RESUMO
Background/Objectives: Post-COVID-19 condition can manifest through various symptoms such as dyspnea, cognitive disturbances, and fatigue, with mechanisms related to these symptoms, particularly those related to fatigue, still requiring further clarification. Therefore, our aim was to assess the clinical and physiological variables in patients with post-COVID-19 condition and persistent fatigue. Methods: After one year post-COVID-19 infection, the patients underwent a comprehensive evaluation, including a complete blood count, a metabolic panel, complete spirometry, and assessments of dyspnea, quality of life, anxiety and depression, physical capacity, body composition, muscle strength, comorbidities, and medications. The participants were categorized into two groups: G1-fatigue and G2-non-fatigue. Results: Seventy-seven patients (53% female; 55 ± 11.8 years) were included, 37 in G1 and 40 in G2. As for clinical markers and symptoms of illness, in those with persistent fatigue symptoms, a greater sensation of dyspnea [BDI score: 7.5 (6-9) vs. 12 (9-12), p < 0.001; mMRC score: 1 (1-2) vs. 0 (0-1), p = 0.002], worse quality of life [SGRQ total score: 1404 (1007-1897) vs. 497 (274-985); p < 0.001], higher levels of anxiety [HADS-A score: 8 (5-9) vs. 3 (0.5-4); p < 0.001], and a reduction in peripheral and inspiratory muscle strength [handgrip strength: 34 (28-40) vs. 40 (30-46.5) kgf, p = 0.044; MIP: -81 ± 31 vs. -111 ± 33 mmHg, p < 0.001)] were observed. Conclusions: Those with persistent fatigue exhibited a greater sensation of dyspnea, higher levels of anxiety, reduced peripheral and inspiratory muscle strength, and a greater impairment of quality of life. The severity of fatigue was influenced by the worsening quality of life, heightened anxiety levels, and decreased peripheral muscle strength. Additionally, the worse quality of life was associated with a higher sensation of dyspnea, lower muscle strength, and reduced physical capacity.
RESUMO
Mevalonate kinase deficiency (MKD) an orphan drug rare disease affecting humans with different clinical presentations, is still lacking information about its pathogenesis; no animal or cell model mimicking the genetic defect, mutations at MVK gene, and its consequences on the mevalonate pathway is available. Trying to clarify the effects of MVK gene impairment on the mevalonate pathway we used a yeast model, the erg12-d mutant strain Saccharomyces cerevisiae (orthologous of MKV) retaining only 10% of mevalonate kinase (MK) activity, to describe the effects of reduced MK activity on the mevalonate pathway. Since shortage of isoprenoids has been described in MKD, we checked this observation using a physiologic approach: while normally growing on glucose, erg12-d showed growth deficiency in glycerol, a respirable carbon source, that was not rescued by supplementation with non-sterol isoprenoids, such as farnesol, geraniol nor geranylgeraniol, produced by the mevalonate pathway. Erg12-d whole genome expression analysis revealed specific downregulation of RSF2 gene encoding general transcription factor for respiratory genes, explaining the absence of growth on glycerol. Moreover, we observed the upregulation of genes involved in sulphur amino acids biosynthesis that coincided with the increasing in the amount of proteins containing sulfhydryl groups; upregulation of ubiquinone biosynthesis genes was also detected. Our findings demonstrated that the shortage of isoprenoids is not the main mechanism involved in the respiratory deficit and mitochondrial malfunctioning of MK-defective cells, while the scarcity of ubiquinone plays an important role, as already observed in MKD patients.
Assuntos
Deficiência de Mevalonato Quinase/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Respiração/genética , Saccharomyces cerevisiae/genética , Regulação Fúngica da Expressão Gênica , Genoma Fúngico , Humanos , Deficiência de Mevalonato Quinase/metabolismo , Deficiência de Mevalonato Quinase/patologia , Mutação , Fosfotransferases (Aceptor do Grupo Álcool)/deficiência , Saccharomyces cerevisiae/enzimologia , Proteínas de Saccharomyces cerevisiae/genética , Terpenos/metabolismo , Fatores de Transcrição/genética , Ubiquinona/genética , Ubiquinona/metabolismoRESUMO
In fuel ethanol production, recycling of yeast biomass includes treatment of cells with diluted sulphuric acid in order to control bacterial population. However, this strategy might lead to a loss of cell viability, with potential negative consequences to the fermentation yield. In a recent paper we showed that the proteins Slt2 and Hog1 are essential for yeast tolerance to sulphuric acid. As a complement of the aforementioned work, we used DNA microarray technology to search for differentially expressed genes in hog1Δ and slt2Δ deletion mutants after treatment with sulphuric acid. Our results show how Slt2p and Hog1p could coordinate the interplay among protein kinase A (PKA), protein kinase C and high-osmolarity glycerol pathways. Moreover, the SSK22 and KDX1 genes may be part of this network, although their proteins were shown to be non-essential for cell growth/survival at low pH. These proteins might work by enhancing the signal which downregulates the PKA pathway leading to cell cycle arrest, in order to regenerate the integrity of yeast cell wall and cell homeostasis under acid shock.