Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 835
Filtrar
1.
Biochim Biophys Acta Bioenerg ; : 149486, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38986826

RESUMO

The persistent growth of cancer cells is underscored by complex metabolic reprogramming, with mitochondria playing a key role in the transition to aerobic glycolysis and representing new therapeutic targets. Mitochondrial uncoupling protein 2 (UCP2) has attracted interest because of its abundance in rapidly proliferating cells, including cancer cells, and its involvement in cellular metabolism. However, the specific contributions of UCP2 to cancer biology remain poorly defined. Our investigation of UCP2 expression in various human and mouse cancer cell lines aimed to elucidate its links to metabolic states, proliferation, and adaptation to environmental stresses such as hypoxia and nutrient deprivation. We observed significant variability in UCP2 expression across cancer types, with no direct correlation to their metabolic activity or proliferation rates. UCP2 abundance was also differentially affected by nutrient availability in different cancer cells, but UCP2 was generally downregulated under hypoxia. These findings challenge the notion that UCP2 is a marker of malignant potential and suggest its more complex involvement in the metabolic landscape of cancer.

2.
Bol. latinoam. Caribe plantas med. aromát ; 23(4): 568-576, jul. 2024. ilus
Artigo em Espanhol | LILACS | ID: biblio-1538065

RESUMO

This study aimed to determine the repellent and insecticidal activity of four essential oils (EOs) from plants collected in the Chocó rain forest, Colombia, against T. castaneum . Conventional hydrodistillation was used to obtain the EOs. The repellent and insecticidal activities were evaluated by the preference area and gas dispersion methods, espectively. Statistical differences (p<0.05) were determined by applying a student's t-test. EOs of Siparuna guianensis, S. conica, Piper marginatum, and Nectandra acutifolia showed excellent repellent properties as the main findings, highlighting S. conicaEO with 84% repellency (1-hµL/cm2), while P. marginatum showed to be bioactive to the dose of 500 µL/mL (72 h), inducing mortality of 100% of the exposed population. In conclusion, the results evidenced the repellent properties of the EOs evaluated against T. castaneum , which allows us to conclude that these plant species are potential natural sources producing bio-repellents that contribute to the integrated control of T. castaneum.


Se evaluaron cuatro aceites esenciales (AEs) de plantas recolectadas en la selva pluvial del Chocó, Colombia, para determinar su actividad repelente e insecticida contra T. castaneum. Los AEs fueron obtenidos por hidrodestilación convencional. Las actividades repelentes e insecticidas se evaluaron por los métodos de área de preferencia y dispersión de gas, respectivamente. Las diferencias significativas (p<0,05) fueron determinadas aplicando una prueba t de student. Los AEs de Siparuna guianensis, S. conica, Piper marginatum y Nectandra acutifolia mostraron excelentes propiedades repelentes, destacando el AE de S. conicacon un 84% de repelencia (1µL/cm2), mientras que el AE de P. marginatummostró ser bioactivo a la dosis de 500 µL/mL (72 h) al inducir la mortalidad del 100% de la población expuesta. Se concluye que estas especies de plantas son fuentes naturales potencialmente viables para la producción de biorepelentes que contribuyan en el control integrado de T. castaneum.


Assuntos
Tribolium/efeitos dos fármacos , Óleos Voláteis/farmacologia , Inseticidas/farmacologia , Colômbia , Repelentes de Insetos/farmacologia
3.
ACS Appl Mater Interfaces ; 16(24): 30847-30859, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38853353

RESUMO

Antibacterial formulations based on zinc oxide nanoparticles (ZnO NPs) are widely used for antibiotic replacement in veterinary medicine and animal nutrition. However, the undesired environmental impact of ZnO NPs triggers a search for alternative, environmentally safer solutions. Here, we show that Zn2+ in its ionic form is a more eco-friendly antibacterial, and its biocidal action rivals that of ZnO NPs (<100 nm size), with a minimal biocidal concentration being 41(82) µg mL-1 vs 5 µg mL-1 of ZnO NPs, as determined for 103(106) CFU mL-1 E. coli. We demonstrate that the biocidal activity of Zn2+ ions is primarily associated with their uptake by E. coli and spontaneous in vivo transformation into insoluble ZnO nanocomposites at an internal bacterial pH of 7.7. Formed in vivo nanocomposite then damages E. coli membrane and intracellular components from the inside, by forming insoluble biocomposites, whose formation can also trigger ZnO characteristic reactions damaging the cells (e.g., by generation of high-potential reactive oxygen species). Our study defines a special route in which Zn2+ metal ions induce the death of bacterial cells, which might be common to other metal ions capable of forming semiconductor oxides and insoluble hydroxides at a slightly alkaline intracellular pH of some bacteria.


Assuntos
Antibacterianos , Escherichia coli , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Zinco/química , Zinco/farmacologia , Íons/química , Testes de Sensibilidade Microbiana , Espécies Reativas de Oxigênio/metabolismo , Concentração de Íons de Hidrogênio , Nanocompostos/química
4.
Front Biosci (Landmark Ed) ; 29(6): 218, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38940042

RESUMO

Mitochondrial DNA (mtDNA) is located in the mitochondrial matrix, in close proximity to major sources of reactive oxygen species (ROS) in the cell. This makes mtDNA one of the most susceptible components to damage in the cell. The nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway is an important cytoprotective mechanism. It is well-studied and described that Nrf2 can regulate the expression of mitochondrial-targeted antioxidant systems in the cell, indirectly protecting mtDNA from damage. However, the Nrf2/ARE pathway can also directly impact on the mtDNA repair processes. In this review, we summarize the existing data on the impact of Nrf2 on mtDNA repair, primarily base excision repair (BER), as it is considered the main repair pathway for the mitochondrial genome. We explore the crosstalk between Nrf2/ARE, BRCA1, and p53 signaling pathways in their involvement in maintaining mtDNA integrity. The role of other repair mechanisms in correcting mismatched bases and double-strand breaks is discussed. Additionally, the review addresses the role of Nrf2 in the repair of noncanonical bases, which contribute to an increased number of mutations in mtDNA and can contaminate the nucleotide pool.


Assuntos
Elementos de Resposta Antioxidante , Reparo do DNA , DNA Mitocondrial , Fator 2 Relacionado a NF-E2 , Transdução de Sinais , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Humanos , Elementos de Resposta Antioxidante/genética , Animais , Proteína BRCA1/metabolismo , Proteína BRCA1/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Dano ao DNA
5.
Appl Environ Microbiol ; 90(6): e0076024, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38775579

RESUMO

Motile plant-associated bacteria use chemotaxis and dedicated chemoreceptors to navigate gradients in their surroundings and to colonize host plant surfaces. Here, we characterize a chemoreceptor that we named Tlp2 in the soil alphaproteobacterium Azospirillum brasilense. We show that the Tlp2 ligand-binding domain is related to the 4-helix bundle family and is conserved in chemoreceptors found in the genomes of many soil- and sediment-dwelling alphaproteobacteria. The promoter of tlp2 is regulated in an NtrC- and RpoN-dependent manner and is most upregulated under conditions of nitrogen fixation or in the presence of nitrate. Using fluorescently tagged Tlp2 (Tlp2-YFP), we show that this chemoreceptor is present in low abundance in chemotaxis-signaling clusters and is prone to degradation. We also obtained evidence that the presence of ammonium rapidly disrupts Tlp2-YFP localization. Behavioral experiments using a strain lacking Tlp2 and variants of Tlp2 lacking conserved arginine residues suggest that Tlp2 mediates chemotaxis in gradients of nitrate and nitrite, with the R159 residue being essential for Tlp2 function. We also provide evidence that Tlp2 is essential for root surface colonization of some plants (teff, red clover, and cowpea) but not others (wheat, sorghum, alfalfa, and pea). These results highlight the selective role of nitrate sensing and chemotaxis in plant root surface colonization and illustrate the relative contribution of chemoreceptors to chemotaxis and root surface colonization.IMPORTANCEBacterial chemotaxis mediates host-microbe associations, including the association of beneficial bacteria with the roots of host plants. Dedicated chemoreceptors specify sensory preferences during chemotaxis. Here, we show that a chemoreceptor mediating chemotaxis to nitrate is important in the beneficial soil bacterium colonization of some but not all plant hosts tested. Nitrate is the preferred nitrogen source for plant nutrition, and plants sense and tightly control nitrate transport, resulting in varying nitrate uptake rates depending on the plant and its physiological state. Nitrate is thus a limiting nutrient in the rhizosphere. Chemotaxis and dedicated chemoreceptors for nitrate likely provide motile bacteria with a competitive advantage to access this nutrient in the rhizosphere.


Assuntos
Azospirillum brasilense , Proteínas de Bactérias , Quimiotaxia , Nitratos , Raízes de Plantas , Azospirillum brasilense/genética , Azospirillum brasilense/metabolismo , Azospirillum brasilense/fisiologia , Nitratos/metabolismo , Raízes de Plantas/microbiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
6.
Rofo ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740063

RESUMO

Ultrasound is a powerful technique in pediatric imaging and musculoskeletal (MSK) imaging in many specific clinical scenarios. This article will feature some common and less common spot diagnoses in pediatric musculoskeletal ultrasound.Cases were collected by members of the Educational Committee of the ESSR (European Society of musculoSkeletal Radiology) and the Pediatric Subcommittee of the ESSR with expertise in musculoskeletal ultrasound.Fifteen clinical entities are discussed based on the features that allow diagnosis by ultrasound.Clinical history, location, and ultrasound appearance are the keys to spot diagnoses when performing pediatric musculoskeletal ultrasound. · Ultrasound in pediatric musculoskeletal imaging can achieve a diagnosis in specific clinical settings.. · Clinical history, location, and ultrasound appearance are keys to spot diagnoses.. · Knowledge of spot diagnoses in pediatric musculoskeletal ultrasound facilitates daily clinical practice..

7.
AJR Am J Roentgenol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775432

RESUMO

Peripheral nerve imaging provides information that can be critical to the diagnosis, staging, and management of peripheral neuropathies. MRI and ultrasound are the imaging modalities of choice for clinical evaluation of the peripheral nerves given their high soft tissue contrast and high resolution, respectively. This AJR Expert Panel Narrative Review describes MRI- and ultrasound-based techniques for peripheral nerve imaging; highlights considerations for imaging in the settings of trauma, entrapment syndromes, diffuse inflammatory neuropathies, and tumor; and discusses image-guided nerve interventions, focusing on nerve blocks and ablation.

8.
Acta Physiol (Oxf) ; 240(6): e14143, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38577966

RESUMO

AIMS: Metabolic reprogramming in cancer cells has been linked to mitochondrial dysfunction. The mitochondrial 2-oxoglutarate/malate carrier (OGC) has been suggested as a potential target for preventing cancer progression. Although OGC is involved in the malate/aspartate shuttle, its exact role in cancer metabolism remains unclear. We aimed to investigate whether OGC may contribute to the alteration of mitochondrial inner membrane potential by transporting protons. METHODS: The expression of OGC in mouse tissues and cancer cells was investigated by PCR and Western blot analysis. The proton transport function of recombinant murine OGC was evaluated by measuring the membrane conductance (Gm) of planar lipid bilayers. OGC-mediated substrate transport was measured in proteoliposomes using 14C-malate. RESULTS: OGC increases proton Gm only in the presence of natural (long-chain fatty acids, FA) or chemical (2,4-dinitrophenol) protonophores. The increase in OGC activity directly correlates with the increase in the number of unsaturated bonds of the FA. OGC substrates and inhibitors compete with FA for the same protein binding site. Arginine 90 was identified as a critical amino acid for the binding of FA, ATP, 2-oxoglutarate, and malate, which is a first step towards understanding the OGC-mediated proton transport mechanism. CONCLUSION: OGC extends the family of mitochondrial transporters with dual function: (i) metabolite transport and (ii) proton transport facilitated in the presence of protonophores. Elucidating the contribution of OGC to uncoupling may be essential for the design of targeted drugs for the treatment of cancer and other metabolic diseases.


Assuntos
2,4-Dinitrofenol , Ácidos Graxos , Animais , 2,4-Dinitrofenol/farmacologia , Camundongos , Ácidos Graxos/metabolismo , Humanos , Malatos/metabolismo , Mitocôndrias/metabolismo , Transporte de Íons/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Prótons , Ácidos Cetoglutáricos/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Proteínas de Membrana Transportadoras
9.
Front Neurosci ; 18: 1348999, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660226

RESUMO

Introduction: The plasticity of the nervous system plays a crucial role in shaping adaptive neural circuits and corresponding animal behaviors. Understanding the mechanisms underlying neural plasticity during development and its implications for animal adaptation constitutes an intriguing area of research. Sea urchin larvae offer a fascinating subject for investigation due to their remarkable evolutionary and ecological diversity, as well as their diverse developmental forms and behavioral patterns. Materials and methods: We conducted immunochemical and histochemical analyses of serotonin-containing (5-HT-neurons) and dopamine-containing (DA-positive) neurons to study their developmental dynamics in two sea urchin species: Mesocentrotus nudus and Paracentrotus lividus. Our approach involved detailed visualization of 5-HT- and DA-positive neurons at gastrula-pluteus stages, coupled with behavioral assays to assess larval upward and downward swimming in the water column, with a focus on correlating cell numbers with larval swimming ability. Results: The study reveals a heterochronic polymorphism in the appearance of post-oral DA-positive neuroendocrine cells and confirms the stable differentiation pattern of apical 5-HT neurons in larvae of both species. Notably, larvae of the same age exhibit a two- to four-fold difference in DA neurons. An increased number of DA neurons and application of dopamine positively correlate with larval downward swimming, whereas 5-HT-neurons and serotonin application induce upward swimming. The ratio of 5-HT/DA neurons determines the stage-dependent vertical distribution of larvae within the water column. Consequently, larvae from the same generation with a higher number of DA-positive neurons tend to remain at the bottom compared to those with fewer DA-positive neurons. Discussion: The proportion of 5-HT and DA neurons within larvae of the same age underlies the different potentials of individuals for upward and downward swimming. A proposed model illustrates how coordination in humoral regulation, based on heterochrony in DA-positive neuroendocrine cell differentiation, influences larval behavior, mitigates competition between siblings, and ensures optimal population expansion. The study explores the evolutionary and ecological implications of these neuroendocrine adaptations in marine species.

10.
J Clin Med ; 13(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38610812

RESUMO

Over the past two decades, the prognosis in adolescents and young adults (AYAs) diagnosed with acute myeloid leukemia (AML) has significantly improved. The standard intensive cytotoxic treatment approach for AYAs with AML, consisting of induction chemotherapy with anthracycline/cytarabine combination followed by consolidation chemotherapy or stem cell transplantation, has lately been shifting toward novel targeted therapies, mostly in the fields of clinical trials. One of the most recent advances in treating AML is the combination of the B-cell lymphoma 2 (Bcl-2) inhibitor venetoclax with hypomethylating agents, which has been studied in elderly populations and was approved by the Food and Drug Administration (FDA) for patients over 75 years of age or patients excluded from intensive chemotherapy induction schemas due to comorbidities. Regarding the AYA population, venetoclax combination therapy could be a therapeutic option for patients with refractory/relapsed (R/R) AML, although data from real-world studies are currently limited. Venetoclax is frequently used by AYAs diagnosed with advanced hematologic malignancies, mainly acute lymphoblastic leukemia and myelodysplastic syndromes, as a salvage therapeutic option with considerable efficacy and safety. Herein, we aim to summarize the evidence obtained from clinical trials and observational studies on venetoclax use in AYAs with AML. Based on the available evidence, venetoclax is a safe and effective therapeutic option for R/R AML AYA patients. However, further research in larger cohorts is needed to confirm these data, establishing the benefits of a venetoclax-based regimen for this special population.

11.
Front Neurosci ; 18: 1346610, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638695

RESUMO

Introduction: The remarkable diversity observed in the structure and development of the molluscan nervous system raises intriguing questions regarding the molecular mechanisms underlying neurogenesis in Mollusca. The expression of SoxB family transcription factors plays a pivotal role in neuronal development, thereby offering valuable insights into the strategies of neurogenesis. Methods: In this study, we conducted gene expression analysis focusing on SoxB-family transcription factors during early neurogenesis in the gastropod Lymnaea stagnalis. We employed a combination of hybridization chain reaction in situ hybridization (HCR-ISH), immunocytochemistry, confocal microscopy, and cell proliferation assays to investigate the spatial and temporal expression patterns of LsSoxB1 and LsSoxB2 from the gastrula stage to hatching, with particular attention to the formation of central ring ganglia. Results: Our investigation reveals that LsSoxB1 demonstrates expanded ectodermal expression from the gastrula to the hatching stage, whereas expression of LsSoxB2 in the ectoderm ceases by the veliger stage. LsSoxB1 is expressed in the ectoderm of the head, foot, and visceral complex, as well as in forming ganglia and sensory cells. Conversely, LsSoxB2 is mostly restricted to the subepithelial layer and forming ganglia cells during metamorphosis. Proliferation assays indicate a uniform distribution of dividing cells in the ectoderm across all developmental stages, suggesting the absence of distinct neurogenic zones with increased proliferation in gastropods. Discussion: Our findings reveal a spatially and temporally extended pattern of SoxB1 expression in a gastropod representative compared to other lophotrochozoan species. This prolonged and widespread expression of SoxB genes may be interpreted as a form of transcriptional neoteny, representing a preadaptation to prolonged neurogenesis. Consequently, it could contribute to the diversification of nervous systems in gastropods and lead to an increase in the complexity of the central nervous system in Mollusca.

12.
Pediatrics ; 153(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38548700

RESUMO

BACKGROUND AND OBJECTIVES: The messenger RNA (mRNA)-based coronavirus disease 2019 vaccines approved for use in children <5 years of age have different antigen doses and administration schedules that could affect vaccine immunogenicity and effectiveness. We sought to compare the strength and breadth of serum binding and neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicited by monovalent mRNA-based coronavirus disease 2019 vaccines in young children. METHODS: We conducted a prospective cohort study of children 6 months to 4 years of age who completed primary series vaccination with monovalent mRNA-1273 or BNT162b2 vaccines. Serum was collected 1 month after primary vaccine series completion for the measurement of SARS-CoV-2-specific humoral immune responses, including antibody binding responses to Spike proteins from an ancestral strain (D614G) and major variants of SARS-CoV-2 and antibody neutralizing activity against D614G and Omicron subvariants (BA.1, BA.4/5). RESULTS: Of 75 participants, 40 (53%) received mRNA-1273 and 35 (47%) received BNT162b2. Children receiving either primary vaccine series developed robust and broad SARS-CoV-2-specific binding and neutralizing antibodies, including to Omicron subvariants. Children with a previous history of SARS-CoV-2 infection developed significantly higher antibody binding responses and neutralization titers to Omicron subvariants, which is consistent with the occurrence of identified infections during the circulation of Omicron subvariants in the region. CONCLUSIONS: Monovalent mRNA-1273 and BNT162b2 elicited similar antibody responses 1 month after vaccination in young children. In addition, previous infection significantly enhanced the strength of antibody responses to Omicron subvariants. The authors of future studies should evaluate incorporation of these vaccines into the standard childhood immunization schedule.


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162 , COVID-19 , Imunogenicidade da Vacina , Humanos , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Lactente , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Pré-Escolar , Masculino , Anticorpos Neutralizantes/sangue , Estudos Prospectivos , Feminino , Imunogenicidade da Vacina/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Estudos de Coortes , Glicoproteína da Espícula de Coronavírus/imunologia
13.
Proc Natl Acad Sci U S A ; 121(14): e2315586121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38498726

RESUMO

Heparins have been invaluable therapeutic anticoagulant polysaccharides for over a century, whether used as unfractionated heparin or as low molecular weight heparin (LMWH) derivatives. However, heparin production by extraction from animal tissues presents multiple challenges, including the risk of adulteration, contamination, prion and viral impurities, limited supply, insecure supply chain, and significant batch-to-batch variability. The use of animal-derived heparin also raises ethical and religious concerns, as well as carries the risk of transmitting zoonotic diseases. Chemoenzymatic synthesis of animal-free heparin products would offer several advantages, including reliable and scalable production processes, improved purity and consistency, and the ability to produce heparin polysaccharides with molecular weight, structural, and functional properties equivalent to those of the United States Pharmacopeia (USP) heparin, currently only sourced from porcine intestinal mucosa. We report a scalable process for the production of bioengineered heparin that is biologically and compositionally similar to USP heparin. This process relies on enzymes from the heparin biosynthetic pathway, immobilized on an inert support and requires a tailored N-sulfoheparosan with N-sulfo levels similar to those of porcine heparins. We also report the conversion of our bioengineered heparin into a LMWH that is biologically and compositionally similar to USP enoxaparin. Ultimately, we demonstrate major advances to a process to provide a potential clinical and sustainable alternative to porcine-derived heparin products.


Assuntos
Heparina de Baixo Peso Molecular , Heparina , Animais , Suínos , Heparina/metabolismo , Heparina de Baixo Peso Molecular/química , Anticoagulantes/química , Peso Molecular , Contaminação de Medicamentos
14.
Nat Commun ; 15(1): 2175, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467646

RESUMO

In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p < 0.05]. VE differed by residue match vs. mismatch to the vaccine-insert at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20); significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 antibody-epitope escape scores and 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccinee sera. VE against severe-critical COVID-19 was stable across most sequence features but lower against the most distant viruses.


Assuntos
Ad26COVS1 , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Eficácia de Vacinas , Aminoácidos , Anticorpos Antivirais , Anticorpos Neutralizantes
15.
Metabolites ; 14(3)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38535328

RESUMO

The clinical blood metabogram (CBM) was developed to match a tailored analysis of the blood metabolome to the time, cost, and reproducibility constraints of clinical laboratory testing. By analyzing the main blood metabolite groups, CBM offers clinically relevant information about the intake of low-molecular substances into the organism, humoral regulation, liver function, amino acid level, and the lipid and carbohydrate metabolism. The purpose of this work was to investigate the relevance of using the CBM in patients with diabetes mellitus. For this, a CBM was obtained for 18 healthy individuals, 12 individuals with prediabetes, and 64 individuals with type 2 diabetes mellitus, separated into groups according to fasting blood glucose and oral glucose tolerance tests. The results showed that the CBM reveals diabetes-associated metabolic alterations in the blood, including changes in the levels of carbohydrates, ketone bodies, eicosanoids, phospholipids, and amino acids, which are consistent with the scientific data available to date. The CBM enabled the separation of diabetic patients according to their metabolic metabotypes, providing both a general overview of their metabolic alterations and detailing their individual metabolic characteristics. It was concluded that the CBM is a precise and clinically applicable test for assessing an individual's metabolic status in diabetes mellitus for diagnostic and treatment purposes.

16.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474164

RESUMO

The interaction of plants and soil bacteria rhizobia leads to the formation of root nodule symbiosis. The intracellular form of rhizobia, the symbiosomes, are able to perform the nitrogen fixation by converting atmospheric dinitrogen into ammonia, which is available for plants. The symbiosis involves the resource sharing between two partners, but this exchange does not include equivalence, which can lead to resource scarcity and stress responses of one of the partners. In this review, we analyze the possible involvement of the autophagy pathway in the process of the maintenance of the nitrogen-fixing bacteria intracellular colony and the changes in the endomembrane system of the host cell. According to in silico expression analysis, ATG genes of all groups were expressed in the root nodule, and the expression was developmental zone dependent. The analysis of expression of genes involved in the response to carbon or nitrogen deficiency has shown a suboptimal access to sugars and nitrogen in the nodule tissue. The upregulation of several ER stress genes was also detected. Hence, the root nodule cells are under heavy bacterial infection, carbon deprivation, and insufficient nitrogen supply, making nodule cells prone to autophagy. We speculate that the membrane formation around the intracellular rhizobia may be quite similar to the phagophore formation, and the induction of autophagy and ER stress are essential to the success of this process.


Assuntos
Medicago truncatula , Rhizobium , Simbiose/fisiologia , Medicago truncatula/genética , Proteínas de Plantas/genética , Fixação de Nitrogênio/genética , Rhizobium/metabolismo , Autofagia , Nitrogênio/metabolismo , Carbono/metabolismo , Nódulos Radiculares de Plantas/metabolismo
17.
J Pediatr Hematol Oncol ; 46(3): e220-e222, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447071

RESUMO

Acquired thrombotic thrombocytopenic (aTTP) purpura is a life-threatening condition that can lead to devastating thromboembolic events. Recently, caplacizumab has been shown to rapidly restore platelet numbers and reduce the risk of severe end-organ damage when added to plasma exchanges (PEXs) and immunosuppression (IST). Here, we report the outcomes in 3 children with aTTP who were treated with caplacizumab in combination with PEXs and IST. In all 3 patients, platelet count increased to >15,000/mm 3 in 24 h and normalized on day 4, whereas normalization of ADAMTS13 activity >50% and elimination of the inhibitor was achieved after 18 to 89 days. Epistaxis was observed in 2 patients and was the only side effect related to caplacizumab. Caplacizumab is a promising agent for first-line treatment of children with aTTP.


Assuntos
Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Criança , Humanos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Troca Plasmática , Fator de von Willebrand , Terapia de Imunossupressão , Proteína ADAMTS13
18.
Int J Pediatr Otorhinolaryngol ; 178: 111897, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367603

RESUMO

OBJECTIVES: To depict the novel use of steroid-eluting stents in the treatment of choanal atresia (CA) restenosis and subglottic stenosis (SGS). METHODS: A retrospective chart review of three pediatric patients, one with CA and two with SGS, treated with mometasone furoate eluting mini stents (PROPEL) was performed. Patients were evaluated for restenosis and adverse events between one to twelve months postoperatively. RESULTS: Postoperatively, patient one with CA showed no signs of restenosis and required no further intervention. Patient two with SGS demonstrated an open subglottic lumen with no signs of restenosis as well as improved phonation following his planned serial procedures. Post-operatively, patient three with SGS exhibited no restenosis of the subglottic lumen, tolerated intermittent tracheostomy capping, and demonstrated improved phonation. CONCLUSION: In this case series, we outline successful treatments for the management of CA restenosis and SGS with mometasone furoate-eluting stents. To our knowledge, this is the first reported application of this treatment in pediatric patients with CA restenosis and the second reported application in pediatric patients with SGS.


Assuntos
Atresia das Cóanas , Stents Farmacológicos , Humanos , Criança , Constrição Patológica , Estudos Retrospectivos , Atresia das Cóanas/cirurgia , Stents , Furoato de Mometasona , Resultado do Tratamento
19.
Artigo em Inglês | MEDLINE | ID: mdl-38300283

RESUMO

PURPOSE: Utilizing ultrasound for the detection of distal forearm fractures in children presents a potential safe and radiation-free alternative compared to X-ray. METHODS: A systematic review was undertaken to compare the diagnostic accuracy of ultrasound in detecting distal forearm fractures in children with X-ray imaging within the period spanning January 2010 to August 2023. The electronic databases MEDLINE and Cochrane CENTRAL were utilized for data retrieval. The QUADAS-2 tool was employed to assess the quality of the included studies. Subsequent statistical analysis was performed to calculate pooled sensitivity and specificity, positive and negative likelihood ratios, as well as the diagnostic odds ratio. RESULTS: Our meta-analysis included seventeen studies, encompassing a total of 2003 patients, 2546 ultrasound scans, and 1203 fracture cases as identified by the reference test (X-ray). The pooled sensitivity and specificity were 0.96 (95% CI: 0.93-0.98) and 0.96 (95% CI: 0.89-0.98), respectively. The positive likelihood ratio was 13.40 (95% CI: 7.97-21.50), the negative likelihood ratio was 0.06 (95% CI: 0.04-0.1), and the pooled diagnostic odds ratio was 209 (95% CI: 92.20-412.00). Our statistical analysis revealed low heterogeneity within our studied cohort. CONCLUSIONS: Our study indicates that ultrasound exhibits exceptionally high accuracy in the detection of distal forearm fractures in children and adolescents. It can be employed safely to either confirm or rule out a fracture, thus circumventing the need for potentially harmful radiation exposure in this vulnerable population. Future research endeavors should focus on establishing a universally accepted protocol for training and scanning methods to standardize practices and eliminate disparities in diagnostic procedures.

20.
Int J Toxicol ; 43(3): 243-252, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38183303

RESUMO

This work investigated the safety of extracts obtained from plants growing in Colombia, which have previously shown UV-filter/antigenotoxic properties. The compounds in plant extracts obtained by the supercritical fluid (CO2) extraction method were identified using gas chromatography coupled to mass spectrometry (GC/MS) analysis. Cytotoxicity measured as cytotoxic concentration 50% (CC50) and genotoxicity of the plant extracts and some compounds were studied in human fibroblasts using the trypan blue exclusion assay and the Comet assay, respectively. The extracts from Pipper eriopodon and Salvia aratocensis species and the compound trans-ß-caryophyllene were clearly cytotoxic to human fibroblasts. Conversely, Achyrocline satureioides, Chromolaena pellia, and Lippia origanoides extracts were relatively less cytotoxic with CC50 values of 173, 184, and 89 µg/mL, respectively. The C. pellia and L. origanoides extracts produced some degree of DNA breaks at cytotoxic concentrations. The cytotoxicity of the studied compounds was as follows, with lower CC50 values representing the most cytotoxic compounds: resveratrol (91 µM) > pinocembrin (144 µM) > quercetin (222 µM) > titanium dioxide (704 µM). Quercetin was unique among the compounds assayed in being genotoxic to human fibroblasts. Our work indicates that phytochemicals can be cytotoxic and genotoxic, demonstrating the need to establish safe concentrations of these extracts for their potential use in cosmetics.


Assuntos
Sobrevivência Celular , Fibroblastos , Extratos Vegetais , Protetores Solares , Humanos , Protetores Solares/toxicidade , Protetores Solares/química , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Fibroblastos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Salvia/química , Dano ao DNA/efeitos dos fármacos , Células Cultivadas , Lippia/química , Cromatografia Gasosa-Espectrometria de Massas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...