RESUMEN

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.

Asunto(s)

Neoplasias de la Boca , Proteoma , Saliva , Humanos , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Neoplasias de la Boca/diagnóstico , Saliva/química , Saliva/metabolismo , Proteoma/análisis , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/diagnóstico , Femenino , Biomarcadores de Tumor/metabolismo , Masculino , Metástasis Linfática , Conformación Proteica , Persona de Mediana Edad , Pronóstico , Proteómica/métodos , Transcetolasa/metabolismo , Anciano , Espectrometría de Masas , Proteínas y Péptidos Salivales/metabolismo , Proteínas y Péptidos Salivales/análisis

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Natural products (or specialized metabolites) are historically the main source of new drugs. However, the current drug discovery pipelines require miniaturization and speeds that are incompatible with traditional natural product research methods, especially in the early stages of the research. This article introduces the NP3 MS Workflow, a robust open-source software system for liquid chromatography-tandem mass spectrometry (LC-MS/MS) untargeted metabolomic data processing and analysis, designed to rank bioactive natural products directly from complex mixtures of compounds, such as bioactive biota samples. NP3 MS Workflow allows minimal user intervention as well as customization of each step of LC-MS/MS data processing, with diagnostic statistics to allow interpretation and optimization of LC-MS/MS data processing by the user. NP3 MS Workflow adds improved computing of the MS2 spectra in an LC-MS/MS data set and provides tools for automatic [M + H]+ ion deconvolution using fragmentation rules; chemical structural annotation against MS2 databases; and relative quantification of the precursor ions for bioactivity correlation scoring. The software will be presented with case studies and comparisons with equivalent tools currently available. NP3 MS Workflow shows a robust and useful approach to select bioactive natural products from complex mixtures, improving the set of tools available for untargeted metabolomics. It can be easily integrated into natural product-based drug-discovery pipelines and to other fields of research at the interface of chemistry and biology.

Asunto(s)

Productos Biológicos , Descubrimiento de Drogas , Metabolómica , Programas Informáticos , Espectrometría de Masas en Tándem , Productos Biológicos/química , Productos Biológicos/metabolismo , Productos Biológicos/análisis , Cromatografía Liquida/métodos , Flujo de Trabajo

RESUMEN

The magnitude of muscle hypertrophy in response to resistance training (RT) is highly variable between individuals (response heterogeneity). Manipulations in RT variables may modulate RT-related response heterogeneity; yet, this remains to be determined. Using a within-subject unilateral design, we aimed to investigate the effects of RT volume manipulation on whole muscle hypertrophy [quadriceps muscle cross-sectional area (qCSA)] among nonresponders and responders to a low RT dose (single-set). We also investigated the effects of RT volume manipulation on muscle strength in these responsiveness groups. Eighty-five older individuals [41M/44F, age = 68 ± 4 yr; body mass index (BMI) = 26.4 ± 3.7 kg/m2] had one leg randomly allocated to a single (1)-set and the contralateral leg allocated to four sets of unilateral knee-extension RT at 8-15 repetition maximum (RM) for 10-wk 2 days/wk. Pre- and postintervention, participants underwent magnetic resonance imaging (MRI) and unilateral knee-extension 1-RM strength testing. MRI typical error (2× TE = 3.27%) was used to classify individuals according to responsiveness patterns. n = 51 were classified as nonresponders (≤2× TE) and n = 34 as responders (>2× TE) based on pre- to postintervention change qCSA following the single-set RT protocol. Nonresponders to single-set training showed a dose response, with significant time × set interactions for qCSA and 1-RM strength, indicating greater gains in response to the higher volume prescription (time × set: P < 0.05 for both outcomes). Responders improved qCSA (time: P < 0.001), with a tendency toward higher benefit from the four sets RT protocol (time × set: P = 0.08); on the other hand, 1-RM increased similarly irrespectively of RT volume prescription (time × set: P > 0.05). Our findings support the use of higher RT volume to mitigate nonresponsiveness among older adults.NEW & NOTEWORTHY Using a within-subject unilateral design, we demonstrated that increasing resistance training (RT) volume may be a simple, effective strategy to improve muscle hypertrophy and strength gains among older adults who do not respond to low-volume RT. In addition, it could most likely be used to further improve hypertrophic outcomes in responders.

Asunto(s)

Músculo Esquelético , Entrenamiento de Fuerza , Humanos , Anciano , Persona de Mediana Edad , Músculo Esquelético/fisiología , Entrenamiento de Fuerza/métodos , Músculo Cuádriceps/fisiología , Fuerza Muscular/fisiología , Hipertrofia

RESUMEN

Introduction: Resistance exercise can significantly increase serum steroid concentrations after an exercise bout. Steroid hormones are involved in the regulation of several important bodily functions (e.g., muscle growth) through both systemic delivery and local production. Thus, we aimed to determine whether resistance exercise-induced increases in serum steroid hormone concentrations are accompanied by enhanced skeletal muscle steroid concentrations, or whether muscle contractions per se induced by resistance exercise can increase intramuscular steroid concentrations. Methods: A counterbalanced, within-subject, crossover design was applied. Six resistance-trained men (26 ± 5 years; 79 ± 8 kg; 179 ± 10 cm) performed a single-arm lateral raise exercise (10 sets of 8 to 12 RM - 3 min rest between sets) targeting the deltoid muscle followed by either squat exercise (10 sets of 8 to 12 RM - 1 min rest) to induce a hormonal response (high hormone [HH] condition) or rest (low hormone [LH] condition). Blood samples were obtained pre-exercise and 15 min and 30 min post-exercise; muscle specimens were harvested pre-exercise and 45 min post-exercise. Immunoassays were used to measure serum and muscle steroids (total and free testosterone, dehydroepiandrosterone sulfate, dihydrotestosterone, and cortisol; free testosterone measured only in serum and dehydroepiandrosterone only in muscle) at these time points. Results: In the serum, only cortisol significantly increased after the HH protocol. There were no significant changes in muscle steroid concentrations after the protocols. Discussion: Our study provides evidence that serum steroid concentration increases (cortisol only) seem not to be aligned with muscle steroid concentrations. The lack of change in muscle steroid after protocols suggests that resistance-trained individuals were desensitized to the exercise stimuli. It is also possible that the single postexercise timepoint investigated in this study might be too early or too late to observe changes. Thus, additional timepoints should be examined to determine if RE can indeed change muscle steroid concentrations either by skeletal muscle uptake of these hormones or the intramuscular steroidogenesis process.

Asunto(s)

Hidrocortisona , Músculo Esquelético , Humanos , Masculino , Dihidrotestosterona , Músculo Esquelético/fisiología , Esteroides , Testosterona , Estudios Cruzados

RESUMEN

The selection of a suitable proteotypic peptide remains a challenge for designing a targeted quantitative proteomics assay. Although the criteria are well-established in the literature, the selection of these peptides is often performed in a subjective and time-consuming manner. Here, we have developed a practical and semiautomated workflow implemented in an open-source program named Typic. Typic is designed to run in a command line and a graphical interface to help selecting a list of proteotypic peptides for targeted quantitation. The tool combines the input data and downloads additional data from public repositories to produce a file per protein as output. Each output file includes relevant information to the selection of proteotypic peptides organized in a table, a colored ranking of peptides according to their potential value as targets for quantitation and auxiliary plots to assist users in the task of proteotypic peptides selection. Taken together, Typic leads to a practical and straightforward data extraction from multiple data sets, allowing the identification of most suitable proteotypic peptides based on established criteria, in an unbiased and standardized manner, ultimately leading to a more robust targeted proteomics assay.

Asunto(s)

Proteoma , Proteómica , Péptidos

RESUMEN

INTRODUCTION: DNA methylation regulates exercise-induced changes in the skeletal muscle transcriptome. However, the specificity and the time course responses in the myogenic regulatory factors DNA methylation and mRNA expression after divergent exercise modes are unknown. PURPOSE: This study aimed to compare the time course changes in DNA methylation and mRNA expression for selected myogenic regulatory factors ( MYOD1 , MYF5 , and MYF6 ) immediately after, 4 h after, and 8 h after a single bout of resistance exercise (RE), high-intensity interval exercise (HIIE), and concurrent exercise (CE). METHODS: Nine healthy but untrained males (age, 23.9 ± 2.8 yr; body mass, 70.1 ± 14.9 kg; peak oxygen uptake [V̇O 2peak ], 41.4 ± 5.2 mL·kg -1 ·min -1 ; mean ± SD) performed a counterbalanced, randomized order of RE (4 × 8-12 repetition maximum), HIIE (12 × 1 min sprints at V̇O 2peak running velocity), and CE (RE followed by HIIE). Skeletal muscle biopsies (vastus lateralis) were taken before (REST) immediately (0 h), 4 h, and 8 h after each exercise bout. RESULTS: Compared with REST, MYOD1 , MYF5 , and MYF6 , mean methylation across all CpGs analyzed was reduced after 4 and 8 h in response to all exercise protocols ( P < 0.05). Reduced levels of MYOD1 methylation were observed after HIIE and CE compared with RE ( P < 0.05). Compared with REST, all exercise bouts increased mRNA expression over time ( MYOD1 at 4 and 8 h, and MYF6 at 4 h; P < 0.05). MYF5 mRNA expression was lower after 4 h compared with 0 h and higher at 8 h compared with 4 h ( P < 0.05). CONCLUSIONS: We observed an interrelated but not time-aligned response between the exercise-induced changes in myogenic regulatory factors demethylation and mRNA expression after divergent exercise modes. Despite divergent contractile stimuli, changes in DNA methylation and mRNA expression in skeletal muscle were largely confined to the late (4-8 h) recovery period and similar between the different exercise challenges.

Asunto(s)

Ejercicio Físico , Factores Reguladores Miogénicos , Masculino , Humanos , Adulto Joven , Adulto , Factores Reguladores Miogénicos/genética , Factores Reguladores Miogénicos/metabolismo , Ejercicio Físico/fisiología , Músculo Esquelético/fisiología , ARN Mensajero/metabolismo , Desmetilación

RESUMEN

Losses in skeletal muscle mass, strength, and metabolic function are harmful in the pathophysiology of serious diseases, including breast cancer. Physical exercise training is an effective non-pharmacological strategy to improve health and quality of life in patients with breast cancer, mainly through positive effects on skeletal muscle mass, strength, and metabolic function. Emerging evidence has also highlighted the potential of exercise-induced crosstalk between skeletal muscle and cancer cells as one of the mechanisms controlling breast cancer progression. This intercellular communication seems to be mediated by a group of skeletal muscle molecules released in the bloodstream known as myokines. Among the myokines, exercise-induced circulating microRNAs (c-miRNAs) are deemed to mediate the antitumoral effects produced by exercise training through the control of key cellular processes, such as proliferation, metabolism, and signal transduction. However, there are still many open questions regarding the molecular basis of the exercise-induced effects on c-miRNA on human breast cancer cells. Here, we present evidence regarding the effect of exercise training on c-miRNA expression in breast cancer, along with the current gaps in the literature and future perspectives.

RESUMEN

There is emerging evidence that decreased muscle mass and cardiorespiratory fitness (CRF) are associated with increased risk of cancer-related mortality. This paper aimed to present recommendations to prescribe effective and safe exercise protocols to minimize losses, maintain or even improve muscle mass, strength, and CRF of the cancer patients who are undergoing or beyond treatment during the COVID-19 era. Overall, we recommend performing exercises with bodyweight, elastic bands, or suspension bands to voluntary interruption (i.e., interrupt the exercise set voluntarily, according to their perception of fatigue, before concentric muscular failure) to maintain or increase muscle strength and mass and CRF during COVID-19 physical distancing. Additionally, rest intervals between sets and exercises (i.e., long or short) should favor maintaining exercise intensities between 50 and 80% of maxHR and/or RPE of 12. In an exercise program with these characteristics, the progression of the stimulus must be carried out by increasing exercise complexity, number of sets, and weekly frequency. With feasible exercises attainable anywhere, modulating only the work-to-rest ratio and using voluntary interruption, it is possible to prescribe exercise for a wide range of patients with cancer as well as training goals. Exercise must be encouraged; however, exercise professionals must be aware of the patient's health condition even at a physical distance to provide a safe and efficient exercise program. Exercise professionals should adjust the exercise prescription throughout home confinement whenever necessary, keeping in mind that minimal exercise stimuli are beneficial to patients in poor physical condition.

RESUMEN

Saliva is a biofluid that maintains the health of oral tissues and the homeostasis of oral microbiota. Studies have demonstrated that Oral squamous cell carcinoma (OSCC) patients have different salivary microbiota than healthy individuals. However, the relationship between these microbial differences and clinicopathological outcomes is still far from conclusive. Herein, we investigate the capability of using metagenomic and metaproteomic saliva profiles to distinguish between Control (C), OSCC without active lesion (L0), and OSCC with active lesion (L1) patients. The results show that there are significantly distinct taxonomies and functional changes in L1 patients compared to C and L0 patients, suggesting compositional modulation of the oral microbiome, as the relative abundances of Centipeda, Veillonella, and Gemella suggested by metagenomics are correlated with tumor size, clinical stage, and active lesion. Metagenomics results also demonstrated that poor overall patient survival is associated with a higher relative abundance of Stenophotromonas, Staphylococcus, Centipeda, Selenomonas, Alloscordovia, and Acitenobacter. Finally, compositional and functional differences in the saliva content by metaproteomics analysis can distinguish healthy individuals from OSCC patients. In summary, our study suggests that oral microbiota and their protein abundance have potential diagnosis and prognosis value for oral cancer patients. Further studies are necessary to understand the role of uniquely detected metaproteins in the microbiota of healthy and OSCC patients as well as the crosstalk between saliva host proteins and the oral microbiome present in OSCC.

Asunto(s)

Saliva/microbiología , Carcinoma de Células Escamosas de Cabeza y Cuello/microbiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Metagenómica/métodos , Microbiota/genética , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/microbiología , Pronóstico , Proteómica/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo

RESUMEN

Bacterial genome sequencing has revealed a vast number of novel biosynthetic gene clusters (BGC) with potential to produce bioactive natural products. However, the biosynthesis of secondary metabolites by bacteria is often silenced under laboratory conditions, limiting the controlled expression of natural products. Here we describe an integrated methodology for the construction and screening of an elicited and pre-fractionated library of marine bacteria. In this pilot study, chemical elicitors were evaluated to mimic the natural environment and to induce the expression of cryptic BGCs in deep-sea bacteria. By integrating high-resolution untargeted metabolomics with cheminformatics analyses, it was possible to visualize, mine, identify and map the chemical and biological space of the elicited bacterial metabolites. The results show that elicited bacterial metabolites correspond to ~45% of the compounds produced under laboratory conditions. In addition, the elicited chemical space is novel (~70% of the elicited compounds) or concentrated in the chemical space of drugs. Fractionation of the crude extracts further evidenced minor compounds (~90% of the collection) and the detection of biological activity. This pilot work pinpoints strategies for constructing and evaluating chemically diverse bacterial natural product libraries towards the identification of novel bacterial metabolites in natural product-based drug discovery pipelines.

RESUMEN

INTRODUCTION: Exercise-induced microRNA (miRNA) expression has been implicated in the regulation of skeletal muscle plasticity. However, the specificity and acute time course in miRNA expression after divergent exercise modes are unknown. In a randomized crossover design, we compared the acute expression profile of eight skeletal muscle miRNAs previously reported to be involved in skeletal muscle development, growth, and maintenance after a bout of either resistance exercise (RE), high-intensity interval exercise (HIIE), and concurrent resistance and high-intensity interval exercises (CE). METHODS: Nine untrained young men (23.9 ± 2.8 yr, 70.1 ± 14.9 kg, 177.2 ± 3.0 cm, 41.4 ± 5.2 mL·kg-1·min-1) underwent a counterbalanced crossover design in which they performed bouts of RE (2 × 10 repetitions maximum 45° leg press and leg extension exercises), HIEE (12 × 1-min sprints at V˙O2peak with 1-min rest intervals between sprints), and CE (RE followed by HIIE), separated by 1 wk. Vastus lateralis biopsies were harvested immediately before (Pre) and immediately (0 h), 4 h, and 8 h after each exercise bout. RESULTS: There were similar increases (main effect of time; P < 0.05) in miR-1-3p, miR-133a-3p, miR-133b, miR-181a-3p, and miR-486 expression at 8 h from Pre with all exercise modes. Besides a main effect of time, miR-23a-3p and miR-206 presented a main effect of condition with lower expression after HIIE compared with RE and CE. CONCLUSIONS: Select miRNAs (miR-1-3p, miR-133a-3p, miR-133b, miR-23a-3p, miR-181a-3p, miR-206, miR-486) do not exhibit an expression specificity in the acute recovery period after a single bout of RE, HIIE, or CE in skeletal muscle. Our data also indicate that RE has a higher effect on the expression of miR-23a-3p and miR-206 than HIIE. As upregulation of these miRNAs seems to be confined to the 8-h period after exercise, this may subsequently affect the expression patterns of target mRNAs forming the basis of exercise-induced adaptive responses.

Asunto(s)

Ejercicio Físico , Entrenamiento de Intervalos de Alta Intensidad , MicroARNs , Músculo Esquelético/metabolismo , Entrenamiento de Fuerza , Adulto , Estudios Cruzados , Humanos , Masculino , MicroARNs/metabolismo , Regulación hacia Arriba , Adulto Joven

RESUMEN

BACKGROUND: Coronavirus disease 2019 (Covid-19) pandemic is a global health crisis that has culminated in thousands of deaths. In order to reduce the spread of the Sars-CoV-2 virus, governments of several countries have adopted social isolation as a strategy. However, social isolation has culminated in deleterious effects on the population's health, including increased physical inactivity, stress and, consequently, adverse changes in body composition, cardiorespiratory capacity, muscle strength, physical functionality, and vascular events, which are increasingly pointed out as the main determinants of cardiovascular health. Staying physically active during lockdown is a challenge, especially for the population with a higher risk of mortality from COVID-19, who are still encouraged to maintain social distance until there is a vaccine available. Strategies to avoid physical inactivity and reduce stress levels can promote cardiovascular protection and must be considered during COVID-19 time. OBJECTIVE: The aim of this paper is to discuss the risks of physical inactivity and stress for the cardiovascular system during the COVID-19 pandemic and propose strategies to protect cardiovascular health. CONCLUSION: A home-based training protocol could be an interesting and effective strategy for the population who need to remain physically active and safe at home.

Asunto(s)

COVID-19 , Sustancias Explosivas , Control de Enfermedades Transmisibles , Ejercicio Físico , Humanos , Pandemias/prevención & control , SARS-CoV-2 , Conducta Sedentaria

RESUMEN

Previous research has suggested that concurrent training (CT) may attenuate resistance training (RT)-induced gains in muscle strength and mass, i.e.' the interference effect. In 2000, a seminal theoretical model indicated that the interference effect should occur when high-intensity interval training (HIIT) (repeated bouts at 95-100% of the aerobic power) and RT (multiple sets at ~ 10 repetition maximum;10 RM) were performed in the same training routine. However, there was a paucity of data regarding the likelihood of other HIIT-based CT protocols to induce the interference effect at the time. Thus, based on current HIIT-based CT literature and HIIT nomenclature and framework, the present manuscript updates the theoretical model of the interference phenomenon previously proposed. We suggest that very intense HIIT protocols [i.e., resisted sprint training (RST), and sprint interval training (SIT)] can greatly minimize the odds of occurring the interference effect on muscle strength and mass. Thus, very intensive HIIT protocols should be implemented when performing CT to avoid the interference effect. Long and short HIIT-based CT protocols may induce the interference effect on muscle strength when HIIT bout is performed before RT with no rest interval between them.

Asunto(s)

Entrenamiento de Intervalos de Alta Intensidad , Entrenamiento de Fuerza , Humanos , Fuerza Muscular , Descanso

RESUMEN

AIMS: Evaluate the abundance of the selected targets, alpha-1-antitrypsin (A1AT) and macrophage migration inhibitory factor (MIF), and correlate these findings with the risk of developing severe oral mucositis (OM). MATERIALS AND METHODS: Head and neck squamous cell carcinoma (HNSCC) patients submitted to radiotherapy (RT) or chemoradiotherapy (CRT) were assessed. OM grade and pain were evaluated daily during treatment. Two protein targets, A1AT and MIF, were evaluated, using selected reaction monitoring-mass spectrometry (SRM-MS), in whole saliva, collected prior to oncologic treatment. The results obtained from the targeted proteomic analysis were correlated with OM clinical outcomes. RESULTS: A total of 27 patients were included, of whom 21 (77.8%) had locally advanced disease (clinical stage III or IV). Most patients (70.4%) received CRT. OM grades 2 (40.8%) and 3 (33.3%) were the most prevalent during RT with a mean highest reported OM-related pain of 3.22 through the visual analogue scale (VAS). The abundance of A1AT and MIF correlated significantly with severe (grades 3 or 4, p < 0.02) compared with moderate-low (grades 1 or 2, p < 0.04) OM grade. CONCLUSIONS: There is a correlation between the abundance of salivary A1AT and MIF and oncologic treatment-induced OM. The correlation of MIF expression with severe OM appears to be compatible with its physiological pro-inflammatory role. These results open up great possibilities for the use of salivary MIF and A1AT levels as prognostic markers for effective therapeutic interventions, such as photobiomodulation therapy, patient-controlled analgesia, or personalized medicaments.

Asunto(s)

Biomarcadores/metabolismo , Neoplasias de Cabeza y Cuello/complicaciones , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Calidad de Vida/psicología , Saliva/metabolismo , Estomatitis/inducido químicamente , alfa 1-Antitripsina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Adulto Joven

RESUMEN

BACKGROUND: The construction of a suffix array for a collection of strings is a fundamental task in Bioinformatics and in many other applications that process strings. Related data structures, as the Longest Common Prefix array, the Burrows-Wheeler transform, and the document array, are often needed to accompany the suffix array to efficiently solve a wide variety of problems. While several algorithms have been proposed to construct the suffix array for a single string, less emphasis has been put on algorithms to construct suffix arrays for string collections. RESULT: In this paper we introduce gsufsort, an open source software for constructing the suffix array and related data indexing structures for a string collection with N symbols in O(N) time. Our tool is written in ANSI/C and is based on the algorithm gSACA-K (Louza et al. in Theor Comput Sci 678:22-39, 2017), the fastest algorithm to construct suffix arrays for string collections. The tool supports large fasta, fastq and text files with multiple strings as input. Experiments have shown very good performance on different types of strings. CONCLUSIONS: gsufsort is a fast, portable, and lightweight tool for constructing the suffix array and additional data structures for string collections.

RESUMEN

While performing aerobic exercise during chemotherapy has been proven feasible and safe, the efficacy of aerobic training on cardiorespiratory fitness (CRF) in women with breast cancer undergoing chemotherapy has not yet been systematically assessed. Therefore, the objective of this work was to determine (a) the efficacy of aerobic training to improve CRF; (b) the role of aerobic training intensity (moderate or vigorous) on CRF response; (c) the effect of the aerobic training mode (continuous or interval) on changes in CRF in women with breast cancer (BC) receiving chemotherapy. A systematic review and meta-analysis were conducted as per PRISMA guidelines, and randomized controlled trials comparing usual care (UC) and aerobic training in women with BC undergoing chemotherapy were eligible. The results suggest that increases in CRF are favored by (a) aerobic training when compared to usual care; (b) vigorous-intensity aerobic exercise (64-90% of maximal oxygen uptake, VO2max) when compared to moderate-intensity aerobic exercise (46-63% of VO2max); and (c) both continuous and interval aerobic training are effective at increasing the VO2max. Aerobic training improves CRF in women with BC undergoing chemotherapy. Notably, training intensity significantly impacts the VO2max response. Where appropriate, vigorous intensity aerobic training should be considered for women with BC receiving chemotherapy.

RESUMEN

BACKGROUND: In Citrus cultures, three species of Xanthomonas are known to cause distinct diseases. X. citri subsp. citri patothype A, X. fuscans subsp. aurantifolii pathotypes B and C, and X. alfalfae subsp. citrumelonis, are the causative agents of cancrosis A, B, C, and citrus bacterial spots, respectively. Although these species exhibit different levels of virulence and aggressiveness, only limited alternatives are currently available for proper and early detection of these diseases in the fields. The present study aimed to develop a new molecular diagnostic method based on genomic sequences derived from the four species of Xanthomonas. RESULTS: Using comparative genomics approaches, primers were synthesized for the identification of the four causative agents of citrus diseases. These primers were validated for their specificity to their target DNA by both conventional and multiplex PCR. Upon evaluation, their sensitivity was found to be 0.02 ng/µl in vitro and 1.5 × 104 CFU ml-1 in infected leaves. Additionally, none of the primers were able to generate amplicons in 19 other genomes of Xanthomonas not associated with Citrus and one species of Xylella, the causal agent of citrus variegated chlorosis (CVC). This denotes strong specificity of the primers for the different species of Xanthomonas investigated in this study. CONCLUSIONS: We demonstrated that these markers can be used as potential candidates for performing in vivo molecular diagnosis exclusively for citrus-associated Xanthomonas. The bioinformatics pipeline developed in this study to design specific genomic regions is capable of generating specific primers. It is freely available and can be utilized for any other model organism.

Asunto(s)

Ejercicio Físico , Fibras Musculares Esqueléticas/citología , Células Satélite del Músculo Esquelético/fisiología , Anciano , Envejecimiento/fisiología , Humanos

RESUMEN

INTRODUCTION: Low-intensity endurance training (ET) performed with blood flow restriction (BFR) can improve muscle strength, cross-sectional area (CSA) and cardiorespiratory capacity. Whether muscle strength and CSA as well as cardiorespiratory capacity (i.e., V˙O2max) and underlying molecular processes regulating such respective muscle adaptations are comparable to resistance and ET is unknown. PURPOSE: To determine the respective chronic (i.e., 8 wk) functional, morphological, and molecular responses of ET-BFR training compared with conventional, unrestricted resistance training (RT) and ET. METHODS: Thirty healthy young men were randomly assigned to one of three experimental groups: ET-BFR (n = 10, 4 d·wk, 30-min cycling at 40% of V˙O2max), RT (n = 10, 4 d·wk, 4 sets of 10 repetitions leg press at 70% of one repetition maximum with 60 s rest) or ET (n = 10, 4 d·wk, 30-min cycling at 70% of V˙O2max) for 8 wk. Measures of quadriceps CSA, leg press one repetition maximum, and V˙O2max as well as muscle biopsies were obtained before and after intervention. RESULTS: Both RT and ET-BFR increased muscle strength and hypertrophy responses. ET-BFR also increased V˙O2max, total cytochrome c oxidase subunit 4 isoform 1 abundance and vascular endothelial growth factor mRNA abundance despite the lower work load compared to ET. CONCLUSIONS: Eight weeks of ET-BFR can increase muscle strength and induce similar muscle hypertrophy responses to RT while V˙O2max responses also increased postintervention even with a significantly lower work load compared with ET. Our findings provide new insight to some of the molecular mechanisms mediating adaptation responses with ET-BFR and the potential for this training protocol to improve muscle and cardiorespiratory capacity.

Asunto(s)

Ciclismo/fisiología , Capacidad Cardiovascular/fisiología , Fuerza Muscular/fisiología , Resistencia Física/fisiología , Músculo Cuádriceps/irrigación sanguínea , Flujo Sanguíneo Regional , Entrenamiento de Fuerza/métodos , Adaptación Fisiológica , Biopsia , Complejo IV de Transporte de Electrones/metabolismo , Humanos , Masculino , Consumo de Oxígeno , Músculo Cuádriceps/anatomía & histología , Músculo Cuádriceps/diagnóstico por imagen , Músculo Cuádriceps/fisiología , ARN Mensajero/metabolismo , Flujo Sanguíneo Regional/fisiología , Ultrasonografía , Factor A de Crecimiento Endotelial Vascular/metabolismo

RESUMEN

Different regions of oral squamous cell carcinoma (OSCC) have particular histopathological and molecular characteristics limiting the standard tumor-node-metastasis prognosis classification. Therefore, defining biological signatures that allow assessing the prognostic outcomes for OSCC patients would be of great clinical significance. Using histopathology-guided discovery proteomics, we analyze neoplastic islands and stroma from the invasive tumor front (ITF) and inner tumor to identify differentially expressed proteins. Potential signature proteins are prioritized and further investigated by immunohistochemistry (IHC) and targeted proteomics. IHC indicates low expression of cystatin-B in neoplastic islands from the ITF as an independent marker for local recurrence. Targeted proteomics analysis of the prioritized proteins in saliva, combined with machine-learning methods, highlights a peptide-based signature as the most powerful predictor to distinguish patients with and without lymph node metastasis. In summary, we identify a robust signature, which may enhance prognostic decisions in OSCC and better guide treatment to reduce tumor recurrence or lymph node metastasis.

Asunto(s)

Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/mortalidad , Neoplasias de la Boca/mortalidad , Recurrencia Local de Neoplasia/diagnóstico , Proteómica/métodos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Toma de Decisiones Clínicas , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Metástasis Linfática , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/patología , Recurrencia Local de Neoplasia/prevención & control , Péptidos/análisis , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Saliva/química , Tasa de Supervivencia