The study aimed to protect patients' skin against ionizing irradiation during radiotherapy by using astaxanthin-encapsulated nanostructured lipid carriers (NLC-ATX).
NLC-ATX was prepared by a ...combined method of hot homogenization and sonication. Cytotoxicity of NLC-ATX was evaluated by MTT colorimetric assay. The in vitro radioprotection of NLC-ATX for human fibroblast (HF) cells was investigated based on the level of ROS (reactive oxygen species), DNA damage, and cell death caused by X-irradiation. In addition, the in vivo radioprotection was evaluated based on the appearance and histological structure of the irradiated skin.
NLC-ATX was successfully prepared, with a mean particle size, zeta potential, and encapsulation efficiency of 114.4 nm, -34.1 mV, and 85.67%, respectively. Compared to the control, NLC-ATX, at an optimum ATX concentration under in vitro condition, reduced the amount of generated ROS and DNA damage of 81.6% and 41.6%, respectively, after X-radiation, resulting in a significant decrease in cell death by 62.69%. Under in vivo condition, after the 9th day of X-irradiation (equivalent to an accumulated dose of 14 Gy), the dorsal skin of five out of six NLC-ATX-untreated mice exhibited grade-1 skin damage, according to CTCAE v5.0, while treatment with NLC-ATX protected 6/6 mice from acute skin damage. Moreover, on the 28th day after the first X-irradiation, the histological images illustrated that NLC-ATX at an ATX concentration of 0.25 µg/mL exhibited good recovery of the skin, with barely any difference noted in the collagen fibers and sebaceous glands compared to normal skin.
NLC-ATX shows potential for application in skin protection against adverse effects of ionizing rays during radiotherapy.
The aim of this note is to investigate the structure of skew linear groups of finite rank. Among our results, it is proved that a subgroup
G
of
GL
n
(
D
)
has finite rank if and only if there exists ...a solvable normal subgroup
N
in
G
of finite rank such that the factor group
G
/
N
is finite provided
D
is a locally finite division ring which is not necessarily commutative.
(1) Background: Magnetite (Fe3O4) nanoparticles have great potential for biomedical applications, including hyperthermia and magnetic resonance imaging. In this study, we aimed to identify the ...biological activity of nanoconjugates composed of superparamagnetic Fe3O4 nanoparticles coated with alginate and curcumin (Fe3O4/Cur@ALG) in cancer cells. (2) Methods: The nanoparticles were evaluated for the biocompatibility and toxicity on mice. The MRI enhancement and hyperthermia capacities of Fe3O4/Cur@ALG were determined in both in vitro and in vivo sarcoma models. (3) Results: The results show that the magnetite nanoparticles exhibit high biocompatibility and low toxicity in mice at Fe3O4 concentrations up to 120 mg/kg when administered via intravenous injection. The Fe3O4/Cur@ALG nanoparticles enhance the magnetic resonance imaging contrast in cell cultures and tumor-bearing Swiss mice. The autofluorescence of curcumin also allowed us to observe the penetration of the nanoparticles into sarcoma 180 cells. In particular, the nanoconjugates synergistically inhibit the growth of sarcoma 180 tumors via magnetic heating and the anticancer effects of curcumin, both in vitro and in vivo. (4) Conclusions: Our study reveals that Fe3O4/Cur@ALG has a high potential for medicinal applications and should be further developed for cancer diagnosis and treatment.
Cardiac fibroblasts (CFs) drive extracellular matrix remodeling after inflammatory injury, leading to cardiac fibrosis and diastolic dysfunction. Recent studies described the role of epigenetics in ...cardiac fibrosis. Nevertheless, detailed reports on epigenetics regulating CFs pyroptosis and describing their implication in cardiac fibrosis are still unclear. Here, we found that DNMT3A reduces the expression of lncRNA Neat1 and promotes the NLRP3 axis leading to CFs pyroptosis, using cultured cells, animal models, and clinical samples to shed light on the underlying mechanism. We report that pyroptosis-related genes are increased explicitly in cardiac fibrosis tissue and LPS-treated CFs, while lncRNA Neat1 decreased. Mechanistically, we show that loss of DNMT3A or overexpression of lncRNA Neat1 in CFs after LPS treatment significantly enhances CFs pyroptosis and the production of pyroptosis-related markers in vitro. It has been demonstrated that DNMT3A can decrease lncRNA Neat1, promoting NLRP3 axis activation in CFs treated with LPS. In sum, this study is the first to identify that DNMT3A methylation decreases the expression of lncRNA Neat1 and promotes CFs pyroptosis and cardiac fibrosis, suggesting that DNMT3A and NEAT1 may function as an anti-fibrotic therapy target in cardiac fibrosis.
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•Cardiac fibroblasts pyroptosis plays key role in cardiac fibrosis.•LncRNA NEAT1 controls cardiac fibroblasts pyroptosis and fibrosis.•DNMT3A silencing of NEAT1 triggers cardiac fibroblasts pyroptosis via NLRP3 axis.
The re-mobilization risks of potentially toxic elements (PTEs) during stabilization deserve to be considered. In this study, artificial simulation evaluation methods based on the environmental stress ...of freeze–thaw (F-T), acidification and variable pH were conducted to assess the long-term effectiveness of PTEs stabilized by MgO in Pb/Zn smelter contaminated soils. Among common stabilizing materials, MgO was considered as the best remediation material, since PTEs bioavailability reduced by 55.48% for As, 19.58% for Cd, 10.57% for Cu, and 26.33% for Mn, respectively. The stabilization effects of PTEs by MgO were best at the dosage of 5 wt%, but these studied PTEs would re-mobilize after 30 times F-T cycles. Acid and base buffering capacity results indicated that the basicity of contaminated soils with MgO treatment reduced under F-T action, and the leached PTEs concentrations would exceed the safety limits of surface water quality standard in China (GB3838–2002) after acidification of 2325 years. No significant changes were found in the pH-dependent patterns of PTEs before and after F-T cycles. However, after F-T cycles, the leaching concentrations of PTEs increased due to the destruction of soil microstructure and the functionality of hydration products formed by MgO, as indicated by scanning electron microscopy (SEM) coupled with energydispersive Xray spectroscopy (EDS) results. Hence, these findings would provide beneficial references for soil remediation assessments of contaminated soils under multi-environmental stress.
Human pancreatic cancer cell lines have a remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit ...the survival of cancer cells under low nutrient conditions represents a novel antiausterity strategy in anticancer drug discovery. In this investigation, a methanol extract of the rhizomes of Boesenbergia pandurata showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC50 value of 6.6 μg/mL. Phytochemical investigation of this extract led to the isolation of 15 compounds, including eight new cyclohexene chalcones (1–8). The structures of the new compounds were elucidated by NMR spectroscopic data analysis. Among the isolated compounds obtained, isopanduratin A1 (14) and nicolaioidesin C (15) exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions, with PC50 values of 1.0 and 0.84 μM, respectively.
Acute myeloid leukemia (AML) is initiated and maintained by a subset of self-renewing leukemia stem cells (LSCs), which contribute to the progression, recurrence and therapeutic resistance of ...leukemia. However, the mechanisms underlying the maintenance of LSCs drug resistance have not been fully defined. In this study, we attempted to elucidate the mechanisms of LSCs drug resistance.
We performed reverse phase protein arrays to analyze the expression of anti-apoptotic proteins in the LSC-enriched leukemia cell line KG-1a. Immuno-blotting, cell viability and clinical AML samples were evaluated to verify the micro-assay results. The characteristics and transcriptional regulation of survivin were analyzed with the relative luciferase reporter assay, mutant constructs, chromatin immuno-precipitation (ChIP), quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), and western blotting. The levels of Sp1, c-Myc, phospho-extracellular signal-regulated kinase (p-ERK), phospho-mitogen and stress-activated protein kinase (p-MSK) were investigated in paired CD34+ and CD34- AML patient samples.
Survivin was highly over-expressed in CD34 + CD38- KG-1a cells and paired CD34+ AML patients compared with their differentiated counterparts. Functionally, survivin contributes to the drug resistance of LSCs, and Sp1 and c-Myc concurrently regulate levels of survivin transcription. Clinically, Sp1 and c-Myc were significantly up-regulated and positively correlated with survivin in CD34+ AML patients. Moreover, Sp1 and c-Myc were further activated by the ERK/MSK mitogen-activated protein kinase (MAPK) signaling pathway, modulating survivin levels.
Our findings demonstrated that ERK/MSK/Sp1/c-Myc axis functioned as a critical regulator of survivin expression in LSCs, offering a potential new therapeutic strategy for LSCs therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80%–85% of total cases and leading to millions of deaths worldwide. Drug resistance is the primary cause of ...treatment failure in NSCLC, which urges scientists to develop advanced approaches for NSCLC treatment. Among novel approaches, the miRNA-based method has emerged as a potential approach as it allows researchers to modulate target gene expression. Subsequently, cell behaviors are altered, which leads to the death and the depletion of cancer cells. It has been reported that miRNAs possess the capacity to regulate multiple genes that are involved in various signaling pathways, including the phosphoinositide 3-kinase, receptor tyrosine kinase/rat sarcoma virus/mitogen-activated protein kinase, wingless/integrated, retinoblastoma, p53, transforming growth factor β, and nuclear factor-kappa B pathways. Dysregulation of these signaling pathways in NSCLC results in abnormal cell proliferation, tissue invasion, and drug resistance while inhibiting apoptosis. Thus, understanding the roles of miRNAs in regulating these signaling pathways may enable the development of novel NSCLC treatment therapies. However, a comprehensive review of potential miRNAs in NSCLC treatment has been lacking. Therefore, this review aims to fill the gap by summarizing the up-to-date information on miRNAs regarding their targets, impact on cancer-associated pathways, and prospective outcomes in treating NSCLC. We also discuss current technologies for delivering miRNAs to the target cells, including virus-based, non-viral, and emerging extracellular vesicle-based delivery systems. This knowledge will support future studies to develop an innovative miRNA-based therapy and select a suitable carrier to treat NSCLC effectively.
This paper presents an effective control method for three‐dimensional (3D) overhead cranes with six degrees of freedom (DOF). Two payload swings and an axial payload oscillation should be minimized ...besides driving the bridge, trolley, and hoisting drum to bring the payload to the desired position in space. First, a novel 3D‐6DOF crane model is developed, where the sixth degree of freedom is axial cargo oscillation that has never been considered in previous studies. A controller is then designed using the hierarchical sliding mode control method. Moreover, a radial basis function neural network (RBFNN) is used to approximate the system's unknown dynamic model accurately. According to the Lyapunov principle, a control law and an updated law for the neural network's weight matrices are designed to ensure the stability of the closed‐loop system. Simulation results on Matlab software show the proposed approach's effectiveness, such as smaller swing, minor axial oscillation, and precise position as desired.
This article presents a composite (COM) method to obtain the high-resolution pulse shape discrimination (PSD) for the neutron and gamma-ray pulses generated from scintillation detectors. The method, ...which is based on a selective combination of the digital charge integration (DCI) with the reference pulse method, aims to reduce the mixed radiation events in the low-energy range. An EJ-301 liquid scintillation detector together with a fast sampling analog-to-digital converter (ADC) is used to measure and digitize the pulses induced from the radioactive decays of 60 Co and 252 Cf, which are then analyzed by our COM method. The proposed method is evaluated using the figure of merit (FoM) and separation quality function <inline-formula> <tex-math notation="LaTeX">F(u) </tex-math></inline-formula>, and the results are compared with three known methods, namely the DCI, standard event fit (SEF), and artificial neural network (ANN) methods. We show that the average values of FoM and <inline-formula> <tex-math notation="LaTeX">F(u) </tex-math></inline-formula> obtained within the COM method are about ten times higher than those obtained within the DCI and SEF in the whole energy range from 50 to 1000 keV electron equivalent (keVee). In particular, by using the COM method, the percentage of gamma events being confused as neutrons ranges from 0.32% to 8.80% when the energy is reduced from 400 to 50 keVee. This finding, which is significantly lower than those obtained by using the DCI and SEF, indicates that the proposed COM method should be considered as a leading method for producing a neutron/gamma PSD counter system with high resolution.
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