BACKGROUND:The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These ...areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated.
METHODS:To investigate the effects of gut microbiota on cardiac repair after MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.
RESULTS:Antibiotic-treated mice displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells and SCFAs, more specifically acetate, butyrate, and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved after fecal reconstitution, transplantation of monocytes, or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community such as a reduction in Lactobacillus. Supplementing antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward propionate.
CONCLUSIONS:Gut microbiota–derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI and indeed human health and disease as a whole.
A White Random Laser Chang, Shu-Wei; Liao, Wei-Cheng; Liao, Yu-Ming ...
Scientific reports,
02/2018, Letnik:
8, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Random laser with intrinsically uncomplicated fabrication processes, high spectral radiance, angle-free emission, and conformal onto freeform surfaces is in principle ideal for a variety of ...applications, ranging from lighting to identification systems. In this work, a white random laser (White-RL) with high-purity and high-stability is designed, fabricated, and demonstrated via the cost-effective materials (e.g., organic laser dyes) and simple methods (e.g., all-solution process and self-assembled structures). Notably, the wavelength, linewidth, and intensity of White-RL are nearly isotropic, nevertheless hard to be achieved in any conventional laser systems. Dynamically fine-tuning colour over a broad visible range is also feasible by on-chip integration of three free-standing monochromatic laser films with selective pumping scheme and appropriate colour balance. With these schematics, White-RL shows great potential and high application values in high-brightness illumination, full-field imaging, full-colour displays, visible-colour communications, and medical biosensing.
Most orally administered drugs fail to reach the intracerebral regions because of the intestinal epithelial barrier (IEB) and the blood–brain barrier (BBB), which are located between the gut and the ...brain. Herein, an oral prodrug delivery system that can overcome both the IEB and the BBB noninvasively is developed for treating gliomas. The prodrug is prepared by conjugating an anticancer drug on β‐glucans using a disulfide‐containing linker. Following oral administration in glioma‐bearing mice, the as‐prepared prodrug can specifically target intestinal M cells, transpass the IEB, and be phagocytosed/hitchhiked by local macrophages (Mϕ). The Mϕ‐hitchhiked prodrug is transported to the circulatory system via the lymphatic system, crossing the BBB. The tumor‐overexpressed glutathione then cleaves the disulfide bond within the prodrug, releasing the active drug, improving its therapeutic efficacy. These findings reveal that the developed prodrug may serve as a gut‐to‐brain oral drug delivery platform for the well‐targeted treatment of gliomas.
Following oral administration, a prodrug transpasses the intestinal epithelial barrier via M cells, and then undergoes endocytosis by resident macrophages. The macrophage‐hitchhiked prodrug is transported to the circulatory system via the lymphatic system, crossing the blood–brain barrier, ultimately penetrating a brain tumor. The tumor‐overexpressed glutathione cleaves the disulfide bond within the prodrug, releasing the active drug, facilitating antitumor efficacy.
Multidrug resistance (MDR) resulting from the overexpression of drug transporters such as P‐glycoprotein (Pgp) increases the efflux of drugs and thereby limits the effectiveness of chemotherapy. To ...address this issue, this work develops an injectable hollow microsphere (HM) system that carries the anticancer agent irinotecan (CPT‐11) and a NO‐releasing donor (NONOate). Upon injection of this system into acidic tumor tissue, environmental protons infiltrate the shell of the HMs and react with their encapsulated NONOate to form NO bubbles that trigger localized drug release and serve as a Pgp‐mediated MDR reversal agent. The site‐specific drug release and the NO‐reduced Pgp‐mediated transport can cause the intracellular accumulation of the drug at a concentration that exceeds the cell‐killing threshold, eventually inducing its antitumor activity. These results reveal that this pH‐responsive HM carrier system provides a potentially effective method for treating cancers that develop MDR.
Two is better than one: A carrier system is developed that can generate NO bubbles in the acidic environment of tumor tissues to trigger localized drug release (specifically irinotecan, denoted CPT‐11) and to reverse Pgp‐mediated multidrug resistance (Pgp=P‐glycoprotein). The combined system enhances intracellular drug accumulation in cancer cells so that the concentration exceeds the therapeutic threshold, eventually leading to antitumor activity.
Flavones found in plants display various biological activities, including anti-allergic, anti-viral, anti-inflammatory, anti-oxidation, and anti-tumor effects. In this study, we investigated the ...anti-tumor effects of flavone, apigenin and luteolin on human breast cancer cells.
The anti-cancer activity of flavone, apigenin and luteolin was investigated using the MTS assay. Apoptosis was analyzed by Hoechst 33342 staining, flow cytometry and western blot. Cell migration was determined using the culture inserts and xCELLigence real-time cell analyzer instrument equipped with a CIM-plate 16. Real-time quantitative PCR and western blot were used to determine the signaling pathway elicited by flavone, apigenin and luteolin.
Flavone, apigenin and luteolin showed potent inhibitory effects on the proliferation of Hs578T, MDA-MB-231 and MCF-7 breast cancer cells in a concentration and time-dependent manner. The ability of flavone, apigenin and luteolin to inhibit the growth of breast cancer cells through apoptosis was confirmed by Hoechst33342 staining and the induction of sub-G1 phase of the cell cycle. Flavone, apigenin and luteolin induced forkhead box O3 (FOXO3a) expression by inhibiting Phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB)/Akt. This subsequently elevated the expression of FOXO3a target genes, including the Cyclin-dependent kinase inhibitors p21Cip1 (p21) and p27kip1 (p27), which increased the levels of activated poly(ADP) polymerase (PARP) and cytochrome c.
Taken together, these data demonstrated that flavone, apigenin and luteolin induced cell cycle arrest and apoptosis in breast cancer cells through inhibiting PI3K/Akt activation and increasing FOXO3a activation, which suggest that flavone, apigenin and luteolin will be the potential leads for the preventing and treating of breast cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Targeted oral delivery of a drug via the intestinal lymphatic system (ILS) has the advantages of protecting against hepatic first‐pass metabolism of the drug and improving its pharmacokinetic ...performance. It is also a promising route for the oral delivery of vaccines and therapeutic agents to induce mucosal immune responses and treat lymphatic diseases, respectively. This article describes the anatomical structures and physiological characteristics of the ILS, with an emphasis on enterocytes and microfold (M) cells, which are the main gateways for the transport of particulate delivery vehicles across the intestinal epithelium into the lymphatics. A comprehensive overview of recent advances in the rational engineering of particulate vehicles, along with the challenges and opportunities that they present for improving ILS drug delivery, is provided, and the mechanisms by which such vehicles target and transport through enterocytes or M cells are discussed. The use of naturally sourced materials, such as yeast microcapsules and their derived polymeric β‐glucans, as novel ILS‐targeting delivery vehicles is also reviewed. Such use is the focus of an emerging field of research. Their potential use in the oral delivery of nucleic acids, such as mRNA vaccines, is proposed.
The rational engineering of effective vehicles for lymphatic delivery of drugs, through targeting enterocytes or M cells, prevents their first‐pass metabolism by the liver, markedly increasing the bioavailability of oral drugs. By achieving increased bioavailability, high drug concentrations are attainable at the lesions of interest with beneficial therapeutic effects, making intestinal lymphatic transport a unique modality of drug delivery.
Following a mixed-methods approach, this study investigated the effect of a virtual reality (VR) creative project on EFL learners’ creative self-efficacy as well as their intrinsic motivation toward ...using VR technology. A class of 39 university students in Taiwan participated in the VR-supported creative project with the instructor’s guidance step by step. A creative self-efficacy student scale, an intrinsic motivation inventory and an open-ended survey were given to the students to explore how the project might have influenced their efficacy for creativity and learning of English. Results indicate that the VR-supported project facilitated the students’ efficacy for creative thinking in particular; yet, their efficacy for creative production as well as for their own competence while facing negative feedback did not change significantly. Moreover, those who had high creative self-efficacy also felt less pressure and tension toward this VR-supported project than their counterparts with low creative self-efficacy. Furthermore, working on the VR-supported project was perceived by the students to be a refreshing and relaxing learning experience that also benefited their learning of English. Based on the research findings, pedagogical implications are discussed with regard to how VR technology can be effectively integrated into an English classroom to facilitate students’ creative self-efficacy and intrinsic motivation.
While basal insulin remains the most effective antidiabetic agent and substantially reduces the risk of hypoglycemia, few studies have examined the comparative effect of basal insulin in the ...real-world setting. This study aimed to assess the outcomes of adding basal insulin compared with thiazolidinediones (TZDs) or dipeptidyl peptidase-4 inhibitors (DPP-4is) as a third antidiabetic agent in patients with type 2 diabetes mellitus (T2DM). A retrospective cohort study involving T2DM was conducted with health administrative data in Taiwan. Patients starting a third antidiabetic agent after receiving a metformin-containing dual combination were identified. The study endpoints included composite major adverse cardiovascular events (MACEs), all-cause mortality, and hypoglycemia. Propensity score matching and Cox modeling were used for analysis. After matching, the basal insulin and TZD groups contained 6,101 and 11,823 patients, respectively, and the basal insulin and DPP-4i groups contained 6,051 and 11,900 patients, respectively. TZDs and DPP-4is were both associated with similar risks of MACEs and hypoglycemia but a lower risk of all-cause mortality than basal insulin (TZDs: HR 0.55, 95% CI 0.38-0.81; DPP-4is: HR 0.56, 95% CI 0.39-0.82). Further studies are needed to elucidate the findings of increased all-cause mortality risk in patients receiving basal insulin, especially those with advanced diabetes.
We aimed to determine the prognostic significance of cardiac dose and hematological immunity parameters in esophageal cancer patients after concurrent chemoradiotherapy (CCRT). During 2010-2015, we ...identified 101 newly diagnosed esophageal squamous cell cancer patients who had completed definitive CCRT. Patients' clinical, dosimetric, and hematological data, including absolute neutrophil count, absolute lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR), at baseline, during, and post-CCRT were analyzed. Cox proportional hazards were calculated to identify potential risk factors for overall survival (OS). Median OS was 13 months (95% confidence interval CI: 10.38-15.63). Univariate analysis revealed that male sex, poor performance status, advanced nodal stage, higher percentage of heart receiving 10 Gy (heart V10), and higher NLR (baseline and follow-up) were significantly associated with worse OS. In multivariate analysis, performance status (ECOG 0 & 1 vs. 2; hazard ratio HR 3.12, 95% CI 1.30-7.48), heart V10 (> 84% vs. ≤ 84%; HR 2.24, 95% CI 1.26-3.95), baseline NLR (> 3.56 vs. ≤ 3.56; HR 2.36, 95% CI 1.39-4.00), and follow-up NLR (> 7.4 vs. ≤ 7.4; HR 1.95, 95% CI 1.12-3.41) correlated with worse OS. Volume of low cardiac dose and NLR (baseline and follow-up) were associated with worse patient survival.
Abstract
Background and Aims
This study aimed to update the epidemiology, clinical, and economic outcomes of patients diagnosed with chronic hepatitis B (CHB) infection in Taiwan.
Methods
This is a ...retrospective observational study using claims data from the National Health Insurance Research Database. Cases were identified between 2010 and 2019 using CHB diagnosis codes and claims for alanine aminotransferase laboratory tests or CHB treatment within one year of the first CHB diagnosis. Patient characteristics, epidemiology, clinical, and economic outcomes were described.
Results
A total of 730 154 CHB‐diagnosed cases were identified. The prevalence of diagnosed CHB increased from 1.13% in 2010 to 2.43% in 2019, with the highest occurring among those aged 55–64 years (4.76%) and 45–54 years (4.37%) and being higher in men (2.98%) than in women (2.21%). The majority of newly diagnosed CHB patients were 35 years of age or older (86.6%), with a median age of 49 years. After a median follow‐up period of 6.42 years, 12.5%, 7.9%, 2.8%, and 0.35% were diagnosed with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation respectively. Among 456 706 incident CHB‐diagnosed patients, 17.4% had received at least one CHB medication, with the majority taking entecavir (67.9%). Patients with increasing disease severity had higher healthcare resource utilization, and inpatient costs accounted for 48.9%–65.5% of the overall medical cost in different health states.
Conclusion
Despite the decreasing incidence of newly diagnosed CHB, the prevalence of diagnosed CHB remains high and poses a significant healthcare challenge owing to the high economic burden associated with the complications of CHB.
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