Exosomes secreted by adipose-derived stem cells (ADSCs) enhance angiogenesis and wound healing. However, in clinical settings, wounds may be infected by various bacteria or pathogens. We investigated ...whether human ADSCs stimulated with lipopolysaccharide (LPS) secrete exosomes (ADSC-LPS-exo) that augment the angiogenesis of human umbilical vein endothelial cells (HUVECs). ExoQuick-TC exosome precipitation solution was used to purify exosomes from human ADSC culture media in the presence or absence of 1 µg/mL LPS treatment for 24 h. The uptake of ADSC-LPS-exo significantly induced the activation of cAMP response element binding protein (CREB), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) signaling pathways and increased the migration of and tube formation in HUVECs. RNA interference with CREB, AP-1, or NF-κB1 significantly reduced the migration of and tube formation in HUVECs treated with ADSC-LPS-exo. An experiment with an antibody array for 25 angiogenesis-related proteins revealed that only interleukin-8 expression was significantly upregulated in HUVECs treated with ADSC-LPS-exo. In addition, proteomic analysis revealed that eukaryotic translation initiation factor 4E, amyloid beta A4 protein, integrin beta-1, and ras-related C3 botulinum toxin substrate 1 may be potential candidates involved in ADSC-LPS-exo-mediated enhanced angiogenesis.
In 2011, a large community outbreak of human adenovirus (HAdV) in Taiwan was detected by a nationwide surveillance system. The epidemic lasted from week 11 through week 41 of 2011 (March 14-October ...16, 2011). Although HAdV-3 was the predominant strain detected (74%), an abrupt increase in the percentage of infections caused by HAdV-7 occurred, from 0.3% in 2008-2010 to 10% in 2011. Clinical information was collected for 202 inpatients infected with HAdV; 31 (15.2%) had severe infection that required intensive care, and 7 of those patients died. HAdV-7 accounted for 10%, 12%, and 41% of infections among outpatients, inpatients with nonsevere infection, and inpatients with severe infection, respectively (p<0.01). The HAdV-7 strain detected in this outbreak is identical to a strain recently reported in the People's Republic of China (HAdV7-HZ/SHX/CHN/2009). Absence of circulating HAdV-7 in previous years and introduction of an emerging strain are 2 factors that caused this outbreak.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite advances being made in techniques and devices, certain chronic total occlusion (CTO) lesions remain uncrossable or undilatable. Rotational atherectomy (RA) is usually necessary for such ...lesions to achieve successful revascularization.
Information regarding consecutive patients who underwent coronary RA was retrieved from the catheterization laboratory database. Patients who underwent RA for CTO lesion refractory using other conventional devices were recruited, with propensity score-matched cases serving as controls.
A total of 411 patients underwent coronary RA in the study period. Most patients had high-risk features (65.7% had acute coronary syndrome (ACS), 14.1% ischemic cardiomyopathy, and 5.1% cardiogenic shock), while only 20.2% of the patients had stable angina. Among them, 44 patients underwent RA for CTO lesions (CTO group), whereas the propensity score matched controls consist of 37 patients (non-CTO group). The baseline characteristics, high-risk features, coronary artery disease (CAD) vessel numbers, left ventricular function and biochemistry profiles of both groups were the same except for more patients with diabetes (67.6% vs. 45.5%,
= 0.046) in the non-CTO group and more 1.25 mm burr uses in the CTO group. There were no significant differences in acute procedural outcomes or incidence of acute contrast-induced nephropathy (CIN), and no patient demanded emergent CABG or died during the procedure. There was no significant difference in major adverse cardiovascular events (MACE), CV MACE or individual components between the two groups in the hospital, at 30, 90, and 180 days or at 1 year.
In comparison with the propensity risk factor scores-matched controls, there was no difference in procedural complications, acute CIN or clinical outcomes during various stages of RA for CTO lesions. RA for CTO patients was highly efficient and showed safety and outcome profiles similar to those for non-CTO lesions.
To investigate the association between primary insomnia and dementia using a Taiwanese population-based database.
This case-control study involved a subset of Taiwan's National Health Insurance ...Research Database of reimbursement claims. We included 51,734 patients who were diagnosed with primary insomnia from 2002 to 2004 as the test group and 258,715 nonprimary insomnia participants aged 20 years or older as the reference group. We excluded patients under 20 and those with depression, post-traumatic stress disorder, and/or sleep disorders caused by organic lesion(s), drugs, or alcohol. We used a Cox proportional hazards model to assess the primary insomnia on the risk of developing dementia after adjusting for sociodemographic characteristics and comorbidities.
The primary insomnia cohort had a higher prevalence of diabetes, dyslipidemia, hypertension, coronary heart disease, chronic liver disease, and chronic kidney disease at baseline. After adjusting for select comorbidities, primary insomnia remained a significant predisposing factor for developing dementia, and was associated with a 2.14-fold (95% confidence interval, 2.01-2.29) increase in dementia risk. We also found a higher risk of dementia in younger patients.
Taiwanese patients with primary insomnia, especially those under 40, had a higher risk of developing dementia than those without primary insomnia.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An extended-gate field-effect transistor (EGFET) of coaxial-structured ZnO/silicon nanowires as pH sensor was demonstrated in this paper. The oriented 1-μm-long silicon nanowires with the diameter of ...about 50nm were vertically synthesized by the electroless metal deposition method at room temperature and were sequentially capped with the ZnO films using atomic layer deposition at 50°C. The transfer characteristics (IDS–VREF) of such ZnO/silicon nanowire EGFET sensor exhibited the sensitivity and linearity of 46.25mV/pH and 0.9902, respectively for the different pH solutions (pH 1–pH 13). In contrast to the ZnO thin-film ones, the ZnO/silicon nanowire EGFET sensor achieved much better sensitivity and superior linearity. It was attributed to a high surface-to-volume ratio of the nanowire structures, reflecting a larger effective sensing area. The output voltage and time characteristics were also measured to indicate good reliability and durability for the ZnO/silicon nanowires sensor. Furthermore, the hysteresis was 9.74mV after the solution was changed as pH 7→pH 3→pH 7→pH 11→pH 7.
► Coaxial-structured ZnO/silicon nanowire EGFET was demonstrated as pH sensor. ► EMD and ALD methods were proposed to fabricate ZnO/silicon nanowires. ► ZnO/silicon nanowire EGFET sensor achieved better sensitivity and linearity. ► ZnO/silicon nanowire EGFET sensor had good reliability and durability.
Targeting protein kinase C (PKC) family was found to repress the migration and resistance of non‐small cell lung cancer cells to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors ...(TKIs). However, none of the PKC inhibitors has been approved for anticancer therapy yet due to the limited efficacy in clinical trials, and the underlying mechanisms remain unclear. l‐lactic acidosis, a common condition comprising high l‐lactate concentration and acidic pH in the tumor microenvironment, has been known to induce tumor metastasis and drug resistance. In this study, l‐lactic acid was found to reverse the inhibitory effects of pan‐PKC inhibitors GO6983 on PKC activity, cell migration, and EGFR‐TKI resistance, but these effects were not affected by the modulators of lactate receptor GPR81. Interestingly, blockade of lactate transporters, monocarboxylate transporter‐1 and ‐4 (MCT1 and MCT4), attenuated the intracellular level of GO6983, and its inhibitory effect on PKC activity, suggesting that lactic acid promotes the resistance to PKC inhibitors by competing for the uptake through these transporters rather than by activating its receptor, GPR81. Our findings explain the underlying mechanisms of the limited response of PKC inhibitors in clinical trials.
Targeting protein kinase C (PKC) family was found to repress the migration and resistance of non‐small cell lung cancer (NSCLC) cells to epidermal growth factor receptor tyrosine kinase inhibitors. The l‐lactic acidosis condition in the tumor microenvironment might be one of the factors that cause the resistance to PKC inhibitors by competing for the uptake via monocarboxylate transporters and limiting the response of NSCLC patients to this therapy
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs of ∼ 22 nucleotides that are involved in negative regulation of mRNA at the post-transcriptional level. Previously, we developed miRTarBase which ...provides information about experimentally validated miRNA-target interactions (MTIs). Here, we describe an updated database containing 422 517 curated MTIs from 4076 miRNAs and 23 054 target genes collected from over 8500 articles. The number of MTIs curated by strong evidence has increased ∼1.4-fold since the last update in 2016. In this updated version, target sites validated by reporter assay that are available in the literature can be downloaded. The target site sequence can extract new features for analysis via a machine learning approach which can help to evaluate the performance of miRNA-target prediction tools. Furthermore, different ways of browsing enhance user browsing specific MTIs. With these improvements, miRTarBase serves as more comprehensively annotated, experimentally validated miRNA-target interactions databases in the field of miRNA related research. miRTarBase is available at http://miRTarBase.mbc.nctu.edu.tw/.
Stent implantation impairs local endothelial function and may be associated with subsequent adverse cardiovascular events. Telmisartan, an angiotensin II receptor blocker that has unique peroxisome ...proliferator-activated-receptor-gamma-mediated effects on cardiovascular disease, has been shown to enhance endothelial function and limit neointimal hyperplasia. This study utilized hybrid biodegradable/stent nanofibers to facilitate sustained and local delivery of telmisartan to injured arterial vessels. Telmisartan and poly(d,l)-lactide-
-glycolide (PLGA) (75:25) were dissolved in hexafluoroisopropyl alcohol and electrospun into biodegradable nanofibrous tubes which were coated onto metal stents. By releasing 20% of the loaded telmisartan in 30 days, these hybrid biodegradable/stent telmisartan-loaded nanofibers increased the migration of endothelial progenitor cells in vitro, promoted endothelialization, and reduced intimal hyperplasia. As such, this work provides insights into the use of PLGA nanofibers for treating patients with an increased risk of stent restenosis.
Previous epidemiologic and toxicological studies provide some inconsistent evidence that exposure to phthalates may affect thyroid function and growth hormone homeostasis.
To assess the relations ...between exposure to phthalates and indicators of thyroid function and growth hormone homeostasis disturbances both among adults and minors.
We conducted a population-based cross-sectional study of 279 Taiwanese adults (≥18 years old) and 79 minors (<18 years old) in 2013. Exposure assessment was based on urinary biomarkers, 11 phthalate metabolites measured by using online liquid chromatography/tandem mass spectrometry. Indicators of thyroid function included serum levels of thyroxine (T4), free T4, triiodothyronine, thyroid-stimulating hormone, and thyroxine-binding globulin (TBG). Growth hormone homeostasis was measured as the serum levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3). We applied multivariate linear regression models to examine these associations after adjusting for covariates.
Among adults, serum T4 levels were negatively associated with urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate (β=−0.028, P=0.043) and the sum of urinary di-(2-ethylhexyl) phthalate (DEHP) metabolite (β=−0.045, P=0.017) levels. Free T4 levels were negatively associated with urinary mono-ethylhexyl phthalate (MEHP) (β=−0.013, P=0.042) and mono-(2-ethyl-5-oxohexyl) phthalate (β=−0.030, P=0.003) levels, but positively associated with urinary monoethyl phthalate (β=0.014, P=0.037) after adjustment for age, BMI, gender, urinary creatinine levels, and TBG levels. Postive associations between urinary MEHP levels and IGF-1 levels (β=0.033, P=0.006) were observed. Among minors, free T4 was positively associated with urinary mono benzyl phthalate levels (β=0.044, P=0.001), and IGF-1 levels were negatively associated with the sum of urinary DEHP metabolite levels (β=−0.166, P=0.041) after adjustment for significant covariance and IGFBP3.
Our results are consistent with the hypothesis that exposure to phthalates influences thyroid function and growth hormone homeostasis.
•We measured urinary phthalate metabolites, thyroid, growth hormones in the general Taiwanese.•Serum T4 and Free T4 levels were negatively associated with DEHP metabolites, among adults.•Serum IGF-1 levels were negatively associated with DEHP metabolites among minors.
The current treatment of atherosclerotic coronary heart disease with limus-eluting stents can lead to incomplete endothelialization and substantial impairment of arterial healing relative to ...treatment with bare-metal stents. The sustained and local delivery of ticagrelor, a reversibly binding P2Y12 receptor inhibitor, using hybrid biodegradable nanofibers/stents, was developed to reduce neointimal formation and endothelial dysfunction.
In this investigation, a solution of ticagrelor, poly(D,L)-lactide-co-glycolide, and hexafluoro isopropanol was electrospun to fabricate ticagrelor-eluting nanofibrous drug-eluting stents. The in vitro and in vivo ticagrelor concentrations were measured using a high-performance liquid chromatography assay. The effectiveness of ticagrelor-eluting stents was examined relative to that of sirolimus-eluting stents.
Adequate ticagrelor levels were detected for four weeks in vitro. Less HES5-positive labeling was found near the ticagrelor-eluting stented vessels (0.33±0.12) than close to the sirolimus-eluting stented vessels (0.57±0.15) (
<0.05). Four weeks after deployment, the ticagrelor-eluting stent also exhibited an up-regulated local expression of SOD1 in the stenting area (
<0.001). The ticagrelor-eluting stent substantially preserved endothelial function and re-endothelialization, minimized inflammatory responses, and inhibited neointimal hyperplasia.
Ticagrelor-eluting stents may provide an alternative route for treating patients at a high risk of bleeding to preserve endothelial recovery and to reduce smooth muscle proliferation.
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