Fucoidan is a fucose-rich polysaccharide that has gained attention for its various anticancer properties. However, the effect and underlying mechanism of fucoidan on triple-negative breast cancer ...(TNBC) are still unknown. Herein, we investigated the anticancer potential of fucoidan from Laminaria japonica. We found that fucoidan showed modest antiproliferative activity against TNBC cells, while it effectively reduced migratory and invasive capacities. Mechanistically, fucoidan suppressed activation of MAPK and PI3K followed by inhibition of AP-1 and NF-κB signaling in TNBC. Additionally, fucoidan downregulated expressions of proangiogenic factors in TNBC cells, and fucoidan blocked tumor-elicited tube formation by human umbilical vascular endothelial cells (HUVECs). We also observed that fucoidan blocked tumor adhesion and invasion towards HUVECs. Surprisingly, fucoidan robustly suppressed tube formation on HUVECs. Moreover, fucoidan inhibited in vivo angiogenesis and micrometastasis in a transgenic zebrafish model. Together, L. japonica fucoidan exhibits potent antitumor effects by its attenuation of invasiveness and proangiogenesis in TNBC.
•Fucoidan from Laminaria japonica exerts antitumor effects.•Fucoidan suppresses proangiogenesis and micrometastasis in TNBC.•Fucoidan blocks MAPK and PI3K signaling in TNBC.
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•ITC quantitatively determines the purity of recombinantly produced proteins.•Protein capability of binding a specific ligand is observed in a single experiment.•ITC is convenient for ...the determination of the intrinsic binding parameters.
Isothermal titration calorimetry is widely used to measure the affinities and enthalpies of interaction between proteins and/or small molecules. The quantitative nature of the technique is especially useful in the characterization of recombinant proteins while determining the fraction of protein capable of binding a specific ligand and thus the protein purity. The revealed thermodynamic information sheds light on the binding mechanism, important for the targeted drug design of the biologics. Here we show examples how, together with the thermal shift assay, combination of both techniques enables characterization of protein stability and ligand binding. Furthermore, the binding-linked reactions that strongly affect the observed thermodynamic parameters and must be dissected to obtain the intrinsic parameters that are necessary for the structure-based rational drug design are being demonstrated using inhibitors of Hsp90, an anticancer target protein.
Xanthohumol (XN), a natural prenylated flavonoid isolated from Humulus lupulus L. (hops), possess the therapeutic effects in glioblastoma multiforme (GBM), which is a grade IV aggressive glioma in ...adults. However, low bioavailability and extractive yield limit the clinical applications of XN. To comprehensively investigate XN-mediated gene networks in inducing cell death is helpful for drug development and cancer research. Therefore, we aim to identify the detailed molecular mechanisms of XN's effects on exhibiting cytotoxicity for GBM therapy.
XN significantly induced GBM cell death and enhanced temozolomide (TMZ) cytotoxicity, a first-line therapeutic drug of GBM. XN-mediated transcriptome profiles and canonical pathways were identified. DNA repair signaling, a well-established mechanism against TMZ cytotoxicity, was significantly correlated with XN-downregulated genes. Replication factor C subunit 2 (RFC2), a DNA repair-related gene, was obviously downregulated in XN-treated cells. Higher RFC2 levels which occupied poor patient survival were also observed in high grade GBM patients and tumors. Inhibition of RFC2 reduced cell viability, induced cell apoptosis, and enhanced both XN and TMZ cytotoxicity. By intersecting array data, bioinformatic prediction, and in vitro experiments, microRNA (miR)-4749-5p, a XN-upregulated microRNA, was identified to target to RFC2 3′UTR and inhibited RFC2 expression. A negative correlation existed between miR-4749-5p and RFC2 in GBM patients. Overexpression of miR-4749-5p significantly promoted XN- and TMZ-mediated cytotoxicity, and reduced RFC2 levels.
Consequently, we suggest that miR-4749-5p targeting RFC2 signaling participates in XN-enhanced TMZ cytotoxicity of GBM. Our findings provide new potential therapeutic directions for future GBM therapy.
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•Xanthohumol-reduced RFC2 expression enhances temozolomide cytotoxicity of GBM.•GBM patients with higher RFC2 levels occupy poor survival.•RFC2 may act as an oncogene in GBM progression.•miR-4749-5p, upregulated by Xanthohumol, targets and inhibits RFC2 expression.•miR-4749-5p-supressed RFC2 signaling promotes XN- and TMZ-mediated cytotoxicity.
Background
The efficacy of adjuvant sublingual immunotherapy (SLIT) in correcting structural problems in patients with allergic rhinitis (AR) caused by mite who have undergone septomeatoplasty (SMP) ...has not been studied.
Methods
This non‐randomized controlled study recruited patients with AR (caused by mite) and concurrent septal deviation and inferior turbinate hypertrophy, at a tertiary hospital in Taiwan. SMP was performed on all patients as a surgical intervention. The patients were then divided into two groups: the control group, which underwent surgery only, and the experimental group, which received SLIT as an adjuvant treatment. Demographic data and rhinitis control assessment test (RCAT) results were analyzed.
Results
A total of 96 patients were enrolled in the study (SMP + SLIT group, n = 52; SMP only group, n = 44). No significant differences were observed in any of the variables between the two groups before and one month after surgery. However, during evaluations at the third and sixth month, the SMP + SLIT group showed significant improvement in the total RCAT scores compared to the SMP only group (28.6 ± 1.56 vs. 24.5 ± 3.66, p < 0.001; 27.1 ± 2.87 vs. 19.9 ± 5.56, p < 0.001). In addition, significantly better control of all RCAT sub‐categories was observed in the SMP + SLIT group at the third and sixth month evaluations.
Conclusions
SLIT may serve as an ideal adjuvant therapy after SMP in patients with AR.
Level of Evidence
3 Laryngoscope, 134:3073–3079, 2024
Sublingual immunotherapy(SLIT) may serve as an ideal adjuvant therapy after septomeatoplasty in patients with allergic rhinitis (AR), providing beneficial effects within a short timeframe. SLIT may prevent recurrence of AR symptoms, especially sneezing.
Uremic pruritus (UP) is prevalent among patients with end-stage renal disease (ESRD), which causes severe itching and affects their quality of life. Additionally, patients experience fatigue and ...depression, and an increased risk of mortality has also been reported. A meta-analysis of 17 randomized controlled trials (RCTs) has indicated that Chinese herbal bath therapy (CHBT) had adjuvant benefits in improving UP in ESRD patients, and previous studies have reported that herb combinations were more useful than treatment with a single herb. Association rule analysis has been used to evaluate potential correlations between herb combinations, and Apriori algorithms are one of the most powerful machine-learning algorithms available for identifying associations within databases. Therefore, we used the Apriori algorithm to analyze association rules of potential core herb combinations for use in CHBT for UP treatment using data from a meta-analysis of 17 RCTs that used CHBT for UP treatment. Data on 43 CHBT herbs were extracted from 17 RCTs included for analysis and we found 19 association rules. The results indicated that the following herb combinations {Chuanxiong, Baijili} ≥ {Dahuang} and {Dahuang, Baijili} ≥ {Chuanxiong} were most strongly associated, implying that these herb combinations represent potential CHBT treatments for UP.
Mosquitoes act as vectors for many life-threatening diseases, including malaria, dengue fever, and Zika virus infection. Management of mosquitoes mainly relies on synthetic insecticides, which ...usually result in the rapid development of resistance; therefore, alternative mosquito control strategies are urgently needed. This study characterized the major component of essential oils (EOs) derived from the vegetative parts of four herbal plants and their larvicidal activity toward important mosquito vectors. The EOs were extracted by hydro-distillation and subjected to gas chromatography–mass spectrometry (GC–MS) analysis and a larvicidal activity assay toward Aedes aegypti, Ae. albopictus and Culex quinquefasciatus. In total, 14, 11, 11 and 9 compounds were identified from the EOs of Plectranthus amboinicus, Mentha requienii, Vitex rotundifolia and Crossostephium chinense, respectively. The EOs derived from four herbal plants exhibited remarkable larvicidal activity against the three mosquito species. In particular, the EOs of P. amboinicus showed the highest larvicidal activity, and the larvae of Cx. quinquefasciatus were more sensitive to the P. amboinicus EOs than that of Ae. Aegypti. Although carvacrol (61.53%) was the predominant constituent of the P. amboinicus EOs, its precursors, γ-terpinene (8.51%) and p-cymene (9.42%), exhibited the most larvicidal activity toward Ae. aegypti and Cx. quinquefasciatus. However, ß-caryophyllene (12.79%) might be the major component responsible for the differential toxicity of the P. amboinicus EOs, as indicated by the significant differences in its LC₅₀ values toward both mosquitoes. Information from these studies will benefit the incorporation of EOs into integrated vector management.
•Type III necrotizing fasciitis (NF) is encountered predominantly in Asian countries.•Type III NF has a mortality risk two-fold higher than type I or type II NF.•Type III NF caused by extraintestinal ...pathogenic Escherichia coli (ExPEC) exhibits the highest mortality risk.•Type III NF caused by Klebsiella pneumoniae has the second highest mortality risk.
The aim of this study was to investigate the prognostic value of reclassified new type III monomicrobial gram-negative necrotizing fasciitis (NF) and the microbial factors associated with an increased risk of mortality.
This study included 235 NF cases treated at National Taiwan University Hospital. We compared the mortality risk of NF caused by different causal microorganisms and examined the bacterial virulence genes profile and antimicrobial susceptibility pattern associated with an increase in mortality risk.
Type III NF (n = 68) had a mortality risk two-fold higher than type I (polymicrobial, n = 64) or type II (monomicrobial gram-positive, n = 79) NF (42.6% vs 23.4% or 19.0%, P = 0.019 and 0.002, respectively). Mortality differed by causal microorganism (Escherichia coli 61.5%, Klebsiella pneumoniae 40.0%, Aeromonas hydrophila 37.5%, Vibrio vulnificus 25.0%, polymicrobial 23.4%, group A streptococci 16.7%, and Staphylococcus aureus 16.2%, in decreasing rank, P <0.001). Type III NF caused by E. coli, identified as extraintestinal pathogenic E. coli (ExPEC) via virulence gene analyses, was associated with a particularly high mortality risk (adjusted odds ratio: 6.51, P = 0.003) after adjusting for age and comorbidities. Some (38.5%/7.7%) of the E. coli strains were non-susceptible to third/fourth-generation cephalosporins but remained susceptible to carbapenems.
Type III NF, especially cases caused by E. coli or K. pneumoniae, are associated with a comparatively higher mortality risk than type I or type II NF. Wound gram stain-based rapid diagnosis of type III NF may inform empirical antimicrobial therapy to include a carbapenem.
Two types of intraocular lenses (IOLs), namely ultraviolet-filtering IOL (UVF-IOL) and blue-light-filtering IOL (BF-IOL), are used to replace the aging lens in cataract patients. This provides a ...clinical scenario to investigate the BF and UVF effects on circadian rhythm. We revisited this topic and conducted an updated meta-analysis investigating the effects of UVF-IOL and BF-IOL on sleep quality.
A literature search was conducted using the PubMed, Embase, and Cochrane Library databases, and finally, four randomized controlled trials, one nonrandomized controlled study, and two cohort studies were included in this meta-analysis.
The fixed-effect model revealed a significantly larger sleep quality improvement in the UVF-IOL group than in the BF-IOL group (standard mean difference SMD = 0.10, 95% confidence interval CI: 0.00-0.21) at 3-8 weeks but not 7-12 months after IOL implantation (SMD = 0.03, 95% CI: -0.08 to 0.13). The random effects model revealed no difference between groups at 3-8 weeks (SMD = 0.16, 95% CI: -0.07 to 0.39) and 7-12 months (SMD = 0.03, 95% CI: -0.08 to 0.13) after IOL implantation.
Our study found some weak evidence supporting that UVF-IOL implantation demonstrated a greater improvement in subjective sleep quality than the BF-IOL implantation only in a shorter period but not in a longer period. More trials should be conducted before further recommendations. Nevertheless, our study provides some insights into the effects of short wavelength electromagnetic radiation on the circadian rhythm. PROSPERO registration number: CRD42019128832.
Abstract
Nowadays, solar energy is the most environmentally friendly energy source to drive many chemical reactions and physical processes. However, the corresponding fabrication procedures for ...obtaining excellent energy-storage devices are relatively complicated and expensive. In this work, we report an innovative strategy on plasmon-activated water (PAW) serving as energy-storage medium from solar energy. The lifetime of the created energetic PAW solution from hot electron transfer (HET) on Au nanoparticles (AuNPs) illuminated with sunshine can last for 2 days, making the energy-storage system is practically available. Encouragingly, the energy-conversion efficiency from the solar energy in the PAW solution is ca. 6.7%. Compared to conventional deionized (DI) water solution, the prepared metastable PAW solution exhibited distinctly higher chemical potential at room temperature. It demonstrates abilities in faster evaporation and enhancing chemical reactions, including hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Our proposed strategy on the simple and cheap energy-storage system based on prepared PAW utilizing solar energy is the first time shown in the literature.
The polysaccharides from Ophiopogon japonicus (OJPs) were known to have protective effects against diabetes, and cardiovascular and chronic inflammatory diseases. However, OJPs were poorly absorbed ...after oral administration, resulting in limited efficacy because of the low bioavailability. In this study, OJPs extracted and fractionated from Ophiopogon japonicus were used to prepare OJPs/chitosan (CS)/whey protein (WP) co-assembled nanoparticles. The OJPs/CS/WP nanoparticles showed high biocompatibility and inhibited the cytotoxicity of RAW264.7 cells induced by nickel. With the assistance of CS and WP, the anti-inflammatory and antioxidant activities of OJPs were enhanced because the nanoparticles improved OJPs uptake by RAW264.7 macrophage cells as evidenced by efficient scavenging of DPPH and ABTS free radicals and effective inhibition of NO production and the gene expressions of iNOS, COX2, TNF-α, CCL2, and CXCL2 inflammatory signals. Determining the transepithelial electrical resistance and paracellular permeability of Caco-2 monolayer/macrophage co-cultured system suggested that the OJPs-loaded nanoparticles effectively protected the intestinal epithelial barrier integrity against the damage caused by LPS-stimulated macrophage inflammation and attenuated the defects of intestinal epithelial TJ barrier and permeability. These findings suggest that the OJPs/CS/WP nanoparticles may be potential carriers for oral delivery of OJPs to treat intestinal barrier defects, such as inflammatory bowel disease (IBD).
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•OJPs/chitosan (CS)/whey protein (WP) co-assembled nanoparticles were successfully prepared.•OJPs/CS/WP nanoparticles inhibited the cytotoxicity of RAW264.7 cells induced by nickel.•OJPs/CS/WP nanoparticles improved OJPs uptake by RAW264.7 macrophage cells.•OJPs/CS/WP nanoparticles enhanced anti-inflammatory and antioxidant activities of OJPs.•OJPs/CS/WP nanoparticles attenuated the defects of intestinal epithelial TJ barrier and permeability.
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