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.
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.
Cell death and inflammation play critical roles in cardiac fibrosis. During the fibrosis process, inflammation and tissue injury were triggered; however, the mechanisms initiating cardiac fibrosis ...and driving fibroblast pyroptosis remained largely unknown. In this study, we identified long non-coding RNA (LncRNA)-GAS5 as the key onset of cardiac fibroblast pyroptosis and cardiac fibrosis. Here, we detected ISO-induced cardiac fibrosis models and cardiac fibroblast pyroptosis model by stimulating with LPS. We found that the expression of pyroptosis-related proteins such as caspase 1, NLRP3, and DNMT1 was increased in cardiac fibrosis tissue, while the expression of GAS5 was decreased. The overexpressing of LncRNA GAS5 was shown to increase and inhibit cardiac fibroblast pyroptosis, as well as attenuate caspase 1 and NLRP3 expression in cardiac fibroblast. However, the silencing of GAS5 was also observed; it shows the opposite situation. Furthermore, further studies revealed that treatment of DNMT inhibitor, 5-aza-2-deoxycytidine, or downregulation of DNMT1 led to increased GAS5 expression by reversion of promoter hypermethylation in cardiac fibroblast. Importantly, we have demonstrated that DNMT1 methylation of LncRNA GAS5 leads to cardiac fibroblast pyroptosis
via
affecting NLRP3 axis. Our findings indicate a new regulatory mechanism for cardiac fibroblast pyroptosis under LPS stress, providing a novel therapeutic target for cardiac fibrosis.
Graphical Abstract
Tumor necrosis factor α (TNF-α), a pro-inflammatory cytokine, regulates inflammatory and immune responses by up-regulating gene expression in a manner that is dependent on the transcription factor ...nuclear factor κB (NF-κB). In the present study, we found that 4-hydroxypanduratin A and isopanduratin A, constituents of the rhizomes of Boesenbergia pandurata, inhibited the TNF-α-stimulated up-regulation of intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells. 4-Hydroxypanduratin A and isopanduratin A also reduced ICAM-1 mRNA expression and NF-κB-responsive luciferase activity in TNF-α-stimulated A549 cells. Moreover, 4-hydroxypanduratin A and isopanduratin A prevented the TNF-α-stimulated translocation of the NF-κB subunit p65 to the nucleus and the phosphorylation and proteasomal degradation of the inhibitor of the NF-κB α protein. The present results revealed that 4-hydroxypanduratin A and isopanduratin A inhibit TNF-α-stimulated gene expression and the NF-κB-dependent signaling pathway in A549 cells.
Abstract
In fabric-reinforced cementitious matrix (FRCM) systems, one technique to increase the strengthening efficiency is to utilize the deformability of dry fiber bundles and anchor them at their ...ends. In this study, the effectiveness of anchored carbon fiber bundles was thoroughly investigated through pull-out tests of 220 specimens and corresponding microstructural analyses. The results show that the peak pull-out load can be increased by up to 165% after anchoring the fiber bundles, and the dominant failure mode shifts from fiber pull-out to fiber rupture. Parametric analyses show that a larger anchorage angle and a larger total embedded length help to increase the pull-out strength, while a proper combination of the bonded length and the anchorage length is essential for high strengthening efficiency. Further microstructure analyses suggest that these improvements are primarily attributed to the additional constraint at the anchorage point, and the anchorage length is critical for the pull-out behavior.
Drug resistance is one of the leading causes of failed cancer therapy in the treatment of acute myeloid leukemia. Although the mechanisms of resistance are poorly understood, they may be related to ...the presence of leukemia stem cells (LSCs). Down-regulation of the miR-203 reportedly contributes to oncogenesis and chemo-resistance in multiple cancers. We found that miR-203 expression was down-regulated in CD34 + AML cells as compared with CD34- cells isolated from patients as well as in LSC-enriched (CD34 + CD38-) cell lines KG-1a or MOLM13. Additionally, re-expression of miR-203 led to decreased cell proliferation, self-renewal, and sphere formation in LSCs. Moreover, miR-203 was found to directly target the 3'un-translated regions of survivin and Bmi-1 mRNAs affecting proliferation and self-renewal in LSCs. In this study, we identified a novel miR-203/survivin/Bmi-1 axis involved in the regulation of biological properties of LSCs. This axis may represent a new therapeutic target for acute myeloid leukemia and a potential prognosis/diagnostic marker for LSCs therapy.
A normalization procedure has been applied to improve the descriptive and predictive power of the enhanced generalized superfluid (EGS) model for the nuclear level density (NLD). In this procedure, ...the EGS model is normalized based on the experimental average level spacing at the neutron binding energy
D
0
and the cumulative number of experimental discrete levels in the low-energy region
N
(
E
). The values of normalization parameters are determined by systematically analyzing a set of 288 nuclei from
25
Mg to
251
Cf, whose experimental
D
0
and
N
(
E
) data are available. The systematical analysis permits to determine the values of the normalization parameters for any nucleus. The descriptive and predictive power of the normalized EGS (NEGS) model are demonstrated by making the comparison of the NEGS NLDs with the experimental NLD data of 70 nuclei obtained from the Oslo method. The results obtained show that the NEGS model describes reasonably well almost all the experimental NLDs and should be better used in the reaction codes than the conventional EGS, in particular for nuclei whose experimental NLDs are not available.
Inflammation has been recognized to be a factor that substantially influences tumorigenesis and tumor prognosis. Hence, this study was aimed to investigate an inflammatory marker with the most potent ...prognostic ability and to evaluate the survival estimation capability of dynamic change in this marker for patients suffered from oral squamous cell carcinoma (OSCC).
469 patients' inflammatory indicators including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory response index (SIRI), were calculated. Their predictive abilities for overall survival (OS) were evaluated by Kaplan-Meier curves to screen for the one with the most potent prognostic value. The predictive ability of dynamic changes in this marker was verified and a predictive nomogram incorporating inflammatory indicators was developed.
A high LMR was identified to be an indicator of a satisfactory survival rate. Compared with that of other inflammatory markers, area under the receiver operating characteristics (ROC) curve (AUC) of LMR for 1-year and 3-year OS was significantly larger (P<0.001). Dynamic LMR change remained an significant parameter for predicting OS (OR: 2.492, 95% CI: 1.246-4.981, p = 0.010). The nomogram incorporating LMR exhibited a superior prognostic significance than the TNM system, as suggested by the C-index (0.776 vs 0.651 in primary cohort; 0.800 vs 0.707 in validation cohort, P<0.001) and AUC.
LMR was demonstrated to possess a more potent survival estimation capability than the other three inflammatory parameters. Dynamic changes in LMR serves as a significant parameter for overall survival estimation of primary OSCC patients. The established nomogram incorporating inflammatory markers showed more accuracy and sensitivity for survival estimation of primary OSCC patients.
The famous Kurosh Problem for division rings asks whether a finitely generated algebraic division ring is centrally finite. This longstanding problem posed in 1941 by Kurosh remains without answer up ...to now. In this paper, we study some questions related to this problem for some classes of division rings.
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.
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