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1.
Chem Biodivers ; : e202401547, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136586

RESUMO

The fungus Phialomyces macrosporus was cultured using the One Strain Many Compounds (OSMAC) strategies to evaluate its metabolome. Variations in the nutrient culture media, culture regime, and cultivation parameters can significantly influence fungal extract quantity and chemical diversity. This study aimed to explore the mycobolome of P. macrosporus in five different culture media and two different cultivation conditions using NMR-based metabolomics. Principal component analysis (PCA) of 1H NMR spectra revealed clear differentiation between these samples, highlighting the rice dextrose agar medium (RDA) and potato dextrose broth (PDB) as standard complex media for conducting a fungal metabolite screening program.

2.
Clin Transl Oncol ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39147936

RESUMO

PURPOSE: To describe the molecular profile of a real-world cohort of patients with metastatic urothelial carcinoma (mUC) and to evaluate the benefit of next-generation sequencing (NGS) panels in guiding therapy in patients with mUC and the outcomes of DNA-matched treatments recommended by a multidisciplinary molecular tumor board (MMTB). METHODS: This was a single-center analysis of a real-world cohort of adult patients with mUC included in an ongoing trial that aimed to evaluate the clinical utility of NGS for solid tumors. Genomic analysis was performed for each patient, most of them using the Ion Torrent Oncomine Focus Assay. Genomic results were discussed during MMTB meetings. RESULTS: We included 43 patients with mUC treated with platinum-based combinations and immunotherapy. Twenty-five patients (58.1%; 95% CI 43.4-72.9) had at least one tumor pathogenic alteration. The MMTB classified 16 (48.5%) of the 33 tumor pathogenic alterations found in our real-world cohort of mUC patients as ESCAT I, which is the maximum grade of actionability. After excluding patients who were not candidates for targeted therapies, the MMTB provided guidance on matched therapy for seven patients. Among these patients, three achieved a partial response for an overall response rate of 42.9%, a median progression-free survival of 7.3 months (95% CI 6.7-7.9) and a median overall survival of 10.9 months (95% CI 2.4-19.5). CONCLUSIONS: We recommend that all patients with mUC undergo NGS at diagnosis given the high percentage of patients with pathogenic alterations in our real-world cohort and the efficacy data of patients treated with targeted therapies.

3.
World J Microbiol Biotechnol ; 40(9): 260, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967730

RESUMO

This study aimed to isolate and characterize a native strain of Beauveria bassiana, coded as Bv065, showcasing its potential as a biological control agent targeting the palm weevil Dynamis borassi. Originating from a naturally infected D. borassi specimen collected in southwestern Colombia, the fungus underwent molecular identification and was identified as B. bassiana, exhibiting high sequence similarity with known reference strains. The physiological characterization revealed that Bv065 thrived within a temperature range of 25 to 30 °C and a pH range of 6 to 9. Moreover, the key carbon sources that allow optimal growth of the strain were identified through metabolic profiling, including sucrose, D-mannose, and γ-amino-butyric acid. These findings offer strategic insights for scalability and formulation methodologies. Additionally, enzymatic analyses unveiled robust protease activity within Bv065, crucial for catalysing insect cuticle degradation and facilitating host penetration, thus accentuating its entomopathogenic potential. Subsequent evaluations exposed Bv065's pathogenicity against D. borassi, causing significant mortality within nine days of exposure, albeit exhibiting limited effectiveness against Rhynchophorus palmarum. This study underscores the importance of understanding optimal growth conditions and metabolic preferences of B. bassiana strains for developing effective biopesticides. The findings suggest Bv065 as a promising candidate for integrated pest management strategies in neotropical regions, particularly for controlling palm weevil infestations in coconut and peach palm cultivation. Future research avenues include refining mass production methodologies, formulating novel delivery systems, and conducting comprehensive field efficacy trials to unlock the full potential of Bv065 in fostering sustainable pest management practices. Overall, this study contributes to the growing body of knowledge on entomopathogenic fungi and their pivotal role in biological control, offering nuanced perspectives on eco-friendly alternatives to conventional insecticidal interventions.


Assuntos
Beauveria , Controle Biológico de Vetores , Gorgulhos , Beauveria/fisiologia , Beauveria/patogenicidade , Animais , Gorgulhos/microbiologia , Controle Biológico de Vetores/métodos , Colômbia , Filogenia , Temperatura , Concentração de Íons de Hidrogênio
4.
JCI Insight ; 9(16)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39024554

RESUMO

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy linked to high-risk human papillomavirus (HPV) infection, which develops from precursor lesions like low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions (HGSILs). ASCC incidence varies across populations and poses increased risk for people living with HIV. Our investigation focused on transcriptomic and metatranscriptomic changes from squamous intraepithelial lesions to ASCC. Metatranscriptomic analysis highlighted specific bacterial species (e.g., Fusobacterium nucleatum, Bacteroides fragilis) more prevalent in ASCC than precancerous lesions. These species correlated with gene-encoding enzymes (Acca, glyQ, eno, pgk, por) and oncoproteins (FadA, dnaK), presenting potential diagnostic or treatment markers. Unsupervised transcriptomic analysis identified distinct sample clusters reflecting histological diagnosis, immune infiltrate, HIV/HPV status, and pathway activities, recapitulating anal cancer progression's natural history. Our study unveiled molecular mechanisms in anal cancer progression, aiding in stratifying HGSIL cases based on low or high risk of progression to malignancy.


Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Transcriptoma , Humanos , Neoplasias do Ânus/genética , Neoplasias do Ânus/imunologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/virologia , Neoplasias do Ânus/microbiologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/microbiologia , Carcinoma de Células Escamosas/patologia , Microbiota/imunologia , Masculino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/imunologia , Lesões Intraepiteliais Escamosas/genética , Lesões Intraepiteliais Escamosas/patologia , Lesões Intraepiteliais Escamosas/virologia , Feminino , Progressão da Doença , Pessoa de Meia-Idade , Infecções por HIV/complicações , Infecções por HIV/imunologia
6.
Forensic Sci Int ; 361: 112114, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38941898

RESUMO

We present an assessment of several geospatial layers proposed as models for detecting clandestine graves in Mexico. The analyses were based on adapting the classical ROC curves to geospatial data (gROC) using the fraction of the predicted area instead of the false positive rate. Grave locations were obtained for ten Mexican states that represent the most conflicting regions in Mexico, and 30 layers were computed to represent geospatial models for grave detection. The gROC analysis confirmed that the travel time from urban streets to grave locations was the most critical variable for detecting graves, followed by nighttime light brightness and population density, whereas, contrary to the rationale, a previously proposed visibility index is less correlated with grave locations. We were also able to deduce which variables are most relevant in each state and to determine optimal thresholds for the selected variables.


Assuntos
Sepultamento , México , Humanos , Densidade Demográfica , Curva ROC
7.
Clin Transl Oncol ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869741

RESUMO

This revised consensus statement of the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathological Anatomy (SEAP) updates the recommendations for biomarkers use in the diagnosis and treatment of breast cancer that we first published in 2018. The expert group recommends determining in early breast cancer the estrogen receptor (ER), progesterone receptor (PR), Ki-67, and Human Epidermal growth factor Receptor 2 (HER2), as well as BReast CAncer (BRCA) genes in high-risk HER2-negative breast cancer, to assist prognosis and help in indicating the therapeutic options, including hormone therapy, chemotherapy, anti-HER2 therapy, and other targeted therapies. One of the four available genetic prognostic platforms (Oncotype DX®, MammaPrint®, Prosigna®, or EndoPredict®) may be used in ER-positive patients with early breast cancer to establish a prognostic category and help decide with the patient whether adjuvant treatment may be limited to hormonal therapy. In second-line advanced breast cancer, in addition, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and estrogen receptor 1 (ESR1) should be tested in hormone-sensitive cases, BRCA gene mutations in HER2-negative cancers, and in triple-negative breast cancer (TNBC), programmed cell death-1 ligand (PD-L1). Newer biomarkers and technologies, including tumor-infiltrating lymphocytes (TILs), homologous recombination deficiency (HRD) testing, serine/threonine kinase (AKT) pathway activation, and next-generation sequencing (NGS), are at this point investigational.

8.
Transl Oncol ; 46: 102003, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38838438

RESUMO

METHODS: One-hundred-six patients diagnosed with non-muscle invasive bladder cancer and treated with intravesical BCG were included and divided into two groups, BCG-responsive (n = 47) and -unresponsive (n = 59). Immunohistochemistry was used to evaluate PD-L1 expression and MSI was assessed by a commercial multiplex PCR kit. The mRNA expression profile of 15 immune checkpoints was performed using the nCounter technology. For in silico validation, two distinct cohorts sourced from the Gene Expression Omnibus (GEO) database were used. RESULTS: Among the 106 patients, only one (<1 %) exhibited MSI instability. PD-L1 expression was present in 9.4 % of cases, and no association was found with BCG-responsive status. We found low gene expression of canonic actionable immune checkpoints PDCD1 (PD-1), CD274 (PD-L1), and CTLA4, while high expression was observed for CD276 (B7-H3), CD47, TNFRSF14, IDO1 and PVR (CD155) genes. High IDO1 expression levels was associated with worst overall survival. The PDCD1, CTLA4 and TNFRSF14 expression levels were associated with BCG responsiveness, whereas TIGIT and CD276 were associated with unresponsiveness. Finally, CD276 was validated in silico cohorts. CONCLUSION: In NMIBC, MSI is rare and PD-L1 expression is present in a small subset of cases. Expression levels of PDCD1, CTLA4, TNFRSF14, TIGIT and CD276 could constitute predictive biomarkers of BCG responsiveness.

9.
Braz J Microbiol ; 55(3): 2293-2312, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38773046

RESUMO

Antibiotic-resistant bacteria causing nosocomial infections pose a significant global health concern. This study focused on examining the lipid profiles of both non-resistant and clinically resistant strains of Staphylococcus aureus (MRSA 1418), E. coli (ESBL 1384), and Acinetobacter 1379. The main aim was to investigate the relationship between lipid profiles, hydrophobicity, and antibiotic resistance so as to identify the pathogenic potential and resistance factors of strains isolated from patients with sepsis and urinary tract infections (UTIs). The research included various tests, such as antimicrobial susceptibility assays following CLSI guidelines, biochemical tests, biofilm assays, and hydrophobicity assays. Additionally, gas chromatography mass spectrometry (GC-MS) and GC-Flame Ionization Detector (GC-FID) analysis were used for lipid profiling and composition. The clinically isolated resistant strains (MRSA-1418, ESBL-1384, and Acinetobacter 1379) demonstrated resistance phenotypes of 81.80%, 27.6%, and 63.6%, respectively, with a multiple antibiotic resistance index of 0.81, 0.27, and 0.63. Notably, the MRSA-1418 strain, which exhibited resistance, showed significantly higher levels of hemolysin, cell surface hydrophobicity, biofilm index, and a self-aggregative phenotype compared to the non-resistant strains. Gene expression analysis using quantitative real-time PCR (qPCR). Indicated elevated expression levels of intercellular adhesion biofilm-related genes (icaA, icaC, and icaD) in MRSA-1418 (pgaA, pgaC, and pgaB) and Acinetobacter 1379 after 24 h compared to non-resistant strains. Scanning electron microscopy (SEM) was employed for structural investigation. These findings provide valuable insights into the role of biofilms in antibiotic resistance and suggest potential target pathways for combating antibiotic-resistant bacteria.


Assuntos
Acinetobacter , Antibacterianos , Biofilmes , Escherichia coli , Testes de Sensibilidade Microbiana , Humanos , Antibacterianos/farmacologia , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Acinetobacter/genética , Acinetobacter/efeitos dos fármacos , Acinetobacter/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Fenótipo , Infecções Estafilocócicas/microbiologia , Infecções por Acinetobacter/microbiologia , Farmacorresistência Bacteriana Múltipla/genética , Farmacorresistência Bacteriana
10.
Biol Res ; 57(1): 26, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735981

RESUMO

BACKGROUND: Vitamin C (ascorbate) is a water-soluble antioxidant and an important cofactor for various biosynthetic and regulatory enzymes. Mice can synthesize vitamin C thanks to the key enzyme gulonolactone oxidase (Gulo) unlike humans. In the current investigation, we used Gulo-/- mice, which cannot synthesize their own ascorbate to determine the impact of this vitamin on both the transcriptomics and proteomics profiles in the whole liver. The study included Gulo-/- mouse groups treated with either sub-optimal or optimal ascorbate concentrations in drinking water. Liver tissues of females and males were collected at the age of four months and divided for transcriptomics and proteomics analysis. Immunoblotting, quantitative RT-PCR, and polysome profiling experiments were also conducted to complement our combined omics studies. RESULTS: Principal component analyses revealed distinctive differences in the mRNA and protein profiles as a function of sex between all the mouse cohorts. Despite such sexual dimorphism, Spearman analyses of transcriptomics data from females and males revealed correlations of hepatic ascorbate levels with transcripts encoding a wide array of biological processes involved in glucose and lipid metabolisms as well as in the acute-phase immune response. Moreover, integration of the proteomics data showed that ascorbate modulates the abundance of various enzymes involved in lipid, xenobiotic, organic acid, acetyl-CoA, and steroid metabolism mainly at the transcriptional level, especially in females. However, several proteins of the mitochondrial complex III significantly correlated with ascorbate concentrations in both males and females unlike their corresponding transcripts. Finally, poly(ribo)some profiling did not reveal significant enrichment difference for these mitochondrial complex III mRNAs between Gulo-/- mice treated with sub-optimal and optimal ascorbate levels. CONCLUSIONS: Thus, the abundance of several subunits of the mitochondrial complex III are regulated by ascorbate at the post-transcriptional levels. Our extensive omics analyses provide a novel resource of altered gene expression patterns at the transcriptional and post-transcriptional levels under ascorbate deficiency.


Assuntos
Ácido Ascórbico , Fígado , Proteômica , Animais , Ácido Ascórbico/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Feminino , Masculino , Camundongos , L-Gulonolactona Oxidase/genética , L-Gulonolactona Oxidase/metabolismo , Perfilação da Expressão Gênica , Transcriptoma , Análise de Componente Principal , Antioxidantes/metabolismo
11.
J Forensic Sci ; 69(4): 1198-1211, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38691107

RESUMO

The illegal drug market is constantly evolving, with new drugs being created and existing ones being modified. Adulterants are often added to the mix, and the primary substance may be secretly replaced by a new one. Once-known tablets can now be vastly different from what they are sold as, all due to the pursuit of profit and evasion of current drug regulations. These alterations in drug composition pose a threat to society, as their effects are still not well understood. Therefore, it is crucial for police intelligence and public health development to obtain the chemical profiles of illicit drugs. This study presents the chemical fingerprinting of ecstasy tablets seized in the state of Rio de Janeiro (Brazil) between 2012 and 2021. The tablet samples were weighed, extracted, diluted with methanol, and acidified before analysis using gas chromatography high-resolution mass spectrometry and attenuated total reflection Fourier transform infrared spectroscopy. The major constituents found were MDMA and clobenzorex, with fewer occurrences of MDA, MDEA, and 2C-B. The results also indicate that the occurrence of mega-events in the study location impacted the chemical fingerprints of ecstasy. A total of 27 combinations of cutting agents, including caffeine, ephedrine, and anesthetics, were identified. Samples composed of clobenzorex were observed throughout the evaluated period in areas near highways, suggesting that this product is mainly used by truck drivers. These findings can help police intelligence units anticipate the behavior of the illicit market during major events, identify traffic routes, and support public health initiatives.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Alucinógenos , Drogas Ilícitas , N-Metil-3,4-Metilenodioxianfetamina , Brasil , N-Metil-3,4-Metilenodioxianfetamina/análise , Humanos , Drogas Ilícitas/química , Drogas Ilícitas/análise , Alucinógenos/análise , Alucinógenos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Contaminação de Medicamentos , Tráfico de Drogas
12.
Oncologist ; 29(7): 554-559, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38761380

RESUMO

Genomic profiling and other new technologies have increased the volume and complexity of information available for guiding clinical decision-making in precision oncology. Consequently, there is a need for multidisciplinary expert teams, in the form of molecular tumor boards (MTBs), who can translate this information into a therapeutic plan, including matching patients to suitable clinical trials. Virtual MTBs (vMTBs) can help to overcome many of the challenges associated with in-person MTBs, such as limited time availability, access to appropriate experts or datasets, or interactions between institutions. However, real-world experience from vMTBs is lacking. Here, we describe oncologists' vMTB experiences and the value of working with multicenter and/or multinational vMTBs. We also address knowledge gaps and barriers that could affect the implementation of vMTBs in routine clinical practice. Case studies from Argentina, Turkey, and Portugal illustrate the value of informed clinical decision-making by vMTBs, including expansion of therapeutic options for patients, faster time to treatment, and the resulting improvement in patient outcomes or impact of vMTB discussions on patients. With the uptake of comprehensive genomic profiling and the evolution of some cancers now being conceptualized as a collection of rare diseases with small patient populations based on molecular profiling, the importance of MTBs has increased in modern cancer management. However, an adjustment in clinical decision-making by healthcare professionals is required and evidence of the added value of vMTBs is lacking. Existing vMTBs and recommendations from participating oncologists could point toward a structured evaluation and analysis of this new platform.


Assuntos
Tomada de Decisão Clínica , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão/métodos
13.
J Proteome Res ; 23(8): 3108-3123, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38648199

RESUMO

The expansion of agriculture and the need for sustainable practices drives breeders to develop plant varieties better adapted to abiotic stress such as nutrient deficiency, which negatively impacts yields. Phosphorus (P) is crucial for photosynthesis and plant growth, but its availability in the soil is often limited, hampering crop development. In this study, we examined the response of two popcorn inbred lines, L80 and P7, which have been characterized previously as P-use inefficient and P-use efficient, respectively, under low (stress) and high P (control) availability. Physiological measurements, proteomic analysis, and metabolite assays were performed to unravel the physiological and molecular responses associated with the efficient use of P in popcorn. We observed significant differences in protein abundances in response to the P supply between the two inbred lines. A total of 421 differentially expressed proteins (DEPs) were observed in L80 and 436 DEPs in P7. These proteins were involved in photosynthesis, protein biosynthesis, biosynthesis of secondary metabolites, and energy metabolism. In addition, flavonoids accumulated in higher abundance in P7. Our results help us understand the major components of P utilization in popcorn, providing new insights for popcorn molecular breeding programs.


Assuntos
Fósforo , Fotossíntese , Proteínas de Plantas , Proteômica , Zea mays , Fósforo/metabolismo , Zea mays/metabolismo , Zea mays/genética , Zea mays/crescimento & desenvolvimento , Proteômica/métodos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Flavonoides/metabolismo , Proteoma/metabolismo
14.
15.
Braz J Microbiol ; 55(2): 1465-1476, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38662153

RESUMO

Due to their distinctive physicochemical characteristics, hot springs are extremely important. The whole genome metagenomic sequencing technology can be utilized to analyze the diverse microbial community that thrives in this habitat due to the particular selection pressure that prevails there. The current investigation emphasizes on culture-independent metagenomic study of the Panamik hot spring and its nearby areas from Ladakh, India. Based on different diversity indices, sequence analysis of the soil reservoir showed higher species richness and diversity in comparison to water and sediment samples. The mineral content and various physicochemical pameters like temperature, pH had an impact on the composition of the microbial community of the geothermal springs. The phyla Proteobacteria, Cyanobacteria, Bacteroidetes, Actinobacter, Firmicutes, and Verrucomicrobia in bacterial domain dominate the thermos-alkaline spring at Panamik in different concentrations. Economically significant microbes from the genera Actinobacter, Thermosynechoccus, Candidatus Solibacter, Chthoniobacter, Synechoccus, Pseudomonas and Sphingomonas, were prevalent in hot spring. In the archaeal domain, the most dominant phylum and genera were Euryarchaeota and Thermococcus in all the samples. Further, the most abundant species were Methanosarcina barkeri, Nitrospumilus maritimus and Methanosarcina acetivorans. The present study which only examined one of the several thermal springs present in the Himalayan geothermal area, should be regarded as a preliminary investigation of the microbiota that live in the hot springs on these remote areas. These findings suggest that further investigations should be undertaken to characterize the ecosystems of the Panamik hot spring, which serve as a repository for unidentified microbial lineages.


Assuntos
Archaea , Bactérias , Sequenciamento de Nucleotídeos em Larga Escala , Fontes Termais , Metagenômica , Microbiota , Fontes Termais/microbiologia , Índia , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Archaea/genética , Archaea/classificação , Archaea/isolamento & purificação , Filogenia , Biodiversidade
16.
Nat Prod Res ; : 1-6, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38516734

RESUMO

Pseudomonas aeruginosa is a well-known pathogen for its rapid development of multi-drug antibiotic resistance. This pathogen is responsible for numerous human diseases, particularly affecting immunocompromised and elderly patients. Hence, discovering novel therapeutics has become necessary in the fight against antimicrobial resistance. This study is focused on evaluating the potential inhibitory activity of eleven phytocompounds from Azadirachta indica against the nucleotide-binding site of the FtsZ protein of P. aeruginosa through a cheminformatics approach. FtsZ is an indispensable and highly conserved protein in prokaryotic cell division. Docking studies revealed favourable binding energies (ΔG= - 8.3 to - 5.4 kcal/mol) for all selected phytoconstituents. Finally, we selected Nimbiol (CID 11119228), as a lead compound, exhibiting a binding energy (ΔG= -7.8 kcal/mol) for the target. Based on our findings, Nimbiol shows potential as an anti-FtsZ compound, making it a promising candidate for further in vitro and in vivo investigations to assess its antimicrobial activity.

17.
Vaccines (Basel) ; 12(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38543943

RESUMO

Bovine babesiosis, caused by the protozoan Babesia bigemina, is one of the most important hemoparasite diseases of cattle in Mexico and the world. An attenuated B. bigemina strain maintained under in vitro culture conditions has been used as a live attenuated vaccine; however, the biological mechanisms involved in attenuation are unknown. The objective of this study was to identify, through a comparative transcriptomics approach, the components of the B. bigemina virulent parasites that are differentially expressed in vivo, as opposed to those expressed by B. bigemina attenuated vaccine parasites when inoculated into naïve cattle. The biological material under study was obtained by inoculating spleen-intact cattle with infected erythrocytes containing either the attenuated strain or a virulent field strain. After RNA extraction, transcriptomic analysis (RNA-seq) was performed, followed by bioinformatic Differential Expression (DE) analysis and Gene Ontology (GO) term enrichment. The high-throughput sequencing results obtained by analyzing three biological replicates for each parasite strain ranged from 9,504,000 to 9,656,000, and 13,400,000 to 15,750,000 reads for the B. bigemina attenuated and virulent strains, respectively. At least 519 differentially expressed genes were identified in the analyzed strains. In addition, GO analysis revealed both similarities and differences across the three categories: cellular components, biological processes, and molecular functions. The attenuated strain of B. bigemina derived from in vitro culture presents global transcriptomic changes when compared to the virulent strain. Moreover, the obtained data provide insights into the potential molecular mechanisms associated with the attenuation or pathogenicity of each analyzed strain, offering molecular markers that might be associated with virulence or potential vaccine candidates.

18.
Biochim Biophys Acta Bioenerg ; 1865(2): 149035, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38360260

RESUMO

Rhodotorula mucilaginosa survives extreme conditions through several mechanisms, among them its carotenoid production and its branched mitochondrial respiratory chain (RC). Here, the branched RC composition was analyzed by biochemical and complexome profiling approaches. Expression of the different RC components varied depending on the growth phase and the carbon source present in the medium. R. mucilaginosa RC is constituted by all four orthodox respiratory complexes (CI to CIV) plus several alternative oxidoreductases, in particular two type-II NADH dehydrogenases (NDH2) and one alternative oxidase (AOX). Unlike others, in this yeast the activities of the orthodox and alternative respiratory complexes decreased in the stationary phase. We propose that the branched RC adaptability is an important factor for survival in extreme environmental conditions; thus, contributing to the exceptional resilience of R. mucilaginosa.


Assuntos
Extremófilos , Rhodotorula , Transporte de Elétrons , Rhodotorula/química , Rhodotorula/metabolismo , Membranas Mitocondriais/metabolismo
19.
Food Res Int ; 178: 113796, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309859

RESUMO

The habanero pepper (Capsicum chinense) is a prominent spicy fruit integral to the historical, social, cultural, and economic fabric of the Yucatan peninsula in Mexico. This study leverages the power of 1H NMR spectroscopy coupled with machine learning algorithms to dissect the metabolomic profile of eleven C. chinense cultivars, including those grown by INIFAP (Habanero-Jaguar, Antillano-HRA 1-1, Antillano-HRA 7-1, Habanero-HAm-18A, Habanero-HC-23C, and Jolokia-NJolokia-22) and commercial hybrids (Habanero-Rey Votán, Habanero-Kabal, Balam, USAPR10117, and Rey Pakal). A total of fifty metabolites, encompassing sugars, amino acids, short-chain organic acids, and nucleosides, were identified from the 1H NMR spectra. The optimized machine learning model proficiently predicted the similarity percentage between the INIFAP-grown cultivars and commercial hybrids, thereby facilitating a comprehensive comparison. Biomarkers unique to each cultivar were delineated, revealing that the Habanero-Rey Votán cultivar is characterized by the highest concentration of sugars. In contrast, the Balam cultivar is rich in amino acids and short-chain organic acids, sharing a similar metabolomic profile with the Jolokia-NJolokia-22 cultivar. The findings of this study underscore the efficacy and reliability of NMR-based metabolomics as a robust tool for differentiating C. chinense cultivars based on their intricate chemical profiles. This approach not only contributes to the scientific understanding of the metabolomic diversity among habanero peppers but also holds potential implications for food science, agriculture, and the culinary arts.


Assuntos
Capsicum , Capsicum/química , Reprodutibilidade dos Testes , Capsaicina , Espectroscopia de Ressonância Magnética , Frutas/química , Aminoácidos/análise , Açúcares/análise
20.
Heliyon ; 10(4): e25542, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38380002

RESUMO

Eight Ribes magellanicum collections from three different places in southern Patagonia were compared for content of different groups of phenolics, antioxidant capacity and inhibition of enzymes related to metabolic syndrome (α-amylase, α-glucosidase and pancreatic lipase). The sample with the highest antioxidant capacity was assessed for glutathione (GSH) synthesis stimulation in human gastric adenocarcinoma (AGS) cells. The chemical profile was determined by high performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) and the main phenolics were quantified. The samples from Navarino Island and Reserva Nacional Magallanes showed higher content of anthocyanins and caffeoylquinic acid, with better activity towards α-glucosidase and antioxidant capacity. A sample from Omora (Navarino Island), significantly increased intracellular GSH content in AGS cells. Some 70 compounds were identified in the fruit extracts by HPLC-MS/MS. The glucoside and rutinoside from delphinidin and cyanidin and 3-caffeoylquinic acid were the main compounds. Different chemical profiles were found according to the collection places.

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