The Effects and Mechanism of Scutellaria baicalensis Georgi Stems and Leaves Flavonoids on Myelin Sheath Degeneration Induced by Composite Aß in Rats.

BACKGROUND: Alzheimer's disease is a degenerative disease of the central nervous system, and its characteristic pathological changes are closely associated with Aß deposition and neurofibrillary tangles. Many studies have found that malignant changes in the myelin sheath and oligodendrocyte (OL) are accompanied by the occurrence and development of AD. Therefore, any method that can resist myelin sheath and OL disorders may be a potential strategy for AD. OBJECTIVE: To investigate the effects and mechanism of Scutellaria baicalensis Georgi stem and leaf flavonoids (SSFs) on the myelin sheath degeneration induced by Aß25-35 combined with AlC13 and RHTGF-ß1 (composite Aß) in rats. METHODS: A rat AD model was established by intracerebroventricular injection of composite Aß. The Morris water maze was used to screen the memory impairment rat model. The successful model rats were divided into the model group and the 35, 70, and 140 mg/kg SSFS groups. The myelin sheath changes in the cerebral cortex were observed with an electron microscope. The expression of the oligodendrocyte- specific protein claudin 11 was detected with immunohistochemistry. The protein expression levels of myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG) and myelin basic protein (MBP), sphingomyelin synthase-1 (SMS1), and sphingomyelinase-2 (SMPD2) were assayed by Western blotting. RESULTS: The intracerebroventricular injection of composite Aß caused degeneration of the myelin sheath structure and was accompanied by the decreased claudin 11, MOG, MAG, MBP, and SMS1, and increased SMPD2 protein expression in the cerebral cortex. However, 35, 70, and 140 mg/kg SSFs can differentially ameliorate the above abnormal changes induced by composite Aß. CONCLUSION: SSFs can alleviate myelin sheath degeneration and increase the protein expression of claudin 11, MOG, MAG, and MBP, and the effective mechanism may be related to the positive regulation of SMS1 and SMPD2 activities.

Evaluation of wastewater-based epidemiology of COVID-19 approaches in Singapore's 'closed-system' scenario: A long-term country-wide assessment.

With the COVID-19 pandemic the use of WBE to track diseases spread has rapidly evolved into a widely applied strategy worldwide. However, many of the current studies lack the necessary systematic approach and supporting quality of epidemiological data to fully evaluate the effectiveness and usefulness of such methods. Use of WBE in a very low disease prevalence setting and for long-term monitoring has yet to be validated and it is critical for its intended use as an early warning system. In this study we seek to evaluate the sensitivity of WBE approaches under low prevalence of disease and ability to provide early warning. Two monitoring scenarios were used: (i) city wide monitoring (population 5,700,000) and (ii) community/localized monitoring (population 24,000 to 240,000). Prediction of active cases by WBE using multiple linear regression shows that a multiplexed qPCR approach with three gene targets has a significant advantage over single-gene monitoring approaches, with R2 = 0.832 (RMSE 0.053) for an analysis using N, ORF1ab and S genes (R2 = 0.677 to 0.793 for single gene strategies). A predicted disease prevalence of 0.001% (1 in 100,000) for a city-wide monitoring was estimated by the multiplexed RT-qPCR approach and was corroborated by epidemiological data evidence in three 'waves'. Localized monitoring setting shows an estimated detectable disease prevalence of ∼0.002% (1 in 56,000) and is supported by the geospatial distribution of active cases and local population dynamics data. Data analysis also shows that this approach has a limitation in sensitivity, or hit rate, of 62.5 % and an associated high miss rate (false negative rate) of 37.5 % when compared to available epidemiological data. Nevertheless, our study shows that, with enough sampling resolution, WBE at a community level can achieve high precision and accuracies for case detection (96 % and 95 %, respectively) with low false omission rate (4.5 %) even at low disease prevalence levels.

The influence of transarterial chemoembolization on serum levels of soluble programed cell death ligand-1 in advanced hepatocellular carcinoma patients.

AIMS: To investigate the implications of soluble programmed cell death-ligand 1 (sPD-L1) in hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE) and to evaluate the potential value of sPD-L1 to guide selection of the optimal time to begin combination therapy with TACE and immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: Thirty-one HCC patients suitable for TACE and 55 healthy volunteers were enrolled in this study. Three milliliters of peripheral venous blood of patients were collected on 1 day before TACE and 3, 7, and 30 days after TACE respectively for assay of sPD-L1 using enzyme-linked immunosorbent assay. The associations of the sPD-L1 level with the clinical features, outcomes, and the fluctuation of sPD-L1 during the treatment were analyzed. RESULTS: The initial sPD-L1 level of patients was significantly higher than that of the control group. And it was significantly associated with BCLC stage, portal venous invasion, tumor size, and number of foci. The sPD-L1 levels of 3 and 7 days after TACE were both significantly higher than the initial level. And that of 30 days after TACE was lower than the initial level, but the difference was not statistically significant. There was no significant difference of sPD-L1 level after embolization with embolic beads of different size. The level of sPD-L1 of CR patients was lower than that of PR, SD patients, but the differences were not significant. CONCLUSION: The level of sPD-L1 was associated with tumor aggressiveness and outcomes, suggesting its role as a possible predictive biomarker. The increases in sPD-L1 after TACE suggests that combined treatment with TACE and ICIs may be a promising therapeutic strategy in HCC. One week after TACE might be a suitable time to begin the administration of immunotherapy.

Human aquaporin 4 gene polymorphisms in Chinese patients with neuromyelitis optica.

OBJECTIVE: To investigate the association between aquaporin 4 (AQP4) gene polymorphisms and Chinese patients with neuromyelitis optica (NMO). METHODS: 122 consecutive anti-AQP4 autoantibody (NMO-IgG) seropositive cases were enrolled for gene sequencing. Furthermore, ten SNPs were selected and genotyped for a case-control association analysis on 208 cases and 204 healthy subjects. RESULTS: 14 novel SNPs were identified, while there were no nonsynonymous mutations and their frequency was low. The heterozygous genotype at two 3' UTR SNPs was significantly higher in cases than controls: the A/T genotype of SNP rs1058424 (54.81% vs. 42.65%, p(adjusted)=0.024, OR=1.670, 95% CI=1.071-2.605) and the C/T genotype of SNP rs3763043 (53.85% vs. 42.65%, p(adjusted)=0.028, OR=1.638, 95% CI=1.054-2.545). Moreover, the 3' UTR haplotype ATATGGAT may be protective for NMO (7.67% vs. 12.18%, p=0.042). CONCLUSIONS: Polymorphisms in the coding region of AQP4 are unlikely to confer NMO susceptibility. However, the 3' UTR of this gene presents several polymorphic sites that may affect NMO risk in the Chinese.