Balamuthia amoebic encephalitis (BAE), caused by Balamuthia mandrillaris, is a rare and life-threatening infectious disease with no specific and effective treatments available. The diagnosis of BAE at an early stage is difficult because of the non-specific clinical manifestations and neuroimaging.
Abstract Background Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant hereditary ataxia worldwide, which is however in a lack of effective treatment. In view of that engineered exosomes are a promising non-invasive gene therapy transporter that can overcome the traditional problem of poor drug delivery, the aim of this study was to evaluate, for the first time, the value of exosome-based microRNA therapy in SCA3 and the therapeutic effects of intravenously administrated ATXN3 targeting microRNAs in transgenic SCA3 mouse models. Methods The rabies virus glycoprotein (RVG) peptide–modified exosomes loaded with miR-25 or miR-181a were peripherally injected to enable targeted delivery of miRNAs to the brain of SCA3 mice. The behaviors, ATXN3 level, purkinje cell and other neuronal loss, and neuroinflammation were evaluated 4 weeks after initial treatment. Results The targeted and efficient delivery of miR-25 and miR-181a by modified exosomes substantially inhibited the mutant ATXN3 expression, reduced neuron apoptosis and induced motor improvements in SCA3 mouse models without increasing the neuroinflammatory response. Conclusions Our study confirmed the therapeutic potential of engineered exosome-based miR-25 and miR-181a treatment in substantially reducing ATXN3 aggregation and cytotoxicity by relying on its targeted and efficient drug delivery performance in SCA3 mice. This treatment method shows a promising prospect for future clinical applications in SCA3.
Abstract In our study, we discovered the presence of tunnelling nanotubes (TNTs) in three oral carcinoma cell lines, suggesting an alternative form of cellular communication. These TNTs act as channels for the movement of membrane-bound vesicles and microRNAs (miRNAs), indicating their potential influence on cancer progression and intercellular interactions. Our findings demonstrate that TNTs can form spontaneously under normal growth conditions, not just as a stress response. Through time-lapse microscopy, we captured the rapid and dynamic process of TNT formation, typically occurring within 20-40 minutes, via two primary methods: actin-driven cellular extensions and sustained connectivity during cell division. We also successfully visualised the active transfer of miRNA mimics through these TNTs. Notably, we detected the presence of AGO2 protein within the TNTs, implying its involvement in the delivery of miRNAs to recipient cells. Our study adds to the overall understanding of TNTs in the context of oral cancer biology and suggests a broader role for these structures in molecular transport.
Background: To determine the prevalence of detectable serum hepatitis B virus (HBV) DNA in patients who are hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive.The correlation between HBV DNA viral load and serological markers, as well as liver and coagulation function indicators were investigated.Furthermore, the effects of immunosuppressive therapy on DNA replication were assessed.Methods: A total of 2,013 HBsAg-negative/HBcAb-positive patients admitted to our hospital between January and December 2019 were enrolled in this study.Patient clinical characteristics including serological markers, HBV DNA viral load, liver function and coagulation function indicators, and immune function status were analyzed.Results: In the Hunan province in China, the prevalence of detectable HBV DNA was 5.4% in HBsAgnegative/HBcAb-positive patients.However, the prevalence of detectable HBV DNA in HBsAg-negative/ HBcAb-positive patients may vary because of different HBV serological markers.In patients with detectable serum HBV DNA, the log10 HBV DNA value was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST) levels, and negatively correlated with antithrombin III (AT III) concentrations.Moreover, in patients receiving immunosuppressive therapy, ALT and AST levels were higher than those of patients who did not receive immunosuppressive therapy.The ALT and AST levels in hepatitis B e antibody (HBeAb)-positive patients were significantly higher than that observed in HBeAb-negative patients.Conclusions: For HBsAg-negative/HBcAb-positive patients, clinicians should pay attention to the patient's immune function status.In situations where HBV DNA cannot be detected, changes in serum ALT, AST, and AT III concentrations can be used to speculate on viral replication status to reduce the risk of HBV infection and transmission.
Background: Long-term physical exercise has been shown to benefit patients with Parkinson disease (PD), but there is a lack of evidence regarding the underlying mechanism. A better understanding of how such benefits are induced by exercise might contribute to the development of therapeutic targets for improving the motor function in individuals with PD. The purpose of this study was therefore to investigate the possible association between exercise-induced motor improvements and the changes in serum microRNA (miRNA) levels of PD patients through small RNA sequencing for the first time. Methods: Thirteen PD patients completed our 3-month home-and-community-based exercise program, while 6 patients were assigned to the control group. Motor functions were measured, and small RNA sequencing with data analysis was performed on serum miRNAs both before and after the program. The results were further validated by quantitative real-time polymerase chain reaction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were then conducted to determine the role of differentially expressed miRNAs. Results: The 3-month home-and-community-based exercise program induced significant motor improvements in PD patients in terms of Unified Parkinson’s Disease Rating Scale activities of daily living and Motor Subscale ( P < .05), comfortable walking speed ( P = .003), fast walking speed ( P = .028), Six-Minute Walk Test ( P = .004), Berg Balance Scale ( P = .039), and Timed Up and Go ( P = .002). A total of 11 miRNAs (10 upregulated and one downregulated) were identified to be remarkably differentially expressed after intervention in the exercise group, but not in the control group. The results of miRNA sequencing were further validated by quantitative real-time polymerase chain reaction. It was found that the targets of altered miRNAs were mostly enriched in the mitogen-activated protein kinase, Wnt, and Hippo signaling pathways and the GO annotations mainly included binding, catalytic activity, and transcription regulator activity. Conclusion: The exercise-induced motor improvements were possibly associated with changes in circulating miRNA levels in PD patients. These miRNAs, as well as the most enriched pathways and GO terms, may play a critical role in the mechanism of exercise-induced benefits in PD and serve as novel treatment targets for the disease, although further investigations are needed.
Objective: To evaluate the diagnostic performance of galactomannan (GM) detection in serum and bronchoalveolar lavage fluid (BALF) for invasive pulmonary aspergillosis (IPA) in non-neutropenic patients. Methods: A total of 291 non-neutropenic patients in the Second Xiangya Hospital of Central South University were included. According to the 2019 EORTC/MSG guidelines, all cases were divided into an IPA group (n = 24) and a non-IPA group (n = 267). Receiver operating characteristic (ROC) curves were drawn to compare the diagnostic efficiency of GM detection in BALF and serum. Results: According to the receiver operating characteristic curves of BALF and serum GM, the areas under the curve were 0.961 and 0.699, respectively. The optimal BALF GM detection was found when the cutoff value was set to 0.87, whereas the sensitivity and specificity were 91.7% and 92.5%, respectively. Conclusions: BALF GM detection is more sensitive than serum GM detection for diagnosing IPA, and the optimal cutoff value for BALF GM is 0.87.
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