Systematic review and evidence gap mapping of biomarkers associated with neurological manifestations in patients with COVID-19.

OBJECTIVE: This study aimed to synthesize the existing evidence on biomarkers related to coronavirus disease 2019 (COVID-19) patients who presented neurological events. METHODS: A systematic review of observational studies (any design) following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Collaboration recommendations was performed (PROSPERO: CRD42021266995). Searches were conducted in PubMed and Scopus (updated April 2023). The methodological quality of nonrandomized studies was assessed using the Newcastle‒Ottawa Scale (NOS). An evidence gap map was built considering the reported biomarkers and NOS results. RESULTS: Nine specific markers of glial activation and neuronal injury were mapped from 35 studies published between 2020 and 2023. A total of 2,237 adult patients were evaluated in the included studies, especially during the acute phase of COVID-19. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) biomarkers were the most frequently assessed (n = 27 studies, 77%, and n = 14 studies, 40%, respectively). Although these biomarkers were found to be correlated with disease severity and worse outcomes in the acute phase in several studies (p < 0.05), they were not necessarily associated with neurological events. Overall, 12 studies (34%) were judged as having low methodological quality, 9 (26%) had moderate quality, and 9 (26%) had high quality. CONCLUSIONS: Different neurological biomarkers in neurosymptomatic COVID-19 patients were identified in observational studies. Although the evidence is still scarce and conflicting for some biomarkers, well-designed longitudinal studies should further explore the pathophysiological role of NfL, GFAP, and tau protein and their potential use for COVID-19 diagnosis and management.

Biosynthesis and mass spectral fragmentation pathways of (13)C and (15)N labeled cytochalasin D produced by Xylaria arbuscula.

The fungus Xylaria arbuscula was isolated as an endophyte from Cupressus lusitanica and has shown to be a prominent producer of cytochalasins, mainly cytochalasins C, D and Q. Cytochalasins comprise an important class of fungal secondary metabolites that have aroused attention due to their uncommon molecular structures and pronounced biological activities. Due to the few published studies on the ESI-MS/MS fragmentation of this important class of secondary metabolites, in the first part of our work, we studied the cytochalasin D fragmentation pathways by using an ESI-Q-ToF mass spectrometer coupled with liquid chromatography. We verified that the main fragmentation routes were generated by hydrogen and McLafferty rearrangements which provided more ions than just the ones related to the losses of H2 O and CO as reported in previous studies. We also confirmed the diagnostic ions at m/z 146 and 120 as direct precursor derived from phenylalanine. The present work also aimed the production of structurally diverse cytochalasins by varying the culture conditions used to grow the fungus X. arbuscula and further insights into the biosynthesis of cytochalasins. HPLC-MS analysis revealed no significant changes in the metabolic profile of the microorganism with the supplementation of different nitrogen sources but indicated the ability of X. arbuscula to have access to inorganic and organic nitrogen, such as nitrate, ammonium and amino acids as a primary source of nitrogen. The administration of 2-13 C-glycine showed the direct correlation of this amino acid catabolism and the biosynthesis of cytochalasin D by X. arbuscula, due to the incorporation of three labeled carbons in cytochalasin chemical structure. Copyright © 2017 John Wiley & Sons, Ltd.

Method validation of nanoparticle tracking analysis to measure pulmonary nanoparticle content: the size distribution in exhaled breath condensate depends on occupational exposure.

A particle exposure assessment based on the dose deposited in the lungs would be the gold standard for the evaluation of any resulting health effects. Measuring particles in exhaled breath condensate (EBC)-a matrix containing water and airway lining fluid-could help to evaluate particle retention in the lungs. This study aimed to (1) validate a nanoparticle tracking analysis (NTA) method for determining the particle number concentration and their hydrodynamic size distribution in EBC, and (2) apply this method to EBC collected from workers exposed to soapstone (n = 55) or quartz dust (n = 12) and controls (n = 11). A standard latex bead solution was used to determine the linear range, limit of detection (LOD), repeatability (coefficient of variation, CV), and bias in spiked EBC. An LM10 NanoSight instrument with NTA version 3.1 software was used for measurement. RTubes® were used for field collection of EBC. The repeatability obtained for a D50 size distribution in EBC showed less than 8% variability, with a bias <7%. The particle concentration was linear in the range ≤2.5 × 108 particles ml-1 with a LOD of 4 × 106 particles ml-1. A recovery of 117 ± 20% at 6.2 × 107 particles ml-1 was obtained with a CV <10% and a bias <20%. EBC from workers exposed to quartz, who experienced the largest exposure to silica particles, consistently exhibited a statistically significant (p < 0.01) higher concentration of particles in their EBC, with a size distribution shift towards larger values than the other groups. Results showed that the NTA technique performed well for characterizing the size distribution and concentrations of particles in EBC. The technique needs to be corroborated with a larger population of workers.

Renal changes in the early stages of diet-induced obesity in ovariectomized rats.

The relationship between obesity and renal lesions, especially in low estrogen levels, has been less documented. The aim of this study was to assess the renal changes in diet-induced obesity in ovariectomized rats. Wistar rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a standard diet (SSD); ovariectomized rats fed a standard diet (OSD); sham-operated rats fed a high-fat diet (SHFD); ovariectomized rats fed a high-fat diet (OHFD). Body weight and blood pressure were measured weekly. The rats were killed 24 weeks after initiation of standard or high-fat diet treatment, the kidneys were removed for immunohistochemical and histological studies. Blood and urine samples were collected to quantify sodium, potassium and creatinine. OHFD rats presented increases in visceral adipose tissue, serum insulin levels, blood pressure and proteinuria, and a decrease in fractional excretion of sodium as well. Histological and morphometric studies showed focal alterations in the renal cortex. Expression of macrophages, lymphocytes, nuclear factor-kappa B (NF-kappaB), Proliferating Cell Nuclear Antigen (PCNA), angiotensin II (ANG II) and vimentin was greater in OHFD rats than in control rats. Thus, these results demonstrate that the high-fat diet in ovariectomized rats promoted renal function and structure changes, renal interstitial infiltration of mononuclear cells and increased expression of ANG II and NF-kappaB.

Metformin inhibits inflammatory angiogenesis in a murine sponge model.

To investigate the effects of metformin on angiogenesis, on inflammatory cell accumulation and on production of endogenous cytokines in sponge implant in mice. Polyester-polyurethane sponges were implanted in Swiss mice and metformin (40 or 400mg/kg/day) was given orally for six days. The implants collected at day 7 postimplantation were processed for the assessment of hemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) e collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Metformin treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of transforming growth factor (TGF-beta1) intraimplant. A regulatory function of metformin on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of metformin.

Chronic lipoic acid treatment worsens energy imbalances in streptozotocin-induced diabetic rats.

AIM: Our objective was to verify the energy balance in streptozotocin-induced diabetic rats chronically treated with lipoic acid (LA). METHODS: Diabetes was induced in rats by streptozotocin and the animals divided into four groups, comprising controls and diabetic rats, with each group receiving either daily intraperitoneal LA (30 mg/kg) or a buffer solution for 30 days. Body weight, food intake and stool and urine collections were recorded daily. On day 30, animals were sacrificed and the carcasses, faeces and urine collected and processed for calorimetric analysis. Blood glucose and insulin were also determined. RESULTS: All parameters of energy balance were affected by diabetes. LA treatment reduced weight gain, energy gain and gross food efficiency in both control and diabetic animals. However, the LA-treated animals tended to show higher energy expenditure than non-treated animals. Body composition was also affected by diabetes: fat content was impaired by LA treatment in both control and diabetic animals. The latter also showed increased glycaemia and decreased insulinaemia, but LA had no effect on these parameters. CONCLUSION: Our results indicate that chronic treatment with LA aggravates energy imbalances in diabetic animals. Moreover, our data suggest the need to reconsider the use of LA as an adjuvant in the prevention and treatment of type 1 diabetes.