Absorption enhancement of peach kernel oil on hydroxysafflor yellow A in safflower extracts and its mechanisms.

Carthamus tinctorius L. (Safflower) is extensively used as a functional food and herbal medicine, with its application closely associated with hydroxysafflor yellow A (HSYA). However, the low oral bioavailability of HSYA in safflower extract (SFE) limits its health benefits and application. Our study found that co-administration of 250, 330, and 400 mg/kg peach kernel oil (PKO) increased the oral bioavailability of HSYA in SFE by 1.99-, 2.11-, and 2.49-fold, respectively. The enhanced bioavailability is attributed to improved lipid solubility and intestinal permeability of HSYA in SFE due to PKO. PKO is believed to modify membrane fluidity and tight junctions, increase paracellular penetration, and inhibit the expression and function of P-glycoprotein, enhancing the transcellular transport of substrates. These mechanisms suggest that PKO is an effective absorption enhancer. Our findings provide valuable insights for developing functional foods with improved bioavailability.

Isorhamnetin induces cell cycle arrest and apoptosis by triggering DNA damage and regulating the AMPK/mTOR/p70S6K signaling pathway in doxorubicin-resistant breast cancer.

BACKGROUND: Acquired resistance to doxorubicin (DOX) inevitably limits its clinical use against breast cancer (BC). Isorhamnetin (IS), a native flavonoid which extensively available in vegetables, fruits, and phytomedicine, has been deemed to the probable cancer chemopreventive agent in preceding explorations since it exhibits satisfied antitumor activity. So far, the strategy for alleviating DOX resistance by using IS as a sensitizer against resistant BC has not yet been covered. PURPOSE: To investigate the effect of IS on potentiating the chemoreceptivity of drug-resistant BC cells to DOX in vitro and in vivo and elucidate the possible molecular mechanisms. METHODS: MTS assays, colony formation assays, three-dimensional (3D) tumor spheroid model, and migration assay were deployed to verify the inhibiting action of IS in the presence or absence of DOX on resistant BC cells in vitro. Apoptosis, cell cycle regulation, and endocellular reactive oxygen species (ROS) were determined by flow cytometry. Protein levels were monitored by western blotting. Nuclear staining and EdU proliferation were photographed with a confocal laser scanning microscope. The effects of the IS and DOX combination on the tumorigenesis in the xenograft experiments were evaluated for further confirming the in vitro cytotoxicity. RESULTS: IS significantly inhibited cell proliferation and migration and enhanced the antitumor competence of DOX against resistant BC cells both in vitro and in vivo. Adjuvant IS (50 µM) effectively enhanced the proapoptotic impacts of DOX in resistant BC cells (35.38 ± 3.18%, vs. 5.83 ± 0.68% in the DOX group) by suppressing the expression of bcl 2 in addition to enhancing cleaved caspase 3, ultimately leading to DNA condensation and fragmentation. IS (20, 30, and 50 µM) treatments induced significant increases in the G2/M populations (41.60 ± 1.28%, 44.60 ± 1.14%, and 50.64 ± 0.67%, vs. 35.84 ± 1.56% in the untreated control in MCF7/ADR cells, p < 0.01) via regulating CDK1/Cyclin B1 complex expression, subsequently triggering the inhibition of BC proliferation. In addition, IS (10, 20, 30, and 50 µM) stimulated the production of interstitial ROS in MCF7/ADR cells, by 3.99-, 4.20-, 6.29-, and 6.78-fold, respectively, versus the untreated group (p < 0.001), which were involved in DNA damage and AMPK-caused intercept of the mTOR/p70S6K signaling. CONCLUSION: Our study suggested the anti-breast cancer actions of IS as a DOX sensitizer and expounded the underlying molecular mechanisms, showing that IS could be deemed to a capable alternative for resistant BC cure.

Ursolic acid augments the chemosensitivity of drug-resistant breast cancer cells to doxorubicin by AMPK-mediated mitochondrial dysfunction.

Multidrug resistance remains the major obstacle to successful therapy for breast carcinoma. Ursolic acid (UA), a triterpenoid compound, has been regarded as a potential neoplasm chemopreventive drug in some preclinical studies since it exerts multiple biological activities. In this research, we investigated the role of UA in augmenting the chemosensitivity of drug-resistant breast carcinoma cells to doxorubicin (DOX), and we further explored the possible molecular mechanisms. Notably, we found that UA treatment led to inhibition of cellular proliferation and migration and cell cycle arrest in DOX-resistant breast cancers. Furthermore, combination treatment with UA and DOX showed a stronger inhibitory effect on cell viability, colony formation, and cell migration; induced more cell apoptosis in vitro; and generated a more potent inhibitory effect on the growth of the MCF-7/ADR xenograft tumor model than DOX alone. Mechanistically, UA effectively increased p-AMPK levels and concomitantly reduced p-mTOR and PGC-1α protein levels, resulting in impaired mitochondrial function, such as mitochondrial respiration inhibition, ATP depletion, and excessive reactive oxygen species (ROS) generation. In addition, UA induced a DNA damage response by increasing intracellular ROS production, thus causing cell cycle arrest at the G0/G1 phase. UA also suppressed aerobic glycolysis by prohibiting the expression and function of Glut1. Considered together, our data demonstrated that UA potentiated the susceptibility of DOX-resistant breast carcinoma cells to DOX by targeting energy metabolism through the AMPK/mTOR/PGC-1α signaling pathway, and it is a potential adjuvant chemotherapeutic candidate in MDR breast cancer.

A Nanosized Codelivery System Based on Intracellular Stimuli-Triggered Dual-Drug Release for Multilevel Chemotherapy Amplification in Drug-Resistant Breast Cancer.

Lacking nano-systems for precisely codelivering the chemotherapeutics paclitaxel (PTX) and the natural P-glycoprotein (P-gp) inhibitor, quercetin (QU), into cancer cells and controlling their intracellular release extremely decreased the anticancer effects in multidrug resistant (MDR) tumors. To overcome this hurdle, we constructed hybrid polymeric nanoparticles (PNPs) which consist of redox-sensitive PTX/polyethyleneimine-tocopherol hydrogen succinate-dithioglycollic acid PNPs and pH-sensitive hyaluronic acid-QU conjugates. The obtained hybrid PNPs can be internalized into drug-resistant breast cancer cells by the hyaluronic acid/CD44-mediated endocytosis pathway and escape from the lysosome through the "proton sponge effect". Under the trigger of intracellular stimuli, the nanoplatform used the pH/glutathione dual-sensitive disassembly to release QU and PTX. The PTX diffused into microtubules to induce tumor cell apoptosis, while QU promoted PTX retention by down-regulating P-gp expression. Moreover, tocopherol hydrogen succinate and QU disturbed mitochondrial functions by generating excessive reactive oxygen species, decreasing the mitochondrial membrane potential, and releasing cytochrome c into the cytosol which consequently achieved intracellular multilevel chemotherapy amplification in MDR cancers. Importantly, the PNPs substantially suppressed tumors growth with an average volume 2.54-fold lower than that of the control group in the MCF-7/ADR tumor-bearing nude mice model. These presented PNPs would provide a valuable reference for the coadministration of natural compounds and anticarcinogens for satisfactory combination therapy in MDR cancers.

Influence of the PM2.5 Water-Soluble Compound on the Biophysical Properties of A549 Cells.

Understanding the influence of fine atmospheric particles (PM2.5) on cellular biophysical properties is an integral part for comprehending the mechanisms underlying PM2.5-induced diseases because they are closely related to the behaviors and functions of cells. However, hitherto little work has been done in this area. In the present work, we aimed to interrogate the influence of the PM2.5 water-soluble compound (PM2.5-WSC) on the biophysical performance of a human lung carcinoma epithelial cell line (A549) by exploring the cellular morphological and mechanical changes using atomic force microscopy (AFM)-based imaging and nanomechanics. AFM imaging showed that PM2.5-WSC treated cells exhibited evidently reduced lamellipodia and an increased height when compared to the control group. AFM nanomechanical measurements indicated that the treated cells had higher elastic energy and lower adhesion work than the control group. Our western blot assay and transmission electron microscopy (TEM) results revealed that after PM2.5-WSC treatment, the contents of cytoskeletal components (ß-actin and ß-tubulin) increased, but the abundance of cell surface microvilli decreased. The biophysical changes of PM2.5-WSC-treated cells measured by AFM can be well correlated to the alterations of the cytoskeleton and surface microvilli identified by the western blot assay and TEM imaging. The above findings confirm that the adverse risks of PM2.5 on cells can be reliably assessed biophysically by characterizing the cellular morphology and nanomechanics. The demonstrated technique can be used to diminish the gap of our understanding between PM2.5 and its harmful effects on cellular functions.

Near-Field Nanoscopic Terahertz Imaging of Single Proteins.

Terahertz (THz) biological imaging has attracted intense attention due to its capability of acquiring physicochemical information in a label-free, noninvasive, and nonionizing manner. However, extending THz imaging to the single-molecule level remains a challenge, partly due to the weak THz reflectivity of biomolecules with low dielectric constants. Here, the development of graphene-mediated THz scattering-type scanning near-field optical microscope for direct imaging of single proteins is reported. Importantly, it is found that a graphene substrate with high THz reflectivity and atomic flatness can provide high THz contrast against the protein molecules. In addition, a platinum probe with an optimized shaft length is found enabling the enhancement of the amplitude of the scattered THz near-field signals. By coupling these effects, the topographical and THz scattering images of individual immunoglobulin G (IgG) and ferritin molecules with the size of a few nanometers are obtained, simultaneously. The demonstrated strategy thus opens new routes to imaging single biomolecules with THz.

Synchrotron Radiation-Based FTIR Microspectroscopic Imaging of Traumatically Injured Mouse Brain Tissue Slices.

Traumatic brain injury (TBI) is a health problem of global concern because of its serious adverse effects on public health and social economy. A technique that can be used to precisely detect TBI is highly demanded. Here, we report on a synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopic imaging technique that can be exploited to identify TBI-induced injury by examining model mouse brain tissue slices. The samples were first examined by conventional histopathological techniques including hematoxylin and eosin (H&E) staining and 2,3,5-triphenyltetrazolium chloride staining and then spectroscopically imaged by SR-FTIR. SR-FTIR results show that the contents of protein and nucleic acid in the injured region are lower than their counterparts in the normal region. The injured and normal regions can be unambiguously distinguished from each other by the principle component analysis of the SR-FTIR spectral data corresponding to protein or nucleic acid. The images built from the spectral data of protein or nucleic acid clearly present the injured region of the brain tissue, which is in good agreement with the H&E staining image and optical image of the sample. Given the label-free and fingerprint features, the demonstrated method suggests potential application of SR-FTIR spectroscopic mapping for the digital and intelligent diagnosis of TBI by providing spatial and chemical information of the sample simultaneously.

A competitive colorimetric chloramphenicol assay based on the non-cross-linking deaggregation of gold nanoparticles coated with a polyadenine-modified aptamer.

A competitive colorimetric assay has been established to detect chloramphenicol (CAP). It is based on the use of colloidal and electrostatically stabilized aptamer-modified gold nanoparticles (GNPs). The CAP aptamer is modified by a sequence of 5 adenosine groups to anchor it on the surface of GNPs. It can competitively capture two compounds, viz. D-(-)-threo-2-amino-1-(4-nitrophenyl)-1,3-propanediol (CAP-base, with a positive charge) and CAP (which is uncharged). The capture of the positively charged CAP-base triggers the aggregation of modified GNPs in salt-containing solution, and this causes a color change from red to purple. However, in the presence of CAP and CAP-base, the capture of the uncharged CAP weakens this color change by a competing process for capture. Thus, the concentration of CAP is associated with the degree of deaggregation of GNPs and can be quantified by the ratio of absorbances at 620 nm and 520 nm. The assay has a 22 nM limit of detection in acidic solution, and the response is linear in the range of 0.20 to 3.20 µM CAP concentration. This assay was successfully applied to the determination of CAP in spiked environmental water samples. Conceivably, this method has a wide scope in that it may be applied to a wide range of analytes if respective aptamers are available. Graphical abstract Schematic presentation of a competitive non-cross linking deaggregating method for detecting chloramphenicol. The surface charge of polyA-Apt@GNPs and its aggregation degree (purple) are determined by the charge of target. (CAP-base: precursor of CAP; PolyA-Apt@GNPs: 5'-polyA-modified DNA aptamer functionalized gold nanoparticles.).

Mixed-solvent liquid exfoliated MoS2 NPs as peroxidase mimetics for colorimetric detection of H2O2 and glucose.

Ultra-small molybdenum disulfide nanoparticles (MoS2 NPs) were prepared by a facile liquid exfoliation method with ethanol/water as the solvent. The produced MoS2 NPs were of high purity due to the easily removable ethanol/water solution. The prepared MoS2 NPs exhibited an intrinsic peroxidase-like activity in analogy to that of horseradish peroxidase (HRP). A custom-made spectrometer was employed to investigate the peroxidase-like activity of MoS2 NPs in the presence of H2O2 and glucose. The change in absorption detected from MoS2 NPs is proportional to the amount of target. The calibration curve of H2O2 and glucose shows a good relationship between the concentration of target and the change in the absorption of MoS2 NPs. The limit of detection of H2O2 and glucose achieved by this method could approach 1.25 µM and 7 µM respectively. This method has been applied for the detection of glucose in serum from humans. Therefore, these produced MoS2 NPs offer an alternative high-efficiency and economic way to detect diabetes.