RESUMO
Organoids are self-organized, three-dimensional structures derived from stem cells that can mimic the structure and physiology of human organs. Patient-specific induced pluripotent stem cells (iPSCs) and 3D organoid model systems allow cells to be analyzed in a controlled environment to simulate the characteristics of a given disease by modeling the underlying pathophysiology. The recent development of 3D cell models has offered the scientific community an exceptionally valuable tool in the study of rare diseases, overcoming the limited availability of biological samples and the limitations of animal models. This review provides an overview of iPSC models and genetic engineering techniques used to develop organoids. In particular, some of the models applied to the study of rare neuronal, muscular and skeletal diseases are described. Furthermore, the limitations and potential of developing new therapeutic approaches are discussed.
Assuntos
Células-Tronco Pluripotentes Induzidas , Doenças Raras , Animais , Humanos , Organoides , Engenharia Genética , MúsculosRESUMO
Accessible SARS-CoV-2-specific immunoassays may inform clinical management in people with HIV, particularly in case of persisting immunodysfunction. We prospectively studied their application in vaccine recipients with HIV, purposely including participants with a history of advanced HIV infection. Participants received one (n = 250), two (n = 249) or three (n = 42) doses of the BNT162b2 vaccine. Adverse events were documented through questionnaires. Sample collection occurred pre-vaccination and a median of 4 weeks post-second dose and 14 weeks post-third dose. Anti-spike and anti-nucleocapsid antibodies were measured with the Roche Elecsys chemiluminescence immunoassays. Neutralising activity was evaluated using the GenScript cPass surrogate virus neutralisation test, following validation against a Plaque Reduction Neutralization Test. T-cell reactivity was assessed with the Roche SARS-CoV-2 IFNγ release assay. Primary vaccination (2 doses) was well tolerated and elicited measurable anti-spike antibodies in 202/206 (98.0%) participants. Anti-spike titres varied widely, influenced by previous SARS-CoV-2 exposure, ethnicity, intravenous drug use, CD4 counts and HIV viremia as independent predictors. A third vaccine dose significantly boosted anti-spike and neutralising responses, reducing variability. Anti-spike titres > 15 U/mL correlated with neutralising activity in 136/144 paired samples (94.4%). Three participants with detectable anti-S antibodies did not develop cPass neutralising responses post-third dose, yet displayed SARS-CoV-2 specific IFNγ responses. SARS-CoV-2 vaccination is well-tolerated and immunogenic in adults with HIV, with responses improving post-third dose. Anti-spike antibodies serve as a reliable indicator of neutralising activity. Discordances between anti-spike and neutralising responses were accompanied by detectable IFN-γ responses, underlining the complexity of the immune response in this population.
Assuntos
COVID-19 , Infecções por HIV , Aranhas , Adulto , Animais , Humanos , SARS-CoV-2 , Vacina BNT162 , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Imunoensaio , Anticorpos , Vacinação , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
Despite intense research towards the understanding of abiotic stress adaptation in tomato, the physiological adjustments and transcriptome modulation induced by combined salt and low nitrate (low N) conditions remain largely unknown. Here, three traditional tomato genotypes were grown under long-term single and combined stresses throughout a complete growth cycle. Physiological, molecular, and growth measurements showed extensive morphophysiological modifications under combined stress compared to the control, and single stress conditions, resulting in the highest penalty in yield and fruit size. The mRNA sequencing performed on both roots and leaves of genotype TRPO0040 indicated that the transcriptomic signature in leaves under combined stress conditions largely overlapped that of the low N treatment, whereas root transcriptomes were highly sensitive to salt stress. Differentially expressed genes were functionally interpreted using GO and KEGG enrichment analysis, which confirmed the stress and the tissue-specific changes. We also disclosed a set of genes underlying the specific response to combined conditions, including ribosome components and nitrate transporters, in leaves, and several genes involved in transport and response to stress in roots. Altogether, our results provide a comprehensive understanding of above- and below-ground physiological and molecular responses of tomato to salt stress and low N treatment, alone or in combination.
RESUMO
Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2 doses of 4-component group B meningococcal vaccine in antiretroviral therapy-treated children with PHIV and healthy controls (HCs). Assessments included the standard human serum bactericidal antibody (hSBA) assay and measurement of IgG titers against capsular group B Neisseria meningitidis antigens (fHbp, NHBA, NadA). The B cell compartment and vaccine-induced antigen-specific (fHbp+) B cells were investigated by flow cytometry, and gene expression was investigated by multiplexed real-time PCR. A good safety and immunogenicity profile was shown in both groups; however, PHIV demonstrated a reduced immunogenicity compared with HCs. Additionally, PHIV showed a reduced frequency of fHbp+ and an altered B cell subset distribution, with higher fHbp+ frequency in activated memory and tissue-like memory B cells. Gene expression analyses on these cells revealed distinct mechanisms between PHIV and HC seroconverters. Overall, these data suggest that PHIV presents a diverse immune signature following vaccination. The impact of such perturbation on long-term maintenance of vaccine-induced immunity should be further evaluated in vulnerable populations, such as people with PHIV.