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1.
Nutrients ; 16(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39125348

RESUMO

BACKGROUND: The most frequent body composition alterations in post-COVID-19 syndrome include low muscle mass, dynapenia, sarcopenia, and obesity. These conditions share interconnected pathophysiological mechanisms that exacerbate each other. The relationship between body composition phenotypes and metabolic abnormalities in post-COVID-19 syndrome remains unclear. OBJECTIVE: To evaluate the association between body composition phenotypes and insulin resistance (IR) and metabolic abnormalities in non-diabetic individuals with post-COVID-19 syndrome. METHODS: A cross-sectional, single-center study involving 483 subjects with post-COVID-19 syndrome following moderate to severe acute COVID-19 requiring hospitalization. Individuals with diabetes, those who declined to participate, or those who could not be contacted were excluded. Body composition phenotypes were classified as normal weight, dynapenia, sarcopenia, dynapenic obesity, and sarcopenic obesity (SO). RESULTS: The average age was 52.69 ± 14.75 years; of note, 67.08% were male. The prevalence of body composition phenotypes was as follows: 13.25% were of normal weight, 9.52% had dynapenia, 9.94% had sarcopenia, 43.69% had obesity, 18.84% had dynapenic obesity, and 4.76% had SO. Additionally, 58.18% had IR. Obesity (OR: 2.98, CI95%; 1.64-5.41) and dynapenic obesity (OR: 4.98, CI95%; 1.46-6.88) were associated with IR. CONCLUSION: The most common body composition phenotypes were obesity, dynapenic obesity, and dynapenia. Furthermore, obesity and dynapenic obesity were associated with IR in post-COVID-19 syndrome.


Assuntos
Composição Corporal , COVID-19 , Resistência à Insulina , Obesidade , Fenótipo , Sarcopenia , Humanos , Masculino , COVID-19/complicações , Estudos Transversais , Pessoa de Meia-Idade , Feminino , Adulto , Obesidade/complicações , Sarcopenia/epidemiologia , Idoso , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda
2.
mSystems ; 9(6): e0042924, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38819150

RESUMO

In silico tools such as genome-scale metabolic models have shown to be powerful for metabolic engineering of microorganisms. Saccharomyces pastorianus is a complex aneuploid hybrid between the mesophilic Saccharomyces cerevisiae and the cold-tolerant Saccharomyces eubayanus. This species is of biotechnological importance because it is the primary yeast used in lager beer fermentation and is also a key model for studying the evolution of hybrid genomes, including expression pattern of ortholog genes, composition of protein complexes, and phenotypic plasticity. Here, we created the iSP_1513 GSMM for S. pastorianus CBS1513 to allow top-down computational approaches to predict the evolution of metabolic pathways and to aid strain optimization in production processes. The iSP_1513 comprises 4,062 reactions, 1,808 alleles, and 2,747 metabolites, and takes into account the functional redundancy in the gene-protein-reaction rule caused by the presence of orthologous genes. Moreover, a universal algorithm to constrain GSMM reactions using transcriptome data was developed as a python library and enabled the integration of temperature as parameter. Essentiality data sets, growth data on various carbohydrates and volatile metabolites secretion were used to validate the model and showed the potential of media engineering to improve specific flavor compounds. The iSP_1513 also highlighted the different contributions of the parental sub-genomes to the oxidative and non-oxidative parts of the pentose phosphate pathway. Overall, the iSP_1513 GSMM represent an important step toward understanding the metabolic capabilities, evolutionary trajectories, and adaptation potential of S. pastorianus in different industrial settings. IMPORTANCE: Genome-scale metabolic models (GSMM) have been successfully applied to predict cellular behavior and design cell factories in several model organisms, but no models to date are currently available for hybrid species due to their more complex genetics and general lack of molecular data. In this study, we generated a bespoke GSMM, iSP_1513, for this industrial aneuploid hybrid Saccharomyces pastorianus, which takes into account the aneuploidy and functional redundancy from orthologous parental alleles. This model will (i) help understand the metabolic capabilities and adaptive potential of S. pastorianus (domestication processes), (ii) aid top-down predictions for strain development (industrial biotechnology), and (iii) allow predictions of evolutionary trajectories of metabolic pathways in aneuploid hybrids (evolutionary genetics).


Assuntos
Genoma Fúngico , Redes e Vias Metabólicas , Saccharomyces , Saccharomyces/genética , Saccharomyces/metabolismo , Redes e Vias Metabólicas/genética , Genoma Fúngico/genética , Modelos Biológicos , Engenharia Metabólica/métodos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Evolução Molecular , Microbiologia Industrial/métodos
3.
Heliyon ; 10(1): e23629, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192840

RESUMO

Background: Pediatric COVID-19 patients have lower rates of hospitalization and fatal outcomes compared to adults with COVID-19; however, children represent a challenge in the detection, diagnosis, and treatment of COVID-19. Our aim was to determine the risk factors for hospital admission, invasive mechanical ventilation, and mortality in pediatric COVID-19 patients in Mexico during the COVID-19 pandemic. Material and methods: A retrospective cohort of pediatric patients with COVID-19 from February 2020 to April 2021 was reported on the National Epidemiological Surveillance System for Viral Respiratory Disease (SISVER) platform. Results: Among the 104,133 patients included in our study, 6214 were hospitalized, and 621 patients underwent invasive mechanical ventilation. A total of 0.65 % died during hospitalization. Children aged <12 months (odds ratio [OR]: 17.1; 95 % confidence interval [CI]: 15.9-19.4, p < 0.001), 1-4 years (OR: 3.69; 95 % CI: 3.2-4.1, p < 0.001), 5-9 years (OR: 1.86; 95 % CI: 1.66-2.08, p < 0.001), and 10-14 years (OR: 1.23; 95 % CI: 1.11-1.37, p < 0.001), and those diagnosed with diabetes (OR: 2.32; 95 % CI 1.68-3.20, p < 0.001) and obesity (OR: 1.24; 95 % CI 1.04-1.48, p = 0.015) were associated with hospital admission. Renal disease (OR: 3.85; 95 % CI: 2.25-6.59, p < 0.001) was associated with invasive mechanical ventilation. Pneumonia (OR: 15.9; 95 % CI: 12.6-20.1, p < 0.001) and renal disease (OR: 3.85; 95 % CI: 2.25-6.59, p value < 0.001) were associated with death. Conclusion: Pneumonia increases the risk of death. The youngest age group has a higher risk of hospital admission. Comorbidities such as renal disease or immunosuppression increase the risk of death in all age groups.

4.
Curr Probl Cancer ; 48: 101041, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37988902

RESUMO

BACKGROUND: Cervical cancer (CC) in Mexico is diagnosed mainly in locally advanced (LACC) and advanced (ACC) stages, where ureteral obstruction is more frequent. The standard treatment for this population is concurrent chemoradiotherapy (CCRT) with cisplatin, which is nephrotoxic and could lead to further deterioration of renal function in LACC patients with renal function decline. We aimed to evaluate the effect of CCRT with Gemcitabine on renal function in LACC patients. METHODS: This retrospective study included LACC patients treated with CCRT with Gemcitabine as a radiosensitizer from February 2003 to December 2018. Data were collected from medical archives and electronic records. We assessed renal function before and after CCRT treatment and analyzed the patient's response to treatment and survival. RESULTS: 351 LACC patients treated were included and stratified into two groups: 198 with Glomerular Filtration Rate (GFR) ≥60ml/min (group A) and 153 with GFR<60ml/min (group B). An improvement in GFR was observed after CCRT in patients in group B, from 33 ml/min to 57.5 ml/min (p<0.001). Complete response was observed in 64.1% of patients in Group A and 43.8% in Group B (p<0.0001). Factors associated with increased risk of death included having a GFR of 15-29 ml/min (HR: 2.17; 1.08-4.35), having GFR<15 ml/min (HR: 3.08; 1.63-5.79), and receiving Boost treatment (HR: 2.09; 1.18-3.69). On the other hand, receiving brachytherapy is a positive predictor for OS (HR:0.51; 0.31-0.84). CONCLUSION: CCRT with gemcitabine is an appropriate treatment option for patients diagnosed with LACC who present impaired renal function due to the disease's obstructive nature or other comorbidities.


Assuntos
Nefropatias , Neoplasias do Colo do Útero , Feminino , Humanos , Gencitabina , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/terapia , Estudos Retrospectivos , Quimiorradioterapia/efeitos adversos , Rim
5.
BMC Pulm Med ; 23(1): 442, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968677

RESUMO

BACKGROUND: The SARS-CoV2 pandemic impacted many critically ill patients, causing sequelae, affecting lung function, and involving the musculoskeletal system. We evaluated the association between lung function and muscle quality index in severely ill post-COVID-19 patients. METHODS: A cross-sectional study was conducted on a post-COVID-19 cohort at a third-level center. The study included patients who had experienced severe-to-critical COVID-19. Anthropometric measurements, such as body mass index (BMI) and handgrip strength, were obtained to calculate the muscle quality index (MQI). Additionally, spirometry, measurements of expiratory and inspiratory pressure, and an assessment of DLCO in the lungs were performed. The MQI was categorized into two groups: low-MQI (below the 50th percentile) and high-MQI (above the 50th percentile), based on sex. Group differences were analyzed, and a multivariate linear regression analysis was performed to assess the association between respiratory function and MQI. RESULTS: Among the 748 patients analyzed, 61.96% required mechanical ventilation, and the median hospital stay was 17 days. In patients with a low MQI, it was observed that both mechanical respiratory function and DLCO were lower. The multivariate analysis revealed significantly lower findings in mechanical respiratory function among patients with a low MQI. CONCLUSION: The Low-MQI is an independent predictor associated with pulmonary function parameters in subjects with Post-COVID-19 syndrome.


Assuntos
COVID-19 , Sistema Musculoesquelético , Humanos , Força da Mão/fisiologia , Estudos Transversais , Síndrome de COVID-19 Pós-Aguda , RNA Viral , SARS-CoV-2 , Pulmão , Músculos
6.
Commun Biol ; 6(1): 918, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679437

RESUMO

Kazachstania bulderi is a non-conventional yeast species able to grow efficiently on glucose and δ-gluconolactone at low pH. These unique traits make K. bulderi an ideal candidate for use in sustainable biotechnology processes including low pH fermentations and the production of green chemicals including organic acids. To accelerate strain development with this species, detailed information of its genetics is needed. Here, by employing long read sequencing we report a high-quality phased genome assembly for three strains of K. bulderi species, including the type strain. The sequences were assembled into 12 chromosomes with a total length of 14 Mb, and the genome was fully annotated at structural and functional levels, including allelic and structural variants, ribosomal array and mating type locus. This high-quality reference genome provides a resource to advance our fundamental knowledge of biotechnologically relevant non-conventional yeasts and to support the development of genetic tools for manipulating such strains towards their use as production hosts in biotechnological processes.


Assuntos
Saccharomycetales , Saccharomycetales/genética , Alelos , Biotecnologia , Concentração de Íons de Hidrogênio
7.
Clin Gastroenterol Hepatol ; 21(10): 2597-2605.e2, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36731585

RESUMO

BACKGROUND & AIMS: Cardiovascular disease is the leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effects of saroglitazar, a dual peroxisome proliferator-activated receptor α/γ agonist, on serum lipids in patients with NAFLD. METHODS: A total of 221 patients (saroglitazar, 130; placebo, 91) with NAFLD from phase 2 and 3 double-blinded placebo-controlled randomized clinical trials were pooled to assess the impact of saroglitazar magnesium 4 mg on traditional lipids, very low density lipoprotein cholesterol (VLDL-C), and small dense LDL-C (sdLDL-C). Change from baseline in lipid parameters was performed by using analysis of covariance including treatment as fixed effect and baseline value, diabetes, hypertension, and statin use as covariates. RESULTS: Treatment with saroglitazar significantly improved total cholesterol (-17 mg/dL, 95% confidence interval [CI], -24 to 9; P < .001), triglyceride (-45 mg/dL, 95% CI, -60 to 31; P < .001), low-density lipoprotein cholesterol (-8 mg/dL, 95% CI, -15 to -1; P = .01), and VLDL-C (-8 mg/dL, -14 to -3; P < .001). Saroglitazar improved serum lipids as early as 4-6 weeks of initiation of therapy, and these effects persisted for duration of therapy. Saroglitazar also improved the highly atherogenic sdLDL-C (-10 mg/dL, -17 to -2; P = .01). In subgroup analysis of patients with either diabetes or hypertension, saroglitazar significantly improved serum lipids. CONCLUSIONS: Saroglitazar improved the serum atherogenic lipoprotein profile in patients with NAFLD, irrespective of comorbid conditions and statin use. Saroglitazar has the potential to not only positively affect liver disease but also reduce cardiovascular risk in patients with NAFLD. (Trials registrations: CTRI 2015/10/006236, CTRI 173300410A0106, NCT03863574, and NCT03061721).


Assuntos
Diabetes Mellitus Tipo 2 , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , PPAR alfa/agonistas , PPAR alfa/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Agonistas PPAR-gama , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Triglicerídeos , Colesterol
8.
Int J Mol Sci ; 23(15)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35955668

RESUMO

The quantification of low abundant membrane-binding proteins such as transcriptional factors and chaperones has proven difficult, even with the most sophisticated analytical technologies. Here, we exploit and optimise the non-invasive Fluorescence Correlation Spectroscopy (FCS) for the quantitation of low abundance proteins, and as proof of principle, we choose two interacting proteins involved in the fission of mitochondria in yeast, Fis1p and Mdv1p. In Saccharomyces cerevisiae, the recruitment of Fis1p and Mdv1p to mitochondria is essential for the scission of the organelles and the retention of functional mitochondrial structures in the cell. We use FCS in single GFP-labelled live yeast cells to quantify the protein abundance in homozygote and heterozygote cells and to investigate the impact of the environments on protein copy number, bound/unbound protein state and mobility kinetics. Both proteins were observed to localise predominantly at mitochondrial structures, with the Mdv1p bound state increasing significantly in a strictly respiratory environment. Moreover, a compensatory mechanism that controls Fis1p abundance upon deletion of one allele was observed in Fis1p but not in Mdv1p, suggesting differential regulation of Fis1p and Mdv1p protein expression.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
9.
BMC Pulm Med ; 22(1): 106, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35346135

RESUMO

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation. Different factors that modify pulmonary function include age, sex, muscular strength, and a history of exposure to toxic agents. However, the impact of body composition compartments and sarcopenia on pulmonary function is not well-established. This study aimed to evaluate how body composition compartments and sarcopenia affect pulmonary function in COPD patients. METHODS: In a cross-sectional study, patients with a confirmed diagnosis of COPD, > 40 years old, and forced expiratory volume in the first second /forced vital capacity ratio (FEV1/FVC) < 0.70 post-bronchodilator were included. Patients with cancer, HIV, and asthma were excluded. Body composition was measured with bioelectrical impedance. Sarcopenia was defined according to EWGSOP2, and pulmonary function was assessed by spirometry. RESULTS: 185 patients were studied. The mean age was 72.20 ± 8.39 years; 55.14% were men. A linear regression adjusted model showed associations between body mass index, fat-free mass, skeletal muscle mass index, appendicular skeletal muscle mass index, and phase angle (PhA), and sarcopenia with FEV1 (%). As regards FVC (%), PhA and exercise tolerance had positive associations. CONCLUSION: Body composition, especially PhA, SMMI, ASMMI, and sarcopenia, has a significant impact on pulmonary function. Early detection of disturbances of these indexes enables the early application of such therapeutic strategies in COPD patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Estudos Transversais , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade
10.
Sci Rep ; 12(1): 1216, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35075255

RESUMO

Chronic Obstructive Pulmonary Disease (COPD) patients have alterations in body composition. Bioelectrical impedance analysis (BIA) evaluates body composition, hydration status, and fluid distribution. Subjects with fluid disturbances have been found to have lower FEV1, respiratory muscle strength, and poor prognosis. We aimed to evaluate the effect of hydration status and fluid distribution on pulmonary function in COPD patients. A cross-sectional study, 180 patients with a confirmed diagnosis of COPD were included. Patients with asthma, advanced renal or liver disease, acute HF, exacerbation of COPD, or pacemakers were excluded. Hydration status variables (TBW, ECW, ICW) and disturbance of fluid distribution [impedance ratio (IR) > 0.84 and phase angle (PhA)] were evaluated by BIA. Pulmonary function was assessed by spirometry. The mean population age was 71.55 ± 8.94 years; 55% were men. Subjects were divided into two groups according to the IR ≥ 0.84 or < 0.84. The group with higher IR ≥ 0.84 had lower FEV1, FVC, FEV1/FVC, DLCO and, PhA compared to those with IR < 0.84. After adjusting for confounding variables TBW, ECW, IR ≥ 0.84, PhA, and resistance/height increase were associated with decreased FEV1. In the same way, with IR ≥ 0.84, edema index ≥ 0.48, trunk and abdominal IR were negatively associated with FVC, and PhA had a positive association with FVC. Fluid distribution, especially IR and PhA, could be a useful parameter for predicting pulmonary function in COPD patients.


Assuntos
Pulmão/fisiopatologia , Estado de Hidratação do Organismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Estudos Transversais , Impedância Elétrica , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Capacidade Vital
11.
Crit Rev Food Sci Nutr ; 62(16): 4371-4392, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33506690

RESUMO

Chronic diseases are responsible for approximately 71% global deaths. These are characterized by chronic low-grade inflammation and metabolic alterations. "Functional foods" have been attributed with anti-inflammatory properties, demonstrated in cell lines and murine models; however, studies in humans are inconclusive. The purpose of this systematic review is to identify clinical trials that analyzed changes in inflammatory and metabolic mediators, in response to consumption of specific functional foods. A total of 3581 trials were screened and 88 were included for this review. Foods identified to regulate inflammation included cranberries, grapes, pomegranate, strawberries, wheat, whole grain products, low fat dairy products, yogurt, green tea, cardamom, turmeric, soy foods, almonds, chia seeds, flaxseed, pistachios, algae oil, flaxseed oil and grape seed oil. Clinical trials that focus on a dietary pattern rich in functional foods are necessary to explore if the additive effect of these foods lead to more clinically relevant outcomes.


Assuntos
Dieta , Alimento Funcional , Animais , Doença Crônica , Humanos , Inflamação , Óleo de Semente do Linho , Camundongos
12.
Mol Biol Evol ; 38(12): 5437-5452, 2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34550394

RESUMO

Saccharomyces pastorianus is a natural yeast evolved from different hybridization events between the mesophilic S. cerevisiae and the cold-tolerant S. eubayanus. This complex aneuploid hybrid carries multiple copies of the parental alleles alongside specific hybrid genes and encodes for multiple protein isoforms which impart novel phenotypes, such as the strong ability to ferment at low temperature. These characteristics lead to agonistic competition for substrates and a plethora of biochemical activities, resulting in a unique cellular metabolism. Here, we investigated the transcriptional signature of the different orthologous alleles in S. pastorianus during temperature shifts. We identified temperature-dependent media-independent genes and showed that 35% has their regulation dependent on extracellular leucine uptake, suggesting an interplay between leucine metabolism and temperature response. The analysis of the expression of ortholog parental alleles unveiled that the majority of the genes expresses preferentially one parental allele over the other and that S. eubayanus-like alleles are significantly over-represented among the genes involved in the cold acclimatization. The presence of functionally redundant parental alleles may impact on the nature of protein complexes established in the hybrid, where both parental alleles are competing. Our expression data indicate that the majority of the protein complexes investigated in the hybrid are likely to be either exclusively chimeric or unispecific and that the redundancy is discouraged, a scenario that fits well with the gene balance hypothesis. This study offers the first overview of the transcriptional pattern of S. pastorianus and provides a rationalization for its unique industrial traits at the expression level.


Assuntos
Genoma Fúngico , Saccharomyces cerevisiae , Saccharomyces , Alelos , Cerveja , Fermentação , Saccharomyces/genética , Saccharomyces cerevisiae/genética , Temperatura
13.
Int J Gynecol Cancer ; 31(9): 1228-1235, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34353855

RESUMO

OBJECTIVE: Cervical cancer is the fourth most frequent neoplasm among women in terms of incidence and mortality. Health-related quality of life (HRQL) is an important outcome in oncology. The QLQ-CX24 instrument was developed to measure HRQL in patients with cervical cancer, and its Mexican-Spanish version had not been validated. METHODS: Between March 2018 and May 2019, Mexican women older than 18, with any-stage cervical cancer were invited to participate in the study. Patients answered the QLQ-C30 and QLQ-CX24 questionnaires. Current tests for psychometric and clinical validation were performed. RESULTS: Three hundred and thirty patients with cervical cancer were included in this study. All women invited to participate accepted and were included. The QLQ-CX24 internal consistency test demonstrated adequate convergent (Spearman correlation coefficient 0.001-0.847) and divergent validity (Spearman correlation coefficient <0.0001-0.45). Cronbach's alpha coefficients of the three multi-item scales were >0.7 (minimum 0.76, maximum 0.89). Four scales of the QLQ-CX24 distinguished patients in different clinical stages. The evaluation of responsiveness demonstrated that the peripheral neuropathy scale was sensitive to change over time during chemo-radiation therapy. Six scales of the QLQ-CX24 instrument were associated with survival. CONCLUSION: The Mexican-Spanish version of the QLQ-CX24 questionnaire is reliable and valid for the assessment of HRQL in patients with cervical cancer.


Assuntos
Qualidade de Vida/psicologia , Neoplasias do Colo do Útero/epidemiologia , Feminino , Humanos , México , Pessoa de Meia-Idade , Psicometria , Inquéritos e Questionários , Neoplasias do Colo do Útero/psicologia
14.
PLoS Genet ; 17(1): e1008761, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33493158

RESUMO

Non-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable Transcripts (CUTs), are increasingly being shown to play pivotal roles in the transcriptional and post-transcriptional regulation of genes in eukaryotes. Here, we carried out a large-scale screening of ncRNAs in Saccharomyces cerevisiae, and provide evidence for SUT and CUT function. Phenotypic data on 372 ncRNA deletion strains in 23 different growth conditions were collected, identifying ncRNAs responsible for significant cellular fitness changes. Transcriptome profiles were assembled for 18 haploid ncRNA deletion mutants and 2 essential ncRNA heterozygous deletants. Guided by the resulting RNA-seq data we analysed the genome-wide dysregulation of protein coding genes and non-coding transcripts. Novel functional ncRNAs, SUT125, SUT126, SUT035 and SUT532 that act in trans by modulating transcription factors were identified. Furthermore, we described the impact of SUTs and CUTs in modulating coding gene expression in response to different environmental conditions, regulating important biological process such as respiration (SUT125, SUT126, SUT035, SUT432), steroid biosynthesis (CUT494, SUT053, SUT468) or rRNA processing (SUT075 and snR30). Overall, these data capture and integrate the regulatory and phenotypic network of ncRNAs and protein-coding genes, providing genome-wide evidence of the impact of ncRNAs on cellular homeostasis.


Assuntos
Redes Reguladoras de Genes/genética , RNA não Traduzido/genética , Transcrição Gênica , Transcriptoma/genética , Regulação Fúngica da Expressão Gênica/genética , Genoma Fúngico , Haploidia , Fenótipo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética
15.
Eur J Clin Nutr ; 75(5): 852-855, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33149254

RESUMO

The objective was to evaluate body composition and nutritional status in women with locally advanced cervical cancer (LACC) before receiving oncologic treatment. Women with cervical cancer diagnoses in clinical stage IB2 to IIIB were studied. Body composition was measured with bioimpedance, sarcopenia determined according to the European Consensus, and nutritional status according to the Patient-Generated Subjective Global Assessment. A total of 155 women with age 50.4 ± 13.7, 29 clinical stage I, 82 II, and 44 III, were studied. Patients in advanced clinical stage III, compared with patients in stage II and stage I, lower phase angle (III: 5.2 ± 0.98 vs. II: 5.7 ± 1.9 and I: 5.8 ± 0.69, p = 0.007). Impedance vector distribution was different in patients in clinical stage III vs. those in clinical stage II (p = 0.014) and I (p = 0.039). LACC patients in advanced stages had worse body composition and nutritional status before treatment.


Assuntos
Sarcopenia , Neoplasias do Colo do Útero , Adulto , Composição Corporal , Impedância Elétrica , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estado Nutricional , Neoplasias do Colo do Útero/patologia
16.
Rev Invest Clin ; 72(4): 219-230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064687

RESUMO

In the development of cervical cancer (CC), the immune response plays an essential role, from the elimination of human papillomavirus (HPV) infection to the response against the tumor. For optimal function of the immune response, various factors are required, one of the most important being an adequate nutrition. The complex interaction between nutrients and microbiota maintains the immune system in homeostasis and in case of infection, it provides the ability to fight against pathogen invasion, as occurs in HPV infection. The purpose of this article is to describe the role of diet, food, and specific nutrients in the immune response from the onset of infection to progression to precancerous lesions and CC, as well as the role of diet and nutrition during oncological treatment. The immunomodulatory role of microbiota is also discussed. A detailed analysis of the evidence leads us to recommend a nutritional pattern very similar to the Mediterranean diet or the prudent diet for an optimal immune response. Moreover, pre- and probiotics favorably modulate the microbiota and induce preventive and therapeutic effects against cancer.


Assuntos
Imunidade , Estado Nutricional , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Dieta , Feminino , Microbioma Gastrointestinal , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/imunologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/terapia
17.
Hepatol Int ; 14(5): 817-827, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32813194

RESUMO

BACKGROUND AND AIMS: Pirfenidone (PFD), an oral antifibrotic drug, has been authorized by the EMA and FDA for treatment of idiopathic pulmonary fibrosis. Few studies have addressed its use in advanced liver fibrosis (ALF). We evaluated a prolonged-release formulation (PR-PFD) plus standard of care on disease progression in ALF. METHODS: 281 ALF patients from 12 centers receiving PR-PFD (600 mg bid) were screened; 122 completed 1 year of treatment. Additionally, 74 patients received only standard of care regimen. Average age was 64 ± 12 years, 58% female. 43.5% had fatty liver disease (NAFLD), 22.5% viral hepatitis C (VHC), 17% autoimmune hepatitis (AIH), and 17% alcoholic liver disease (ALD). Baseline fibrosis was F4 in 74% and F3 in 26%. Antifibrotic effects were assessed by transient elastography (Fibroscan®) and Fibro Test® (FT); Cytokines and PFD plasma levels were tracked and quality of life evaluated. RESULTS: We found a significant reduction in fibrosis in 35% of PR-PFD patients and only in 4.1% in non PR-PFD patients. Child-Pugh score improved in 29.7%. Biochemical values remained stable; 40.6% and 43.3% decreased ALT or AST, respectively. TGFß1 (pg/mL) levels were lower in PFD-treated patients. PFD serum concentration (µg/mL) was higher (8.2 ± 1.7) in fibrosis regression profile (FRP) patients compared to fibrosis progression profile (FPP) patients (4.7 ± 0.3 µg/mL, p < 0.01). 12% reported transient burning or nausea and 7% photosensitivity. Quality of life (Euro-Qol scale) improved from 62 ± 5 to 84 ± 3 (p < 0.001) and from 32 ± 3 to 42 ± 2 (p < 0.008) (FACIT scale). CONCLUSIONS: PR-PFD is efficacious and safe in ALF and associated with promising antifibrotic effects. TRIAL REGISTRATION: Clinical trial number: NCT04099407.


Assuntos
Cirrose Hepática , Hepatopatias , Fígado , Piridonas , Qualidade de Vida , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/efeitos adversos , Progressão da Doença , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Cirrose Hepática/psicologia , Hepatopatias/classificação , Hepatopatias/complicações , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Padrão de Cuidado , Resultado do Tratamento
18.
Rev. invest. clín ; 72(4): 219-230, Jul.-Aug. 2020.
Artigo em Inglês | LILACS | ID: biblio-1251859

RESUMO

ABSTRACT In the development of cervical cancer (CC), the immune response plays an essential role, from the elimination of human papillomavirus (HPV) infection to the response against the tumor. For optimal function of the immune response, various factors are required, one of the most important being an adequate nutrition. The complex interaction between nutrients and microbiota maintains the immune system in homeostasis and in case of infection, it provides the ability to fight against pathogen invasion, as occurs in HPV infection. The purpose of this article is to describe the role of diet, food, and specific nutrients in the immune response from the onset of infection to progression to precancerous lesions and CC, as well as the role of diet and nutrition during oncological treatment. The immunomodulatory role of microbiota is also discussed. A detailed analysis of the evidence leads us to recommend a nutritional pattern very similar to the Mediterranean diet or the prudent diet for an optimal immune response. Moreover, pre- and probiotics favorably modulate the microbiota and induce preventive and therapeutic effects against cancer.


Assuntos
Humanos , Feminino , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/terapia , Estado Nutricional , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/imunologia , Imunidade , Dieta , Microbioma Gastrointestinal
19.
Ecol Lett ; 23(4): 674-681, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32043741

RESUMO

Decades of research suggest that species richness depends on spatial characteristics of habitat patches, especially their size and isolation. In contrast, the habitat amount hypothesis predicts that (1) species richness in plots of fixed size (species density) is more strongly and positively related to the amount of habitat around the plot than to patch size or isolation; (2) habitat amount better predicts species density than patch size and isolation combined, (3) there is no effect of habitat fragmentation per se on species density and (4) patch size and isolation effects do not become stronger with declining habitat amount. Data on eight taxonomic groups from 35 studies around the world support these predictions. Conserving species density requires minimising habitat loss, irrespective of the configuration of the patches in which that habitat is contained.


Assuntos
Ecossistema
20.
Data Brief ; 24: 103882, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31193185

RESUMO

We present a complete dataset from the literature on functional traits including morphological measurements, dietary information, foraging strategy, and foraging location for all 398 extant species of parrots. The morphological measurements include: mass, total length, wing chord, culmen length, tarsus length, and tail length. The diet data describe whether each species is known to consume particular food items (e.g. nectar, berries, and carrion), foraging strategy data describes how each species captures or accesses food, and foraging location data describe the habitat from which each species finds food (e.g. ground, canopy, and subcanopy). We also present a time-calibrated phylogenetic supertree that contains all 398 extant species as well as 15 extinct species (413 total species). These data are hosted on the Figshare data depository (https://figshare.com/s/6cdf8cf00793deab7ba6).

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