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Role of pge2-regulated neuroinflammation in constructing neuron-nk-glioma circuit for glioblastoma
No full text[[abstract]]Glioblastoma (GBM), known for its aggressive nature and poor prognosis, frequently recurs and resists standard treatments such as temozolomide (TMZ). This resistance is partly due to complex interactions within the tumor microenvironment, particularly involving neuronal excitation. Recent insights suggest that neuronal activity, through mechanisms like neurogliomal synapses, not only promotes glioma cell proliferation but also contributes to the chemoresistance observed in recurrent tumors. Our focus is on Prostaglandin E2 (PGE2), a mediator that regulates neuronal excitation, and its role in the recurrence and resistance of GBM. We discovered that PGE2 upregulates synaptic proteins and alters neurotransmitter profiles, enhancing tumor cell survival and resistance to TMZ. Specifically, increased levels of neurotransmitters such as glutamine and asparagine were observed in PGE2-rich environments, correlating with heightened chemoresistance and tumor recurrence. Co-culture experiments further demonstrated that PGE2-treated neuronal cells could induce resistance in adjacent GBM cells. These findings highlight the potential of targeting PGE2 pathways as a therapeutic strategy. A significant advancement in our study was the development and application of compound #038, a novel celecoxib derivative designed to cross the blood-brain barrier (BBB). This compound demonstrated enhanced efficacy in inhibiting GBM growth and improving survival rates in mouse models, indicating its potential as an effective therapeutic agent against GBM
Therapeutic strategies of denosumab sequential therapy: A four-armed multi-institutional randomized controlled trial
No full text[[abstract]]Objective: Denosumab, a RANKL inhibitor, is renowned for its long-term efficacy in improving BMD and reducing fracture risks. However, its discontinuation leads to a rapid rebound and BMD loss, necessitating effective follow-up interventions. This study aimed to evaluate four treatment regimens post-denosumab discontinuation in patients with osteoporosis. Methods: The 2-y, multicenter, randomized controlled trial involved 101 postmenopausal women and men who had received biannual denosumab treatments for at least 2 y. The patients were randomized into four groups continued denosumab, zoledronate followed by denosumab, zoledronate for 2 y, and zoledronate followed by a supervised drug holiday. The primary outcome was the percent change from baseline at 24 months in BMD at various sites. Results: An alternating regimen of denosumab and zoledronate could lead to a BMD enhancement (LS-BMD, 2.25%; IQR, 0.02–5.82%). A strategically timed zoledronate injection can maintain BMD for two years post-denosumab (BMD at the lumbar spine [LS-BMD], -0.71%; interquartile range [IQR], − 3.67% to 2.69%). However, a single zoledronate dose post-denosumab brings significant BMD loss (LS-BMD, − 2.76%; IQR, − 6.12% to 2.06%). Conclusion: The study highlighted the "catch-up effect" in BMD upon resuming denosumab after a break, suggesting a potential reset in the body's response. Despite limitations like the short follow-up duration, the study provides novel insights into managing bone health post-denosumab discontinuation. Future studies should aim to validate the long-term therapeutic effect and the safety of the alternative regimen
Association between current medical decision-making participation self-efficacy and advance care planning engagement among older adults: baseline findings from a nationwide longitudinal cohort study
No full text[[abstract]]Background and Objectives: Misconceptions of and cultural differences in aging influence older adults' medical decision-making self-efficacy and engagement in advance care planning (ACP). This study aims to investigate the association between current medical decision-making participation self-efficacy and ACP engagement among older individuals receiving home-based medical care (HBMC) in Taiwan.Design: Baseline data analysis of a nationwide cohort study.Setting and Participants: Patients aged >= 50 years who had been consistently receiving HBMC for > two months between November 2019 and December 2022 were recruited. Study recruitment took place at six hospitals and 12 community home care institutions.Measurement and Analysis: A structured questionnaire was used to collect data on sociodemographic characteristics, decision-making participation self-efficacy, and ACP engagement. Descriptive, stratified, and multivariate logistic regression analyses were performed.Results: In total, 408 HBMC recipients were enrolled (average age: 80.4 years; 55% women). The respondents reported moderate decision-making participation self-efficacy but low ACP engagement. In light of the transtheoretical model of behavior change, participants with moderate or high self-efficacy had a significantly higher chance of reaching the "contemplation stage" for ACP decisions (odds ratio or OR 4.06-27.13). Participants were more likely to reach the "preparation and action stages" for ACP decisions only when they had high self-efficacy (OR 2.76-14.73).Conclusions: Although participants with better current medical decision-making self-efficacy were more likely to contemplate ACP, many did not take action beyond appointing a medical surrogate(s). Strategies to enhance decisional self-efficacy, thereby increasing timely ACP discussions among older adults in home settings in Chinese culture, are warranted. Trial registration number: ClinicalTrials.gov Identifier is NCT04250103 which has been registered on 31st January 2020
Reversible photomechanical actuators with liquid crystal polymer graphene oxide nanocomposites
No full text[[abstract]]This study investigates the quantitative photomechanical actuation properties of a bifunctional acrylate liquid crystal (LC242) doped with azo dye and graphene oxide (GO) nanocomposites under a 40 mW cm-2 green laser. A photo-responsive liquid crystal polymer (LCP) was developed via UV curing, utilizing methyl red (MR) for its photoisomerism and GO for its photothermal properties. This investigation focuses on optimizing photo-actuating performance by tuning MR and GO doping concentrations as well as photopolymerization conditions. Experimental results show that with a doping concentration of 20% MR, the LCP achieves a photo-induced bending angle of approximately 35 degrees and a response of 2 seconds and a recovery time of 1 second. Additionally, GO incorporation significantly reduces the critical laser power required for deformation; at a 10% concentration, the critical optical power is lowered to 25 mW cm-2. UV curing for 65 minutes (with a 5 : 1 front-to-back exposure ratio) optimizes strain characteristics, enhancing both bending deformation and recovery stability in LCP samples. The tailored photomechanical response allows for efficient and controllable actuation, enabling applications such as PDMS film switching in micropump systems. This LCP film demonstrates improved actuation strain and repeatability, promising advancements for smart material systems and biomedical devices. These results underscore the potential of doping strategies and photopolymerization control to enhance LCP photo-actuation capabilities for light-driven innovations
Upper extremity function and disability recovery with vibration therapy after stroke: A systematic review and meta-analysis of RCTs
No full text[[abstract]]Background This study aimed to investigate the therapeutic effects of vibration therapy for improving upper extremity motor impairment, function, and disability recovery in people with stroke. Design We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. PubMed, EMBASE, the Cochrane Library Database, Physiotherapy Evidence Database (PEDro), China Knowledge Resource Integrated Database, and Google Scholar were searched from inception to May 31, 2024. Randomized controlled trials (RCTs) that evaluated the effects of vibration therapy on upper extremity motor impairment, function, and disability recovery post-stroke were analyzed. Setting and participants Participants with a diagnosis of stroke with hemiplegia (or hemiparesis) were recruited. Methods Methodological quality assessment was performed using the PEDro quality score. Upper extremity motor impairment, function, and disability were the primary outcomes. Upper extremity motor impairment was measured using the Fugl-Meyer Assessment scale and other methods. Upper extremity functions were evaluated using the Wolf Motor Function test or other tools assessing manipulative activities. Disability was assessed using the Functional Independence Measure, Barthel index, and other methods. Results Overall, 30 RCTs including 1621 people with stroke were selected. Compared with the control, vibration therapy exerted significant effects on upper extremity motor impairment [standardized mean difference (SMD) = 1.19; p < 0.00001)], function (SMD = 0.62; p < 0.00001), and disability recovery (SMD = 1.01; p < 0.00001). The subgroup analysis revealed that focal vibration therapy (SMD = 2.14) had favorable effects on disability recovery compared with whole-body vibration therapy (SMD = 2.0). Interventions lasting 4-8 weeks showed significant improvements in motor impairment (SMD = 1.19), motor function (SMD = 0.57), and disability (SMD = 0.84); additionally, the effects of vibration therapy combined with conventional rehabilitation (SMD = 1.03) were superior to those of vibration therapy alone (SMD = 0.21). Conclusions Vibration therapy may be a reliable rehabilitation program to improve upper extremity motor functions and disabilities. Furthermore, vibration therapy should be performed at the earliest possibility after stroke for at least 4-8 weeks
Artificial tears solution combination
No full text[[abstract]]An artificial tears solution combination is composed mainly of an anti-inflammation and anti-oxidation material, a liquid viscosity-enhancing agent, and an artificial tears solution. The artificial tears solution combination is capable keeping moisture, and meanwhile having anti-inflammation and anti-oxidation capabilities. As such, it can prolong the liquid retention on ocular surfaces, to effective reduce the repeated dosing, and shorten the schedule for the dry eye syndrome
[[alternative]]Reactant carrier structure of thiolated polymer gel with intestinal absorption barrier
No full text[[abstract]]一種具有小腸吸收屏障的硫聚物凝膠之反應物載體結構，主要包括：一反應物載體結構，其組成結構外部是選自顆粒狀口香糖、顆粒狀糖果，顆粒狀巧克力、顆粒狀餅乾、圓球形狀之丸劑、圓形片狀之片劑、或長橢圓形殼之膠囊的其中一種；該反應物載體結構，其組成內部是由海藻酸鈉(Sodium alginate)溶液混合巰基乙酸(thioglycolic acid,TGA)在70℃~90℃的酸性環境(pH 2)中混合的硫醇化海藻酸鹽(Thiolated Alginate,TA)材料所構成。藉此以達到延長材料在腸道的停留時間，並在腸道形成一層薄膜減少吸收以減少能量攝取，達到預防或控制肥胖的效果
[[alternative]]Therapeutic ultrasonic device and the use thereof
No full text[[abstract]]本發明係揭示一種治療型超音波裝置，其係由至少一可組裝之弧形超音波換能器所組成，該可組裝之弧形超音波換能器係包含一突出部、一凹部及複數個壓電振動部，該突出部及該凹部係分別位於該可組裝之弧形超音波換能器之兩端，且該些壓電振動部係位於該可組裝之弧形超音波換能器之內側弧面；透過不同數量之該可組裝之弧形超音波換能器搭配使用，或於相互組接後獲得一環形超音波裝置，即可因應各種不同組織相應之軀體大小及之焦區需求，而廣泛應用在各種不同適應症之治療上
ADAM9 drives immunosuppressive environment for lung tumor progression
No full text[[abstract]]Cancer cells develop the immune suppressive tumor environment, but the underlying molecular mechanism for it is still elusive. Here, we demonstrated that ADAM9 contributed to lung tumor progression and promoted IFN-related gene expression in lung cancer cells that participated in immune regulation in the tumor environment. ADAM9 knockout (KO) lung cancer cells reduced lung cancer metastasis with a decrease in neutrophil infiltration and an increase in CD8+ T cell infiltration. By performing the genome-wide approach to explore ADAM9-regulated genes in lung cancer cells, we revealed that ADAM9 regulated cytokine production and lymphocyte activation. It enhanced the master transcription factor of IFN signaling, STAT1 activation in lung cancer cells. Moreover, ADAM9 promoted IL6/IL6 receptor-STAT3 axis signaling that lead to suppression of IL12p40 secretion and MHC class II expression in dendritic cells and macrophages. Notably, we found that type I IFN related-proteins and steroid biosynthesis-related proteins were related to ADAM9-mediated STAT signaling activation by LC-MS/MS analysis. We demonstrated that ADAM9 created an immune suppressive environment by regulating IFN signaling for tumor progression
VP1 codon deoptimization and high-fidelity substitutions in 3D polymerase as potential vaccine strategies for eliciting immune responses against enterovirus A71
No full text[[abstract]]Enterovirus A71 (EV-A71) can induce severe neurological complications and even fatal encephalitis in children, and it has caused several large outbreaks in Taiwan since 1998. We previously generated VP1 codon-deoptimized (VP1-CD) reverse genetics (rg) EV-A71 viruses (rgEV-A71s) that harbor a high-fidelity (HF) 3D polymerase. These VP1-CD-HF rgEV-A71s showed lower replication kinetics in vitro and decreased virulence in an Institute of Cancer Research (ICR) mouse model of EV-A71 infection, while still retaining their antigenicity in comparison to the wild-type virus. In this study, we aimed to further investigate the humoral and cellular immune responses elicited by VP1-CD-HF rgEV-A71s to assess the potential efficacy of these EV-A71 vaccine candidates. Following intraperitoneal (i.p.) injection of VP1-CD-HF rgEV-A71s in mice, we observed a robust induction of EV-A71-specific neutralizing IgG antibodies in the antisera after 21 days. Splenocytes isolated from VP1-CD-HF rgEV-A71s-immunized mice exhibited enhanced proliferative activities and cytokine production (IL-2, IFN-gamma, IL-4, IL-6, and TNF-alpha) upon re-stimulation with VP1-CD-HF rgEV-A71, as compared to control mice treated with adjuvant only. Importantly, administration of antisera from VP1-CD-HF rgEV-A71s-immunized mice protected against lethal EV-A71 challenge in neonatal mice. These findings highlight that our generated VP1-CD-HF rgEV-A71 viruses are capable of inducing both cellular and humoral immune responses, supporting their potential as next-generation EV-A71 vaccines for combating EV-A71 infection.IMPORTANCEEV-A71 can cause severe neurological diseases and cause death in young children. Here, we report the development of synthetic rgEV-A71s with the combination of codon deoptimization and high-fidelity (HF) substitutions that generate genetically stable reverse genetics (rg) viruses as potential attenuated vaccine candidates. Our work provides insight into the development of low-virulence candidate vaccines through a series of viral genetic editing for maintaining antigenicity and genome stability and suggests a strategy for the development of an innovative next-generation vaccine against EV-A71. EV-A71 can cause severe neurological diseases and cause death in young children. Here, we report the development of synthetic rgEV-A71s with the combination of codon deoptimization and high-fidelity (HF) substitutions that generate genetically stable reverse genetics (rg) viruses as potential attenuated vaccine candidates. Our work provides insight into the development of low-virulence candidate vaccines through a series of viral genetic editing for maintaining antigenicity and genome stability and suggests a strategy for the development of an innovative next-generation vaccine against EV-A71