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2.
Iran J Immunol ; 21(1): 53-64, 2024 03 12.
Article En | MEDLINE | ID: mdl-38310368

Background: Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation. Objective: To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma. Methods: Female BALB/c mice were randomly assigned to different groups. They were then injected with ovalbumin (OVA)/lipopolysaccharides (LPS) to induce neutrophilic asthma. The mice were then treated with either anti-ICOSL (the I group), control IgG (the G group), or no treatment (the N group). Additionally, a control group of mice received vehicle PBS and was labeled as the C group (n=6 per group). One day after the last allergen exposure, cytokine levels were measured in plasma and bronchoalveolar lavage fluid (BALF) using ELISA. After analyzing and categorizing BALF cells, the lung tissues were examined histologically and immunohistochemically. Results: Administering anti-ICOSL resulted in a significant decrease in the total number of inflammatory infiltrates and neutrophils found in BALF. Moreover, it led to a decrease in the levels of interleukin (IL)-6, IL-13, and IL-17 in both BALF and plasma. Additionally, there was an increase in IFN-γ levels in the BALF of asthmatic mice (p<0.05 for all). Treatment with anti-ICOSL also reduced lung interstitial inflammation, mucus secretion, and ICOSL expression in asthmatic mice. Conclusion: The treatment of anti-ICOSL effectively improved lung interstitial inflammation and mucus secretion in mice with neutrophilic asthma by restoring the balance of Th1/Th2/Th17 responses. These findings indicate that blocking the ICOS/ICOSL signaling could be an effective way to manage neutrophilic asthma.


Asthma , Female , Animals , Mice , Inducible T-Cell Co-Stimulator Ligand , Asthma/drug therapy , Lung/metabolism , Bronchoalveolar Lavage Fluid , Inflammation/pathology , Antibodies , Mice, Inbred BALB C , Ovalbumin/therapeutic use , Disease Models, Animal
3.
Br J Haematol ; 204(4): 1207-1218, 2024 Apr.
Article En | MEDLINE | ID: mdl-37967471

The coronavirus disease 2019 (COVID-19) pandemic has a significant impact on the immune system. This is the first and largest study on pre-existing immune thrombocytopenia (ITP) patients infected with COVID-19 in China. We prospectively collected ITP patients infected with COVID-19 enrolled in the National Longitudinal Cohort of Hematological Diseases (NICHE, NCT04645199) and followed up for at least 1 month after infection. One thousand and one hundred forty-eight pre-existing ITP patients were included. Two hundred and twelve (18.5%) patients showed a decrease in the platelet (PLT) count after infection. Forty-seven (4.1%) patients were diagnosed with pneumonia. Risk factors for a decrease in the PLT count included baseline PLT count <50 × 109/L (OR, 1.76; 95% CI, 1.25-2.46; p = 0.001), maintenance therapy including thrombopoietin receptor agonists (TPO-RAs) (OR, 2.27; 95% CI, 1.60-3.21; p < 0.001) and previous splenectomy (OR, 1.98; 95% CI, 1.09-3.61; p = 0.03). Risk factors for pneumonia included age ≥40 years (OR, 2.45; 95% CI, 1.12-5.33; p = 0.02), ≥2 comorbidities (OR, 3.47; 95% CI, 1.63-7.64; p = 0.001), maintenance therapy including TPO-RAs (OR, 2.14; 95% CI, 1.17-3.91; p = 0.01) and immunosuppressants (OR, 3.05; 95% CI, 1.17-7.91; p = 0.02). In this cohort study, we described the characteristics of pre-existing ITP patients infected with COVID-19 and identified several factors associated with poor outcomes.


COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Humans , Adult , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Purpura, Thrombocytopenic, Idiopathic/therapy , Cohort Studies , Prospective Studies , Thrombocytopenia/epidemiology , Thrombocytopenia/etiology , Thrombopoietin , Recombinant Fusion Proteins , Receptors, Fc , Hydrazines
4.
BMC Infect Dis ; 23(1): 588, 2023 Sep 07.
Article En | MEDLINE | ID: mdl-37679703

OBJECTIVE: To investigate the etiological characteristics of plastic bronchitis (PB) caused by pulmonary infections in children and to identify any differences in the clinical features of PB cases caused by different pathogens. METHOD: We collected data on children diagnosed with PB and admitted to the Respiratory Department at Soochow University Children's Hospital between July 2021 and March 2023 utilizing electronic bronchoscopy. We analyzed clinical characteristics and the species of pathogens causing the illness in these children. RESULT: A total of 45 children were enrolled. The main clinical symptoms observed were cough (100%), fever (80%), shortness of breath (28.9%), and wheezing (20.0%). Pathogens were identified in 38 (84.4%) patients. Mycoplasma pneumoniae (MP) had the highest detection rate at 53.3%, followed by the Boca virus at 26.7%. MP-induced PB typically occurs in older children with an average age of 7.46 ± 2.36 years, with the main symptoms including high fever (85.7%) and local hyporespiration (42.9%). In contrast, Boca virus-induced PB tends to occur in younger children, with the main symptoms of moderate fever (54.5%), and wheezing (54.5%). The MP group exhibited a higher incidence of both internal and external pulmonary complications, including pleural effusion (42.9%), elevated aspartate aminotransferase (52.4%), lactic dehydrogenase (76.2%), and D-D dimer (90.5%). Conversely, the Boca virus group primarily showed pulmonary imaging of atelectasis (81.8%), with no pleural effusion. The average number of bronchoscopic interventions in the MP group was 2.24 ± 0.62, which was significantly higher than that required in the Boca virus group (1.55 ± 0.52). During the second bronchoscopy, 57.1% of children in the MP group still had visible mucus plugs, while none were observed in the Boca virus group. CONCLUSION: MP and Boca virus are the primary pathogens responsible for PB among children. The clinical manifestations of PB typically vary significantly based on the pathogen causing the condition.


Bronchitis , Pleural Effusion , Humans , Child , Child, Preschool , Respiratory Sounds , Bronchitis/diagnosis , Bronchitis/etiology , Aspartate Aminotransferases , Fever/etiology , Mycoplasma pneumoniae , Plastics
5.
Acta Haematol ; 146(6): 465-472, 2023.
Article En | MEDLINE | ID: mdl-37524052

INTRODUCTION: This retrospective study aimed to compare a range of conditioning regimens in children with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the Seventh Medical Center of PLA General Hospital between January 2008 and June 2017. METHODS: Patients were categorized into the Bu (Bu + Flu + Cy + ATG-F regimen) and control (Flu + Cy + ATG-F) groups, with a median follow-up time after HSCT of 3.5 (range, 3.1-6.2) and 3.7 (3.2-5.9) years in the Bu and control groups, respectively. RESULTS: No differences were observed between the two groups regarding the median time of peripheral blood neutrophil and platelet engraftment (p = 0.538 and p = 0.491); the 28-day engraftment rates of neutrophils were similar (p = 0.199), although higher for platelets with Bu (p = 0.044). Additionally, graft failure was 0% and 20.0% in the Bu and control groups, respectively (p = 0.004). In both groups, the incidence of grades III-IV (or grades II-IV) acute graft-versus-host disease (GVHD) and chronic GVHD was not significantly different (p > 0.05). Moreover, the 3-year overall survival and failure-free survival did not show significant differences (p = 0.670 and p = 0.908). DISCUSSION: In children with SAA undergoing allo-HSCT, conditioning regimen with Bu + Flu + Cy + ATG-F is capable of enhancing the myeloablation effect, promoting donor hematopoietic stem cell engraftment, and reducing the graft failure rate. Furthermore, it does not increase the incidence of complications, including GVHD.


Anemia, Aplastic , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Child , Humans , Busulfan/therapeutic use , Retrospective Studies , Anemia, Aplastic/therapy , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Transplantation Conditioning , Cyclophosphamide
6.
Res Pract Thromb Haemost ; 7(3): 100132, 2023 Mar.
Article En | MEDLINE | ID: mdl-37113987

Background: Thrombosis is an important cause of death in patients with polycythemia vera (PV). The conventional stratification of thrombosis may ignore some potential risk factors. Objectives: This study aimed to develop and validate a multiple factor-based prediction model of thrombosis for the 2016 World Health Organization-dened PV. Methods: Clinical and next-generation sequencing data from 2 cohorts of patients with PV were analyzed. Multivariable Cox regression analyses were conducted for the identification of thrombotic risk factors and model development. Results: The study involved 372 patients in the training cohort and another 195 patients in the external validation cohort. Multivariable analyses indicated that age ≥60 years (hazard ratio [HR] 2.56, 95% CI 1.51-4.35, P < .001), cardiovascular risk factors (HR 4.22, 95% CI 2.00-8.92, P < .001), at least 1 high-risk mutation for thrombosis (mutations in DNMT3A, ASXL1, or BCOR/BCORL1) (HR 4.35, 95% CI 2.62-7.21, P < .001), and previous thrombosis (HR 5.93, 95% CI 3.29-10.68, P < .001) were independent risk factors of thrombosis. After assigning coefficient-weighted scores to each risk factor mentioned above, a multiple factor-based prognostic score system of thrombosis (MFPS-PV) was developed, classifying patients into low-risk, intermediate-risk, and high-risk groups. Patients in the 3 groups had notably different thrombosis-free survival rates (P < .001). The MFPS-PV outperformed the conventional model in discrimination power (C-statistic: 0.87 [95% CI 0.83-0.91] vs 0.80 [95% CI 0.74-0.86]). The MFPS-PV was well calibrated and remained consistent during external validation. Conclusion: The MFPS-PV, integrating genetic and clinical characteristics for the first time, shows excellent accuracy and utility for thrombosis prediction in WHO-defined PV.

7.
Chembiochem ; 24(7): e202200719, 2023 04 03.
Article En | MEDLINE | ID: mdl-36734180

Optically active epoxides play important roles in pharmaceutical, agricultural and fine chemical syntheses. There are many chiral medications with pharmacodynamic activity in nature that can be synthesized by chiral epoxides. In recent years, researchers have developed a variety of biocatalysts for the asymmetric epoxidation of alkenes, which use oxygen or hydrogen peroxide as eco-friendly and low-cost oxidants, to provide better chemo-, regio- and stereoselectivity under moderate reaction conditions. In this paper, the advances, opportunities and challenges of the asymmetric epoxidation of unactive alkenes by biocatalyst are reviewed.


Alkenes , Oxidants , Catalysis , Hydrogen Peroxide , Epoxy Compounds , Stereoisomerism
8.
PeerJ ; 11: e14678, 2023.
Article En | MEDLINE | ID: mdl-36684682

Background: Invasive prenatal evaluation by chromosomal microarray analysis (CMA) and karyotyping might represent an important option in pregnant women, but limited reports have applied CMA and karyotyping of fetuses conceived by assisted reproductive technology (ART). This study aimed to examine the value of CMA and karyotyping in prenatal diagnosis after ART. Methods: This retrospective study included all singleton fetuses conceived by ART from January 2015 to December 2021. Anomalies prenatally diagnosed based on karyotyping and CMA were analyzed. Prevalence rates for various CMA and karyotyping results were stratified based on specific testing indications including isolated-and non-isolated ART groups. The rates of CMA findings with clinical significance (pathogenic/likely pathogenic) and karyotype anomalies were assessed and compared to those of local control individuals with naturally conceived pregnancies and without medical indications. Results: In total, 224 subjects were assessed by karyotyping and CMA. In the examined patients, chromosomal and karyotype abnormality rates were 3.57% (8/224) and 8.93% (20/224), respectively. This finding indicated a 5.35% (12/224)-incremental rate of abnormal CMA was obtained over karyotype analysis (p = 0.019). The risk of CMA with pathogenic findings for all pregnancies conceived by ART (5.80%, 13/224) was markedly elevated in comparison with the background value obtained in control individuals (1.47%, 9/612; p = 0.001). In addition, risk of CMA with clinically pathogenic results in isolated ART groups was significant higher compared to the background risk reported in the control cohort (p = 0.037). Conclusions: Prenatal diagnosis including karyotyping and CMA is recommended for fetuses conceived by ART, with or without ultrasound findings.


Fetus , Prenatal Diagnosis , Pregnancy , Female , Humans , Retrospective Studies , Prenatal Diagnosis/methods , Karyotyping , Microarray Analysis/methods , Fetus/abnormalities , Karyotype
9.
Int Immunopharmacol ; 115: 109658, 2023 Feb.
Article En | MEDLINE | ID: mdl-36608444

PM2.5 is one of the main harmful environmental pollutants and can damage nasal epithelial carriers to worsen allergic rhinitis. Ferroptosis is a novel form of regulated cell death with iron-dependent lipid peroxidation. However, whether ferroptosis is involved in PM2.5-induced nasal epithelial injury has not been elucidated. To verify the vital role of ferroptosis in PM2.5-induced nasal epithelial injury and further explore the potential mechanism, we detected intracellular iron content, ROS release and lipid peroxidation and ferroptosis-related proteins in vitro as well as the pathological changes in the nasal epithelium and the levels of proinflammatory factors in nasal lavage fluid in vivo. Our results showed that PM2.5 exposure led to oxidative stress, labile iron accumulation and lipid peroxidation in HNEPCs. In addition, the expression levels of xCT, GPx4, FTH1 and FTL in HNEPCs were greatly inhibited by PM2.5. Treatment with the ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (Fer-1) significantly reversed the toxicity of PM2.5 to human nasal epithelial cells (HNEPCs). Mechanistically, AMPK-mediated autophagy was initiated during PM2.5 exposure, which drove ferroptosis of HNEPCs. Autophagy inhibitor remarkably improved cell death, oxidative stress, labile iron accumulation, lipid peroxidation, and the downregulated expression of xCT, GPx4, FTH1 and FTL in HNEPCs induced by PM2.5. Furthermore, an AMPK inhibitor (Compound C, CC) and siRNA-AMPKα suppressed autophagy activation and ferroptosis stimulated by PM2.5. In vivo, Fer-1 reduced nasal epithelial injury and mucus secretion in PM2.5-exposed mice. In addition, CC significantly improved nasal epithelial damage and proinflammatory factor production in mice caused by PM2.5 intranasal treatment. In addition, CC greatly inhibited autophagy activation but reversed the downregulation of GPX4 and FTH1 induced by PM2.5 in the nasal epithelium of mice. Together, these data suggest that AMPK-mediated autophagy plays an important role in PM2.5-induced ferroptosis and that AMPK might be a potential treatment target for PM2.5-induced nasal epithelial injury.


Ferroptosis , Humans , Mice , Animals , AMP-Activated Protein Kinases , Iron/metabolism , Autophagy , Particulate Matter/toxicity
10.
Br J Haematol ; 201(4): 690-703, 2023 05.
Article En | MEDLINE | ID: mdl-36708268

JAK2V617F is the most frequent mutation in BCR-ABL-negative myeloproliferative neoplasms (MPNs). It is an important but not the only determinant of MPN phenotype. We performed high-throughput sequencing on JAK2V617F+ essential thrombocythaemia (ET) and polycythaemia vera (PV) patient samples to unveil factors involved in phenotypic heterogeneity and to identify novel therapeutic targets for MPN. Two concurrent mutations that may affect phenotype were identified, including mutations in SH2B3, which is primarily prevalent in PV, and SF3B1, which is more commonly mutated in ET. Next, we conducted transcriptomic analysis at the haematopoietic stem cell (HSC) and megakaryocyte (MK)-erythroid progenitor (MEP) levels. Inflammatory signalling pathways were elevated in both ET HSCs and MEPs, unlike in PV HSCs and MEPs. Notably, Wnt/ß-catenin signalling was uniquely upregulated during ET haematopoietic differentiation from HSC to MEP, and inhibiting Wnt/ß-catenin signalling blocked MK differentiation in vitro. Consistently, Wnt/ß-catenin inhibitor administration decreased platelet counts in JAK2V617F+ MPN mice by blocking MEPs and MK progenitors and by inhibiting maturation of MKs, while in wild-type mice, Wnt/ß-catenin inhibitor did not significantly reduce platelet counts. In conclusion, our findings provide new insights into the mechanisms underlying phenotypic differentiation of JAK2V617F+ PV and ET and indicate Wnt/ß-catenin signalling as a potential therapeutic target for MPN.


Myeloproliferative Disorders , Polycythemia Vera , Thrombocythemia, Essential , Animals , Mice , beta Catenin , Myeloproliferative Disorders/drug therapy , Myeloproliferative Disorders/genetics , Polycythemia Vera/drug therapy , Polycythemia Vera/genetics , Thrombocythemia, Essential/drug therapy , Thrombocythemia, Essential/genetics , Mutation , Phenotype , Janus Kinase 2/genetics
11.
Orphanet J Rare Dis ; 17(1): 422, 2022 12 02.
Article En | MEDLINE | ID: mdl-36461028

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) is a rare but life-threatening progressive disease. Human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is the best choice as sometimes HLA-matched donor is not accessible. However, graft-versus-host-disease (GVHD) following transplantation remains a major cause of treatment failure and elevated mortality. Post-transplant cyclophosphamide (PTCy) has recently emerged for effective GVHD prophylaxis in a haploidentical setting in many hematologic malignancies. Here, we report the performance of PTCy for GVHD prophylaxis in a series of CEABV patients treated with haplo-HSCT. METHODS: Consecutive pediatric CAEBV patients who were treated with haplo-HSCT and give PTCy for GVHD prophylaxis were analyzed. 1-year GVHD and relapse-free survival (GRFS), overall survival (OS) and cumulative incidence of moderate-to-severe chronic GVHD (cGVHD) were estimated. RESULTS: A total of 8 patients ranging from 2 to 15 years old were included. Among them, 4 patients had early complications after haplo-HSCT. Counts of T-cell subsets increased within 6 months post transplantation, indicating an immune reconstitution. Only 1 patient developed grade II acute GVHD, and 2 patients had moderate cGVHD. One patient died from diffuse alveolar hemorrhage within the first year after transplantation. The 1-year GRFS rate, OS rate and cumulative incidence of moderate-to-severe cGVHD were 62.5%, 87.5% and 25.0%, respectively. CONCLUSION: Our findings suggest that, among CAEBV patients treated with haplo-HSCT, PTCy may be an alternative choice for the prevention of GVHD.


Epstein-Barr Virus Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Child , Humans , Child, Preschool , Adolescent , Epstein-Barr Virus Infections/prevention & control , Graft vs Host Disease/drug therapy , Graft vs Host Disease/prevention & control , Herpesvirus 4, Human , Cyclophosphamide/therapeutic use , Persistent Infection
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(12): 1351-1355, 2022 Dec 15.
Article Zh | MEDLINE | ID: mdl-36544418

OBJECTIVES: To investigate the epidemiological characteristics of respiratory Haemophilus influenzae (HI) infection in children in Suzhou, China and its association with climatic factors and air pollutants. METHODS: The data on air pollutants and climatic factors in Suzhou from January 2016 to December 2019 were collected. Respiratory secretions were collected from 7 940 children with acute respiratory infection who were hospitalized during this period, and bacterial culture results were analyzed for the detection of HI. A stepwise regression analysis was used to investigate the association of HI detection rate with air pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) and climatic factors (monthly mean temperature, monthly mean humidity, monthly total rainfall, monthly total sunshine duration, and monthly mean wind speed). RESULTS: In 2016-2019, the 4-year overall detection rate of HI was 9.26% (735/7 940) among the children in Suzhou. The children aged <1 year and 1-<3 years had a significantly higher HI detection rate than those aged ≥3 years (P<0.01). The detection rate of HI in spring was significantly higher than that in the other three seasons, and the detection rate of HI in autumn was significantly lower than that in the other three seasons (P<0.001). The multiple linear regression analysis showed that PM10 and monthly mean wind speed were independent risk factors for the detection rate of HI: the detection rate of HI was increased by 0.86% for every 10 µg/m3 increase in the concentration of PM10 and was increased by 5.64% for every 1 m/s increase in monthly mean wind speed. Air pollutants and climatic factors had a lag effect on the detection rate of HI. CONCLUSIONS: HI is an important pathogen for acute respiratory infection in children in Suzhou and is prevalent in spring. PM10 and monthly mean wind speed are independent risk factors for the detection rate of HI.


Air Pollutants , Air Pollution , Haemophilus Infections , Respiratory Tract Infections , Child , Humans , Air Pollutants/adverse effects , Air Pollutants/analysis , Seasons , China/epidemiology , Haemophilus Infections/etiology , Haemophilus Infections/chemically induced , Air Pollution/adverse effects , Air Pollution/analysis
14.
Respir Res ; 23(1): 286, 2022 Oct 17.
Article En | MEDLINE | ID: mdl-36253857

The role of micro RNAs (miRNAs) in asthma remains unclear. In this study, we examined the role of miRNA in targeting FOXO1 in asthma. Results showed that miR-493-5p was one of the differentially expressed miRNAs in the PBMCs of asthmatic children, and was also associated with Th cell differentiation. The miR-493-5p expression decreased significantly in the OVA-induced asthma mice than the control groups. The miR-493-5p mimic inhibited the expression of the IL-9, IRF4 and FOXO1, while the inhibitor restored these effects. Moreover, the Dual-Luciferase analysis results showed FOXO1 as a novel valid target of miR-493-5p. According to the rescue experiment, miR-493-5p inhibited Th9 cell differentiation by targeting FOXO1. Then the exosomes in association with the pathogenesis of asthma was identified. Various inflammatory cells implicated in asthmatic processes including B and T lymphocytes, DCs, mast cells, and epithelial cells can release exosomes. Our results demonstrated that the DC-derived exosomes can inhibit Th9 cell differentiation through miR-493-5p, thus DC-derived exosomal miR-493-5p/FOXO1/Th9 may serve as a potential therapeutic target in the development of asthma.


Asthma , Forkhead Box Protein O1 , MicroRNAs , T-Lymphocytes, Helper-Inducer , Animals , Mice , Asthma/genetics , Cell Differentiation , Forkhead Box Protein O1/genetics , Forkhead Box Protein O1/metabolism , Interleukin-9/metabolism , MicroRNAs/genetics , Ovalbumin , T-Lymphocytes, Helper-Inducer/metabolism
15.
Ecotoxicology ; 31(8): 1310-1320, 2022 Oct.
Article En | MEDLINE | ID: mdl-36149570

Sulfoxaflor is a new systemic insecticide developed as a replacement for older neonicotinoids which are known to be toxic to pollinators. However, its metabolism in nectar and effect on nectar biosynthesis have not been investigated. After soil and foliar application, sulfoxaflor and its main metabolites in soil, leaf and Salvia splendens nectar, were measured by liquid chromatography coupled with triple quadrupole mass spectrometer (LC-MS/MS). The chemical composition between the clean and sulfoxaflor spiked nectar were also compared. The activities of two possible sulfoxaflor detoxifying enzymes in S. splendens nectar, nitrile hydratase and glutathione-s-transferase, were measured by LC-MS and spectrophotometry. S. splendens nectar proteome was investigated by high-resolution orbitrap-based MS/MS to screen for sulfoxaflor detoxifying relevant proteins. S. splendens could absorb sulfoxaflor through root or leaf surface and secrete a proportion of sulfoxaflor along with its metabolites into the nectar. After soil application, sulfoxaflor's low toxic metabolite X11719474 was dominant in the nectar and reached an average concentration of 8905 ppb. However, after foliar application, sulfoxaflor was dominant over its metabolites in the nectar. S. splendens nectar has no nitrile hydratase and glutathione-s-transferase activity and none of the 106 proteins identified in the nectar were predicted to function in detoxifying sulfoxaflor. Soil and foliar sulfoxaflor application can result in different profiles of sulfoxaflor and its metabolites presented in the nectar. However, sulfoxaflor had no effects on S. splendens nectar secretion and chemical composition and cannot be directly detoxified by components in the nectar.


Insecticides , Salvia , Chromatography, Liquid , Glutathione , Insecticides/analysis , Insecticides/toxicity , Neonicotinoids/analysis , Plant Nectar/chemistry , Proteome , Pyridines , Soil/chemistry , Sulfur Compounds , Tandem Mass Spectrometry , Transferases
16.
Int Immunopharmacol ; 111: 109060, 2022 Oct.
Article En | MEDLINE | ID: mdl-35930910

This study aimed to explore the effects of forkhead box P2 gene (Foxp2) on T-helper 9 (Th9) differentiation in asthmatic mice. An in vivo asthmatic mouse model was induced with ovalbumin (OVA). An in vitro model was established by culturing CD4+ T cells with TGF-ß, IL-4, and anti-IFN-γ. ELISA, flow cytometry, qRT-PCR and Western blot were performed to examine IL-9 secretion, Th9 cell number, and Th9 cell transcription factor expression, respectively. Pathological changes in lung tissues and airway mucus secretion were assessed with HE and PAS glycogen staining. Anti-IL-9 mAb reversed the elevation in Th9 cells and IL-9 expression in lung tissues and bronchoalveolar lavage fluid (BALF) of asthmatic mice. Foxp2 was downregulated in BALF and lung tissue of asthmatic mice and Th9 cells. Overexpression of Foxp2 inhibited Th9 cell differentiation in vitro and improved airway inflammation in vivo. Our study suggests that overexpression of Foxp2 attenuates allergic asthma by inhibiting Th9 cell differentiation.


Asthma , Animals , Asthma/chemically induced , Asthma/drug therapy , Asthma/metabolism , Bronchoalveolar Lavage Fluid , Cell Differentiation , Disease Models, Animal , Forkhead Transcription Factors/genetics , Inflammation , Lung/metabolism , Mice , Mice, Inbred BALB C , Ovalbumin , Repressor Proteins , T-Lymphocytes, Helper-Inducer
17.
BMC Cancer ; 22(1): 753, 2022 Jul 11.
Article En | MEDLINE | ID: mdl-35820883

BACKGROUND: Progestin is used for fertility-sparing treatment in cases of endometrial cancer (EC). Progestin can induce hyperprolactinemia by increasing pituitary secretion and endometrial decidualization. However, progestin induces prolactin (PRL) secretion, which stimulates cell proliferation and deleteriously affects treatment. To date, the detrimental effect of PRL, the secretion of which is induced by medroxyprogesterone acetate (MPA) during fertility-sparing treatment, has not yet been fully elucidated. Therefore, we aimed to assess the effects of PRL on EC cells during combined treatment with progestin and metformin. METHODS: In total, 71 patients with EC/endometrial atypical hyperplasia who underwent fertility-sparing treatment at our institution from 2009-2019 were enrolled. Serum PRL levels were determined using enzyme immunoassays; mRNA levels in endometrial tissues were determined using quantitative reverse-transcription PCR. To evaluate MPA-induced decidualization, cancer-associated stromal cells were enzymatically released from surgically removed specimens of six patients with EC. To examine PRL-induced cell proliferation, the EC cell lines Ishikawa, HEC1B, and HEC265 were used. In vitro cell proliferation was evaluated using the WST assay; protein levels of signaling molecules were determined using western blotting. RESULTS: MPA administration significantly increased serum PRL levels at 3 and 6 months and upregulated IGFBP-1 and PRL mRNA expression in tissues at 3 months of fertility-sparing treatment. Metformin significantly reduced MPA-induced IGFBP-1 and PRL mRNA expression during fertility-sparing treatment and significantly inhibited the upregulation of IGFBP-1 and PRL mRNA and PRL levels due to decidualization induced by MPA and cAMP treatment in primary cultured EC stromal cells. In vitro, PRL increased cell proliferation and ERK1/2 phosphorylation levels, whereas metformin attenuated these increases. CONCLUSIONS: MPA upregulated PRL levels in serum and endometrial tissues during fertility-sparing treatment. Metformin co-administration reduced PRL production and attenuated PRL-induced cell-proliferation activity. This study may provide valuable insights on the application of metformin to improve the outcomes of fertility-sparing treatment.


Endometrial Neoplasms , Metformin , Endometrial Neoplasms/drug therapy , Female , Humans , Insulin-Like Growth Factor Binding Protein 1 , Medroxyprogesterone Acetate/pharmacology , Medroxyprogesterone Acetate/therapeutic use , Metformin/pharmacology , Metformin/therapeutic use , Progestins , Prolactin , RNA, Messenger
18.
Bioengineering (Basel) ; 9(6)2022 Jun 04.
Article En | MEDLINE | ID: mdl-35735489

With the progress and innovation of table tennis technology, individualized training programs may deserve special attention. This study aimed to analyze elite table tennis athletes in chasse-step, with a particular focus on sex-based biomechanical differences. A total of 36 (18 males and 18 females) elite table tennis athletes performed topspin forehand of chasse-step. Angles and moments of hip, knee, and ankle joints were calculated using OpenSim (v4.2) with marker trajectories and ground reaction forces were measured via Vicon motion capture system and AMTI in-ground force platform. Males had greater hip and knee flexion angles during the entire motion phase and greater internal rotation angles of the hip during the forward swing phase. The joint stiffness of knee in males was greater than females in the frontal plane. Females in the forward swing phase showed greater hip flexion, adduction, and internal rotation moments than males. It was suggested that the difference may be due to the limitation of anatomical structures in sexes. Male table tennis athletes should strengthen lower extremity muscle groups to improve performance, while female table tennis athletes should focus on hip joint groups to avoid injury. The sex differences presented in this study could help coaches and athletes to develop individualized training programs for table tennis.

19.
Front Microbiol ; 13: 911228, 2022.
Article En | MEDLINE | ID: mdl-35770160

Plastic bronchitis (PB) is a rare respiratory condition which can result in severe respiratory complications such as respiratory failure and death. Mycoplasma pneumoniae infection is a main etiology cause of plastic bronchitis. However, the pathogenesis of plastic bronchitis complicated by Mycoplasma pneumoniae pneumonia (MPP) has not yet been fully elucidated. Our article aims to explore biomarkers for early prediction of MPP cases complicated with plastic bronchitis. We utilized a protein chip to screen for significantly different proteins among the groups of healthy, general Mycoplasma pneumoniae pneumonia (GMPP) and refractory Mycoplasma pneumoniae pneumonia (RMPP) patients, where layilin exhibited a potent change across biology information technology. Next, we demonstrated the high expression of MUC5AC, MUC5B, and layilin in bronchoalveolar lavage fluid (BALF) of MPP cases complicated with plastic bronchitis. Further study suggested that the level of layilin had a positive correlation with both MUC5AC and MUC5B. A receiver operating characteristic (ROC) analysis was performed to assess the diagnostic values of MUC5AC, MUC5B, and layilin in MPP cases with PB. Data show that the three indicators have similar diagnostic ability for MPP children with plastic bronchitis. Then, we used different concentrations of community-acquired respiratory distress syndrome (CARDS) toxin or lipid-associated membrane proteins (LAMPs) to simulate an in vitro experiment. The in vitro assay revealed that CARDS toxin or LAMPs induced A549 cells to secrete MUC5AC, MUC5B, layilin, and proinflammatory factors. These findings suggest that MUC5AC, MUC5B, and layilin are correlated with MPP. The high expression of MUC5AC, MUC5B, and layilin play an essential role in prediction in the development of plastic bronchitis caused by MPP. The high expression of MUC5AC, MUC5B, and layilin may be relevant to the severity of illness.

20.
Mol Immunol ; 147: 180-186, 2022 07.
Article En | MEDLINE | ID: mdl-35633613

BACKGROUND: Pollen allergens are vital contributors to allergic diseases. The frequency and coreactivity pattern of allergens are closely related to geographical distribution. OBJECTIVE: In this study, we aimed to characterize the prevalence of the molecular components of the common weed pollen allergens, birch pollen, walnut, and cross-reactive carbohydrate determinant (CCD), as well as investigate the relationship between the allergens and CCD in Chinese pollen-sensitized patients with allergic diseases. METHODS: Based on previous vegetation surveys, serum samples from 165 pollen-sensitized patients with allergic diseases in Guangdong Province in southern China were used to test 19 crude allergen extracts, their components, and CCD using component-resolved diagnosis (CRD). Moreover, the potential associations among CCD, allergens, and their components were described. RESULTS: In the 165 samples, the most common sensitized allergens were goosefoot (43.0%), ragweed (40.6%), walnut (37.6%), walnut tree (37.6%), and mugwort (37.0%), followed by platane (35.2%), cocklebur (27.9%), and birch (24.2%). The positivity rate of CCD was 39.4%. Among the samples positive for mugwort, 11 (18.0%), 15 (24.6%), and 15 (24.6%) were positive for Art v 1, Art v 2, and Art v 3, respectively. Among the 67 patients sensitized to ragweed, only five (7.5%) were positive for Amb a 1. In the 40 patients sensitized to birch, Bet v 2 had the highest positivity rate (40.0%). There were 62 patients who were sensitized to walnut. Their components had a lower positivity rate (less than 15%). The hierarchical clustering and optimal scale analysis showed that Art v 4 and Bet v 2 were closely related, and 91.9% of CCD-positive samples were polysensitized. Meanwhile, Spearman's rank correlation method showed that CCD was closely correlated with the sensitization of crude allergen extracts, and there was a low correlation between CCD and allergen components. CCD was highly correlated with goosefoot, ragweed, and walnut trees (r>0.8). Moreover, there was a strong relationship between the levels of Jug r 3 and Art v 3 (r = 0.78; P < 0.001). CONCLUSIONS: In southern China, the weed pollens (ragweed, cocklebur, and goosefoot) exhibited higher positivity rates in adults and had a stronger relationship with CCD but not with mugwort. The positivity rate of allergen components was not high. CCD-positive samples were always polysensitized.


Artemisia , Hypersensitivity , Rhinitis, Allergic, Seasonal , Adult , Allergens , Ambrosia , Antigens, Plant , Cross Reactions , Humans , Immunoglobulin E , Plant Extracts , Plant Proteins , Pollen , Rhinitis, Allergic, Seasonal/epidemiology
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