RESUMO
Mus81 is a well-conserved DNA structure-specific endonuclease which belongs to the XPF/Rad1 family of proteins that are involved in DNA nucleotide excision repair. Mus81 forms a heterodimer with a non-catalytic subunit, Mms4, in Saccharomyces cerevisiae (Eme1/EME1 in Schizosaccharomyces pombe and mammals). Recent evidence shows that Mus81 functions redundantly with Sgs1, a member of the ubiquitous RecQ family of DNA helicases, to process toxic recombinant intermediates. In budding yeast, homologous recombination is regulated by the Rad52 epistasis group of proteins, including Rad52, which stimulates the main steps of DNA sequence-homology searching. Mus81 was proven to act in the Rad52-dependent pathway. Here, we demonstrate that Rad52 and Mus81-Mms4 possesses a functional interaction; the presence of Rad52 significantly enhances the endonuclease activity of Mus81-Mms4 on a broad range of its preferred synthetic substrates. Furthermore, this functional interaction is demonstrated to be species specific. We fragmented Rad52 and found that the N-terminal fragment from the 86th to 169th amino acid residue, which belongs to DNA-binding and self-association domains, can stimulate Mus81-Mms4 endonuclease. These results strongly support the notion that Rad52 and Mus81-Mms4 collaborate and work jointly in processing of homologous recombination intermediates.
Assuntos
DNA Fúngico/metabolismo , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Endonucleases Flap/metabolismo , Recombinação Homóloga , Proteína Rad52 de Recombinação e Reparo de DNA/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Análise Mutacional de DNA , DNA Fúngico/genética , Mapeamento de Interação de Proteínas , Proteína Rad52 de Recombinação e Reparo de DNA/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
Background: Cerebral venous thrombosis (CVT) is a challenging condition with potential long-term consequences, but it is also a treatable disorder that offers the possibility of complete recovery. This study was conducted to comprehensively investigate the clinical features, brain imaging findings, and treatment outcomes of patients diagnosed with cerebral venous thrombosis. Materials and Methods: Conducted as a cross-sectional descriptive study, patients diagnosed with cerebral venous thrombosis were enrolled at Can Tho Central General Hospital between January 2021 and June 2022. Results: Notably, a substantial proportion of patients (83.4%) exhibited signs of brain damage, with intracranial hemorrhage (50%), brain infarction (30.9%), subarachnoid hemorrhage (16.6%), and hemorrhagic infarct (4.7%) being the predominant findings. Thrombosis primarily affected the superior sagittal sinus (85.7%), transverse sinus (52.4%), and sigmoid sinus (42.8%). All patients received anticoagulation treatment, resulting in a favorable recovery upon hospital discharge for the majority (90.5%), while a small percentage (9.5%) experienced critical illness or death. Conclusion: Our study on cerebral venous thrombosis found diverse clinical presentations, primarily headache. Intracranial hemorrhage was common, affecting superior sagittal, transverse, and sigmoid sinuses. Most patients achieved favorable recoveries with anticoagulation treatment, emphasizing early intervention's importance.
RESUMO
BACKGROUND AND PURPOSE: Recurrent ischemic stroke (RIS) induces additional functional limitations in patients. Prognosticating globally functional outcome (GFO) in RIS patients is thereby important to plan a suitable rehabilitation programme. This study sought to investigate the ability of baseline features for classifying the patients with and without improving GFO (task 1) and identifying patients with poor GFO (task 2) at the third month after discharging from RIS. METHODS: A total of 86 RIS patients were recruited and divided into the training set and testing set (50:50). The clinical and pre-clinical data were recorded. The outcome was the changes in Modified Rankin Scale (mRS) (task 1) and the mRS score at the third month (mRS 0-2: good GFO, mRS >2: poor GFO) (task 2). The permutation importance ranking method selected features. Four algorithms were trained on the training set with five-fold cross-validation. The best model was tested on the testing set. RESULTS: In task 1, the support vector machine (SVM) model outperformed the other models, with the high performance matrix on the training set (sensitivity = 0.80; specificity = 1.00) and the testing set (sensitivity = 0.80; specificity = 0.95). In task 2, the SVM model with selected features also performed well on both datasets (training set: sensitivity = 0.76; specificity = 0.92; testing set: sensitivity = 0.72; specificity = 0.88). CONCLUSION: A machine learning model could be used to classify GFO responses to treatment and identify the third-month poor GFO in RIS patients, supporting physicians in clinical practice.
RESUMO
Novel research on the chemical compositions and biochemical activities of Camellia longii Orel and Luu leaf extracts revealed valuable resources with potential applications in Alzheimer's disease treatment. Qualitative phytochemicals detected various compound groups, including polyphenols, saponins, tannins, flavonoids, alkaloids, amino acids, coumarins, and polysaccharides. HPLC-MS identified 23 compounds in C. longii leaves with compounds found at significant levels, including epicatechin gallate (17.12%), tryptophan (13.73%), isovitexin (12.91%), gallic acid (3.06%), and quercetin (3.06%). Interestingly, the ethanol extract (CLL-Ew) exhibited the highest extraction yield (26.6%) and potent antioxidant and acetylcholinesterase (AChE) inhibitory effects in vitro. In the Drosophila melanogaster model, CLL-Ew improved longevity, movement, and memory by reducing malondialdehyde and increasing glutathione levels. Docking simulations suggested that the above compounds bind tightly to AChE's active site, potentially contributing to memory enhancement. Interestingly, observations of male and female mice after administration of a dose of 5000 mg/kg C. longii leaf extract were recorded normally throughout the 14 day experiment. These findings highlight the potential of C. longii leaf extracts in functional foods and therapeutic interventions for memory impairment prevention and treatment.
RESUMO
This study aimed to investigate the correlation between beta-2 microglobulin (B2M) concentration and some nerve conduction indices and evaluate the changes in some nerve conduction indices after treatment with hemodialysis (HD) combined with hemodiafiltration online in end-stage renal disease patients. From July 2021 to July 2022, a cross-sectional study was conducted on 80 end-stage renal disease patients on HD at Can Tho General Hospital, Viet Nam. All the patients had B2M testing and nerve conduction measurements. Patients with nerve conduction disorders were treated and remeasured after 6 months to evaluate the treatment results. At baseline, there was a moderate negative correlation between B2M and the tibial nerve and motor branch of the ulnar conduction velocity (V) (r = -0.305 and -0.315, P < .05). There was a moderate positive correlation between B2M and motor latency of the tibial and peroneal nerve (r = 0.434 and 0.440, P < .05). After 6 months of using the combination of HD and hemodiafiltration online, the V (31.3 ± 7.96 up to 44.88 ± 9.67 m/s) and the amplitude (A) (1.71 ± 1.16 up to 2.61 ± 1.51 mV) of the peroneal nerve increased, the motor latency decreased (8.21 ± 2.65 down to 5.23 ± 3.58 ms). With the tibial nerve, motor conduction V increased from 30.53 ± 8.05 m/s to 43.56 ± 8.99 m/s and the A increased from 5.04 ± 3.16 mV to 7.75 ± 4.45 mV. With the ulnar nerve, the A increased, and motor latency decreased after 6 months. The nerve conduction indices also improved significantly in the median nerve.