Production and characterization of recombinant Aliivibrio fischeri L-Asparaginase with low L-Glutamine affinity: a potential antileukemic drug obtained by genetic engineering

L-Asparaginase has been successfully applied in the treatment of lymphoid malignancies. Some limitations in the use of the commercial preparations of this drug include several side effects that may be correlated to L-Glutaminase activity, as immunosuppressive effects (Castro et al., 2021). The objective of this study was to evaluate the characteristics of a novel engineered Aliivibrio fischeri L-asparaginase type II expressed by Bacillus subtilis. Cultivations were carried out in shaken flasks at 30 ºC, 200 rpm, 24 h, using Luria-Bertani medium. Intracellular enzyme was recovered by sonication and enzymatic activities were evaluated by Nessler colorimetric method (Mashburn; Wriston, 1963). Recovered enzymatic extracts achieved L-Asparaginase activity up to 1.43 U.mL-1 at optimum pH 7.5. Substrate affinity was much higher for L-Asparagine than for L-Glutamine (Km= 1.226 mmol.L-1 and Km= 28.584 mmol.L-1, respectively), which indicate the potential application of the recombinant enzyme as biopharmaceutical.publishe

L-asparaginase production review: bioprocess design and biochemical characteristics

In the past decades, production of biopharmaceuticals has gained high interest due to its high sensitivity, specificity and lower risk of negative effects to patients. Biopharmaceuticals are mostly therapeutic recombinant proteins produced through biotechnological processes. In this context, L-Asparaginase (L-Asparagine amidohydrolase, L-ASNase (E.C. 3.5.1.1)) is a therapeutic enzyme that has been abundantly studied by researchers due to its antineoplastic properties. As a biopharmaceutical, L-ASNase has been used in the treatment of acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML) and other lymphoid malignancies, in combination with other drugs. Besides its application as a biopharmaceutical, this enzyme is widely used in food processing industries as an acrylamide mitigation agent and as a biosensor for the detection of L-Asparagine in physiological fluids at nano-levels. The great demand for L-ASNase is supplied by recombinant enzymes from Escherichia coli and Erwinia chrysanthemi. However, production processes are associated to low yields and proteins associated to immunogenicity problems, which leads to the search for a better enzyme source. Considering the L-ASNase pharmacological and food importance, this review provides an overview of the current biotechnological developments in L-ASNase production and biochemical characterization aiming to improve the knowledge about its production.publishe

Facing unemployment : study protocol for the implementation and evaluation of a community-based intervention for psychological well-being promotion

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Economic crises and unemployment have profound impact on mental health and well-being. Main goal of the Healthy Employment (HE) project is to enhance intersectoral actions promoting mental health among unemployed, namely through the implementation and effectiveness-evaluation of short-term and sustainable group interventions. Methods: The project follows a RE-AIM-based (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework for assessing a cognitive-behavioural and psychoeducational intervention that has been developed for promoting mental health among unemployed people. It is a short-term group intervention (five sessions, four hours each, 20 unemployed persons per group) focused on mental health literacy, interpersonal communication and of emotional regulation. Implementation of the intervention will be carried out by clinical psychologists, following a standardized procedure manual. Effectiveness will be assessed through a randomized field study with two arms (intervention and control). Participants are unemployed people (18–65 years old, both genders, having at least nine years of formal education) registered at public employment centres from different geographical regions for less than 12 months (including first-job seekers). Allocation to arms of the study will follow a random match-to-case process, considering gender, age groups and educational level. Three moments of evaluation will occur: before intervention (baseline), immediately after its ending and three months later. Main outcomes are mental health literacy, mental health related personal and perceived stigma, psychological well-being, satisfaction with life and resilience. Intention-to-treat and per-protocol analyses will be conducted. Cohen’s d coefficient and odds ratio will be used for assessing the size of the intervention effect, when significant. Discussion: Scientific and clinical knowledge will be applied to promote/protect psychological well-being of unemployed people. While the first phases of the project are funded by the European Economic Area Grants, longterm assessments of the intervention require a larger timeframe. Further funding and institutional support will be sought for this purpose. Already established intersectoral collaborations are key-assets to reach long-term sustainability of this project.Public Health Initiatives Programme (PT06), financed by EEA Grants Financial Mechanism 2009–2014.info:eu-repo/semantics/publishedVersio

Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

OBJECTIVES: Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro. METHODS: We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations. RESULTS: No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047). A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009), whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094). In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010). However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories. CONCLUSION: The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles for the multidrug resistance 1 gene in regulating gut-microbiota interactions and in mediating fibrosis. Understanding the effects of several drugs associated with multidrug resistance 1 gene variants may aid in the selection of customized therapeutic regimens

Higher Adherence to the Mediterranean Dietary Pattern Is Inversely Associated With Severity of COVID-19 and Related Symptoms: A Cross-Sectional Study

Background and AimsAdherence to the Mediterranean diet (MD) has been associated with a decreased risk of developing a variety of chronic diseases that are comorbidities in COVID-19 patients. However, its association to the severity and symptoms of COVID-19 are still unknown. This study aimed to examine the association between adherence to the MD pattern and COVID-19 severity and symptoms in Iranian hospitalized patients.MethodsIn this cross-sectional study, 250 COVID-19 patients aged 18 to 65 were examined. We employed a food frequency questionnaire (FFQ) to obtain data on dietary intake of participants in the year prior to their COVID-19 diagnosis. COVID-19 severity was determined using the National Institutes of Health's Coronavirus Disease 2019 report. Additionally, symptoms associated with COVID-19, inflammatory markers, and other variables were evaluated. The scoring method proposed by Trichopoulou et al. was used to assess adherence to the MD.ResultsThe participants' mean age was 44.1 ± 12.1 years, and 46% of them had severe COVID-19. Patients who adhered more closely to the MD had lower serum C-reactive protein levels (7.80 vs. 37.36 mg/l) and erythrocyte sedimentation rate (14.08 vs. 42.65 mm/h). Those with the highest MD score were 77% less likely to have severe COVID-19 after controlling for confounding variables. The MD score was also found to be inversely associated with COVID-19 symptoms, including dyspnea, cough, fever, chills, weakness, myalgia, nausea and vomiting, and sore throat.ConclusionHigher adherence to the MD was associated with a decreased likelihood of COVID-19 severity and symptoms, as well as a shorter duration of hospitalization and convalescence, and inflammatory biomarkers

Building bridges between industry and academia: what is the profile of an industrial doctorate student?

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Compulsory admissions of patients with mental disorders : State of the art on ethical and legislative aspects in 40 European countries

Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of MedicineBACKGROUND.: Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care. METHODS.: The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions. RESULTS.: We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures. CONCLUSIONS.: We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.Peer reviewe