Fluorescence nanosilica-based cell tracker has been explored and applied in cell biological research. However, the aggregation of these nanoparticles at physiological pH is still the main limitation. ...In this research, we introduced a novel fluorescence nano-based cell tracker suitable for application in live cells. The silica-coated fluorescein isothiocyanate isomer (FITC-SiO
) nanoparticles (NPs) were modified with carboxymethylsilanetriol disodium salt (FITC-SiO
-COOH), integrating the dianion form of FITC molecules. This nanosystem exhibited superior dispersion in aqueous solutions and effectively mitigated dye leakage. These labeled NPs displayed notable biocompatibility and minimal cytotoxicity in both in vitro and in vivo conditions. Significantly, the NPs did not have negative implications on cell migration or angiogenesis. They successfully penetrated primary fibroblasts, human umbilical vein endothelial cells and HeLa cells in both 2D and 3D cultures, with the fluorescence signal enduring for over 72 h. Furthermore, the NP signals were consistently observed in the developing gastrointestinal tract of live medaka fish larvae for extended periods during phases of subdued digestive activity, without manifesting any apparent acute toxicity. These results underscore the promising utility of FITC-SiO
-COOH NPs as advanced live cell trackers in biological research.
Although curcumin in the form of nanoparticles has been demonstrated as a potential anti-tumor compound, the impact of curcumin and nanocurcumin in vitro on normal cells and in vivo in animal models ...is largely unknown. This study evaluated the toxicity of curcumin-loaded micelles in vitro and in vivo on several tumor cell lines, primary stromal cells, and zebrafish embryos. Breast tumor cell line (MCF7) and stromal cells (human umbilical cord vein endothelial cells, human fibroblasts, and human umbilical cord-derived mesenchymal stem cells) were used in this study. A zebrafish embryotoxicity (FET) assay was conducted following the Organisation for Economic Co-operation and Development (OECD) Test 236. Compared to free curcumin, curcumin PM showed higher cytotoxicity to MCF7 cells in both monolayer culture and multicellular tumor spheroids. The curcumin-loaded micelles efficiently penetrated the MCF7 spheroids and induced apoptosis. The nanocurcumin reduced the viability and disturbed the function of stromal cells by suppressing cell migration and tube formation. The micelles demonstrated toxicity to the development of zebrafish embryos. Curcumin-loaded micelles demonstrated toxicity to both tumor and normal primary stromal cells and zebrafish embryos, indicating that the use of nanocurcumin in cancer treatment should be carefully investigated and controlled.
In recent years, extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) have emerged as a potential cell-free therapy against osteoarthritis (OA). Thus, we investigated the ...therapeutic effects of EVs released by cytokine-primed umbilical cord-derived MSCs (UCMSCs) on osteoarthritic chondrocyte physiology. Priming UCMSCs individually with transforming growth factor beta (TGFβ), interferon alpha (IFNα), or tumor necrosis factor alpha (TNFα) significantly reduced the sorting of miR-181b-3p but not miR-320a-3p; two negative regulators of chondrocyte regeneration, into EVs. However, the EV treatment did not show any significant effect on chondrocyte proliferation. Meanwhile, EVs from both non-priming and cytokine-primed UCMSCs induced migration at later time points of measurement. Moreover, TGFβ-primed UCMSCs secreted EVs that could upregulate the expression of chondrogenesis markers (
COL2
and
ACAN
) and downregulate fibrotic markers (
COL1
and
RUNX2
) in chondrocytes. Hence, priming UCMSCs with cytokines can deliver selective therapeutic effects of EV treatment in OA and chondrocyte-related disorders.
Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been illustrated for their roles in immunological modulation and tissue regeneration through the secretome. Additionally, culture ...conditions can trigger the secretion of extracellular vesicles (EVs) into extracellular environments with significant bioactivities. This study aims to investigate the roles of three EV sub-populations released by UCMSCs primed with transforming growth factor β (TGFβ) and their capacity to alter dermal fibroblast functions for skin aging. Results show that three EV sub-populations, including apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXs), were separated from conditioned media. These three EVs carried growth factors, such as FGF-2, HGF, and VEGF-A, and did not express noticeable effects on fibroblast proliferation and migration. Only EX from TGFβ-stimulated UCMSCs exhibited a better capacity to promote fibroblasts migrating to close scratched wounds than EX from UCMSCs cultured in the normal condition from 24 h to 52 h. Additionally, mRNA levels of ECM genes (COL I, COL III, Elastin, HAS II, and HAS III) were detected with lower levels in fibroblasts treated with EVs from normal UCMSCs or TGFβ-stimulated UCMSCs compared to EV-depleted condition. On the contrary, the protein levels of total collagen and elastin released by fibroblasts were greater in the cell groups treated with EVs compared to EV-depleted conditions; particularly elastin associated with TGFβ-stimulated UCMSCs. These data indicate the potential roles of EVs from UCMSCs in protecting skin from aging by promoting ECM protein production.
The increasing coverage of Internet has created opportunities and advantages for different aspects of society. However, there come new threats and challenges to information security. One of the ...typical types of attacks that has increasingly occurred is the APT attack (Advanced Persistent Threat). APT is dangerous with clear purposes. APT attacks employ different sophisticated methods and techniques attacking targets in order to steal confidential and sensitive information. In the past, hackers attacked information systems with personal and financial motives. However, there are nowadays other motives such as political ones and they are potentially backed by governments or nations. Nations that own advanced technologies such as United States, India, Russia, UK are also suffering from special purpose attacks. APT is an advanced type of attacks that consists of many stages and concrete strategies. Besides, techniques and technologies employed in APT attack are usually new and developed by hackers in order to break through the monitoring of security software. However, APT is normally implemented through concrete steps and stages. If one of the steps or stages fails, the entire APT attack will fail. This paper presents a method of detecting APT attacks based on monitoring accesses to unknown domains. This detection method results into high effectiveness in the initial stage of APT attacks.
(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.
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.
Because the skin is the first organ to be impacted by radiation, keratinocytes (HaCaT cells) are frequently used as an
in vitro model
for testing potential radioprotective agents. Melanin extracted ...from squid ink was considered an antioxidant compound and a possible radioprotector. In this study, nanomelanin was prepared at a size of 100–200 nm from isolated squid melanin. The zeta potential of melanin nanoparticles and the functional groups on their surface were investigated. The antioxidant activity of nanomelanin was examined by the DPPH method. Keratinocyte cells were incubated with or without melanin particles for 24 h before being irradiated in various doses. The radioprotective properties of nanomelanin after 3 days post-radiation were examined by cell survival rates. Treatment with nanomelanin enhances the percentage of cell viability by 10%, depending on the dose of radiation. At 2 days post-radiation, cell groups treated with nanomelanin were reduced to the transcription levels of gene coding BAX, TNF-α, and Caspase 3 for the cellular apoptosis process at various doses (3–5 Gy) of radiotherapy in comparison with control and eliminated the apoptotic cell rate as analyzed by flow cytometry methods. Furthermore, at 3 Gy, melanin nanoparticles promoted the transcription level gene coding SOD1 enzyme by 3.4 folds compared to control.
Graphical abstract
Hepatocellular carcinoma (HCC), a prevalent type of liver cancer, is mainly diagnosed in the advanced stage, leading to a high mortality rate. Recent advances have identified peripheral cytokines as ...a potential tool to predict disease outcomes and inform therapeutic decisions. Hence, in this study, we aim to build a predictive model for HCC based on serum levels of different cytokines.
We used immunoassay to quantify the concentrations of IL-27, MIP-1β, Perforin, sCD137, sFas, and TNF-α in the serum of 38 HCC patients and 15 healthy controls. Logistic regression was then used to construct classification models detecting HCC based on these cytokines. A nomogram of the best-performing model was generated to visualize HCC prediction.
sFas and MIP-1β were found to be significantly higher in HCC patients compared to controls. Predictive models based on cytokine levels combining sFas, sCD137, and IL-27 performed the best in distinguishing HCC patients from healthy controls. This model has a bias-corrected area under the receiver operating characteristic (ROC) curve (AUC) of 0.948, a sensitivity of 92.11%, a specificity of 93.33%, and an accuracy of 0.925.
Our findings suggest that serum cytokines have the potential to be utilized in HCC screening to improve detection rates.
Based on its simplicity and user-friendly characteristics, OpenMP has become the standard model for programming on shared-memory architectures. Checkpointing-aided parallel execution (CAPE) is an ...approach that utilizes the discontinuous incremental checkpointing technique (DICKPT) to translate and execute OpenMP programs on distributed-memory architectures automatically. Currently, CAPE implements the OpenMP execution model by utilizing the DICKPT to distribute parallel jobs and their data to slave machines, and then collects the results after executing these distributed jobs. Although this model has been proven to be effective in terms of performance and compatibility with OpenMP on distributed-memory systems, it cannot fully exploit the capabilities of multicore processors. This paper presents a novel execution model for CAPE that utilizes two levels of parallelism. In the proposed model, we add another level of parallelism in the form of multithreaded processes on slave machines with the goal of better exploiting their multicore CPUs. Initial experimental results presented near the end of this paper demonstrate that this model provides significantly enhanced CAPE performance.
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