Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin

Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC50 of BA against jack-bean urease was 2.74 ± 0.51 mM, which was proved to be a competitive and concentration-dependent inhibition with slow-binding progress curves. The rapid formation of initial BA-urease complex with an inhibition constant of Ki=3.89 × 10−3 mM was followed by a slow isomerization into the final complex with an overall inhibition constant of Ki*=1.47×10-4 mM. High effectiveness of thiol protectors against BA inhibition indicated that the strategic role of the active-site sulfhydryl group of the urease was involved in the blocking process. Moreover, the inhibition of BA was proved to be reversible due to the fact that urease could be reactivated by dithiothreitol but not reactant dilution. Molecular docking assay suggested that BA made contacts with the important activating sulfhydryl group Cys-592 residues and restricted the mobility of the active-site flap. Taken together, it could be deduced that BA was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for treatments on urease-related diseases

Vaccination in the immunotherapy of glioblastoma

Glioblastoma remains one of the most common central nervous system tumors with an extremely poor prognosis. Recently, rapid progress in immunotherapy has provided new options for the treatment of glioblastoma. Vaccination, the primary method of immunotherapy, stimulates the body's tumor-specific immune response by the injection of foreign antigens. Peptide vaccines involve the injection of tumor-specific antigens, such as EGFRvIII or heat-shock proteins. Cell-based vaccines, which primarily include dendritic cell vaccines and tumor cell vaccines, involve injections of ex vivo-modified cells. Despite the encouraging results of phase I/II clinical trials, no successful phase III clinical trials involving glioblastoma immunotherapy, including glioblastoma vaccinations, have been reported to date. In this review, the authors summarize the published outcomes of glioblastoma vaccine therapy, explore its future prospects based on ongoing clinical trials, and discuss combined therapy as a future direction for glioblastoma treatment

Deep Learning-Based Denoising in Brain Tumor CHO PET: Comparison with Traditional Approaches

18F-choline (CHO) PET image remains noisy despite minimum physiological activity in the normal brain, and this study developed a deep learning-based denoising algorithm for brain tumor CHO PET. Thirty-nine presurgical CHO PET/CT data were retrospectively collected for patients with pathological confirmed primary diffuse glioma. Two conventional denoising methods, namely, block-matching and 3D filtering (BM3D) and non-local means (NLM), and two deep learning-based approaches, namely, Noise2Noise (N2N) and Noise2Void (N2V), were established for imaging denoising, and the methods were developed without paired data. All algorithms improved the image quality to a certain extent, with the N2N demonstrating the best contrast-to-noise ratio (CNR) (4.05 ± 3.45), CNR improvement ratio (13.60% ± 2.05%) and the lowest entropy (1.68 ± 0.17), compared with other approaches. Little changes were identified in traditional tumor PET features including maximum standard uptake value (SUVmax), SUVmean and total lesion activity (TLA), while the tumor-to-normal (T/N ratio) increased thanks to smaller noise. These results suggested that the N2N algorithm can acquire sufficient denoising performance while preserving the original features of tumors, and may be generalized for abundant brain tumor PET images

Prognostic Value of Choline and Other Metabolites Measured Using 1H-Magnetic Resonance Spectroscopy in Gliomas: A Meta-Analysis and Systemic Review

Glioma is the most prevalent primary central nervous system malignant tumor, with high heterogeneity observed among different grades; therefore, non-invasive prediction of prognosis could improve the clinical management of patients with glioma. 1H-magnetic resonance spectroscopy (MRS) can estimate metabolite levels non-invasively. Multiple studies have investigated its prognostic value in gliomas; however, no consensus has been reached. PubMed and Embase databases were searched up to 20 October 2022 to identify studies investigating the prognostic value of metabolites using 1H-MRS in patients with glioma. Heterogeneity across studies was evaluated using the Q and I2 tests, and a fixed- or random-effects model was used to estimate the combined overall hazard ratio (HR). Funnel plots and Begg tests were used to assess publication bias. Higher choline levels were associated with shorter overall survival (HR = 2.69, 95% CI, 1.92–2.99; p < 0.001) and progression-free survival (HR = 2.20, 95% CI, 1.16–4.17; p = 0.02) in all patients; however, in pediatric gliomas, it showed no significant correlation with overall survival (HR = 1.60, 95% CI, 0.97–2.64; p = 0.06). The estimated choline level by 1H-MRS could be used to non-invasively predict the prognosis of patients with adult gliomas, and more studies are needed to evaluate the prognostic value of other metabolites

Additional file 1 of Kruppel-like factor 13 acts as a tumor suppressor in thyroid carcinoma by downregulating IFIT1

Additional file 1. Supplementary figures