODS: We systematically searched relevant randomized controlled trials from various databases such as CBM, CNKI, VIP, Wanfang database, PubMed, Embase, Web of Science, Cochrane Library, and SINOMED, published up to October 2023. To collect randomized controlled trials on pediatric massage therapy or in combination with other therapies for the treatment of tic disorders in children. The risk of bias in the included articles was assessed using the Cochrane guideline. Meta-analyses were performed using Review Manager 5.4, and publication bias was evaluated by using Begg test and Egger test in Stata SE software. RESULTS: This meta-analysis included 19 randomized controlled trials with 1423 patients. Pediatric massage therapy alone or in combination with conventional medication demonstrated a significant increase in clinical effectiveness rates [risk ratiosâ =â 1.15, 95% confidence interval [CI] (1.10, 1.20), Zâ =â 6.54, Pâ <â .001], and reduced Yale Global Tie Severity Scale scores [standardized mean differenceâ =â -0.85, 95% CI (-1.50, -0.19), Zâ =â 2.54, Pâ =â .01] and traditional Chinese medicine syndrome scores [standardized mean differenceâ =â -1.35, 95%CI (-2.08, -0.63), Zâ =â 3.66, Pâ =â .0002]. In terms of adverse reactions, there was no statistical difference between the experimental and control groups [risk ratiosâ =â 0.26, 95% CI (0.14, 0.49), Zâ =â 4.25, Pâ <â .001]. The Begg test and Egger test results indicated no publication bias. CONCLUSION: Evidence suggests that pediatric massage therapy is effective in improving tic disorders in children.
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Masaje , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos de Tic , Humanos , Masaje/métodos , Trastornos de Tic/terapia , Niño , Resultado del Tratamiento , PreescolarRESUMEN
This systematic review and meta-analysis aimed to assess and compare the therapeutic outcomes of cutting balloon angioplasty and high-pressure balloon angioplasty for arteriovenous fistula stenosis in hemodialysis patients. All studies indexed in PubMed, Embase, and Cochrane Library Web of Science were retrieved. The retrieval deadline was July 15, 2023. Risk of bias 2.0 was used to evaluate the quality of the included studies. Revman 5.4 software was used for data analysis. This review included three studies and 180 patients, with 90 patients in the cutting balloon angioplasty group and 90 patients in the high-pressure balloon angioplasty group. The results of the meta-analysis suggested that compared with high-pressure balloon angioplasty, cutting balloon angioplasty can improve primary lesion patency rates of internal arteriovenous fistulas at 6 months (relative risk, 1.45; 95% confidence interval, 1.08-1.96; P = 0.01). However, there were no significant differences between the technical success rate (relative risk, 0.99; 95% confidence interval, 0.93-1.05; P = 0.72) and clinical success rate (relative risk, 1.01; 95% confidence interval, 0.95-1.07; P = 0.73). Therefore, cutting balloon angioplasty is likely to increase primary lesion patency rates at 6 months. However, more high-quality, large-sample, multicenter, randomized controlled trials are needed for further validation due to the limited number of included studies.
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Angioplastia de Balón , Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Humanos , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/terapia , Grado de Desobstrucción Vascular , Constricción Patológica/etiología , Constricción Patológica/cirugía , Resultado del Tratamiento , Derivación Arteriovenosa Quirúrgica/efectos adversos , Angioplastia de Balón/métodos , Diálisis Renal , Fístula Arteriovenosa/terapia , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND: Previous epidemiological studies have shown inconsistent results regarding the relation between the risk of asthma in offspring and parental occupational exposure. Therefore, we conducted a comprehensive and systematic collection of currently available epidemiological data to quantify the correlation between the 2. METHODS: Related studies published before March 2023 were identified through searches of the Cochrane Library, Embase, PubMed, and Web of Science databases. The quality of included studies was assessed using the Newcastle-Ottawa Scale, while pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed using fixed-effect or random-effects models. RESULTS: This systematic review included 10 cohort studies, with a total of 89,571 parent-child pairs included in the quantitative analysis. The results exhibited a substantial association between parental occupational exposure to allergens (ORâ =â 1.11; 95% CI: 1.00, 1.23; Pâ =â .051) and irritants (ORâ =â 1.19; 95% CI: 1.07, 1.32; Pâ =â .001) and an increased risk of asthma in offspring. This association was also observed in the analysis of wheezing (ORâ =â 1.22; 95% CI: 1.11, 1.35; Pâ <â .001 and ORâ =â 1.19; 95% CI: 1.08, 1.32; Pâ =â .001). Subgroup analysis demonstrated that maternal occupational exposure to allergens (ORâ =â 1.07; 95% CI: 1.02, 1.12; Pâ =â .008) and irritants (ORâ =â 1.13; 95% CI: 1.05, 1.21; Pâ =â .001) significantly increased the risk of childhood asthma. Furthermore, parental postnatal occupational exposure to allergens (ORâ =â 1.26; 95% CI: 1.10, 1.46; Pâ =â .001) and irritants (ORâ =â 1.26; 95% CI: 1.06, 1.49; Pâ =â .009) had a more pronounced impact on childhood asthma. Higher levels of exposure (ORâ =â 1.26; 95% CI: 1.10, 1.46; Pâ =â .001 and ORâ =â 1.30; 95% CI: 1.16, 1.47; Pâ <â .001) were recognized as significant risk factors for childhood asthma. CONCLUSION: Parental occupational exposure to allergens and irritants increases the risk of asthma and wheezing in offspring, with maternal exposure, postnatal exposure, and high-dose exposure being the primary risk factors for childhood asthma.
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Asma , Exposición Profesional , Femenino , Humanos , Ruidos Respiratorios/etiología , Irritantes , Exposición Profesional/efectos adversos , Asma/etiología , Asma/complicaciones , Padres , Alérgenos/efectos adversosRESUMEN
Streptococcus pneumoniae (S. pneumoniae) is a major causative agent of respiratory disease in patients and can cause respiratory distress and other symptoms in severe cases. Pneumolysin (PLY) is a pore-forming toxin that induces host tissue injury and inflammatory responses. Sortase A (SrtA), a catalytic enzyme that anchors surface-associated virulence factors, is critical for S. pneumoniae virulence. Here, we found that the active ingredient of the Chinese herb Scutellaria baicalensis, wogonin, simultaneously inhibited the haemolytic activity of PLY and SrtA activity. Consequently, wogonin decreased PLY-mediated cell damage and reduced SrtA-mediated biofilm formation by S. pneumoniae. Furthermore, our data indicated that wogonin did not affect PLY expression but directly altered its oligomerization, leading to reduced activity. Furthermore, the analysis of a mouse pneumonia model further revealed that wogonin reduced mortality in mice infected with S. pneumoniae laboratory strain D39 and S. pneumoniae clinical isolate E1, reduced the number of colony-forming units in infected mice and decreased the W/D ratio and levels of the inflammatory factors TNF-α, IL-6 and IL-1ß in the lungs of infected mice. Thus, wogonin reduces S. pneumoniae pathogenicity by inhibiting the dual targets PLY and SrtA, providing a treatment option for S. pneumoniae infection.
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Proteínas Bacterianas , Streptococcus pneumoniae , Animales , Ratones , Virulencia , Proteínas Bacterianas/metabolismoRESUMEN
Growing evidence suggests that maternal folic acid supplementation during pregnancy may be associated with the risk of childhood asthma, but these findings remain controversial. Therefore, the purpose of this systematic review and meta-analysis was to assess the association between maternal folic acid supplementation during pregnancy and the risk of childhood asthma, and to determine the safe dose of folic acid supplementation during pregnancy based on a dose-response analysis to lower the risk of childhood asthma. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant studies published before April 2022. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of eligible studies, and a fixed-effect model was employed to calculate the odds ratio (OR) of asthma with 95% confidence intervals (CI). In addition, the generalized least-squares trend (GLST) was used to explore a nonlinear dose-response relationship. Stata 15.0 was used for the statistical analysis mentioned above. This systematic review included 18 studies (13 cohort studies, 5 case-control studies) with a total of 252,770 participants, 50,248 of whom were children with asthma. The meta-analysis showed that maternal folic acid supplementation during pregnancy was significantly associated with the risk of childhood asthma (OR = 1.07; 95% CI = 1.04-1.11). The subgroup analysis revealed a significant correlation between the risk of childhood asthma and the folic acid supplementation in the first Trimester (OR = 1.09; 95% CI = 1.05-1.12), the third Trimester (OR = 1.15; 95% CI = 1.04-1.26) and the whole pregnancy (OR = 1.13; 95% CI = 1.10-1.16). At the same time, the dose-response analysis showed a nonlinear relationship between maternal folic acid intake during pregnancy and the risk of childhood asthma. The risk of asthma in children significantly increased when maternal folic acid intake reached 581â µg/day. This meta-analysis showed that maternal folic acid supplementation during pregnancy increased the risk of asthma in children. Based on the results of the dose-response analysis, less than 580â µg folic acid per day is advised in order to effectively prevent birth defects without increasing the risk of childhood asthma. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42022332140.
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Diet/sugar-free soft drinks are considered to be healthier than regular soft drinks. However, few studies have examined the relationship between the types of soft drinks (regular and diet/sugar-free) and lung cancer (LC)/all-cancer (AC) risk. In this study, we comprehensively assessed the influence of the type of soft drink consumption on LC/AC risk based on the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Multivariable Cox proportional hazards and competing risks Fine-Gray regression models adjusted for relevant confounders were used to estimate hazard ratios (HRs) and subdistribution HRs for different types of soft drink consumption. In the PLCO population, female subgroup, and the ever/current smoker subgroup, consumption of both regular and diet soft drinks was associated with a significantly reduced risk of LC compared with no soft drinks at all. For the non-lung cancer (NLC) risk, consumption of only diet soft drinks had a significant positive association for the total population and female subgroup. Based on our findings, it was suggested that partial replacement of regular soft drinks with diet soft drinks might be beneficial to LC prevention, especially for females and ever/current smokers. Additionally, completely replacing regular soft drinks with diet soft drinks might be detrimental to NLC prevention, especially for females.
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(1) Background: The association between metabolic obesity phenotypes and incident lung cancer (LC) remains unclear. (2) Methods: Based on the combination of baseline BMI categories and metabolic health status, participants were categorized into eight groups: metabolically healthy underweight (MHUW), metabolically unhealthy underweight (MUUW), metabolically healthy normal (MHN), metabolically unhealthy normal (MUN), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). The Cox proportional hazards model and Mendelian randomization (MR) were applied to assess the association between metabolic obesity phenotypes with LC risk. (3) Results: During a median follow-up of 9.1 years, 3654 incident LC patients were confirmed among 450,482 individuals. Compared with participants with MHN, those with MUUW had higher rates of incident LC (hazard ratio (HR) = 3.24, 95% confidence interval (CI) = 1.33-7.87, p = 0.009). MHO and MHOW individuals had a 24% and 18% lower risk of developing LC, respectively (MHO: HR = 0.76, 95% CI = 0.61-0.95, p = 0.02; MHO: HR = 0.82, 95% CI = 0.70-0.96, p = 0.02). No genetic association of metabolic obesity phenotypes and LC risk was observed in MR analysis. (4) Conclusions: In this prospective cohort study, individuals with MHOW and MHO phenotypes were at a lower risk and MUUW were at a higher risk of LC. However, MR failed to reveal any evidence that metabolic obesity phenotypes would be associated with a higher risk of LC.
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Neoplasias Pulmonares , Síndrome Metabólico , Obesidad Metabólica Benigna , Bancos de Muestras Biológicas , Índice de Masa Corporal , Humanos , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/genética , Síndrome Metabólico/complicaciones , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/genética , Obesidad Metabólica Benigna/complicaciones , Obesidad Metabólica Benigna/epidemiología , Sobrepeso/complicaciones , Fenotipo , Estudios Prospectivos , Factores de Riesgo , Delgadez/complicaciones , Reino Unido/epidemiologíaRESUMEN
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.
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BACKGROUND: Acute kidney injury (AKI) is a major complication following cardiac surgery that substantially increases morbidity and mortality. Current diagnostic guidelines based on elevated serum creatinine and/or the presence of oliguria potentially delay its diagnosis. We presented a series of models for predicting AKI after cardiac surgery based on electronic health record data. METHODS: We enrolled 1457 adult patients who underwent cardiac surgery at Nanjing First Hospital from January 2017 to June 2019. 193 clinical features, including demographic characteristics, comorbidities and hospital evaluation, laboratory test, medication, and surgical information, were available for each patient. The number of important variables was determined using the sliding windows sequential forward feature selection technique (SWSFS). The following model development methods were introduced: extreme gradient boosting (XGBoost), random forest (RF), deep forest (DF), and logistic regression. Model performance was accessed using the area under the receiver operating characteristic curve (AUROC). We additionally applied SHapley Additive exPlanation (SHAP) values to explain the RF model. AKI was defined according to Kidney Disease Improving Global Outcomes guidelines. RESULTS: In the discovery set, SWSFS identified 16 important variables. The top 5 variables in the RF importance matrix plot were central venous pressure, intraoperative urine output, hemoglobin, serum potassium, and lactic dehydrogenase. In the validation set, the DF model exhibited the highest AUROC (0.881, 95% confidence interval [CI] 0.831-0.930), followed by RF (0.872, 95% CI 0.820-0.923) and XGBoost (0.857, 95% CI 0.802-0.912). A nomogram model was constructed based on intraoperative longitudinal features, achieving an AUROC of 0.824 (95% CI 0.763-0.885) in the validation set. The SHAP values successfully illustrated the positive or negative contribution of the 16 variables attributed to the output of the RF model and the individual variable's effect on model prediction. CONCLUSIONS: Our study identified 16 important predictors and provided a series of prediction models to enhance risk stratification of AKI after cardiac surgery. These novel predictors might aid in choosing proper preventive and therapeutic strategies in the perioperative management of AKI patients.
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Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Adulto , Procedimientos Quirúrgicos Cardíacos/efectos adversos , China , Registros Electrónicos de Salud , Humanos , Medición de Riesgo/métodosRESUMEN
Uropathogenic Escherichia coli (UPEC) is the most common pathogenic bacteria associated with urinary tract infection (UTI). UPEC can cause UTI by adhering to and invading uroepithelial cells. Fimbriae is the most important virulence factor of UPEC, and a potentially promising target in developing novel antibacterial treatments. In this study, the antibacterial properties and effects of the compound dictamnine, extracted from the traditional Chinese medicine Cortex Dictamni, on the bacterial morphology, cell adhesion, and invasion of UPEC were studied. Dictamnine exhibited no obvious antibacterial activity against UPEC, but significantly impeded the ability of UPEC to adhere to and invade uroepithelial cells. RT-qPCR analysis showed that treatment downregulated the expression of type 1 fimbriae, P fimbriae, and curli fimbriae adhesion genes, and also downregulated adhesion-related receptor genes of uroepithelial cells. Transmission electron microscopy showed that dictamnine destroyed the structure of the fimbriae and the surface of the bacteria became smooth. These results suggest that dictamnine may help to prevent UTI by simultaneously targeting UPEC fimbriae and urothelial adhesin receptors, and may have a potential use as a new anti-UPEC drug.
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Adhesión Bacteriana/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Quinolinas/farmacología , Infecciones Urinarias/tratamiento farmacológico , Escherichia coli Uropatógena/metabolismo , Urotelio/microbiología , Línea Celular , Infecciones por Escherichia coli/microbiología , Humanos , Infecciones Urinarias/microbiología , Urotelio/metabolismoRESUMEN
Emerging evidence has revealed the presence in animals of a bidirectional regulatory "lung-gut axis" that provides resistance to respiratory infections. Clues to the existence of this system stem from observations that respiratory infections are often accompanied by gastrointestinal symptoms, whereby intestinal microbiota appear to play pivotal roles in combating pathogenic infections. Importantly, short-chain fatty acids (SCFAs) produced by the gut microbiota appear to serve as the biological link between host immune defenses and gut flora. Streptococcus pneumoniae (S.pn), the main cause of lower respiratory tract infections, is involved in more than 1.189 million deaths per year. QingFei Yin (QFY) is known for its excellent therapeutic efficacy in combating bacterial lung infections. In this study, effects of S.pn infection on gut homeostasis were assessed using 16S RNA-based microbiota community profiling analysis. In addition, potential mechanisms underlying QFY recipe beneficial therapeutic effects against bacterial pneumonia were explored using S.pn-infected gut microbiota-depleted mice. Results of data analysis indicated that QFY treatment alleviated lung infection-associated pathogenic processes, while also promoting repair of disordered gut flora and counteracting S.pn infection-associated decreases in levels of SCFAs, particularly of acetate and butyrate. Mechanistically, QFY treatment suppressed inflammatory lung injury through inhibition of the host NF-κB-NLRP3 pathway. These results inspired us to identify precise QFY targets and mechanisms underlying QFY anti-inflammatory effects. In addition, we conducted an in-depth evaluation of QFY as a potential treatment for bacterial pneumonia.
Asunto(s)
Microbioma Gastrointestinal , Neumonía Neumocócica , Animales , Butiratos , Ácidos Grasos Volátiles , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Recurrent respiratory tract infections (RRTIs) are common respiratory ailments in children. RRTIs are often difficult to control and thus generally have a long-term disease course. Children who receive ineffective treatments or those that experience poor treatment outcomes are prone to developing complications such as edema, cough and asthma. Such complications can seriously hinder a child's growth and development, while also adversely affecting the child's physical and mental health. Tuina massage, a traditional Chinese technique that has been practiced in China for >5000âyears, has recently been used to treat RRTIs, with good effect. However, no systematic review of research studies focusing on massage as a treatment for RRTIs can be found in the literature to date. The purpose of this study will be to evaluate the efficacy and safety of Tuina massage for the treatment of pediatric patients who experience RRTIs. METHODS: We will search the following databases using electronic methods: the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), Wanfang Data (WAN FANG), VIP Information (VIP), MEDLINE, PUBMED, EMBASE, and CINAHL. For each database search, the scope will include articles published between the date of database inception to September 2021. Revman5.4 software will be used to conduct this systematic review and meta-analysis. RESULTS: This meta-analysis will confirm whether Tuina massage is of clinical benefit to pediatric patients who experience RRTIs. CONCLUSION: The results of our systematic review and meta-analysis will be used to formulate conclusions as to whether massage therapy is an effective treatment for children suffering from RRTIs. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of tuina in the treatment of recurrent respiratory tract infections. Since all the data included were published, the systematic review did not require ethical approval. INPLASY REGISTRATION NUMBER: INPLASY202190107.
Asunto(s)
Masaje , Medicina Tradicional China/métodos , Infecciones del Sistema Respiratorio/terapia , Niño , Humanos , Metaanálisis como Asunto , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Asthma is one of the most common chronic airway diseases and is characterized by wheezing, dyspnea, chest tightness, and coughing. These symptoms reduce the patient's quality of life and limit physical activity in daily life. However, there is no systematic review of the efficacy of cupping therapy in the treatment of asthma. To evaluate the efficacy and safety of cupping in the treatment of asthma, we conducted a systematic review and meta-analysis of published randomized clinical trials of cupping in the treatment of asthma. METHODS: We will search the following Chinese and English databases: China National Knowledge Infrastructure, China Science and Periodical Database, Wanfang Database, China Biomedical Literature Database, PubMed, Embase, Cochrane Library. All of the above electronic databases will be searched from inception to August 22, 2021. In addition, we will manually search for conference papers, ongoing experiments, and internal reports to supplement the studies retrieved via electronic search. We will use the Review Manager 5.4 provided by Cochrane Collaboration Network for statistical analysis. RESULTS: The study will prove the effectiveness and safety of cupping in the treatment of asthma. CONCLUSION: We plan to submit this systematic review to a peer-reviewed journal. INPLASY REGISTRATION NUMBER: INPLASY202180104.