The main discussion above of the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has focused substantially on the immediate risks and impact on the respiratory system; however, the effects induced to the central nervous system are currently unknown. Some authors have suggested that SARS-CoV-2 infection can dramatically affect brain function and exacerbate neurodegenerative diseases in patients, but the mechanisms have not been entirely described. In this review, we gather information from past and actual studies on coronaviruses that informed neurological dysfunction and brain damage. Then, we analyzed and described the possible mechanisms causative of brain injury after SARS-CoV-2 infection. We proposed that potential routes of SARS-CoV-2 neuro-invasion are determinant factors in the process. We considered that the hematogenous route of infection can directly affect the brain microvascular endothelium cells that integrate the blood-brain barrier and be fundamental in initiation of brain damage. Additionally, activation of the inflammatory response against the infection represents a critical step on injury induction of the brain tissue. Consequently, the virus' ability to infect brain cells and induce the inflammatory response can promote or increase the risk to acquire central nervous system diseases. Here, we contribute to the understanding of the neurological conditions found in patients with SARS-CoV-2 infection and its association with the blood-brain barrier integrity.

MicroRNAs (miRNAs) play an essential role in the development and progression of acute leukemia (AL). miR-24 promotes the survival of hematopoietic cells. However, little is known concerning the function of miR-24 in human AL. The aim of the present study was to investigate the clinical significance of miR-24 expression in AL. miR-24 expression in 147 patients with AL and 100 healthy individuals was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). The results showed that compared with the healthy individuals, the expression of miR-24 in AL patients was significantly higher (p<0.001). In addition, miR-24 was expressed at significantly higher levels in acute myeloid leukemia (AML) patients and at significantly lower levels in acute lymphoblastic leukemia (ALL) (p<0.001). More importantly, Kaplan-Meier analysis showed that AL patients with high miR-24 expression tended to have shorter overall survival (p<0.05). In the multivariate analysis stratified for known prognostic variables, miR-24 was identified as an independent prognostic marker. Our data indicated that miR-24 upregulation was associated with poor prognosis in AL. miR-24 was identified for the first time as an independent marker for predicting the clinical outcome of AL patients.

The Bacilus subtilis genes tpi, pgm, and eno, encoding triose phosphate isomerase, phosphoglycerate mutase (PGM), and enolase, respectively, have been cloned and sequenced. These genes are the last three in a large putative operon coding for glycolytic enzymes; the operon includes pgk (coding for phosphoglycerate kinase) followed by tpi, pgm, and eno. The triose phosphate isomerase and enolase from B. subtilis are extremely similar to those from all other species, both eukaryotic and prokaryotic. However, B. subtilis PGM bears no resemblance to mammalian, fungal, or gram-negative bacterial PGMs, which are dependent on 2,3-diphosphoglycerate (DPG) for activity. Instead, B. subtilis PGM, which is DPG independent, is very similar to a DPG-independent PGM from a plant species but differs from the latter in the absolute requirement of B. subtilis PGM for Mn2 . The cloned pgm gene has been used to direct up to 25-fold overexpression of PGM in Escherichia coli; this should facilitate purification of large amounts of this novel Mn2'-dependent enzyme.Inactivation ofpgm plus eno in B. subtilis resuIted in extremely slow growth either on plates or in liquid, but growth of these mutants was enhanced by supplementation of media with malate. However, these mutants were asporogenous with or without malate supplementation.The process of sporulation in Bacillus and Clostridium species produces a spore which is extremely resistant to a variety of harsh treatments, such as heat, dessication and radiation, and which can survive for long periods in the absence of exogenous nutrients (19). One reason for the survival of spores in such conditions is that they are metabolically dormant and carry out neither macromolecular biosynthesis nor detectable metabolism of exogenous or endogenous compounds (17-19). Not surprisingly, dormant spores lack significant levels of products of catabolism such as ATP and NADH, which are present at high levels in growing cells, although AMP and NAD are present at significant levels in spores (18). While the spore can remain in this dormant state for long periods of time, with the proper stimulus spore germination is initiated, and within minutes ATP and NADH are produced and macromolecular biosynthesis begins (17, 18). The dormant spore contains a number of energy reserves which are mobilized in the first minutes of germination, thus facilitating the rapid resumption of metabolism. One such reserve is the large depot of small, acid-soluble proteins which are degraded to amino acids early in germination, with a significant amount of these amino acids catabolized for energy (17,18). A second energy reserve is a depot of 3-phosphoglyceric acid (3PGA), which constitutes 0.2 to 0.5% of spore dry weight (18). The 3PGA depot is accumulated late in sporulation within the developing spore, and there is a body of evidence indicating that phosphoglycerate mutase (PGM) is the enzyme which is specifically inhibited to allow 3PGA accumulation (18,20,22). In the first minutes of germination, the 3PGA depot is converted ...

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Analysis of the pH decrease and 3-phosphoglyceric acid (3PGA) accumulation in the forespore compartment of sporulating cells of Bacillus subtilis showed that the pH decrease of 1 to 1.2 units at ϳ4 h of sporulation preceded 3PGA accumulation, as observed previously in B. megaterium. These data, as well as analysis of the forespore pH decrease in asporogenous mutants of B. subtilis, indicated that G -dependent forespore transcription, but not K -dependent mother cell transcription, is required for the forespore pH decrease. Further analysis of these asporogenous mutants showed an excellent correlation between the forespore pH decrease and the forespore's accumulation of 3PGA. These latter results are consistent with our previous suggestion that the decrease in forespore pH results in greatly decreased activity of phosphoglycerate mutase in the forespore, which in turn leads to 3PGA accumulation. In further support of this suggestion, we found that (i) elevating the pH of developing forespores of B. megaterium resulted in rapid utilization of the forespore's 3PGA depot and (ii) increasing forespore levels of PGM ϳ10-fold in B. subtilis resulted in a large decrease in the spore's depot of 3PGA. The B. subtilis strain with a high phosphoglycerate mutase level sporulated, and the spores germinated and went through outgrowth normally, indicating that forespore accumulation of a large 3PGA depot is not essential for these processes.