Artemisinin (ARS) and its semi-synthetic derivatives are effective drugs to treat malaria and possess multiple therapeutic activities based on their endoperoxide bridge. Here, we showed that ARS ...displayed antibacterial efficacy in Drosophila systemic infections caused by bacterial pathogens but killed only Vibrio cholerae (VC) in vitro, involving reactive oxygen species (ROS) generation and/or DNA damage. This selective antibacterial activity of ARS was attributed to the higher intracellular copper levels in VC, in that the antibacterial activity was observed in vitro upon addition of cuprous ions even against other bacteria and was compromised by the copper-specific chelators neocuproine (NC) and triethylenetetramine (TETA) in vitro and in vivo. We suggest that copper can enhance or reinforce the therapeutic activities of ARS to be repurposed as an antibacterial drug for the treatment of bacterial infections.
: Treatment options for most patients with recurrent cervical cancer within the previously irradiated field are limited. This study aimed to investigate the feasibility and safety of re-irradiation ...using intensity-modulated radiation therapy (IMRT) for patients with cervical cancer who experienced intrapelvic recurrence.
: We retrospectively analyzed 22 patients with recurrent cervical cancer who were treated with re-irradiation for intrapelvic recurrence using IMRT between July 2006 and July 2020. The irradiation dose and volume were determined based on the range considered safe for the tumor size, location, and previous irradiation dose.
: The median follow-up period was 15 months (range: 3-120) and the overall response rate was 63.6%. Of the symptomatic patients, 90% experienced symptom relief after treatment. The 1- and 2-year local progression-free survival (LPFS) rates were 36.8% and 30.7%, respectively, whereas the 1- and 2-year overall survival (OS) rates were 68.2% and 25.0%, respectively. Multivariate analysis revealed that the interval between irradiations and gross tumor volume (GTV) were significant prognostic factors for LPFS. The response to re-irradiation showed borderline statistical significance for LPFS. The GTV and response to re-irradiation were also independent prognostic factors for OS. Grade 3 late toxicities were observed in 4 (18.2%) of the 22 patients. Recto- or vesico-vaginal fistula occurred in four patients. The irradiation dose was associated with fistula formation with borderline significance.
: Re-irradiation using IMRT is a safe and effective treatment strategy for patients with recurrent cervical cancer who previously received RT. Interval between irradiations, tumor size, response to re-irradiation, and radiation dose were the main factors affecting efficacy and safety.
Colorectal cancer (CRC), the third most common cancer worldwide, also has the highest rate of cancer-related morbidity and mortality. WNT signaling is initiated by binding of WNT to various ...receptors, including frizzleds (FZDs), and plays a critical role in CRC and other tumor development by regulating proliferation, differentiation, migration, apoptosis, and polarity. Among the members of the FZD family, FZD6 is broadly expressed in various tissues, and its overexpression has been reported in several cancers, suggesting an important role in cancer development. In this study, we investigated the expression of FZD6 in patients with CRC and found it to be increased in tumors, as compared to paired adjacent non-tumor tissues. Additionally, we found that FZD6 expression was negatively regulated by miR199a5p in CRC cells. These results suggest that overexpression of FZD6, mediated by reduced expression of miR-199a-5p, may play an important role in the development of CRC.
Previous studies conducted cell expansion ex vivo using low initial plating densities for optimal expansion and subsequent differentiation of mesenchymal stem cells (MSCs). However, MSC populations ...are heterogeneous and culture conditions can affect the characteristics of MSCs. In this study, differences in gene expression profiles of adipose tissue (AT)-derived MSCs were examined after harvesting cells cultured at different densities. AT-MSCs from three different donors were plated at a density of 200 or 5,000 cells/cm(2). After 7 days in culture, detailed gene expression profiles were investigated using a DNA chip microarray, and subsequently validated using a reverse transcription polymerase chain reaction (RT-PCR) analysis. Gene expression profiles were influenced primarily by the level of cell confluence at harvest. In MSCs harvested at ∼90% confluence, 177 genes were up-regulated and 102 genes down-regulated relative to cells harvested at ∼50% confluence (P<0.05, FC>2). Proliferation-related genes were highly expressed in MSCs harvested at low density, while genes that were highly expressed in MSCs harvested at high density (∼90% confluent) were linked to immunity and defense, cell communication, signal transduction and cell motility. Several cytokine, chemokine and growth factor genes involved in immunosuppression, migration, and reconstitution of damaged tissues were up-regulated in MSCs harvested at high density compared with MSCs harvested at low density. These results imply that cell density at harvest is a critical factor for modulating the specific gene-expression patterns of heterogeneous MSCs.
Background/Aims: Although the Barcelona Clinic Liver Cancer staging system seems to underestimate the impact of curative-intent surgical resection for multifocal hepatocellular carcinoma (HCC), ...recent studies have indicated favorable results for the surgical resection of multiple HCC. This study aimed to assess clinical outcomes and feasibility of surgical resection for multifocal HCC with up to three nodules compared with single tumor cases.
Methods: Patients who underwent surgical resection for HCC with up to three nodules between 2009 and 2020 were included, and those with the American Joint Committee on Cancer (AJCC) 8th edition, T1 and T4 stages were excluded to reduce differences in disease distribution and severity. Finally, 81 and 52 patients were included in the single and multiple treatment groups, respectively. Short- and long-term outcomes including recurrence-free survival (RFS) and overall survival (OS), were evaluated.
Results: All patients were classified as Child-Pugh class A. RFS and OS were not significantly different between the two groups (P=0.176 and P=0.966, respectively). Multivariate analysis revealed that transfusion and intrahepatic metastasis were significantly associated with recurrence (P=0.046 and P=0.005, respectively). Additionally, intrahepatic metastasis was significantly associated with OS (hazard ratio, 1.989; 95% confidence interval, 1.040-3.802; P=0.038).
Conclusions: Since there was no significant difference in survival between the single and multiple groups among patients with AJCC 8th stage T2 and T3, surgical resection with curative intent could be considered with acceptable long-term survival for selected patients with multiple HCC of up to three nodules. (J Liver Cancer 2023;23:377-388)
Alloying of transition metal dichalcogenides (TMDs) is a pioneering method for engineering electronic structures with expanded applications. In this study, MoSe2–VSe2–NbSe2 ternary alloy nanosheets ...are synthesized via a colloidal reaction. The composition is successfully tuned over a wide range to adjust the 2H–1T phase transition. The alloy nanosheets consist of miscible atomic structures at all compositions, which is distinct from immiscible binary alloys. Compared to each binary alloy, the ternary alloys display higher electrocatalytic activity toward the hydrogen evolution reaction (HER) in an acidic electrolyte. The HER performance exhibits a volcano‐type composition dependence, which is correlated with the experimental d‐band center (εd). Spin‐polarized density functional theory (DFT) calculations consistently predict the homogenous atomic distributions. The Gibbs free energy of H adsorption (ΔGH*) and the activation barrier (Ea) support that miscible ternary alloying greatly enhances the HER performance.
MoSe2–VSe2–NbSe2 ternary alloy nanosheets are synthesized via a colloidal reaction. Ternary alloying produces a miscible phase over a wide range. Compared to each binary alloy, the ternary alloys display higher electrocatalytic activity toward the hydrogen evolution reaction (HER) in an acidic electrolyte. Spin‐polarized density functional theory (DFT) calculations consistently predict the homogenous atomic distributions and support that ternary alloying greatly enhances the HER performance.
Abstract
Increased vasoactive-inotropic score (VIS) is a reliable predictor of mortality and morbidity after cardiac surgery. Here, we retrospectively evaluated the association between VIS and ...adverse outcomes in adult patients after off-pump coronary artery bypass grafting (OPCAB). We included 2149 patients who underwent OPCAB. The maximal VIS was calculated for the initial 48 postoperative hours using standard formulae. The primary outcome was 1-year death. The composite adverse outcome was death, resuscitation or mechanical support, myocardial infarction, revascularization, new-onset atrial fibrillation, infection requiring antibacterial therapy, acute kidney injury, and stroke. Path-analysis was conducted using lactate and prognostic nutritional index (PNI). VIS was associated with 1-year death (odds ratio OR 1.07 1.04–1.10,
p
< 0.001) and 1-year composite outcome (OR 1.02 1.0–1.03,
p
= 0.008). In path-analysis, high VIS showed a direct effect on the increased risk of 1-year death and composite outcome. In the pathway using lactate as a mediating variable, VIS showed an indirect effect on the composite outcome but no significant effect on death. Low PNI directly affected the increased risk of 1-year death and composite outcome, and had an indirect effect on both outcomes, even when VIS was used as a mediating variable. In patients undergoing OPCAB, high VIS independently predicted morbidity and 1-year death. Patients with increased lactate levels following high VIS had an increased risk of postoperative complications, although not necessarily resulting in death. However, patients with poor preoperative nutritional status had an increased risk of unfavourable outcomes, including death, implying the importance of preoperative nutritional support.
Human epidermal growth factor (hEGF) gene therapy was achieved with an electrospun nanofibrous mesh with matrix metalloproteinase (MMP) responsiveness to control release of plasmid human epidermal ...growth factor (phEGF) in diabetic ulcers. For MMP responsiveness, linear poly(ethyleneimine) (LPEI) was immobilized on the surface of the nanofiber via an MMP-cleavable linker. phEGF was electrostatically incorporated into LPEI-immobilized nanofibrous meshes with various charge ratios and phEGF incorporation efficiency was increased with increasing charge ratios. The release of both phEGF and LPEI was significantly increased in the presence of MMP-2 due to the enzymatic digestion of the MMP-cleavable linkage between the matrix and LPEI. Human dermal fibroblasts with the released fraction showed a higher expression level of hEGF compared to naked phEGF or phEGF/LPEI complexes. Diabetic wounds treated with phEGF-incorporated nanofibrous meshes showed high hEGF expression level and accelerated wound recovery rates without wound contractions for 14days. Neocollagen and cytokeratin accumulation were significantly increased as well as the expression of the keratinocyte-specific markers at the re-epithelized tissue treated with phEGF nanofibrous meshes, which clearly indicates that EGF gene was transfected to dermal cells and this consequently assisted wound recovery without phenotypic changes of the re-epithelized tissues. Thus, phEGF-incorporated nanofibrous mesh is expected to accelerate the wound-healing process as well as reduce wound contraction during recovery from diabetic ulcers.
The present study investigated the effect of dietary soluble flaxseed oil (SFO), as a source of omega-3 polyunsaturated fatty acids, on the fatty acid composition of egg yolk and various indices ...including laying performance, egg quality, nutrient composition of eggs, egg stability upon storage, and serum characteristics in laying hens. A total of 210 52-week-old Hy-Line Brown laying hens were assigned to one of 5 experimental diets. A corn-soybean meal-based control diet was mixed without or with SFO to reach the concentrations of 0.2, 0.4, 0.6, and 0.8% in diets and fed for 4 wk. Dietary SFO did not affect laying performance and egg quality. Increasing dietary SFO linearly increased the pH of yolk at 7, 14, and 28 d following storage at room temperature (P < 0.05). Malondialdehyde contents in egg yolks were quadratically increased (P < 0.05) at 0, 7, and 21 d following storage as the inclusion levels of SFO increased in diets. A significant increase (P < 0.05) in total omega-3 polyunsaturated fatty acids and docosahexaenoic acid, but not α-linolenic acid and eicosapentaenoic acid, was deposited in egg yolks at 2 and 4 wk following the SFO feeding. Finally, dietary SFO did not affect serum parameters such as total cholesterol, triglyceride, high-density lipoprotein cholesterol, and nitric oxide. It is concluded that adding SFO into the diets of laying hens can be an efficient strategy to enrich the omega-3 polyunsaturated fatty acids, including docosahexaenoic acid in eggs.
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