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The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERS) organized a day-long symposium at the 2024 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research and debates on the mechanisms and management of eosinophilic gastrointestinal diseases (EGIDs). Updates on recent clinical trials and consensus guidelines were also presented. Herein, we summarize the updates on EGIDs presented at the symposium.
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INTRODUCTION: Although IgE-mediated food allergy (FA) and eosinophilic gastrointestinal disorders (EGID) are clinically distinct and treated differently, pathogenic effector Th2 (peTh2) cells are implicated in the pathogenesis of both FA and EGID. The aim of this study was to better characterize peTh2 cells in the context of FA and EGID and the overlap between these two conditions. METHODS: Peripheral blood peTh2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) were profiled by intracellular cytokine flow cytometry in the following patient cohorts: patients with FA alone (n = 8), FA and food-triggered EGID (EGID+FA+FT, n = 7), food-triggered EGID alone (EGID+FT, n = 7), EGID without FA or specific food triggers (ONLY_EGID, n = 9), and healthy volunteers (HV, n = 7). Overnight peripheral blood mononuclear cell (PBMC) culture supernatants were assessed for cytokine production by multiplex analysis. RESULTS: CRTH2+CD161+ (peTh2) memory CD4+ T cells were significantly increased in both patients with FA and those with ALL_EGID (inclusive of EGID+FA+FT, EGID+FT and ONLY_EGID) when compared to HV. However, ALL_EGID patients, particularly those with EGID+FA+FT, had significantly elevated IL-5+IL-13+ peTh2 cells, whereas FA patients had significantly elevated IFN-γ or IL-17A-expressing peTh2 cells. This finding was supported by increased spontaneous IL-5 and IL-13 production in overnight cultures of PBMC from EGID+FA+FT patients compared to spontaneous IL-10 and IFN-γ production by PBMC from FA patients. FA patients had increased IL-9, IL-10, IL-17A, and IFN-γ production in overnight cultures of stimulated PBMC. CONCLUSIONS: EGID and IgE-mediated FA share a common cell subtype defined by specific surface markers and termed CRTH2+CD161+ (peTh2) memory CD4+ T cells. However, the cytokine profiles of these CRTH2+CD161+ (peTh2) memory CD4+ T cells are markedly different between the two disorders.
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Hipersensibilidade Alimentar , Gastroenteropatias , Humanos , Linfócitos T CD4-Positivos , Interleucina-17/metabolismo , Interleucina-10 , Leucócitos Mononucleares/metabolismo , Interleucina-5 , Interleucina-13 , Citocinas/metabolismo , Imunoglobulina ERESUMO
BACKGROUND: Eosinophilic esophagitis (EoE) involves a chronic immune-mediated response to dietary antigens. Recent work identifies T-cell clonality in children with EoE, however, it is unknown whether this is true in adults or whether there is a restricted food-specific T-cell repertoire. We sought to confirm T-cell receptor (TCR) clonality in EoE and assess for differences with specific food triggers. METHODS: Bulk TCR sequencing was performed on mRNA isolated from esophageal biopsies obtained from adults and children with EoE (n = 15) who had food triggers confirmed by endoscopic evaluation. Non-EoE adult and pediatric controls (n = 10) were included. Differences in TCR clonality by disease and treatment status were assessed. Shared and similar V-J-CDR3s were assessed based on specific food triggers. RESULTS: Active EoE biopsies from children but not adults displayed decreased unique TCRα/ß clonotypes and increased relative abundance of TCRs comprising >1% of the total compared to non-EoE controls and paired inactive EoE samples. Among patients in which baseline, post diet elimination, and food trigger reintroduction samples (n = 6) were obtained, we observed ~1% of TCRs were shared only between pre-diet elimination and trigger reintroduction. Patients with a shared EoE trigger (milk) had a greater degree of shared and similar TCRs compared to patients with differing triggers (seafood, wheat, egg, soy). CONCLUSION: We confirmed relative clonality in children but not adults with active EoE and identified potential food-specific TCRs, particularly for milk-triggered EoE. Further studies are needed to better identify the broad TCR repertoire relevant to food triggers.
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Esofagite Eosinofílica , Humanos , Criança , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/genética , Alimentos/efeitos adversos , Alérgenos , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
BACKGROUND: Biomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil-associated diseases treated with mepolizumab, benralizumab, or dexpramipexole. METHODS: Eosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay. RESULTS: Urine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups. CONCLUSIONS: Measurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.
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Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Humanos , Neurotoxina Derivada de Eosinófilo , Prednisona , Reprodutibilidade dos Testes , Eosinófilos , BiomarcadoresRESUMO
BACKGROUND AND AIMS: Chronic liver disease (CLD) patients and liver transplant (LT) recipients have an increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19). The immunogenicity of COVID-19 vaccines in CLD patients and LT recipients is poorly understood. The present study aimed to evaluate the immunogenicity of COVID-19 vaccines in CLD patients and LT recipients. METHODS: We searched electronic databases for eligible studies. Two reviewers independently conducted the literature search, extracted the data and assessed the risk of bias of included studies. The rates of detectable immune response were pooled from single-arm studies. For comparative studies, we compared the rates of detectable immune response between patients and healthy controls. The meta-analysis was conducted using the Stata software with a random-effects model. RESULTS: In total, 19 observational studies involving 4191 participants met the inclusion criteria. The pooled rates of detectable humoral immune response after two doses of COVID-19 vaccination in CLD patients and LT recipients were 95% (95% confidence interval [CI] = 88%-99%) and 66% (95% CI = 57%-74%) respectively. After two doses of vaccination, the humoral immune response rate was similar in CLD patients and healthy controls (risk ratio [RR] = 0.96; 95% CI = 0.90-1.02; p = .14). In contrast, LT recipients had a lower humoral immune response rate after two doses of vaccination than healthy controls (RR = 0.68; 95% CI = 0.59-0.77; p < .01). CONCLUSIONS: Our meta-analysis demonstrated that COVID-19 vaccination induced strong humoral immune responses in CLD patients but poor humoral immune responses in LT recipients.
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COVID-19 , Hepatopatias , Transplante de Fígado , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Bases de Dados Factuais , Transplantados , Anticorpos AntiviraisRESUMO
The imatinib-sensitive fusion gene FIP1L1::PDGFRA is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of PDGFRA-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for FIP1L1::PDGFRA. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for FIP1L1::PDGFRA. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of PDGFRA-associated disease.
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Transtornos Mieloproliferativos , Neoplasias , Humanos , Mesilato de Imatinib/uso terapêutico , Diagnóstico Tardio , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Hibridização in Situ Fluorescente , Benzamidas , Proteínas de Fusão Oncogênica/genética , Transtornos Mieloproliferativos/tratamento farmacológico , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: Hypereosinophilic syndrome is a group of diseases defined by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a monoclonal antibody against interleukin-5 receptor α, which is expressed on human eosinophils. METHODS: In this randomized, double-blind, placebo-controlled, phase 2 trial, we administered a series of three monthly subcutaneous injections of either benralizumab (at a dose of 30 mg) or placebo in 20 symptomatic patients who had PDGFRA-negative hypereosinophilic syndrome and an absolute eosinophil count of at least 1000 cells per cubic millimeter; all the patients were receiving stable therapy (drugs or dietary changes) for this disease. This regimen was followed by an open-label phase, during which the patient's background therapy could be tapered as tolerated, and an extension phase. The primary end point of the randomized phase was a reduction of at least 50% in the absolute eosinophil count at week 12. RESULTS: During the randomized phase, the primary end point occurred in more patients in the benralizumab group than in the placebo group (9 of 10 patients [90%] vs. 3 of 10 patients [30%], P = 0.02). During the open-label phase, clinical and hematologic responses were observed in 17 of 19 patients (89%) and were sustained for 48 weeks in 14 of 19 patients (74%); in the latter group, in 9 of 14 patients (64%), background therapies could be tapered. Bone marrow and tissue eosinophilia were also suppressed with benralizumab therapy. The most common drug-related adverse events, headache and an elevated lactate dehydrogenase level, occurred in 32% of the patients after the first dose of benralizumab and resolved within 48 hours in all patients. Other adverse events occurred with similar frequency in the two groups. Of the many potential predictors of response that were examined, only clinical disease subtype appeared to be associated with the initial response or relapse. CONCLUSIONS: In this small phase 2 trial, patients with PDGFRA-negative hypereosinophilic syndrome who received benralizumab for 12 weeks had lower absolute eosinophil counts than those who received placebo. During the open-label phase, clinical and hematologic responses were sustained for 48 weeks in 74% of the patients. Adverse events did not limit treatment. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov numbers, NCT00001406 and NCT02130882.).
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Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hipereosinofílica/tratamento farmacológico , Subunidade alfa de Receptor de Interleucina-5/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Biópsia , Medula Óssea/imunologia , Medula Óssea/patologia , Colo Ascendente/patologia , Método Duplo-Cego , Eosinófilos , Feminino , Humanos , Síndrome Hipereosinofílica/patologia , Injeções Subcutâneas , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/sangue , Pele/patologia , Estômago/patologiaRESUMO
Background: Acute allergic reactions to messenger RNA (mRNA) vaccines are rare but may limit public health immunization efforts. Objectives: To characterize suspected allergic reactions to the first dose of coronavirus disease 2019 (COVID-19) mRNA vaccine and to assess the safety and utility of a two-step graded-dose protocol for the second dose of the Pfizer-BioNTech vaccine in patients with a history of low suspicion of anaphylaxis to their first dose. Methods: This was a retrospective evaluation of referrals to the allergy and immunology clinic for a presumed allergic reaction to the first dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech or Moderna) between December 17, 2020, and February 28, 2021. Recommendations for the second dose and outcomes were evaluated by trained board-certified allergists. Results: Seventy-seven patients presented with a Pfizer-BioNTech reaction (56 [72.7%]) or with a Moderna reaction (21 [27.3%]). Most patients (69.7%) had symptom onset within 4 hours. Most commonly reported symptoms were cutaneous (51.9%), cardiovascular (48.1%), and respiratory (33.8%) symptoms. Recommendations included to proceed with the single dose (70.1%), two-step graded dose (19.5%), or deferral (10.4%). Twelve of 15 patients completed the second dose with a graded-dose protocol. Of these patients, five reported at least one or more similar symptoms as experienced with their first dose. Conclusion: Of the patients with presumed allergic reactions to their first dose of COVID-19 mRNA vaccine, most were able to safely receive the second dose. For those with a low suspicion of anaphylaxis, the two-step graded protocol with the Pfizer-BioNTech vaccine was well tolerated. A graded-dose protocol could be an effective strategy for second-dose vaccination in those who may otherwise defer the second dose.
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Anafilaxia/induzido quimicamente , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Hipersensibilidade , Vacinas Sintéticas/efeitos adversos , Adulto , Idoso , COVID-19/epidemiologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Vacinas Sintéticas/administração & dosagem , Vacinas de mRNARESUMO
BACKGROUND: The Centers for Disease Control and Prevention advises that patients with moderate to severe asthma belong to a high-risk group that is susceptible to severe coronavirus disease 2019 (COVID-19). However, the association between asthma and COVID-19 has not been well-established. OBJECTIVE: The primary objective was to determine the prevalence of asthma among patients with COVID-19 in a major US health system. We assessed the clinical characteristics and comorbidities in asthmatic and nonasthmatic patients with COVID-19. We also determined the risk of hospitalization associated with asthma and/or inhaled corticosteroid use. METHODS: Medical records of patients with COVID-19 were searched by a computer algorithm (March 1 to April 15, 2020), and chart review was used to validate the diagnosis of asthma and medications prescribed for asthma. All patients had PCR-confirmed COVID-19. Demographic and clinical features were characterized. Regression models were used to assess the associations between asthma and corticosteroid use and the risk of COVID-19-related hospitalization. RESULTS: Of 1526 patients identified with COVID-19, 220 (14%) were classified as having asthma. Asthma was not associated with an increased risk of hospitalization (relative risk, 0.96; 95% CI, 0.77-1.19) after adjusting for age, sex, and comorbidities. The ongoing use of inhaled corticosteroids did not increase the risk of hospitalization in a similar adjusted model (relative risk, 1.39; 95% CI, 0.90-2.15). CONCLUSIONS: Despite a substantial prevalence of asthma in our COVID-19 cohort, asthma was not associated with an increased risk of hospitalization. Similarly, the use of inhaled corticosteroids with or without systemic corticosteroids was not associated with COVID-19-related hospitalization.
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Asma/epidemiologia , Betacoronavirus/patogenicidade , Doença da Artéria Coronariana/epidemiologia , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Obesidade/epidemiologia , Pneumonia Viral/epidemiologia , Administração por Inalação , Corticosteroides/uso terapêutico , Adulto , Fatores Etários , Idoso , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/fisiopatologia , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Comorbidade , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Illinois/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Obesidade/diagnóstico , Obesidade/fisiopatologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2Assuntos
Eosinófilos , Imunoglobulina E , Humanos , RNA Mensageiro/genética , Receptores de IgE/genéticaRESUMO
An 8-year-old girl who had experienced intermittent cough and fever over a 3 year period, was admitted after experiencing a recurrence for one month. One year ago the patient experienced a recurrent oral mucosal ulcer. Physical examination showed vitiligo in the skin of the upper right back. Routine blood tests and immune function tests performed in other hospitals had shown normal results. Multiple lung CT scans showed pulmonary infection. The patient had recurrent fever and cough and persistent presence of some lesions after anti-infective therapy. The antitubercular therapy was ineffective. Routine blood tests after admission showed agranulocytosis. Gene detection was performed and she was diagnosed with dyskeratosis congenita caused by homozygous mutation in RTEL1. Patients with dyskeratosis congenita with RTEL1 gene mutation tend to develop pulmonary complications. Since RTEL1 gene sequence is highly variable with many mutation sites and patterns and can be inherited via autosomal dominant or recessive inheritance, this disease often has various clinical manifestations, which may lead to missed diagnosis or misdiagnosis. For children with unexplained recurrent pulmonary infection, examinations of the oral cavity, skin, and nails and toes should be taken and routine blood tests should be performed to exclude dyskeratosis congenita. There are no specific therapies for dyskeratosis congenita at present, and when bone marrow failure and pulmonary failure occur, hematopoietic stem cell transplantation and lung transplantation are the only therapies. Androgen and its derivatives are effective in some patients. Drugs targeting the telomere may be promising for patients with dyskeratosis congenita.
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Disceratose Congênita/complicações , Doenças da Boca/etiologia , Infecções Respiratórias/etiologia , Úlcera/etiologia , Criança , Disceratose Congênita/terapia , Feminino , Humanos , Mucosa Bucal/patologia , Recidiva , Telômero/efeitos dos fármacosRESUMO
PURPOSE: To compare the diagnostic accuracy of routine magnetic resonance imaging (MRI) (T1 WI and T2 WI), diffusion-weighted MRI (DWI), and DCE-MRI (dynamic contrast-enhanced MRI) at 3.0T for differentiation of cervical cancer and benign cervical lesions. MATERIALS AND METHODS: A cohort of 75 cervical cancer patients, 26 cervical leiomyoma patients, 22 patients with cervical polyps consecutively underwent pelvic MRI scanning on a 3T MR unit. Two radiologists independently evaluated images at three imaging settings; routine MRI alone, DWI combined with routine MRI (DWI+routine MRI), and DCE-MRI. The apparent diffusion coefficients (ADCs) were calculated from b 0, 600 s/mm(2) and b 0, 1000 s/mm(2). RESULTS: DWI+routine MRI was significantly better than routine MRI and obtained high accuracy (0.95); the diagnostic performance was not significantly different between DWI+routine MRI and DCE-MRI. Reader agreement was excellent for both DWI+routine MRI (κ, 0.90) and DCE-MRI (κ, 0.92). The ADCs of cervical cancer were significantly lower than those of benign cervical lesions at both ADC maps (P = 0.0001). The diagnostic accuracy was not different at both ADC maps (P = 0.375). CONCLUSION: For differentiation of cervical cancer and benign cervical lesions, unenhanced MRI with combined diffusion-weighted and routine MRI (DWI+routine MRI) at 3T can provide accurate information and may be preferable to DCE.
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Meios de Contraste , Imagem de Difusão por Ressonância Magnética/métodos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imagem Multimodal/métodos , Neoplasias do Colo do Útero/patologia , Adulto , Algoritmos , Diagnóstico Diferencial , Feminino , Gadolínio DTPA , Humanos , Imageamento Tridimensional/métodos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
A high-throughput screening system for moderately halophilic phenol-degrading bacteria from various habitats was developed to replace the conventional strain screening owing to its high efficiency. Bacterial enrichments were cultivated in 48 deep well microplates instead of shake flasks or tubes. Measurement of phenol concentrations was performed in 96-well microplates instead of using the conventional spectrophotometric method or high-performance liquid chromatography (HPLC). The high-throughput screening system was used to cultivate forty-three bacterial enrichments and gained a halophilic bacterial community E3 with the best phenol-degrading capability. Halomonas sp. strain 4-5 was isolated from the E3 community. Strain 4-5 was able to degrade more than 94% of the phenol (500 mg · L(-1) starting concentration) over a range of 3%-10% NaCl. Additionally, the strain accumulated the compatible solute, ectoine, with increasing salt concentrations. PCR detection of the functional genes suggested that the largest subunit of multicomponent phenol hydroxylase (LmPH) and catechol 1,2-dioxygenase (C12O) were active in the phenol degradation process.
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Halomonadaceae/isolamento & purificação , Halomonadaceae/fisiologia , Ensaios de Triagem em Larga Escala/métodos , Fenóis/metabolismo , Tolerância ao Sal , Diamino Aminoácidos/metabolismo , Proteínas de Bactérias/genética , Biodegradação Ambiental , Catecol 1,2-Dioxigenase/genética , Halomonadaceae/genética , Oxigenases de Função Mista/genéticaRESUMO
Trichloroethylene (TCE) and phenol were often found together as co-contaminants in the groundwater of industrial contaminated sites. An effective method to remove TCE was aerobic biodegradation by co-metabolism using phenol as growth substrates. However, the aerobic biodegradation process was easily limited by low concentration of dissolved oxygen (DO) in groundwater, and DO was improved by air blast technique with difficulty. This study enriched a bacterial community using hydrogen peroxide (H2O2) as the sole oxygen source to aerobically degrade TCE by co-metabolism with phenol in groundwater. The enriched cultures were acclimatized to 2-8â mM H2O2 which induced catalase, superoxide dismutase and peroxidase to decompose H2O2 to release O2 and reduce the toxicity. The bacterial community could degrade 120â mg/L TCE within 12 days by using 8â mM H2O2 as the optimum concentration, and the TCE degradation efficiency reached up to 80.6%. 16S rRNA gene cloning and sequencing showed that Bordetella, Stenotrophomonas sp., Sinorhizobium sp., Variovorax sp. and Sphingobium sp. were the dominant species in the enrichments, which were clustered in three phyla: Alphaproteobacteria, Betaproteobacteria and Gammaproteobacteria. Polymerase chain reaction detection proved that phenol hydroxylase (Lph) gene was involved in the co-metabolic degradation of phenol and TCE, which indicated that hydroxylase might catalyse the epoxidation of TCE to form the unstable molecule TCE-epoxide. The findings are significant for understanding the mechanism of biodegradation of TCE and phenol co-contamination and helpful for the potential applications of an aerobic bioremediation in situ the contaminated sites.
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Peróxido de Hidrogênio/metabolismo , Consórcios Microbianos , Fenol/metabolismo , Tricloroetileno/metabolismo , Poluentes Químicos da Água/metabolismo , Aerobiose , Biodegradação AmbientalRESUMO
Greater exposure to Pb(â ¡) increases the likelihood of harmful effects in the environment. In this study, the aquatic unicellular alga Chlorella protothecoides (C. protothecoides) and Chlorella vulgaris (C. vulgaris) were chosen to assess the acute and chronic toxicity of Pb(â ¡) exposure. Results of the observations show dose-response relationships could be clearly observed between Pb(â ¡) concentration and percentage inhibition (PI). Exposure to Pb(â ¡) increased malondialdehyde (MDA) content by up to 4.22 times compared with the control, suggesting that there was some oxidative damage. ANOVA analysis shows that Pb(â ¡) decreased chlorophyll (chl) content, indicating marked concentration-dependent relationships, and the lowest levels of chl a, chl b, and total-chl were 14.53, 18.80, and 17.95% of the controls, respectively. A real-time PCR assay suggests the changes in transcript abundances of three photosynthetic-related genes. After 120 h exposure Pb(â ¡) reduced the transcript abundance of rbcL, psaB, and psbC, and the relative abundances of the three genes of C. protothecoides and C. vulgaris in response to Pb(â ¡) were 54.66-98.59, 51.68-95.59, 37.89-95.48, 36.04-94.94, 41.19-91.20, and 58.75-96.80% of those of the controls, respectively. As for 28 d treatments, the three genes displayed similar inhibitory trend. This research provides a basic understanding of Pb(â ¡) toxicity to aquatic organisms.
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Chlorella/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Chumbo/toxicidade , Malondialdeído/metabolismo , Fotossíntese/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Chlorella/fisiologia , Chlorella vulgaris/efeitos dos fármacos , Chlorella vulgaris/fisiologia , Clorofila/análogos & derivados , Clorofila/metabolismo , Clorofila A , Oxirredução , Fotossíntese/genética , Especificidade da EspécieRESUMO
The acute and chronic toxic effects of Bisphenol A (BPA) on Chlorella pyrenoidosa (C. pyrenoidosa) and Scenedesmus obliquus (S. obliquus) were not well understood. The indoor experiments were carried out to observe and analyze the BPA-induced changes. Results of the observations showed that in acute tests BPA could significantly inhibit the growth of both algae, whereas chronic exposure hardly displayed similar trend. Superoxide dismutase (SOD) and Catalase (CAT) activities of both algae were promoted in all the treatments. Chlorophyll a synthesis of the two algae exhibited similar inhibitory trend in short-term treatments, and in chronic tests C. pyrenoidosa hardly resulted in visible influence, whereas in contrast, dose-dependent inhibitory effects of S. obliquus could be clearly observed. The experimental results indicated that the growth and Chlorophyll a syntheses of S.obliquus were more sensitive in response to BPA than that of C. pyrenoidosa, whereas for SOD andCAT activities, C. pyrenoidosa was more susceptible. This research provides a basic understanding of BPA toxicity to aquatic organisms.
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Compostos Benzidrílicos/toxicidade , Chlorella/efeitos dos fármacos , Fenóis/toxicidade , Scenedesmus/efeitos dos fármacos , Catalase/metabolismo , Chlorella/crescimento & desenvolvimento , Clorofila/análise , Clorofila A , Relação Dose-Resposta a Droga , Scenedesmus/crescimento & desenvolvimento , Superóxido Dismutase/metabolismo , Testes de Toxicidade Aguda , Testes de Toxicidade CrônicaRESUMO
Cancer is one of the most serious diseases challenging human health and life span. Cancer has claimed millions of lives worldwide. Early diagnosis and effective treatment of cancer are very important for the survival of patients. In recent years, 2D nanomaterials have shown great potential in the development of anticancer treatment by combining their inherent physicochemical properties after surface modification. 2D nanomaterials have attracted great interest due to their unique nanosheet structure, large surface area, and extraordinary physicochemical properties. This article reviews the advantages and application status of emerging 2D nanomaterials for targeted tumor synergistic therapy compared with traditional therapeutic strategies. In order to investigate novel potential anticancer strategies, this paper focuses on the surface modification, cargo delivery capability, and unique optical properties of emerging 2D nanomaterials. Finally, the current problems and challenges in cancer treatment are summarized and prospected.
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Grafite , Nanoestruturas , Neoplasias , Humanos , Grafite/uso terapêutico , Grafite/química , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Nanomedicina Teranóstica , Fototerapia , Neoplasias/tratamento farmacológico , Neoplasias/diagnósticoRESUMO
BACKGROUND: Long-term physical and mental persistent symptoms after COVID-19 represent a growing global public health concern. However, there remains a substantial knowledge gap regarding their prevalence and risk factors. OBJECTIVES: To estimate the prevalence and risk factors for persistent symptoms after COVID-19. METHODS OF DATA SYNTHESIS: We used a random-effects model to pool persistent symptom prevalence and risk ratios comparing COVID-19 patients with non-COVID-19 individuals. DATA SOURCES: Electronic databases were searched for studies published from December 2019 to January 2023. STUDY ELIGIBILITY CRITERIA: Eligible studies that reported the prevalence and risk factors for persistent symptoms after COVID-19 were included. PARTICIPANTS: Patients who recovered from COVID-19. ASSESSMENT OF RISK OF BIAS: The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias in prevalence studies, whereas the risk of bias in cohort studies was evaluated with the Newcastle-Ottawa Scale. RESULTS: After screening 4359 studies, a total of 211 eligible studies were included, covering a population of 13 368 074 individuals. Fatigue, dyspnoea, post-traumatic stress disorder, anxiety, and depression were the most frequently reported persistent symptoms after COVID-19. Subgroup analyses revealed that individuals with more severe illness in the acute phase or from Europe exhibited a higher prevalence of certain symptoms, whereas children demonstrated a lower prevalence. Furthermore, COVID-19 patients had a significantly higher prevalence of most persistent symptoms compared with non-COVID-19 individuals. Factors frequently associated with a higher prevalence of persistent symptoms included female gender, advanced age, severe illness during the acute phase of COVID-19, multiple comorbidities, an extended duration of hospital stay, and a high body mass index. CONCLUSION: This meta-analysis provides a thorough review of the prevalence and risk factors for persistent symptoms following COVID-19. The findings underscore the importance of long-term monitoring and support for individuals recovering from COVID-19.
Assuntos
COVID-19 , Criança , Humanos , Feminino , COVID-19/complicações , COVID-19/epidemiologia , Prevalência , Viés , Fatores de Risco , Estudos de CoortesRESUMO
Photodynamic therapy (PDT) has shown great potential for tumor treatment as the method is noninvasive, highly selective, and causes minimal side effects. However, conventional type II PDT, which relies on 1O2, presents poor therapeutic efficacy for hypoxic tumors due to its reliance on oxygen. Here, CeO2/Ti3C2-MXene (CeO2@MXene) hybrids were successfully designed by growing CeO2in situ using Ti3C2-MXene (MXene) nanosheets. CeO2@MXene serves as a reduction-oxidation (REDOX) center due to the presence of Ce in the lattice of CeO2 nanoparticles. This REDOX center reacts with H2O2 to generate oxygen and weakens the hypoxic tumor cell environment, achieving type II PDT. At the same time, many other ROS (such as â O2- and â OH) can be produced via a type I photodynamic mechanism (electron transfer process). The CeO2@MXene heterojunction performs nanoenzymatic functions for synergistic type I and type II PDT, which improves cancer treatment.
Assuntos
Neoplasias Ósseas , Nitritos , Osteossarcoma , Elementos de Transição , Humanos , Peróxido de Hidrogênio , Hipóxia , OxigênioRESUMO
Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included (1) clinical outcome measures, (2) minimally invasive biomarkers of disease activity, (3) predictors of response to biologic agents, and (4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies.