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1.
Blood ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39316719

ABSTRACT

Oncogenes can be activated in cis through multiple mechanisms including enhancer hijacking events and noncoding mutations that create enhancers or promoters de novo. These paradigms have helped parse somatic variation of noncoding cancer genomes, thereby providing a rationale to identify noncanonical mechanisms of gene activation. Here we describe a novel mechanism of oncogene activation whereby focal copy number loss of an intronic element within the FTO gene leads to aberrant expression of IRX3, an oncogene in T cell acute lymphoblastic leukemia (T-ALL). Loss of this CTCF bound element downstream to IRX3 (+224 kb) leads to enhancer hijack of an upstream developmentally active super-enhancer of the CRNDE long noncoding RNA (-644 kb). Unexpectedly, the CRNDE super-enhancer interacts with the IRX3 promoter with no transcriptional output until it is untethered from the FTO intronic site. We propose that 'promoter tethering' of oncogenes to inert regions of the genome is a previously unappreciated biological mechanism preventing tumorigenesis.

2.
Blood ; 143(10): 933-937, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38194681

ABSTRACT

ABSTRACT: T-ALL relapse usually occurs early but can occur much later, which has been suggested to represent a de novo leukemia. However, we conclusively demonstrate late relapse can evolve from a pre-leukemic subclone harbouring a non-coding mutation that evades initial chemotherapy.


Subject(s)
Leukemia-Lymphoma, Adult T-Cell , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Humans , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Mutation , Recurrence , Chronic Disease , Clone Cells
3.
Mol Plant Microbe Interact ; 37(3): 347-353, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38114082

ABSTRACT

Xanthomonads, including Xanthomonas and Xylella species, constitute a large and significant group of economically and ecologically important plant pathogens. Up-to-date knowledge of these pathogens and their hosts is essential for the development of suitable control measures. Traditional review articles or book chapters have inherent limitations, including static content and rapid obsolescence. To address these challenges, we have developed a Web-based knowledge platform dedicated to xanthomonads, inspired by the concept of living systematic reviews. This platform offers a dynamic resource that encompasses bacterial virulence factors, plant resistance genes, and tools for diagnostics and genetic diversity studies. Our goal is to facilitate access for newcomers to the field, provide continuing education opportunities for students, assist plant protection services with diagnostics, provide valuable information to breeders on sources of resistance and breeding targets, and offer comprehensive expert knowledge to other stakeholders interested in plant-pathogenic xanthomonads. This resource is available for queries and updates at https://euroxanth.ipn.pt. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Subject(s)
Plant Breeding , Xanthomonas , Humans , Virulence/genetics , Xanthomonas/genetics , Virulence Factors/genetics , Plants/microbiology , Plant Diseases/microbiology
4.
Allergy ; 79(4): 977-989, 2024 04.
Article in English | MEDLINE | ID: mdl-38433402

ABSTRACT

BACKGROUND: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions. METHODS: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two-round online-modified Delphi process followed by hybrid consensus meeting to finalize the COS. RESULTS: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in-person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, 'allergic symptoms' and 'quality of life' achieved consensus for inclusion as 'core' outcomes. CONCLUSION: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes.


Subject(s)
Food Hypersensitivity , Quality of Life , Humans , Delphi Technique , Food Hypersensitivity/diagnosis , Food Hypersensitivity/therapy , Immunoglobulin E , Outcome Assessment, Health Care , Research Design , Treatment Outcome , Clinical Trials as Topic , Observational Studies as Topic
5.
J Sleep Res ; : e14215, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750610

ABSTRACT

The long-term effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on sleep remain poorly known. We evaluated the association between probable post-COVID-19 condition and changes in sleep quality and quantity before and after SARS-CoV-2 infection in a consecutive sample of non-hospitalized adults. Individuals were identified with SARS-CoV-2 infection in 2020 at the central laboratory of a tertiary hospital in Porto and followed as outpatients. We included patients diagnosed with SARS-CoV-2 infection ≥3 months before this evaluation, with no missing data on key variables (n = 2445). Participants completed a questionnaire that included sociodemographic, clinical, and infection-related questions. We computed changes in sleep-related parameters referred to 1 month before diagnosis and 1 week before the questionnaire. Multinomial logistic regression models were fitted to compute crude and adjusted odds ratios and 95% confidence intervals (95% CIs). Compared to the pre-infection period, those with probable post-COVID-19 condition reported a greater decrease in hours of sleep, had a 2.60 (95% CI 2.02-3.34) higher adjusted odds of perceiving their sleep quality as worsened and experienced a significant increase in number of days with sleeping disturbances as defined according to multiple items. The association between post-COVID-19 condition and indicators of poor sleep health requires special attention from healthcare professionals and services. It is essential that appropriate multidisciplinary care is provided to mitigate the physical, psychological, social, and professional impact of sleeping problems in these already burdened patients.

6.
Article in English | MEDLINE | ID: mdl-39302571

ABSTRACT

PURPOSE OF REVIEW: Respiratory allergies are non-communicable diseases caused by the hypersensitivity of the immune system to environmental aeroallergens. The culprits are aero-transported proteins eliciting respiratory symptoms in sensitized/allergic individuals. This review intends to provide a holistic overview on the categorization of aeroallergens into protein families (Part 1) and to exploit the impact of physicochemical properties on inhalant protein allergenicity (Part 2). This first part will focus particularly on aeroallergen organization into families and how this classification fits their physicochemical properties. RECENT FINDINGS: Aeroallergen classification into protein families facilitates the identification of common physicochemical properties, thus aiding a better comprehension of known allergens, while predicting the behavior of novel ones. The available online databases gathering important features of aeroallergens are currently scarce. Information on distinct aeroallergen classification is still lacking, as data is dispersed and often outdated, hampering an efficient evaluation of new aeroallergens.

7.
Article in English | MEDLINE | ID: mdl-39302572

ABSTRACT

PURPOSE OF REVIEW: A holistic perspective on how physicochemical properties modulate the allergenicity of proteins has recently been performed for food allergens, launching the challenge of a similar analysis for aeroallergens. After a first review on aeroallergen classification into protein families (Part 1), this second part (Part 2) will exploit the impact of physicochemical properties (abundance/biological function, protein structure/presence of post-translational modifications, ligand/cofactor/lipid-binding) on inhalant protein allergenicity. RECENT FINDINGS: The abundance linked to biological function is correlated with increased allergenic risk for most protein families, while the loss of structural integrity with consequent destruction of conformational epitopes is well linked with decreased allergenicity. Ligand-binding effect totally depends on the ligand type being highly variable among aeroallergens. Knowledge about the physicochemical properties of aeroallergens is still scarce, which highlights the need for research using integrated approaches (in silico and experimental) to generate and analyze new data on known/new aeroallergens.

8.
Eur Arch Otorhinolaryngol ; 281(10): 5153-5157, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38767696

ABSTRACT

PURPOSE: Malignant otitis externa (MOE) is a rare form of invasive osteomyelitis of the external ear canal. It is typically caused by Pseudomonas aeruginosa in immunocompromised patients. The diagnosis is clinical, and the initial treatment involves systemic antibiotics or antifungal therapy. Surgery is usually only considered when medical treatment has failed. Although hyperbaric oxygen therapy (HBOT) is recommended for refractory osteomyelitis, there are no specific guidelines for MOE. METHODS: This is a retrospective study that evaluates clinical data, treatment, and results obtained in patients diagnosed with MOE treated with HBOT at the Pedro Hispano Hospital between 2007 and 2022. RESULTS: During the study period, fifteen patients diagnosed with MOE were admitted for treatment with HBOT. All patients received antibiotic and/or antifungal therapy, and three required surgical intervention before starting HBOT. The pathology was successfully managed on all patients. CONCLUSIONS: HBOT may be an effective adjuvant treatment option in patients with MOE but it lacks robust scientific evidence. However, its therapeutic value should not be underestimated due to the good results and few adverse effects reported in recent retrospective studies and case reports.


Subject(s)
Hyperbaric Oxygenation , Otitis Externa , Humans , Hyperbaric Oxygenation/methods , Otitis Externa/therapy , Retrospective Studies , Male , Female , Middle Aged , Aged , Aged, 80 and over , Adult , Pseudomonas Infections/therapy , Anti-Bacterial Agents/therapeutic use , Treatment Outcome , Pseudomonas aeruginosa
9.
Int J Mol Sci ; 25(6)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38542189

ABSTRACT

The encapsulation of retinol within silica microparticles has emerged as a promising opportunity in the realm of cosmetic and pharmaceutical formulations, driven by the need to reinforce the photoprotection and oxidation stability of retinol. This work examines the process of encapsulating retinol into silica microparticles. The association efficiency, microparticle size, molecular structure, morphology, oxidation, and release profile, as well as biocompatibility and skin sensitization, were evaluated. Results showed that 0.03% of retinol and 9% of emulsifier leads to an association efficiency higher than 99% and a particle size with an average of 5.2 µm. FTIR results indicate that there is an association of retinol with the silica microparticles, and some may be on the surface. Microscopy indicates that when association happens, there is less aggregation of the particles. Oxidation occurs in two different phases, the first related to the retinol on the surface and the second to the associated retinol. In addition, a burst release of up to 3 h (30% free retinol, 17% associated retinol) was observed, as well as a sustained release of 44% of retinol up to 24 h. Encapsulation allowed an increase in the minimal skin cytotoxic concentrations of retinol from 0.04 µg/mL to 1.25 mg/mL without skin sensitization. Overall, retinol is protected when associated with silica microparticles, being safe to use in cosmetics and dermatology.


Subject(s)
Retinoids , Saccharum , Delayed-Action Preparations , Vitamin A , Silicon Dioxide/chemistry , Particle Size
10.
Crit Rev Food Sci Nutr ; 63(25): 7423-7460, 2023.
Article in English | MEDLINE | ID: mdl-35238686

ABSTRACT

This review provides a global overview on Rosaceae allergy and details the particularities of each fruit allergy induced by ten Rosaceae species: almond/peach/cherry/apricot/plum (Amygdaleae), apple/pear (Maleae), and raspberry/blackberry/strawberry (Rosoideae). Data on clinical symptoms, prevalence, diagnosis, and immunotherapies for the treatment of Rosaceae allergy are herein stated. Allergen molecular characterization, cross-reactivity/co-sensitization phenomena, the impact of food processing and digestibility, and the methods currently available for the Rosaceae detection/quantification in foods are also described. Rosaceae allergy has a major impact in context to pollen-food allergy syndrome (PFAS) and lipid transfer protein (LTP) allergies, being greatly influenced by geography, environment, and presence of cofactors. Peach, apple, and almond allergies are probably the ones most affecting the quality of life of the allergic-patients, although allergies to other Rosaceae fruits cannot be overlooked. From patients' perspective, self-allergy management and an efficient avoidance of multiple fruits are often difficult to achieve, which might raise the risk for cross-reactivity and co-sensitization phenomena and increase the severity of the induced allergic responses with time. At this point, the absence of effective allergy diagnosis (lack of specific molecular markers) and studies advancing potential immunotherapies are some gaps that certainly will prompt the progress on novel strategies to manage Rosaceae food allergies.


Subject(s)
Food Hypersensitivity , Malus , Rosaceae , Humans , Antigens, Plant , Quality of Life , Allergens , Fruit , Plant Proteins
11.
Eur J Pediatr ; 182(4): 1601-1609, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36697884

ABSTRACT

Children with elevated liver enzymes are occasionally discovered through laboratory work-up from different clinical scenarios. Although the majority will have transient and/or benign conditions, a subgroup will have underlying liver disorders. The differential diagnosis is broad and therefore, a systematic approach is of utmost importance. In this article, we reviewed the most recent and relevant literature to provide a comprehensive overview of the main disease processes that cause hypertransaminasemia in children. Ultimately, we propose a practical stepwise approach to guide primary care physicians in the evaluation of abnormal liver enzymes in asymptomatic children. The first step is to obtain a complete history along with a thorough physical examination to exclude red flags, which should dictate urgent consultation with a paediatric gastroenterologist or hepatologist.  Conclusion: Hypertransaminasemia is a challenging scenario in the primary care setting. The aetiology can be broad, ranging from hepatic and extrahepatic to transient versus chronic liver disease. Timely referral to a specialised centre is of paramount importance for conducting targeted research and to not miss the chance of identifying a progressive, but still asymptomatic, treatable liver disease. What is Known: • Elevated liver enzyme is a challenging scenario in the primary care setting. • There are few studies guiding the evaluation of asymptomatic hypertransaminasemia in the paediatric population and a standardised approach is lacking. What is New: • We propose a practical stepwise approach to guide primary care physicians in the evaluation of abnormal liver enzymes.


Subject(s)
Liver Diseases , Humans , Child , Liver Diseases/diagnosis , Physical Examination , Diagnosis, Differential , Referral and Consultation , Asymptomatic Diseases , Primary Health Care
12.
Blood Purif ; 52(6): 600-608, 2023.
Article in English | MEDLINE | ID: mdl-37062269

ABSTRACT

INTRODUCTION: The antibody response to SARS-CoV-2 vaccine in haemodialysis (HD) patients is diminished compared to healthy subjects. The aim of this study was to compare the presence of reactive SARS-CoV-2 antibodies in patients with high-flux HD and on-line haemodiafiltration (HDF) three and 6 months after the second dose of SARS-CoV-2 vaccine since previous studies indicate that a sustained antibody response correlates with protection from disease. METHODS: We included 216 HD patients of which 157 had on-line HDF and 59 high-flux HD and 46 health care workers as controls and studied the presence of reactive anti-spike IgG antibodies three and 6 months after the second dose of SARS-CoV-2 vaccine. Clinical features between the patient groups were similar, but patients with on-line HDF had significantly higher Kt/V. RESULTS: The percentage of participants with reactive antibodies was significantly lower in patients compared to controls, both three and 6 months after the second dose of vaccine. Furthermore, the proportion of patients with reactive anti-spike IgG ≥1.0 6 months after the second dose of vaccine was significantly higher in patients with on-line HDF compared to in patients with high-flux HD. In logistic regression analyses adjusted for several clinical features, the variables associated with presence of reactive anti-spike IgG at 3 months after the second dose of vaccine were lower age, HDF treatment, not being obese and not having a previous solid organ transplant. The two variables with the strongest influence on the presence of reactive anti-spike IgG levels 6 months after the second dose of vaccine were treatment with on-line HDF and not having immunosuppressive therapy. CONCLUSION: This is the first study to show that on-line HDF preserves the antibody response better than high-flux HD after vaccination with SARS-CoV-2 vaccine. Treatment strategies that sustain the vaccine response are essential to apply in this vulnerable group of patients.


Subject(s)
COVID-19 , Hemodiafiltration , Humans , COVID-19 Vaccines , Antibody Formation , COVID-19/prevention & control , SARS-CoV-2 , Renal Dialysis , Antibodies, Viral , Immunoglobulin G
13.
J Public Health (Oxf) ; 45(1): 47-56, 2023 03 14.
Article in English | MEDLINE | ID: mdl-35220434

ABSTRACT

BACKGROUND: The use of non-pharmaceutical interventions (NPI) is one of the main tools used in the coronavirus disease 2019 (COVID-19) pandemic response, including physical distancing, frequent hand washing, face mask use, respiratory hygiene and use of contact tracing apps. Literature on compliance with NPI during the COVID-19 pandemic is limited. METHODS: We studied this compliance and associated factors in Portugal, between 28th October 2020 and 11th January 2021 (Portuguese second and third waves of the pandemic), using logistic regressions. Data were collected through a web-based survey and included questions regarding NPI compliance, COVID-19-related concerns, perception of institutions' performance, agreement with the measures implemented and socio-demographic characteristics. RESULTS: From the 1263 eligible responses, we found high levels of compliance among all COVID-19 related NPI, except for the contact tracing app. Females and older participants showed the highest compliance levels, whereas the opposite was observed for previously infected participants. There was heterogeneity of COVID-19 NPI compliance across Portuguese regions and a clear gradient between concern, government performance's perception or agreement and compliance. CONCLUSIONS: Results suggested areas for further study with important implications for pandemic management and communication, for future preparedness, highlighting other factors to be accounted for when recommending policy measures during public health threats.


Subject(s)
COVID-19 , Female , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Pandemics/prevention & control , Cross-Sectional Studies , Portugal/epidemiology , SARS-CoV-2
14.
J Hum Nutr Diet ; 36(4): 1290-1302, 2023 08.
Article in English | MEDLINE | ID: mdl-36808171

ABSTRACT

BACKGROUND: Changes in nutritional status are recognised as predictors of unfavourable outcomes in children and adolescents with cancer, particularly in developing countries. There have been no studies on children and adolescents with cancer from every region of Brazil or on the impact of nutritional status on clinical outcomes. The aim of this study is to assess the association between the nutritional status of children and adolescents with cancer and the prediction of clinical outcomes. METHODS: This was a longitudinal, multicentre, hospital-based study. An anthropometric nutritional assessment was performed, and the Subjective Global Nutritional Assessment (SGNA) was administered within 48 h of admission. Seven hundred and twenty-three patients (aged 2-18 years) were included in the sample, undergoing cancer treatment. They were recruited in 13 reference centres in the five macro-regions of Brazil between March 2018 and August 2019. The outcomes evaluated were readmission within 30 days and death within 60 days of admission. To identify predictors of 60-day survival, Cox regression and log-rank statistics were used to compare Kaplan-Meier curves between the strata. RESULTS: About 36.2% (n = 262) of the samples were malnourished according to the SGNA. Severe malnutrition by the SGNA (relative risk [RR] = 8.44, 95% confidence interval [CI]: 3.35-21.3, P = 0.001) and living in the North region (RR = 11.9, 95% CI: 3.34-42.7, P = 0.001) were associated with the poorest survival. The North (RR = 5.77, 95% CI: 1.29-25.8, P = 0.021), Northeast (RR = 1.46, 95% CI: 1.01-2.11, P = 0.041), Midwest (RR = 0.43, 95% CI: 0.20-0.095, P = 0.036), age group 10-18 years (RR = 0.65, 95% CI: 0.45- 0.94, P = 0.022) and haematologic malignancy (RR = 1.52, 95% CI: 1.10-2.10, P = 0.011) were predictors of readmission within 30 days. CONCLUSIONS: The prevalence of malnutrition was high and related to death. These results highlight the need to use the SGNA in clinical practice alongside classic anthropometric methods for the diagnosis of malnutrition, and the need to standardise care across all Brazilian regions, which should include nutritional care for children and adolescents with cancer.


Subject(s)
Malnutrition , Neoplasms , Pediatrics , Child , Humans , Adolescent , Nutritional Status , Brazil/epidemiology , Malnutrition/diagnosis , Malnutrition/epidemiology , Malnutrition/etiology , Nutrition Assessment , Neoplasms/complications , Neoplasms/therapy , Hospitals
15.
Am J Otolaryngol ; 44(1): 103680, 2023.
Article in English | MEDLINE | ID: mdl-36334419

ABSTRACT

INTRODUCTION: There are several factors that seem to affect the surgical success rate of tympanoplasty, one of them being the pneumatization of the contralateral mastoid. In the current literature, several studies have been published with classification proposals for temporal bone pneumatization pattern. This study aims to evaluate the role of mastoid air cell extension in relation to the sigmoid sinus in predicting the surgical success of tympanoplasty. MATERIAL AND METHODS: This case-control study was performed on patients diagnosed with chronic otitis media (COM) who underwent type I tympanoplasty. The study group did not close the tympanic membrane, or there was a retraction or lateralization of the graft. The control group consisted of patients with surgical success. RESULTS: No statistically significant difference was found between groups regrading age, gender, perforation side/type, previous nasal surgery, and the presence of chronic otitis media in contralateral ear. A statistically significant difference was found when groups were compared in relation to the degree of pneumatization of the contralateral ear (p = 0.046), and this relationship does not seem to be influenced by age. CONCLUSION: To predict surgical success in terms of tympanic membrane closure in tympanoplasty, classification of contralateral ear pneumatization degree using the sigmoid sinus as a reference seems to be a valid and easy to apply method, and makes it possible to restrict the evaluation of pneumatization to the mastoid, a cell complex that does not seem to change with age.


Subject(s)
Otitis Media , Tympanic Membrane Perforation , Humans , Tympanoplasty/methods , Mastoid/diagnostic imaging , Mastoid/surgery , Case-Control Studies , Tympanic Membrane/surgery , Otitis Media/diagnostic imaging , Otitis Media/surgery , Tympanic Membrane Perforation/surgery , Chronic Disease , Retrospective Studies , Treatment Outcome
16.
ORL J Otorhinolaryngol Relat Spec ; 85(3): 119-127, 2023.
Article in English | MEDLINE | ID: mdl-36318894

ABSTRACT

INTRODUCTION: To date, little is known about predisposing factors for persistent COVID-19-induced olfactory dysfunction (pCIOD). The objective was to determine whether olfactory cleft (OC) measurements associate with pCIOD risk. MATERIAL AND METHODS: Three subgroups were recruited: group A included patients with pCIOD, group B included patients without olfactory dysfunction following SARS-CoV-2 infection (ntCIOD), and group C consisted in controls without past history of SARS-CoV-2 infection (noCOVID-19). Olfactory perception threshold (OPT) and visual analog scale for olfactory impairment (VAS-olf) were obtained. OC measurements were obtained through computed tomography scans. Results were subsequently compared. RESULTS: A total of 55 patients with a mean age of 39 ± 10 years were included. OPT was significantly lower in pCIOD patients (group A: 4.2 ± 2.1 vs. group B: 12.3 ± 1.8 and group C: 12.2 ± 1.5, p < 0.001). VAS-olf was significantly higher in pCIOD (group A: 6 ± 2.6 vs. group B: 1.7 ± 1.6 and group C: 1.6 ± 1.5, p < 0.001). OC length was significantly higher in group A (42.8 ± 4.6) compared to group B (39.7 ± 3.4, p = 0.047) and C (39.8 ± 4, p = 0.037). The odd of pCIOD occurring after COVID-19 infection increased by 21% (95% CI [0.981, 1.495]) for a one unit (mm) increase in OC length. The odd of pCIOD occurring was 6.9 times higher when OC length >40 mm. CONCLUSION: Longer OC may be a predisposing factor for pCIOD. This study is expected to encourage further research on OC morphology and its impact on olfactory disorders.


Subject(s)
COVID-19 , Olfaction Disorders , Humans , Adult , Middle Aged , COVID-19/complications , SARS-CoV-2 , Smell , Olfaction Disorders/epidemiology , Olfaction Disorders/etiology , Risk Factors
17.
Compr Rev Food Sci Food Saf ; 22(2): 971-1005, 2023 03.
Article in English | MEDLINE | ID: mdl-36546415

ABSTRACT

New types of protein sources will enter our diet in a near future, reinforcing the need for a straightforward in vitro (cell-based) screening model to test and predict the safety of these novel proteins, in particular their potential risk for de novo allergic sensitization. The Adverse Outcome Pathway (AOP) for allergen sensitization describes the current knowledge of key events underlying the complex cellular interactions that proceed allergic food sensitization. Currently, there is no consensus on the in vitro model to study the intestinal translocation of proteins as well as the epithelial activation, which comprise the first molecular initiation events (ME1-3) and the first key event of the AOP, respectively. As members of INFOGEST, we have highlighted several critical features that should be considered for any proposed in vitro model to study epithelial protein transport in the context of allergic sensitization. In addition, we defined which intestinal cell types are indispensable in a consensus model of the first steps of the AOP, and which cell types are optional or desired when there is the possibility to create a more complex cell model. A model of these first key aspects of the AOP can be used to study the gut epithelial translocation behavior of known hypo- and hyperallergens, juxtaposed to the transport behavior of novel proteins as a first screen for risk management of dietary proteins. Indeed, this disquisition forms a basis for the development of a future consensus model of the allergic sensitization cascade, comprising also the other key events (KE2-5).


Subject(s)
Food Hypersensitivity , Humans , Food Hypersensitivity/prevention & control , Allergens , Diet , Food , Intestinal Absorption
18.
Allergy ; 77(1): 243-257, 2022 01.
Article in English | MEDLINE | ID: mdl-34496033

ABSTRACT

BACKGROUND: SARS-CoV-2 caused one of the most devastating pandemics in the recent history of mankind. Due to various countermeasures, including lock-downs, wearing masks, and increased hygiene, the virus has been controlled in some parts of the world. More recently, the availability of vaccines, based on RNA or adenoviruses, has greatly added to our ability to keep the virus at bay; again, however, in some parts of the world only. While available vaccines are effective, it would be desirable to also have more classical vaccines at hand for the future. Key feature of vaccines for long-term control of SARS-CoV-2 would be inexpensive production at large scale, ability to make multiple booster injections, and long-term stability at 4℃. METHODS: Here, we describe such a vaccine candidate, consisting of the SARS-CoV-2 receptor-binding motif (RBM) grafted genetically onto the surface of the immunologically optimized cucumber mosaic virus, called CuMVTT -RBM. RESULTS: Using bacterial fermentation and continuous flow centrifugation for purification, the yield of the production process is estimated to be >2.5 million doses per 1000-litre fermenter run. We demonstrate that the candidate vaccine is highly immunogenic in mice and rabbits and induces more high avidity antibodies compared to convalescent human sera. The induced antibodies are more cross-reactive to mutant RBDs of variants of concern (VoC). Furthermore, antibody responses are neutralizing and long-lived. In addition, the vaccine candidate was stable for at least 14 months at 4℃. CONCLUSION: Thus, the here presented VLP-based vaccine may be a good candidate for use as conventional vaccine in the long term.


Subject(s)
COVID-19 , Vaccines, Virus-Like Particle , Animals , Antibodies, Neutralizing , Antibody Formation , COVID-19 Vaccines , Communicable Disease Control , Humans , Mice , Rabbits , SARS-CoV-2
19.
Crit Rev Food Sci Nutr ; : 1-17, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-36377716

ABSTRACT

Sesame is an allergenic food with an increasing allergy prevalence among the European/USA population. Sesame allergy is generally life-persisting, being the cause of severe/systemic adverse immune responses in sesame-allergic individuals. Herein, clinical data about sesame allergy, including prevalence, diagnosis, relevance, and treatments are described, with focus on the molecular characterization of sesame allergens, their cross-reactivity and co-sensitization phenomena. The influence of food processing and digestibility on the stability/immunoreactivity of sesame allergens is critically discussed and the analytical approaches available for their detection in foodstuffs. Cross-reactivity between sesame and tree nuts or peanuts is frequent because of the high similarities among proteins of the same family. However, cross-reactivity phenomena are not always correlated with true clinical allergy in sensitized patients. Data suggest that sesame allergens are resistant to heat treatments and digestibility, with little effect on their immunoreactivity. Nevertheless, data are scarce, evidencing the need for more research to understand the effect of food processing on sesame allergenicity modulation. The demands for identifying trace amounts of sesame in foods have prompted the development of analytical methods, which have targeted both protein and DNA markers, providing reliable, specific, and sensitive tools, crucial for the effective management of sesame as an allergenic food.

20.
Crit Rev Food Sci Nutr ; 62(31): 8686-8702, 2022.
Article in English | MEDLINE | ID: mdl-34060381

ABSTRACT

Current approaches based on electrophoretic, chromatographic or immunochemical principles have allowed characterizing multiple allergens, mapping their epitopes, studying their mechanisms of action, developing detection and diagnostic methods and therapeutic strategies for the food and pharmaceutical industry. However, some of the common structural features related to the allergenic potential of food proteins remain unknown, or the pathological mechanism of food allergy is not yet fully understood. In addition, it is also necessary to evaluate new allergens from novel protein sources that may pose a new risk for consumers. Technological development has allowed the expansion of advanced technologies for which their whole potential has not been entirely exploited and could provide novel contributions to still unexplored molecular traits underlying both the structure of food allergens and the mechanisms through which they sensitize or elicit adverse responses in human subjects, as well as improving analytical techniques for their detection. This review presents cutting-edge instrumental techniques recently applied when studying structural and functional aspects of proteins, mechanism of action and interaction between biomolecules. We also exemplify their role in the food allergy research and discuss their new possible applications in several areas of the food allergy field.


Subject(s)
Allergens , Food Hypersensitivity , Humans , Allergens/chemistry , Food Hypersensitivity/therapy , Epitopes
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