Search Results (15)

Hyperuricemia, induced by monosodium urate (MSU) crystals that accumulate in articular joints and periarticular soft tissues, can impair macrophages. Possible causes of macrophage injury include uric acid-induced oxidative stress or inflammation. This study examined the dried fruits of guava (DFG) as a complementary medicine with urate-lowering properties, utilizing THP-1 macrophages to determine if high uric acid-induced cellular damage could be mitigated through the reduction of oxidative stress and inflammation via treatment with a phytochemical extract. The active extract was prescreened using a xanthine oxidase (XO) inhibition assay coupled with fractionation and component analysis. The DFG extracts were used to identify, through an in vitro study of THP-1 cells. The results indicated that the DFG extracts with the highest total flavonoids (12.08 ± 0.81 mg/g DW) exhibited the XO inhibition activity. High-performance liquid chromatography–tandem mass spectrometry analysis showed that DFG extract contained 85.32% flavonoids, including quercetin and kaempferol derivatives. Furthermore, fractionation results of DFG extracts indicated a significant reduction in MSU-induced cytotoxicity in THP-1 cells obtained from the 75% ethanol-eluted fraction (Fr-75). Additionally, kaempferol, an active compound in Fr-75, effectively mitigated MSU-induced NF-κB and NLRP3 gene overexpression. These findings suggest that the prepared Fr-75 is a promising hyperuricemia therapeutic candidate. Full article

The dose–response effect of proton pump inhibitors on colorectal cancer prognosis is still under exploration. This population-based study in Taiwan was designed to examine the effect of proton pump inhibitors on overall death, colorectal cancer-specific death, and recurrence in colorectal cancer patients with different cumulative proton pump inhibitor dose levels. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2005 to 2020. After frequency matching with a 1:1 ratio, a total of 20,889 users with proton pump inhibitors and 20,889 without proton pump inhibitors were analyzed. The cumulative defined daily dose level of proton pump inhibitor was stratified to explore the dose–response relationship. A proton pump inhibitor exposure cumulative defined daily dose > 60 after colorectal cancer diagnosis had higher risk of all-cause death than non-proton pump inhibitor users with adjusted hazard ratios of 1.10 (95% CIs: 1.04–1.18). For recurrence, a proton pump inhibitor exposure cumulative defined daily dose > 60 had reduced recurrence risk with an adjusted hazard ratio of 0.84 (95% CIs: 0.76–0.93). This study demonstrated that the long-term use of proton pump inhibitors in patients with colorectal cancer was associated with an increased risk of death that related to the proton pump inhibitor exposure cumulative defined daily dose > 60 and had different dose–response effect in various dose level. Full article

Chondrosarcoma is the second most common type of bone cancer. Surgical resection is the best choice for clinical treatment. High-grade chondrosarcoma is destructive and is more possible to metastasis, which is difficult to remove using surgery. Doxorubicin (Dox) is the most commonly used chemotherapy drug in the clinical setting; however, drug resistance is a major obstacle to effective treatment. In the present study, we compared Dox-resistant SW1353 cells to their parental cells using RNA sequencing (RNA-Seq). We found that the apelin (APLN) pathway was highly activated in resistant cells. In addition, tissue array analysis also showed that APLN was higher in high-grade tissues compared to low-grade tissues. APLN is a member of the adipokine family, which is a novel secreted peptide with multifunctional and biological activities. Previously, studies have shown that inhibition of the APLN axis may have a therapeutic benefit in cancers. However, the role of APLN in chondrosarcoma is completely unclear, and no related studies have been reported. During in vitro experiments, APLN was also observed to be highly expressed and secreted in Dox-resistant cells. Once APLN was knocked down, it could effectively improve its sensitivity to Dox. We also explored possible upstream regulatory microRNAs (miRNAs) of APLN through bioinformatics tools and the results disclosed that miR-631 was the most likely regulator of APLN. Furthermore, the expression of miR-631 was lower in the resistant cells, but overexpression of miR-631 in the Dox-resistant cell lines significantly increased the Dox sensitivity. These results were also observed in another chondrosarcoma cell line, JJ012 cells. Taken together, these findings will provide rationale for the development of drug resistance biomarkers and therapeutic strategies for APLN pathway inhibitors to improve the survival of patients with chondrosarcoma. Full article

Ever since the first games launched in the 1970s, the rapid growth of the video games market has successfully attracted more and more purchasers. In this study, we use Nintendo Switch as a case study to examine the extended technology acceptance model (TAM), which integrates the factors of Perceived Playfulness and Compatibility to determine their relevance in the usage behavior. A total of 266 questionnaires were obtained using snowball sampling and analyzed using the Structural Equation Modeling (SEM). The study results revealed that the expanded TAM model can be effectively used in this context and it also showed a good fit for the proposed model from the data analyzed. Attitude explained an R2 of 0.85, which indicates that 85% of the variance in user’s behavior intention is accounted by attitude. Perceived Ease of Use and Perceived Usefulness were significantly positively associated with attitude. Perceived Playfulness was significantly positively associated with Perceived Usefulness. This study also addresses the implications of the findings for researchers and the game marketing strategies practitioners. Full article

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon but life-threatening diseases mostly caused by drugs. Although various systemic immunomodulating agents have been used, their therapeutic efficacy has been inconsistent. This study aimed to provide an evidence-based review of systemic immunomodulating treatments for SJS/TEN. We reviewed 13 systematic review and meta-analysis articles published in the last 10 years. The use of systemic corticosteroids and IVIg is still controversial. An increasing number of studies have suggested the effectiveness of cyclosporine and biologic anti-TNF-α in recent years. There were also some promising results of combination treatments. Further large-scale randomized controlled trials are required to provide more definitive evidence of the effectiveness of these treatments. The pathogenesis of SJS/TEN has been elucidated in recent years and advances in the understanding of SJS/TEN may inspire the discovery of potential therapeutic targets. Full article

The number of people living with dementia globally is increasing rapidly, and there is no effective therapy. Dietary pattern is one important risk factor for the development and progression of dementia. We undertake this study to determine whether Taiwanese vegetarian diet in midlife affects dementia incidence in later years in a prospective cohort. We followed 5710 participants (average age less than 60) in the Tzu Chi Vegetarian Study (TCVS). We started recruiting in 2005 and followed until the end of 2014 when the database changed from ICD-9-CM to ICD-10-CM codes. The incidence of dementia was obtained through linkage to the National Health Insurance Research Database. We used Cox proportional hazards regression to estimate the hazard ratio of dementia between vegetarians and nonvegetarians. There were 121 cases of dementia (37 vegetarians and 84 nonvegetarians) diagnosed. Vegetarians were associated with reduced risk of clinically overt dementia compared with nonvegetarians (hazard ratio = 0.671, confidence interval: 0.452–0.996, p < 0.05) after adjusting for gender, age, smoking, drinking, education level, marriage, regular exercise, and comorbidities with stepwise regression. Full article

Large clinical trials have proven the efficacy of the COVID-19 vaccine, and the number of studies about the effectiveness rapidly grew in the first half of the year after mass vaccination was administrated globally. This rapid review aims to provide evidence syntheses as a means to complement the current evidence on the vaccine effectiveness (VE) against various outcomes in real-world settings. Databases (PubMed, EMBASE, and MedRxiv) were searched up to 30 June 2021, (PROSPERO ID: 266866). A total of 39 studies were included, covering over 15 million participants from 11 nations. Among the general population being fully vaccinated, the VE against symptomatic SARS-CoV-2 infection was estimated at 89–97%, 92% (95% CI, 78–97%), and 94% (95% CI, 86–97%) for BNT162b2, ChAdOx1, and mRNA-1273, respectively. As for the protective effects against B.1.617.2-related symptomatic infection, the VE was 88% (95% CI, 85.3–90.1%) by BNT162b2 and 67.0% (95% CI, 61.3–71.8%) by ChAdOx1 after full vaccination. This review revealed a consistently high effectiveness of certain vaccines among the general population in real-world settings. However, scarce data on the major variants of SARS-CoV-2 and the shortness of the study time may limit the conclusions to the mRNA vaccines and ChAdOx1. Full article

Health literacy (HL), which is a determinant of individuals’ health as well as a personal and public asset, can be improved by community healthcare providers (CHPs) with the capability of providing HL services. The purpose of this study was to explore CHPs’ familiarity with and attitudes toward HL and their confidence in implementing HL practices. A cross-sectional online survey was conducted involving a total of 104 CHPs from 20 public health centers in Taiwan. It was based on a structured questionnaire involving self-evaluation by participants. The scores for familiarity, attitudes, and confidence in implementing HL practices were mean = 4.36, SD = 1.99; mean = 7.45, SD = 1.93; and mean = 6.10, SD = 1.77 (out of 10 points), respectively. The results of the multiple regression analysis showed that the two independent variables of familiarity and attitude could predict confidence in implementing HL practices (R² = 0.57, F(2101) = 58.96, p < 0.001). The CHPs surveyed were not especially familiar with HL; thus, they recognized its importance, but they lacked confidence in implementing HL practices. Increasing practitioners’ familiarity with HL may therefore boost their confidence in implementation. The research results can serve as a reference when planning HL education and training. Full article

Type 2 diabetes might be influenced by colonic disease; however, the association between colonic resection and type 2 diabetes has rarely been discussed. This population-based cohort study explored the association between colectomy and type 2 diabetes in patients without colorectal cancer. A total of 642 patients who underwent colectomy for noncancerous diseases at any time between 2000 and 2012 in the National Health Insurance Research Database of Taiwan were enrolled. The enrolled patients were matched with 2568 patients without colectomy at a 1:4 ratio using a propensity score that covered age, sex, and comorbidities. The risk of type 2 diabetes was assessed using a Cox proportional hazards model. The mean (standard deviation) follow-up durations in colectomy cases and non-colectomy controls were 4.9 (4.0) and 5.6 (3.6) years, respectively; 65 (10.1%) colectomy cases and 342 (15.5%) non-colectomy controls developed type 2 diabetes. After adjustment, colectomy cases still exhibited a decreased risk of type 2 diabetes (adjusted HR = 0.80, 95% CI: 0.61–1.04). A stratified analysis for colectomy type indicated that patients who underwent right or transverse colectomy had a significantly lower risk of developing type 2 diabetes (adjusted HR = 0.57, 95% CI: 0.34–0.98). In the present study, colectomy tended to be at a reduced risk of type 2 diabetes in patients without colorectal cancer, and right or transverse colectomies were especially associated with a significantly reduced risk of type 2 diabetes. Full article

Several anaplastic lymphoma kinase inhibitors (ALKIs) have demonstrated excellent efficacy on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and also better adverse effect (AE) profiles compared to cytotoxic chemotherapy in advanced stage anaplastic lymphoma kinase (ALK) rearrangement-positive non-small cell lung cancer (NSCLC) in phase III randomized clinical trials (RCTs). We conducted this systematic review and network meta-analysis to provide a ranking of ALKIs for treatment-naïve ALK-positive patients in terms of PFS, ORR, and AEs. In addition, a sub-group analysis of treatment benefits in patients with baseline brain metastasis was also conducted. Contrast-based analysis was performed for multiple treatment comparisons with the restricted maximum likelihood approach. Treatment rank was estimated using the surface under the cumulative ranking curve (SUCRA), as well as the probability of being the best (Prbest) reference. All next-generation ALKIs were superior to crizotinib in PFS but lorlatinib and brigatinib had increased AEs. The probability of lorlatinib being ranked first among all treatment arms was highest (SUCRA = 93.3%, Prbest = 71.8%), although there were no significant differences in pairwise comparisons with high- (600 mg twice daily) and low- (300 mg twice daily) dose alectinib. In subgroup analysis of patients with baseline brain metastasis, low-dose alectinib had the best PFS (SUCRA = 87.3%, Prbest = 74.9%). Lorlatinib was associated with the best ranking for ORR (SUCRA = 90.3%, Prbest = 71.3%), although there were no significant differences in pairwise comparisons with the other ALKIs. In addition, low-dose alectinib had the best safety performance (SUCRA = 99.4%, Prbest = 97.9%). Lorlatinib and low-dose alectinib had the best PFS and ORR in the overall population and baseline brain metastasis subgroup, respectively. Low-dose alectinib had the lowest AE risk among the available ALKIs. Further head-to-head large-scale phase III RCTs are needed to verify our conclusions. Full article

In the real world, dynamic changes in air pollutants and meteorological factors coexist simultaneously. Studies identifying the effects of individual pollutants on acute exacerbation (AE) of asthma may overlook the health effects of the overall combination. A comprehensive study examining the influence of air pollution and meteorological factors is required. Asthma AE data from emergency room visits were collected from the Taiwan National Health Insurance Research Database. Complete monitoring data for air pollutants (SO₂; NO₂; O₃; CO; PM_2.5; PM₁₀) and meteorological factors were collected from the Environmental Protection Agency monitoring stations. A bi-directional case-crossover analysis was used to investigate the effects of air pollution and meteorological factors on asthma AE. Among age group divisions, a 1 °C temperature increase was a protective factor for asthma ER visits with OR = 0.981 (95% CI, 0.971–0.991) and 0.985 (95% CI, 0.975–0.994) for pediatric and adult patients, respectively. Children, especially younger females, are more susceptible to asthma AE due to the effects of outdoor air pollution than adults. Meteorological factors are important modulators for asthma AE in both asthmatic children and adults. When studying the effects of air pollution on asthma AE, meteorological factors should be considered. Full article

Both vasculature and myocardium in the heart are excessively damaged following myocardial infarction (MI), hence therapeutic strategies for treating MI hearts should concurrently aim for true cardiac repair by introducing new cardiomyocytes to replace lost or injured ones. Of them, mesenchymal stem cells (MSCs) have long been considered a promising candidate for cell-based therapy due to their unspecialized, proliferative differentiation potential to specific cell lineage and, most importantly, their capacity of secreting beneficial paracrine factors which further promote neovascularization, angiogenesis, and cell survival. As a consequence, the differentiated MSCs could multiply and replace the damaged tissues to and turn into tissue- or organ-specific cells with specialized functions. These cells are also known to release potent anti-fibrotic factors including matrix metalloproteinases, which inhibit the proliferation of cardiac fibroblasts, thereby attenuating fibrosis. To achieve the highest possible therapeutic efficacy of stem cells, the other interventions, including hydrogels, electrical stimulations, or platelet-derived biomaterials, have been supplemented, which have resulted in a narrow to broad range of outcomes. Therefore, this article comprehensively analyzed the progress made in stem cells and combinatorial therapies to rescue infarcted myocardium. Full article

The Japanese encephalitis virus (JEV) is the major cause of an acute encephalitis syndrome in many Asian countries, despite the fact that an effective vaccine has been developed. Virus-like particles (VLPs) are self-assembled multi-subunit protein structures which possess specific epitope antigenicities related to corresponding native viruses. These properties mean that VLPs are considered safe antigens that can be used in clinical applications. In this study, we developed a novel baculovirus/mosquito (BacMos) expression system which potentially enables the scalable production of JEV genotype III (GIII) VLPs (which are secreted from mosquito cells). The mosquito-cell-derived JEV VLPs comprised 30-nm spherical particles as well as precursor membrane protein (prM) and envelope (E) proteins with densities that ranged from 30% to 55% across a sucrose gradient. We used IgM antibody-capture enzyme-linked immunosorbent assays to assess the resemblance between VLPs and authentic virions and thereby characterized the epitope specific antigenicity of VLPs. VLP immunization was found to elicit a specific immune response toward a balanced IgG2a/IgG1 ratio. This response effectively neutralized both JEV GI and GIII and elicited a mixed Th1/Th2 response in mice. This study supports the development of mosquito cell-derived JEV VLPs to serve as candidate vaccines against JEV. Full article

Protein-energy wasting is prevalent in peritoneal dialysis patients, which causes a heavy burden for individuals and healthcare systems. We aimed to investigate the effect of nutritional education, and/or protein supplementation on nutritional biomarkers in hypoalbuminemic peritoneal dialysis patients. A quasi-experimental study was conducted in two dialysis centers at Taipei Tzu Chi Hospital and Shin Kong Wu Ho-Su Memorial Hospital. Patients were allocated in three groups including control (n = 12), milk protein (n = 21) and soy protein (n = 20). All patients received dietary guidelines from dietitians and completed 3-day dietary records during monthly visits for consecutive three months. Nutrients were analyzed using Nutritionist Professional software. Blood urea nitrogen (BUN), creatinine, albumin, total protein, hemoglobin, serum calcium, phosphorus, sodium, and potassium were assessed monthly. Total cholesterol and triglycerides were measured every three months. After three-month intervention, protein intake (percent of total calories), and serum albumin were significantly increased in three groups. Protein, phosphorus intake, and BUN were increased in two intervention groups. Total serum protein increased in control and milk protein groups, and creatinine increased the control group. Serum phosphorus was not significantly changed. Nutritional education alone, or combined with protein supplementation, significantly improve protein intake, and nutritional status by increasing serum albumin, but not serum phosphorus in hypoalbuminemic peritoneal dialysis patients. Full article

Major depressive disorder and cardiovascular disease are common serious illnesses worldwide. Selective serotonin reuptake inhibitors and norepinephrine-dopamine reuptake inhibitors may reduce the mortality of cardiovascular disease patients with comorbid depression. Interferon-γ-inducible protein 10 (IP-10), a type 1 T helper cell (Th1)-related chemokine, contributes to manifestations of atherosclerosis during cardiovascular inflammations; however, the pathophysiological mechanisms linking cardiovascular disease and effective antidepressants have remained elusive. We investigated the in vitro effects of six different classes of antidepressants on the IP-10 chemokine expression in lipopolysaccharide (LPS)-stimulated monocytes, and their detailed intracellular mechanisms. The human monocytes were pretreated with antidepressants (10⁻⁸–10⁻⁵ M) before LPS-stimulation. IP-10 was measured by enzyme-linked immunosorbent assay (ELISA) and then intracellular signaling was investigated using Western blotting and chromatin immunoprecipitation. Fluoxetine and bupropion suppressed LPS-induced IP-10 expression in monocytes, and they had no cytotoxic effects. Furthermore, fluoxetine inhibited LPS-induced IP-10 expression via the mitogen-activated protein kinase (MAPK)-p38 pathway. Fluoxetine and bupropion could not only treat depression but also reduce Th1-related chemokine IP-10 production in human monocytes. Our results may indicate a possible mechanism related to how particular antidepressants reduce the risk of cardiovascular disease. Full article