In chronic wounds area, there is an abnormally low amount of extracellular matrix, which urges for the extra new biomimetic material to promote proper wound healing. Because of their unique ...characteristics such as inherent bioactivity, biocompatibility, biodegradability and mimicking the natural ECM, natural polymer and their derivative are widely explored as the functional active wound dressing and carrier of antimicrobial agents or growth factors to enhance wound healing. In this review, the wound healing application of polysaccharides, proteins and their derivatives as the active wound dressing and as the carriers of pharmaceutical agents was briefly reviewed.
Full text
Available for:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Herein, we employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatments on female mice. Controlling the addition of precursor ...HAuCl
allows for the fabrication of different atomic ratios of Au
Cu
. X-ray absorption near edge spectra indicates that Au and Cu are the predominant oxidation states of zero valence. This suggests that the charges of Au and Cu remain unchanged after galvanic replacement. Specifically, Au
Cu
composition reveals the enhanced •OH generation following O
→ H
O
→ •OH. The degradable Au
Cu
released Cu
and Cu
resulting in oxygen reduction and Fenton-like reactions. Simulation studies indicate that Au single atoms boot zero-valent copper to reveal the catalytic capability of Au
Cu
for O
→ H
O
→ •OH as well. Instead of using endogenous H
O
, H
O
can be sourced from the O
in the air through the use of nanocubes. Notably, the Au
Cu
structure is degradable and renal-clearable.
This study identifies a novel mechanism linking IL-17A with colon tissue repair and tumor development. Abrogation of IL-17A signaling in mice attenuated tissue repair of dextran sulfate sodium ...(DSS)-induced damage in colon epithelium and markedly reduced tumor development in an azoxymethane/DSS model of colitis-associated cancer. A novel IL-17A target gene, PLET1 (a progenitor cell marker involved in wound healing), was highly induced in DSS-treated colon tissues and tumors in an IL-17RC-dependent manner. PLET1 expression was induced in LGR5
colon epithelial cells after DSS treatment. LGR5
PLET1
marks a highly proliferative cell population with enhanced expression of IL-17A target genes. PLET1 deficiency impaired tissue repair of DSS-induced damage in colon epithelium and reduced tumor formation in an azoxymethane/DSS model of colitis-associated cancer. Our results suggest that IL-17A-induced PLET1 expression contributes to tissue repair and colon tumorigenesis.
In the last few decades, cancer immunotherapy becomes an important tactic for cancer treatment. However, some immunotherapy shows certain limitations including poor therapeutic targeting and unwanted ...side effects that hinder its use in clinics. Recently, several researchers are exploring an alternative methodology to overcome the above limitations. One of the emerging tracks in this field area is nano-immunotherapy which has gone through rapid progress and revealed considerable potentials to solve limitations related to immunotherapy. Targeted and stimuli-sensitive biocompatible nanoparticles (NPs) can be synthesized to deliver immunotherapeutic agents in their native conformations to the site of interest to enhance their antitumor activity and to enhance the survival rate of cancer patients. In this review, we have discussed cancer immunotherapy and the application of NPs in cancer immunotherapy, as a carrier of immunotherapeutic agents and as a direct immunomodulator.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H
O
→ ‧OH for tumoral therapy. Unfortunately, H
O
is often taken from the limited endogenous supply of ...H
O
in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H
O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe
-N ≡ C-Fe
composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O
, H
O
and ‧OH from H
O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.
Aim
The purpose was to examine the effects of non‐commercial music on quality of sleep and relaxation indices, including heart rate, mean arterial pressure, and respiratory rate in patients in ...intensive care units.
Background
There is currently insufficient scientific knowledge for the effects of music on quality of sleep in critically ill patients.
Design
A randomized controlled trial.
Methods
Between January–December 2010, 28 patients aged 39–78 years were randomly assigned to music and control groups. Participants in the music groups listened to non‐commercial music for 45 minutes at nocturnal sleep time. In the control group, participants slept with no music. Participants were assessed using vital signs monitors, standardized questionnaire, and polysomnography. Polysomnography sleep was recorded for the first 2 hours of the nocturnal sleep. General estimating equation was applied to analyse data.
Findings
Participants in the music group had shorter stage N2 sleep and longer stage N3 sleep in the first 2 hours of the nocturnal sleep and improved self‐reported sleep quality, compared with those in the control group. The music group patients also had significantly lower heart rates than those in the control group. The intensive care units patients experienced fragmented sleep with a high frequency of awakenings and severe reduction in random eye movement sleep during the first 2 hours of the nocturnal sleep.
Conclusion
The findings provided evidence for nurses to use soothing music as a research‐based nursing intervention for intensive care unit patients' sleep improvement.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Abstract
Bone morphogenetic protein 2 (BMP2) is highly overexpressed in human non-small cell lung cancer (NSCLC) and correlates with tumor stage and metastatic burden. Although several lines of ...evidence suggest that BMP2 promotes cell migration and invasiveness in vitro, the in vivo role of BMP2 in the metastasis of lung adenocarcinoma cells remains less well understood. Here, we revealed that BMP2 is highly overexpressed in lung adenocarcinoma patients with lymph node metastasis compared with patients without lymph node metastasis. Using an in vivo orthotopic mouse model, we clearly demonstrated that BMP2 promotes lung adenocarcinoma metastasis. The depletion of BMP2 or its receptor BMPR2 significantly reduced cell migration and invasiveness. We further identified that BMP2/BMPR2-mediated cell migration involves the activation of the SMAD1/5/8 signaling pathway, independent of the KRAS signaling pathway. Significantly, the depletion of SMAD1/5/8 or the inhibition of SMAD1/5/8 by LDN193189 inhibitor significantly reduced cell migration. These findings show that BMP2 promotes NSCLC metastasis, indicating that targeting the BMP2 signaling pathway may represent a potential therapeutic strategy for treating patients with metastatic NSCLC.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Atherosclerosis and its related clinical complications are the leading cause of death. MicroRNA (miR)-92a in the inflammatory endothelial dysfunction leads to atherosclerosis. Krüppel-like ...factor 2 (KLF2) is required for vascular integrity and endothelial function maintenance. Flavonoids possess many biological properties. This study investigated the vascular protective effects of chrysin in balloon-injured carotid arteries.
Materials and methods
Exosomes were extracted from human coronary artery endothelial cell (HCAEC) culture media. Herb flavonoids and chrysin were the treatments in these atheroprotective models. Western blotting and real-time PCRs were performed. In situ hybridization, immunohistochemistry, and immunofluorescence analyses were employed.
Results
MiR-92a increased after balloon injury and was present in HCAEC culture media. Chrysin was treated, and significantly attenuated the miR-92a levels after balloon injury, and similar results were obtained in HCAEC cultures in vitro. Balloon injury-induced miR-92a expression, and attenuated KLF2 expression. Chrysin increased the KLF2 but reduced exosomal miR-92a secretion. The addition of chrysin and antagomir-92a, neointimal formation was reduced by 44.8 and 49.0% compared with balloon injury after 14 days, respectively.
Conclusion
Chrysin upregulated KLF2 expression in atheroprotection and attenuated endothelial cell-derived miR-92a-containing exosomes. The suppressive effect of miR-92a suggests that chrysin plays an atheroprotective role.
Graphic abstract
Proposed pathway for human coronary artery endothelial cell (HCAEC)-derived exosomes induced by chrysin to suppress microRNA (miR)-92a expression and counteract the inhibitory effect of miR-92a on KLF2 expression in HCAECs. This provides an outline of the critical role of the herbal flavonoid chrysin, which may serve as a valuable therapeutic supplement for atheroprotection.
Full text
Available for:
DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, was shown to be clinically active and tolerable in patients with advanced urothelial carcinoma and prespecified ...FGFR alterations in the primary analysis of the BLC2001 study at median 11 months of follow-up. We aimed to assess the long-term efficacy and safety of the selected regimen of erdafitinib determined in the initial part of the study.
The open-label, non-comparator, phase 2, BLC2001 study was done at 126 medical centres in 14 countries across Asia, Europe, and North America. Eligible patients were aged 18 years or older with locally advanced and unresectable or metastatic urothelial carcinoma, at least one prespecified FGFR alteration, an Eastern Cooperative Oncology Group performance status of 0–2, and progressive disease after receiving at least one systemic chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy or were ineligible for cisplatin. The selected regimen determined in the initial part of the study was continuous once daily 8 mg/day oral erdafitinib in 28-day cycles, with provision for pharmacodynamically guided uptitration to 9 mg/day (8 mg/day UpT). The primary endpoint was investigator-assessed confirmed objective response rate according to Response Evaluation Criteria In Solid Tumors version 1.1. Efficacy and safety were analysed in all treated patients who received at least one dose of erdafitinib. This is the final analysis of this study. This study is registered with ClinicalTrials.gov, NCT02365597.
Between May 25, 2015, and Aug 9, 2018, 2328 patients were screened, of whom 212 were enrolled and 101 were treated with the selected erdafitinib 8 mg/day UpT regimen. The data cutoff date for this analysis was Aug 9, 2019. Median efficacy follow-up was 24·0 months (IQR 22·7–26·6). The investigator-assessed objective response rate for patients treated with the selected erdafitinib regimen was 40 (40%; 95% CI 30–49) of 101 patients. The safety profile remained similar to that in the primary analysis, with no new safety signals reported with longer follow-up. Grade 3–4 treatment-emergent adverse events of any causality occurred in 72 (71%) of 101 patients. The most common grade 3–4 treatment-emergent adverse events of any cause were stomatitis (in 14 14% of 101 patients) and hyponatraemia (in 11 11%). There were no treatment-related deaths.
With longer follow-up, treatment with the selected regimen of erdafitinib showed consistent activity and a manageable safety profile in patients with locally advanced or metastatic urothelial carcinoma and prespecified FGFR alterations.
Janssen Research & Development.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein ...kinase (AMPK) pathway. Cisplatin remains the main drug for treating advanced non-small-cell lung cancer. However, drug resistance often develops through several mechanisms during the treatment course, including one mechanism mediated by the activation of the IL-6/signal transducer and activator of transcription (STAT)-3 pathway, related to the generation of reactive oxygen species (ROS). This study demonstrated a correlation between STAT3 phosphorylation and cisplatin cytotoxicity, using AS2 (PC14PE6/AS2)-derived cell lines (AS2/S3C) that contained constitutively active STAT3 plasmids as a model. A STAT3 inhibitor (JSI-124) enhanced the cisplatin sensitivity in AS2 cells, whereas metformin inhibited STAT3 phosphorylation and enhanced cisplatin cytotoxicity. By contrast, another AMPK activator (5-aminoimidazole-4-carboxamide-riboside) failed to produce these effects. LKB1-AMPK silencing by small, interfering RNA or mammalian target of rapamycin (mTOR) inhibition by rapamycin or pp242 did not alter the effect of metformin on STAT3 activity suppression, suggesting that metformin can modulate the STAT3 pathway through an LKB1-AMPK-independent and probably mTOR-independent mechanism. Metformin also inhibited cisplatin-induced ROS production and autocrine IL-6 secretion in AS2 cells. Both mechanisms contributed to the ability of metformin to suppress STAT3 activation in cancer cells, which resulted in the decreased secretion of vascular endothelial growth factor by cancer cells. The growth of subcutaneous tumor xenografts was significantly delayed by a combination of cisplatin and metformin. This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways. Thus, metformin helps to overcome tumor drug resistance by targeting STAT3.