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Materials (Basel, Switzerland) Jun 2024This study reveals the relationship between the Cu precipitates and mechanical properties of a Cu-baring ultra-low carbon steel after two-phase zone quenching and...
This study reveals the relationship between the Cu precipitates and mechanical properties of a Cu-baring ultra-low carbon steel after two-phase zone quenching and tempering at 923 K for 0.5-2.5 h. The tensile and microstructural properties were investigated as a function of heat treatment time. The contribution of the precipitation-strengthening mechanism to yield strength was calculated. The size, morphology, and distribution of the precipitated particles were observed using TEM. As the heat treatment time increased, the strength gradually decreased and then remained stable, and the elongation gradually increased and then remained stable. Additionally, the contributions of each strengthening mechanism to the yield strength under different heat treatments were 117, 107, 102, and 89 MPa, respectively. The size and quantity of the precipitates increased with the increase in heat treatment time. After tempering for more than 2 h, the precipitates continued to coarsen, but their quantity decreased. The precipitated Cu had a 3R structure with a length of approximately 17.1 nm and a width of approximately 9.7 nm, with no twinning inside. The stacking order was ABC/ABC. The stable Cu precipitation structure was FCC, maintaining a K-S orientation relationship 11¯1 //(0 1 1) , 1¯10//[11¯1] .
PubMed: 38930400
DOI: 10.3390/ma17123031 -
Antioxidants (Basel, Switzerland) Jun 2024Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders....
Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders. This study investigated the ethanolic extract of fruits for its phenolic and flavonoid contents, antioxidant activity, and impact on melanogenesis pathways using qRT-PCR and Western blot analysis. Utilizing network pharmacology, molecular docking, and dynamics simulations, researchers explored fruit extract's active compounds, targets, and pharmacological effects on hyperpigmentation. fruit extract exhibited antioxidant properties, scavenging DPPH and ABTS radicals radicals and chelating copper. It inhibited cellular tyrosinase activity and melanin content in stimulated B16F10 cells, downregulating TYR, TRP-1, phosphorylated CREB, CREB, and MITF proteins along with transcription levels of MITF, TYR, and TRP-2. LC-MS analysis identified thirty-three metabolites, with seventeen compounds selected for further investigation. Network pharmacology revealed 41 hyperpigmentation-associated genes and identified significant GO terms and KEGG pathways, including cancer-related pathways. Kaempferol-3-O-α-L-rhamnoside exhibited high binding affinity against MAPK3/ERK1, potentially regulating melanogenesis by inhibiting tyrosinase activity. Stable ligand-protein interactions in molecular dynamics simulations supported these findings. Overall, this study suggests that the ethanolic extract of fruits possesses significant antioxidant, tyrosinase inhibitory, and anti-melanogenic properties mediated through key molecular targets and pathways.
PubMed: 38929152
DOI: 10.3390/antiox13060713 -
International Journal of Molecular... Jun 2024Graphene, when electrified, generates far-infrared radiation within the wavelength range of 4 μm to 14 μm. This range closely aligns with the far-infrared band (3 μm...
Graphene, when electrified, generates far-infrared radiation within the wavelength range of 4 μm to 14 μm. This range closely aligns with the far-infrared band (3 μm to 15 μm), which produces unique physiological effects. Contraction and relaxation of vascular smooth muscle play a significant role in primary hypertension, involving the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway and the renin-angiotensin-aldosterone system. This study utilized spontaneously hypertensive rats (SHRs) as an untr-HT to investigate the impact of far-infrared radiation at specific wavelengths generated by electrified graphene on vascular smooth muscle and blood pressure. After 7 weeks, the blood pressure of the untr-HT group rats decreased significantly with a notable reduction in the number of vascular wall cells and the thickness of the vascular wall, as well as a decreased ratio of vessel wall thickness to lumen diameter. Additionally, blood flow perfusion significantly increased, and the expression of F-actin in vascular smooth muscle myosin decreased significantly. Serum levels of angiotensin II (Ang-II) and endothelin 1 (ET-1) were significantly reduced, while nitric oxide synthase (eNOS) expression increased significantly. At the protein level, eNOS expression decreased significantly, while α-SMA expression increased significantly in aortic tissue. At the gene level, expressions of and in aortic tissue significantly increased. Furthermore, the content of nitric oxide (NO) in the SHR's aortic tissue increased significantly. These findings confirm that graphene far-infrared radiation enhances microcirculation, regulates cytokines affecting vascular smooth muscle contraction, and modifies vascular morphology and smooth muscle phenotype, offering relief for primary hypertension.
Topics: Animals; Rats; Blood Pressure; Rats, Inbred SHR; Male; Muscle, Smooth, Vascular; Graphite; Infrared Rays; Hypertension; Nitric Oxide Synthase Type III; Angiotensin II; Endothelin-1; Nitric Oxide
PubMed: 38928382
DOI: 10.3390/ijms25126675 -
International Journal of Molecular... Jun 2024Arc (also known as Arg3.1) is an activity-dependent immediate early gene product enriched in neuronal dendrites. Arc plays essential roles in long-term potentiation,...
Arc (also known as Arg3.1) is an activity-dependent immediate early gene product enriched in neuronal dendrites. Arc plays essential roles in long-term potentiation, long-term depression, and synaptic scaling. Although its mechanisms of action in these forms of synaptic plasticity are not completely well established, the activities of Arc include the remodeling of the actin cytoskeleton, the facilitation of AMPA receptor (AMPAR) endocytosis, and the regulation of the transcription of AMPAR subunits. In addition, Arc has sequence and structural similarity to retroviral Gag proteins and self-associates into virus-like particles that encapsulate mRNA and perhaps other cargo for intercellular transport. Each of these activities is likely to be influenced by Arc's reversible self-association into multiple oligomeric species. Here, we used mass photometry to show that Arc exists predominantly as monomers, dimers, and trimers at approximately 20 nM concentration in vitro. Fluorescence fluctuation spectroscopy revealed that Arc is almost exclusively present as low-order (monomer to tetramer) oligomers in the cytoplasm of living cells, over a 200 nM to 5 μM concentration range. We also confirmed that an α-helical segment in the N-terminal domain contains essential determinants of Arc's self-association.
Topics: Protein Multimerization; Humans; Cytoskeletal Proteins; Nerve Tissue Proteins; Animals
PubMed: 38928159
DOI: 10.3390/ijms25126454 -
Cancers Jun 2024The skeletal system is a common site for metastasis from breast cancer. In our prior work, we developed induced tumor-suppressing cells (iTSCs) capable of secreting a...
BACKGROUND
The skeletal system is a common site for metastasis from breast cancer. In our prior work, we developed induced tumor-suppressing cells (iTSCs) capable of secreting a set of tumor-suppressing proteins. In this study, we examined the possibility of identifying anticancer peptides (ACPs) from trypsin-digested protein fragments derived from iTSC proteomes.
METHODS
The efficacy of ACPs was examined using an MTT-based cell viability assay, a Scratch-based motility assay, an EdU-based proliferation assay, and a transwell invasion assay. To evaluate the mechanism of inhibitory action, a fluorescence resonance energy transfer (FRET)-based GTPase activity assay and a molecular docking analysis were conducted. The efficacy of ACPs was also tested using an ex vivo cancer tissue assay and a bone microenvironment assay.
RESULTS
Among the 12 ACP candidates, P18 (TDYMVGSYGPR) demonstrated the most effective anticancer activity. P18 was derived from Arhgdia, a Rho GDP dissociation inhibitor alpha, and exhibited inhibitory effects on the viability, migration, and invasion of breast cancer cells. It also hindered the GTPase activity of RhoA and Cdc42 and downregulated the expression of oncoproteins such as Snail and Src. The inhibitory impact of P18 was additive when it was combined with chemotherapeutic drugs such as Cisplatin and Taxol in both breast cancer cells and patient-derived tissues. P18 had no inhibitory effect on mesenchymal stem cells but suppressed the maturation of RANKL-stimulated osteoclasts and mitigated the bone loss associated with breast cancer. Furthermore, the P18 analog modified by N-terminal acetylation and C-terminal amidation (Ac-P18-NH2) exhibited stronger tumor-suppressor effects.
CONCLUSIONS
This study introduced a unique methodology for selecting an effective ACP from the iTSC secretome. P18 holds promise for the treatment of breast cancer and the prevention of bone destruction by regulating GTPase signaling.
PubMed: 38927935
DOI: 10.3390/cancers16122230 -
The Korean Journal of Physiology &... Jul 2024Polychlorinated biphenyls (PCBs) were once used throughout various industries; however, because of their persistence in the environment, exposure remains a global threat...
Polychlorinated biphenyls (PCBs) were once used throughout various industries; however, because of their persistence in the environment, exposure remains a global threat to the environment and human health. The Kv1.3 and Kv1.5 channels have been implicated in the immunotoxicity and cardiotoxicity of PCBs, respectively. We determined whether 3,3',4,4'-tetrachlorobiphenyl (PCB77), a dioxin-like PCB, alters human Kv1.3 and Kv1.5 currents using the Xenopus oocyte expression system. Exposure to 10 nM PCB77 for 15 min enhanced the Kv1.3 current by approximately 30.6%, whereas PCB77 did not affect the Kv1.5 current at concentrations up to 10 nM. This increase in the Kv1.3 current was associated with slower activation and inactivation kinetics as well as right-shifting of the steady-state activation curve. Pretreatment with PCB77 significantly suppressed tumor necrosis factor-α and interleukin-10 production in lipopolysaccharide-stimulated Raw264.7 macrophages. Overall, these data suggest that acute exposure to trace concentrations of PCB77 impairs immune function, possibly by enhancing Kv1.3 currents.
PubMed: 38926840
DOI: 10.4196/kjpp.2024.28.4.323 -
Dental Materials : Official Publication... Jun 2024The commonly used base monomer utilized in resinous commercial dental restorative products is bis-GMA which is derived from bisphenol-A (BPA) - a well-known compound...
OBJECTIVE
The commonly used base monomer utilized in resinous commercial dental restorative products is bis-GMA which is derived from bisphenol-A (BPA) - a well-known compound which may disrupt endocrine functions. To address concerns about its leaching into the oral environment and to optimize the quality of dental composites, a BPA-free alternative base monomer, fluorinated urethane dimethacrylate (FUDMA), was designed by modifying a UDMA monomer system.
METHODS
Nine groups of composites were prepared by mixing the base monomers and TEGDMA in a ratio of 70/30 wt% to which were added silanized glass particles (mean diameter: 0.7 µm) in 3 different volume fractions (40, 45, and 50 vol%). Bis-GMA and UDMA base monomers were used as control groups in the same ratios. Various properties including degree of conversion (DC), flexural strength (FS) and flexural modulus (FM), water sorption (WS), solubility (SL), surface hardness and roughness, and initial adhesion property against S.mutans were investigated. One-way analysis of variance followed by Bonferroni test at α = 0.05 was used to analyze the results.
RESULTS
A significant difference in FS between FUDMA-based composite with 40 vol% filler (120.3 ± 10.4 MPa) and Bis-GMA-based composite with the same filler fraction (105.8 ± 10.0 MPa) was observed but there was no significant difference among other groups. The UDMA based group exhibited the highest WS (1.3 ± 0.3 %). Bis-GMA showed greater initial bacterial adhesion but was not statistically different from the other groups (p = 0.082).
SIGNIFICANCE
FUDMA-based resin composites exhibit comparable mechanical and bacterial adhesion properties compared with Bis-GMA and UDMA-based composites. The FUDMA composites show positive outcomes indicating they could be used as substitute composites to Bis-GMA-based composites.
PubMed: 38926013
DOI: 10.1016/j.dental.2024.06.024 -
Anticancer Research Jul 2024Pulsed electromagnetic field (PEMF) stimulation enhances the efficacy of several anticancer drugs. Doxorubicin is an anticancer drug used to treat various types of...
BACKGROUND/AIM
Pulsed electromagnetic field (PEMF) stimulation enhances the efficacy of several anticancer drugs. Doxorubicin is an anticancer drug used to treat various types of cancer, including breast cancer. However, the effect of PEMF stimulation on the efficacy of doxorubicin and the underlying mechanisms remain unclear. Thus, this study aimed to investigate the effect of PEMF stimulation on the anticancer activity of doxorubicin in MDA-MB-231 human breast cancer cells.
MATERIALS AND METHODS
MDA-MB-231 cells were seeded and allowed to incubate for 48 h. The cells were treated with doxorubicin, cisplatin, 5-fluorouracil, or paclitaxel for 48 h. Subsequently, the cells were stimulated with a 60-min PEMF session thrice a day (with an interval of 4 h between each session) for 24 or 48 h. Cell viability was assessed by trypan blue dye exclusion assay and cell-cycle analysis was analyzed by flow cytometry. Molecular mechanisms involved in late G arrest were confirmed by a western blot assay and confocal microscopy.
RESULTS
MDA-MB-231 cells treated with a combination of doxorubicin and PEMF had remarkably lower viability than those treated with doxorubicin alone. PEMF stimulation increased doxorubicin-induced cell-cycle arrest in the late G phase by suppressing cyclin-dependent kinase 1 (CDK1) activity through the enhancement of myelin transcription factor 1 (MYT1) expression, cell division cycle 25C (CDC25C) phosphorylation, and stratifin (14-3-3σ) expression. PEMF also increased doxorubicin-induced DNA damage by inhibiting DNA topoisomerase II alpha (TOP2A).
CONCLUSION
These findings support the use of PEMF stimulation as an adjuvant to strengthen the antiproliferative effect of doxorubicin on breast cancer cells.
Topics: Humans; Doxorubicin; Breast Neoplasms; Female; Cell Line, Tumor; Cell Survival; G2 Phase Cell Cycle Checkpoints; Electromagnetic Fields; DNA Topoisomerases, Type II; Cell Proliferation; Paclitaxel; Fluorouracil; Poly-ADP-Ribose Binding Proteins; cdc25 Phosphatases; Cyclin-Dependent Kinase 2
PubMed: 38925852
DOI: 10.21873/anticanres.17096 -
Phytochemical Analysis : PCA Jun 20242,6-Disubstituted piperidin-3-ols are an important group of piperidine alkaloids found in species such as Senna spectabilis, whose main constituents include cassine and...
INTRODUCTION
2,6-Disubstituted piperidin-3-ols are an important group of piperidine alkaloids found in species such as Senna spectabilis, whose main constituents include cassine and spectaline, compounds with relevant pharmacological activity. The analysis of these compounds is challenging due to the complexity of plant extracts and the absence of chromophores capable of absorbing ultraviolet (UV) radiation.
OBJECTIVE
This paper presents a new analytical method to separate and quantify the non-UV-absorbing alkaloids present in ethanol extracts from S. spectabilis flowers using capillary zone electrophoresis (CZE) with indirect UV detection.
METHODOLOGY
The optimized CZE method employs a background electrolyte containing 60 mM histidine (His), 15 mM α-cyclodextrin, 20% acetonitrile (ACN), and pH-adjusted to 4.7 with acetic acid (AcOH).
RESULTS
The limit of detection (LOD) values was 10.2 and 13.9 mg L for cassine and spectaline, respectively. For both analytes, the precision data were better than 2% of relative standard deviation (RSD) for migration times and peak areas. To evaluate the applicability of the developed method, ethanolic extracts from S. spectabilis flowers were prepared and analyzed.
CONCLUSIONS
Thereby, the method proved to be efficient and complementary to conventional techniques, offering a cost-effective alternative in the quantification of the non-UV-absorbing piperidine alkaloids present in plant extracts.
PubMed: 38925584
DOI: 10.1002/pca.3411 -
International Journal of Pharmaceutics Jun 2024Nanogels are aqueous dispersions of hydrogel particles formed by physically or chemically cross-linked polymer networks of nanoscale size. Herein, we devised a...
Nanogels are aqueous dispersions of hydrogel particles formed by physically or chemically cross-linked polymer networks of nanoscale size. Herein, we devised a straightforward technique to fabricate a novel class of physically cross-linked nanogels via a self-assembly process in water involving α-cyclodextrin and a mannose molecule that was hydrophobically modified using an alkyl chain. The alkyl chain-modified mannose was synthesized in five steps, starting with D-mannose. Subsequently, nanogels were formed by subjecting α-cyclodextrin and the hydrophobically modified mannose to magnetic stirring in water. By adjusting the mole ratio between the hydrophobically modified mannose and α-cyclodextrin, nanogels with an average 100-150 nm diameter were obtained. Physicochemical and structural analyses by H NMR and X-ray diffraction unveiled a supramolecular and hierarchical mechanism underlying the creation of these nanogels. The proposed mechanism of nanogel formation involves two distinct steps: initial interaction of hydrophobically modified mannose with α-cyclodextrin resulting in the formation of inclusion complexes, followed by supramolecular interactions among these complexes, ultimately leading to nanogel formation after 72 h of stirring. We demonstrated the nanogels' ability to encapsulate a short peptide ([p-BuF, R]SHf) as a water-soluble drug model. This discovery holds promise for potentially utilizing these nanogels in drug delivery applications.
PubMed: 38925235
DOI: 10.1016/j.ijpharm.2024.124379