Amyloid-β (Aβ) peptides play a key role in Alzheimer's disease (AD), the most common type of dementia. In this study, a polysaccharide from
(BSP), with strong antioxidant and anti-inflammatory ...properties, was extracted using a low-temperature method and tested for its efficacy against AD, in vitro using N2a and BV-2 cells, and in vivo using an AD rat model. The characterization of the extracted BSP for its molecular structure and functional groups demonstrated the effectiveness of the modified method for retaining its bioactivity. In vitro, BSP reduced by 20% reactive oxygen species (ROS) levels in N2a cells (
= 0.0082) and the expression levels of inflammation-related genes by 3-fold TNF-α (
= 0.0048), 4-fold IL-6 (
= 0.0019), and 2.5-fold IL-10 (
= 0.0212) in BV-2 cells treated with Aβ fibrils. In vivo, BSP recovered learning memory, ameliorated morphological damage in the hippocampus and cortex, and reduced the expression of the β-secretase protein in AlCl
-induced AD rats. Collectively, these findings demonstrated the efficacy of BSP for preventing and alleviating the effects of AD.
Abstract
Background
Occlusal force represents masticatory function. Using quantifiable occlusal indicators provides a more objective occlusal force evaluation. In the recent dental practice, digital ...methods such as the Dental Prescale II (DP2, GC Corp., Tokyo, Japan) and T-scan (T-Scan III v8; Tekscan Inc.) are commonly used in clinics to evaluate treatment outcomes. The T-scan provides the relative bite force (%) compared to the maximal bite force on individual teeth or the unilateral arch. The DP2 can quantify occlusal force, measured in newtons (N), on the half arch or the overall bite, but it is difficult to identify the bite force on an individual tooth. It is difficult to select a device that fulfils all the requirements to record occlusal force. This study aimed to investigate the association between the bite measured by the DPS2 and T-scan to determine whether the measured bite force is comparable through calculation.
Methods
A total of 80 healthy adults, including 41 women and 39 men with a mean age of 38.2, were requested to bite pressure sensitive film sheets ten minutes apart. Linear regression analysis was used to estimate the measured bite force by the DP2 and T-scan.
Results
There was a significant positive correlation between the occlusal force measured by the DP2 and T-scan (
P
< 0.01) when intercept was equal to zero as confounders were adjused. These results provided the comparability of the measured occlusal forces determined by the DP2 and T-scan.
Conclusion
The estimated bite force determined by DP2 and T-Scan is convertible using the linear equation from this study to increase the value for clinical applications. The estimated bite force from the two quantifiable occlusal indicators are comparable. The two commercially available quantifiable occlusal indicators can be fully adapted to all clinical requirements according to this result.
Purpose
This study investigated the impact of dental prophylaxis on 5-fluorouracil (5-FU)–related oral mucositis (OM) according to the head and neck cancer (HNC) locations and treatment times.
...Methods
A total of 13,969 HNC participants, including 482 5-FU–related OM subjects and 13,487 comparisons were enrolled from the Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan between 2000 and 2008. All subjects were stratified into subgroups based on the times to perform chlorhexidine use, scaling, and fluoride application before 5-FU administration. The dental prophylaxis related to 5-FU–related OM was estimated by multiple logistic regression and represented with odds ratio (OR) and 95% confidence interval (CI).
Results
Fluoride gel application and scaling significantly impacted on OM development (
p
< 0.001), and the joint effect of fluoride gel and scaling induced 5-FU–related OM (OR = 3.46, 95% CI = 2.39–5.01). The risk of OM was raised 2.25-fold as scaling within 3 weeks before 5-FU–related chemotherapy (95% CI = 1.81–2.81), and a 3.22-fold increased risk of OM while fluoride gel was applied during 5-FU–related treatment (95% CI = 1.46–7.13).
Conclusion
Dental prophylaxis significantly affected 5-FU–related OM in the HNC population. A short interval between dental scaling or fluoride application and 5-FU administration may be associated with higher prevalence of OM. Scaling simultaneously combined with chlorohexidine promoted 5-FU–related OM in specific HNC patients excluding the oral cancer and nasopharyngeal cancer population. Proper timing of the prophylactic dental treatments prior to 5-FU therapy could reduce the risk to develop 5-FU–related OM.
With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader ...neutralizing efficacy.
We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants.
A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs.
These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.
Background With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide ...broader neutralizing efficacy. Methods We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. Results A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-gamma+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. Conclusions These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines. Keywords: Omicron vaccine, mRNA vaccine, SARS-CoV-2, COVID-19, Variants of concern, Hybrid vaccine, Booster dose, Next generation vaccine, Cross-protectivity
碩士
國立臺灣大學
醫學工程學研究所
107
Alzheimer’s disease (AD) is the primary cause of age-related dementia. Amyloid-β (Aβ) is regarded as one of the reasons of AD. Amyloid precursor protein is cleaved by ...β-secretase and γ-secretase to produce amyloid-β, whose aggregation implicates in neuronal degeneration and cognitive decline in AD. It induces oxidative stress, chronic neuroinflammation, and synaptic dysfunction, leading to the death of neurons in the brain. Nowadays, there is no effective therapy to cure AD in clinical treatment. Bletilla Striata polysaccharide (BSP) has been proved to have anti-oxidative, anti-inflammatory effects and be able to induce cell proliferation. Therefore, the purpose of this study is to utilize the characteristics of BSP to reduce Aβ-induced cytotoxicity. Further, we explore the effect of BSP on β-secretase levels to achieve the prevention and treatment of AD.
In this study, FTIR and NMR are used to confirm the functional groups and chemical structure of BSP. ThT assay, Western blot and TEM
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the ...miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target interactions (MTIs). The latest update of the miRTarBase expanded it to identify systematically Argonaute-miRNA-RNA interactions from 138 crosslinking and immunoprecipitation sequencing (CLIP-seq) data sets that were generated by 21 independent studies. The database contains 4966 articles, 7439 strongly validated MTIs (using reporter assays or western blots) and 348 007 MTIs from CLIP-seq. The number of MTIs in the miRTarBase has increased around 7-fold since the 2014 miRTarBase update. The miRNA and gene expression profiles from The Cancer Genome Atlas (TCGA) are integrated to provide an effective overview of this exponential growth in the miRNA experimental data. These improvements make the miRTarBase one of the more comprehensively annotated, experimentally validated miRNA-target interactions databases and motivate additional miRNA research efforts.
Matrix metalloproteinases (MMPs), specifically MMP-2, MMP-7, and MMP-9, have been discovered to be linked to many forms of vascular diseases such as stroke, and their detection is crucial to ...facilitate clinical diagnosis. In this work, we prepared a class of optical interference-free SERS nanotags (CO-nanotags) that can be used for the purpose of multiplex sensing of different MMPs. Multiplex detection with the absence of cross-talk was achieved by using CO-nanotags with individual tunable intrinsic Raman shifts of CO in the 1800–2200 cm–1 region determined by the metal core and ligands of the metal carbonyl complex. Boolean logic was used as well to simultaneously probe for two proteolytic inputs. Such nanotags offer the advantages of convenient detection of target nanotags and high sensitivity as validated in the ischemia rat model.
The proliferation of drug-resistant pathogens continues to increase, giving rise to serious public health concerns. Many researchers have formulated metal oxide nanoparticles for use as novel ...antibacterial agents. In the present study, copper oxide (CuO) was synthesized by simple hydrothermal synthesis, and doping was performed to introduce different polymers onto the NP surface for bacteriostasis optimization. The polymer-modified CuO NPs were analyzed further with XRD, FTIR, TEM, DLS and zeta potential to study their morphology, size, and the charge of the substrate. The results indicate that polymer-modified CuO NPs had a significantly higher bacteriostatic rate than unmodified CuO NPs. In particular, polydopamine (PDA)-modified CuO (CuO-PDA) NPs, which carry a weakly negative surface charge, exhibited excellent antibacterial effects, with a bacteriostatic rate of up to 85.8 ± 0.2% within 3 h. When compared to other polymer-modified CuO NPs, CuO-PDA NPs exhibited superior bacteriostatic activity due to their smaller size, surface charge, and favorable van der Waals interactions. This may be attributed to the fact that the CuO-PDA NPs had relatively lipophilic structures at pH 7.4, which increased their affinity for the lipopolysaccharide-containing outer membrane of the Gram-negative bacterium
The optimal duration of anti-PD-1 for cancer therapy has not been tested, especially when using combination therapy. Epidermal growth factor receptor (EGFR) pathway blocker was the top compound that ...enhanced T-cell killing of tumor cells in a high-throughput immune-oncology screen, possibly by stimulate the antigen presentation machinery and other mechanisms. We explored the effect of combination of EGFR inhibition with a short course of anti-PD-1 therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
We analyzed the effect of a short course of anti-PD-1 with continuous afatinib on the survival of a real-world cohort of R/M HNSCC patients. Patient characteristics, treatments, efficacies, and toxicities were reviewed and recorded for analysis.
From November 2016 to May 2018, 51 consecutive patients received pembrolizumab and afatinib. The cutoff date was June 30, 2022. The most common toxicities (all grades) were diarrhea (62.7%), skin rash (43.1%), mucositis (31.4%), and paronychia (23.5%). The objective response rate was 54.9% (95% confidence interval CI 40.3-68.9%). Median progression-free survival was 5.9 months (95% CI: 4.4-7.6 months), and the median overall survival was 10.5 months (95% CI: 6.8-16.5 months). The 12-month, 24-month, 36-month, and 48-month survival rate was 47.0%, 22.5%, 17.7%, and 12.6% respectively.
This retrospective study showed that short course pembrolizumab with afatinib therapy has acceptable efficacy in R/M HNSCC patients. The durable response and long-term survival rates were similar to prospective clinical trials. Short course anti-PD-1 therapy, especially in combination with EGFR blocker, is worth for further prospective study.
PDF
