Brazilian Journal of Medical and Biological Research最新文献

Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.

Depression is a common disorder in patients with chronic kidney disease (CKD), and some data support its relationship with functional capacity and quality of life. However, to date, this has not been evaluated systematically or through meta-analysis. We sought to investigate the relationship of quality of life and functional capacity with depressive disorder in patients with CKD on hemodialysis. This systematic review considered studies published up to 2021 and included cross-sectional and cohort studies. PubMed, Embase, SPORTDiscus, Web of Science, and Cochrane (CENTRAL) databases were used to search for studies. The New Castle-Ottawa Quality Assessment scale was used to measure the quality of the studies. A total of 4,626 studies were found and, after applying the selection criteria, 16 studies (2,175 patients) remained for qualitative analysis and 10 for meta-analysis (1,484 patients). The physical component summary (MD=-6.563; 95%CI: -9.702 to -3.424) and mental component summary (MD=-18.760; 95%CI: -28.641 to -8.879) were lower in depressive patients, as in all Short Form Health Survey 36 (SF-36) domains. Only one study provided data regarding functional capacity, but it was not evaluated by the defined outcome measure. Twelve studies were classified as "moderate quality" (5 to 6 stars) and four were classified as "low-quality" (0 to 4 stars). This meta-analysis with CKD patients on hemodialysis showed a negative relationship between depression and quality of life, with worsening in all physical and mental domains of the SF-36 in depressed patients.

Scoliosis is a condition that affects the spine and causes chest rotation and trunk distortion. Individuals with severe deformities may experience dyspnea on exertion and develop respiratory failure. Respiratory oscillometry is a simple and non-invasive method that provides detailed information on lung mechanics. This work aims to investigate the potential of oscillometry in the evaluation of respiratory mechanics in patients with scoliosis and its association with physical performance. We analyzed 32 volunteers in the control group and 32 in the scoliosis group. The volunteers underwent traditional pulmonary function tests, oscillometry, and the 6-minute walk test (6MWT). Oscillometric analysis showed increased values of resistance at 4 Hz (R4, P<0.01), 12 Hz (R12, P<0.0001), and 20 Hz (R20, P<0.01). Similar analysis showed reductions in dynamic compliance (Cdyn, P<0.001) and ventilation homogeneity, as evaluated by resonance frequency (fr, P<0.001) and reactance area (Ax, P<0.001). Respiratory work, described by the impedance modulus, also showed increased values (Z4, P<0.01). Functional capacity was reduced in the group with scoliosis (P<0.001). A significant direct correlation was found between Cobb angle and R12, AX, and Z4 (P=0.0237, P=0.0338, and P=0.0147, respectively), and an inverse correlation was found between Cdyn and Cobb angle (P=0.0190). These results provided new information on respiratory mechanics in scoliosis and are consistent with the involved pathophysiology, suggesting that oscillometry may improve lung function tests for patients with scoliosis.

Pulmonary fibrosis (PF) is a major public health issue with limited treatment options. As the active ingredient of the n-butanol extract of Amygdalus mongolica (BUT), amygdalin inhibits PF. However, its mechanisms of action are unclear and need further verification. Therefore, the purpose of the present studies was to investigate the anti-fibrotic effects of BUT on PF by serum metabolomics and the transforming growth factor β (TGF-β) pathway. Sixty male Sprague-Dawley rats were randomly divided into control, untreated PF, prednisone-treated (5 mg/kg), and BUT-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. The serum metabolomics profiles were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and metabolism network analysis. The expression of TGF-β1, Smad-3, Smad-7, and α-smooth muscle actin (α-SMA) was measured using a real-time polymerase chain reaction in the lung tissue. BUT significantly alleviated fibrosis by reducing the mRNA expressions of TGF-β1 (from 1.73 to 1.13), Smad-3 (from 2.01 to 1.19), and α-SMA (from 2.14 to 1.19) and increasing that of Smad7 (from 0.17 to 0.62). Twenty-eight potential biomarkers associated with PF were identified. In addition, four key biomarkers were restored to baseline levels following BUT treatment, with the lowest dose showing optimal effect. Furthermore, A. mongolica BUT was found to improve PF by the pentose phosphate pathway and by taurine, hypotaurine, and arachidonic acid metabolism. These findings revealed the mechanism of A. mongolica BUT antifibrotic effects and metabolic activity in PF rats and provided the experimental basis for its clinical application.

Neuropathic pain is a condition with varying origins, including reduced dietary micronutrient intake. Phytate is a polyphosphate found in seeds and grains that can act as an antinutrient due to the ability of sequester essential divalent metals. Here we tested whether moderate dietary phytate intake could alter nociceptive pain. We subjected weaning mice to a chow supplemented with 1% phytate for eight weeks. Body weight gain, glycemic responses, food ingestion, water ingestion, and liver and adipose tissue weights were not altered compared to controls. We observed a decreased mechanical allodynia threshold in the intervention group, although there were no changes in heat- or cold-induced pain. Animals consuming phytate showed reduced spinal cord tumor necrosis factor (TNF), indicating altered inflammatory process. These data provide evidence for a subclinical induction of mechanical allodynia that is independent of phytate consumption in animals with otherwise normal phenotypic pattern.

Darwin's theory of evolution, which is based on variation, heredity, and selection, includes all biological fields and spreads to other areas such as philosophy. Medicine is an example of how the evolutionary perspective can greatly improve the understanding of concepts in an area, as human health and pathological conditions are under the effect of evolution. Evolutionary medicine is an emerging paradigm for understanding human heterogeneity, health, and diseases. Nevertheless, there are indications that medical research and practice are only marginally affected by these ideas. Here, we investigate how concepts of biological evolution are employed in medical research. We use a bibliometric approach to look for the presence and frequency of biological evolution-related concepts in medical articles. The distribution of these concepts over the years is analyzed according to the medical specialty and the impact of the journal. Our data showed that: i) only a small percentage of articles in medical journals have an evolutionary perspective; ii) medical journals where these evolution-based articles are published focus on basic science, theoretical medicine, and less frequently, on applied medicine; iii) these articles are mostly from the microbiology, immunology, neurology, psychology, behavior, and oncology fields; and iv) viruses are the most frequently covered microorganisms, followed by bacteria, fungi, and protozoans. The collection of our results, considering the importance of evolutionary medicine in the medical field, highlights the need for a decisive change in perspective in medical research.