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1.
Biomolecules ; 14(6)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38927115

RESUMO

Resveratrol, a phenylpropanoid compound, exhibits diverse pharmacological properties, making it a valuable candidate for health and disease management. However, the demand for resveratrol exceeds the capacity of plant extraction methods, necessitating alternative production strategies. Microbial synthesis offers several advantages over plant-based approaches and presents a promising alternative. Yarrowia lipolytica stands out among microbial hosts due to its safe nature, abundant acetyl-CoA and malonyl-CoA availability, and robust pentose phosphate pathway. This study aimed to engineer Y. lipolytica for resveratrol production. The resveratrol biosynthetic pathway was integrated into Y. lipolytica by adding genes encoding tyrosine ammonia lyase from Rhodotorula glutinis, 4-coumarate CoA ligase from Nicotiana tabacum, and stilbene synthase from Vitis vinifera. This resulted in the production of 14.3 mg/L resveratrol. A combination of endogenous and exogenous malonyl-CoA biosynthetic modules was introduced to enhance malonyl-CoA availability. This included genes encoding acetyl-CoA carboxylase 2 from Arabidopsis thaliana, malonyl-CoA synthase, and a malonate transporter protein from Bradyrhizobium diazoefficiens. These strategies increased resveratrol production to 51.8 mg/L. The further optimization of fermentation conditions and the utilization of sucrose as an effective carbon source in YP media enhanced the resveratrol concentration to 141 mg/L in flask fermentation. By combining these strategies, we achieved a titer of 400 mg/L resveratrol in a controlled fed-batch bioreactor. These findings demonstrate the efficacy of Y. lipolytica as a platform for the de novo production of resveratrol and highlight the importance of metabolic engineering, enhancing malonyl-CoA availability, and media optimization for improved resveratrol production.


Assuntos
Engenharia Metabólica , Resveratrol , Sacarose , Yarrowia , Resveratrol/metabolismo , Yarrowia/genética , Yarrowia/metabolismo , Engenharia Metabólica/métodos , Sacarose/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Vitis/microbiologia , Vitis/genética , Vitis/metabolismo , Coenzima A Ligases/metabolismo , Coenzima A Ligases/genética , Malonil Coenzima A/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/microbiologia , Rhodotorula/genética , Rhodotorula/metabolismo , Fermentação , Arabidopsis/genética , Arabidopsis/metabolismo , Amônia-Liases , Proteínas de Bactérias
2.
Biomolecules ; 11(6)2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199540

RESUMO

Resveratrol is a plant secondary metabolite known for its therapeutic applications as an antioxidant, anti-cancer, anti-inflammatory, anti-aging, cardio-protective, and neuroprotective agent. Topical formulas of resveratrol are also used for skin disease management and in cosmetic industries. Due to its importance, high resveratrol production is urgently required. Since the last decade, intensive efforts have been devoted to obtaining resveratrol from microorganisms by pathway and metabolic engineering. Yeasts were proven to be excellent host candidates for resveratrol production. In addition to the similar intracellular compartments between yeasts and plants, yeasts exhibit the ability to express genes coding for plant-derived enzymes and to perform post-translational modification. Therefore, this review summarizes the attempts to use yeasts as a platform for resveratrol synthesis as the next promising route in producing high titers of resveratrol from genetically engineered strains.


Assuntos
Engenharia Metabólica , Microrganismos Geneticamente Modificados , Resveratrol/metabolismo , Saccharomyces cerevisiae , Microrganismos Geneticamente Modificados/genética , Microrganismos Geneticamente Modificados/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
3.
MedEdPublish (2016) ; 10: 170, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-38486521

RESUMO

This article was migrated. The article was marked as recommended. Purpose: to assess students' perception of educational environment and to evaluate the difference in perception related to academic performance and demographic characteristics in the Faculty of Medicine, University of Khartoum, 2020. Method: The authors performed an observational analytical cross-sectional study at the Faculty of Medicine, University of Khartoum, using a validated structured closed-ended self -administered questionnaire; the Dundee Ready Educational environment measurement (DREEM). They included all students registered in the faculty for the academic year 2020-2021 except the first semester students. They used proportionate stratified sampling to divide students into strata and sub-strata based on batch number and sex, respectively. Then, they selected students proportionately from each substrata using simple random sampling. Results: out of 405 randomly selected students, 341 (84.2%) filled the questionnaire. The mean total DREEM score was (104.48/200), indicating a positive perception of the learning environment. This, with only student's perception of atmosphere subscale showing negative results. Test results showed a significant difference between different student's age groups, academic phases and batches in regards to their perception of atmosphere (p-value 0.023, 0.001, 0.013 respectively). Regarding residence, a significant difference was found in total DREEM scores, with students residing in university dormitories having a more positive perception. Test results showed no significant difference in student's perception of educational environment in all DREEM subscales between achievers and underachievers. Conclusion: although the overall perception of educational environment was more positive than negative, the study highlighted various areas needing special attention. Theauthors believe that both faculty administration and students must work together to deliver tangible improvement in all aspects of educational environment.

4.
Biomed Res Int ; 2019: 2757450, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886191

RESUMO

BACKGROUND: Parvovirus B19 (B19 V) infection had been reported to be more frequent with serious clinical outcomes in patients with sickle cell disease (SCD) than in the general population. There is a wide variation in data among the existing literature regarding the seroprevalence of B19 V in patients with SCD. These data require further summary and analyses for better accuracy. This systematic review and meta-analysis was done to estimate the seroprevalence of B19 V in patients with SCD. METHODS: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE/PubMed, Virtual Health Library (VHL), ScienceDirect, Google Scholar, and OpenGrey were used for the systematic search. The random-effects model was used to estimate the pooled prevalence with the corresponding 95% confidence interval (CI) using OpenMeta Analyst software. Publication bias was estimated based on Begg's test, Egger's test, and examination of the funnel plot. Subgroup analyses and metaregression were used to explore the moderators of heterogeneity between studies. RESULTS: A total of 18 studies including 2890 patients were analyzed. The overall IgG seroprevalence of B19 V infection among patients with SCD was found to be 48.8% (95% CI 39.5%-58.0%). Evidence of publication bias was not detected. Evidence of acute viral infection detected by positive IgM antibodies among the screened SCD patients was found in 8.30% (95% CI 5.20%-11.4%) of them. There was a statistically significant association between seroprevalence of B19 V and geographical areas. CONCLUSION: There was a high prevalence of B19 V in patients with SCD. Healthcare providers need to be aware of the magnitude of B19 V infection in patients with SCD to ensure effective management. This review could provide a comprehensive view of B19 V prevalence in this susceptible population.


Assuntos
Anemia Falciforme/sangue , Anticorpos Antivirais/sangue , Eritema Infeccioso/sangue , Estudos Soroepidemiológicos , Anemia Falciforme/imunologia , Anemia Falciforme/patologia , Anemia Falciforme/virologia , Anticorpos Antivirais/imunologia , Eritema Infeccioso/imunologia , Eritema Infeccioso/patologia , Eritema Infeccioso/virologia , Humanos , Parvovirus B19 Humano/imunologia , Parvovirus B19 Humano/patogenicidade
5.
BMC Res Notes ; 11(1): 842, 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30486859

RESUMO

OBJECTIVE: This meta-analysis was done to estimate the prevalence of autoimmune thyroid diseases (ATDs) in Turner Syndrome patients, and to determine the clinical status of thyroid autoimmune diseases that occur frequently in association with Turner Syndrome. RESULTS: A total of 18 studies were included in the meta-analysis. The pooled overall prevalence of autoimmune thyroid diseases in Turner Syndrome patients was 38.6% (95% CI 29.7-47.6%), with 12.7% (95% CI 9.30-16.1%) of them had clinical hypothyroidism and 2.6% (95% CI 1.5-3.8%) had hyperthyroidism. I-squared test had a high result of heterogeneity. In subgroup analyses, the prevalence of ATDs was higher in the European region than Asian region. Autoimmune thyroid diseases are commonly associated with Turner Syndrome. Early detection of thyroid diseases by optimal screening among children with Turner Syndrome is required to ensure effective management.


Assuntos
Doenças Autoimunes/epidemiologia , Estudos Transversais , Hipertireoidismo/epidemiologia , Hipotireoidismo/epidemiologia , Síndrome de Turner/epidemiologia , Comorbidade , Feminino , Humanos , Prevalência
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