Bioinspired Tumor-Targeting and Biomarker-Activatable Cell-Material Interfacing System Enhances Osteosarcoma Treatment via Biomineralization.

Osteosarcoma is an aggressive malignant tumor that primarily develops in children and adolescents. The conventional treatments for osteosarcoma often exert negative effects on normal cells, and chemotherapeutic drugs, such as platinum, can lead to multidrug resistance in tumor cells. Herein, this work reports a new bioinspired tumor-targeting and enzyme-activatable cell-material interface system based on DDDEEK-pY-phenylboronic acid (SAP-pY-PBA) conjugates. Using this tandem-activation system, this work selectively regulates the alkaline phosphatase (ALP) triggered anchoring and aggregation of SAP-pY-PBA conjugates on the cancer cell surface and the subsequent formation of the supramolecular hydrogel. This hydrogel layer can efficiently kill osteosarcoma cells by enriching calcium ions from tumor cells and forming a dense hydroxyapatite layer. Owing to the novel antitumor mechanism, this strategy neither hurts normal cells nor causes multidrug resistance in tumor cells, thereby showing an enhanced tumor treatment effect than the classical antitumor drug, doxorubicin (DOX). The outcome of this research demonstrates a new antitumor strategy based on a bioinspired enzyme-responsive biointerface combining supramolecular hydrogels with biomineralization.

Expression and clinical significance of VCAM-1, IL-6, and IL-17A in patients with allergic rhinitis.

BACKGROUND: Allergic rhinitis is a chronic inflammatory disease with a high incidence, affecting the quality of life of patients. The aim of the present study was to explore the expression and clinical significance of vascular endothelial cell adhesion molecule-1 (VCAM-1), interleukin (IL)-6, and IL-17A in patients with allergic rhinitis. METHODS: A total of 180 patients with allergic rhinitis, who were admitted to our hospital from March 2017 to March 2020, were enrolled as the observation group. Patients were further divided into 3 subgroups according to the degree of severity of allergic rhinitis as follows: the mild group (n=66), the moderate group (n=60), and the severe group (n=54). During the same period, 188 people without allergic rhinitis, who underwent physical examination in our hospital, were enrolled as the control group. VCAM-1, IL-6, and IL-17A levels were compared between these groups, and the correlation between the 3 levels and allergic rhinitis was analyzed. RESULTS: VCAM-1, IL-6, and IL-17A levels in the observation group were significantly higher than those in the control group, and the difference was statistically significant (P<0.05). Comparison results of VCAM-1, IL-6 and IL-17A levels among the 3 groups were as follows: mild group < moderate group < severe group, and the differences between the three groups were significant (P<0.05). Pearson linear correlation showed that serum levels of VCAM-1, IL-6 and IL-17A were positively correlated with ARIA (P<0.05). Parent history of allergic rhinitis, living environment pollution, abnormally elevated VCAM-1, abnormally elevated IL-6 and abnormally elevated IL-6 were the related risk factors for inducing allergic rhinitis (P<0.05). CONCLUSIONS: VCAM-1, IL-6, and IL-17A play important roles in allergic rhinitis, and the concentration will increase with disease progression. Clinical testing of VCAM-1, IL-6, IL-17A should be increased to improve the diagnostic rate for early allergic rhinitis and to prevent disease progression.

Bisdemethoxycurcumin Inhibits Hepatocellular Carcinoma Proliferation Through Akt Inactivation via CYLD-Mediated Deubiquitination.

BACKGROUND: Bisdemethoxycurcumin (BDMC), a stable bioactive ingredient in curcuminoids, is associated with various antitumor functions, such as proliferation inhibition, metastasis suppression and apoptosis induction, in many cancer types. However, the mechanism of BDMC in hepatocellular carcinoma (HCC) remains unclear. METHODS: We assessed the toxicity and the inhibitory effect of BDMC in the HepG2 cell line by using CCK-8 and colony formation assays. The regulatory effects of BDMC on Akt and MAPK signaling were investigated by Western blotting and immunoprecipitation. RESULTS: We found that the half-maximum inhibitory concentration (IC50) of BDMC after 48 hrs of treatment was 59.13 µM, and BDMC inhibited proliferation in a time- and dose-dependent manner in HepG2 cells. The inhibitory effect was caused by the inactivation of Akt signaling, but not Erk, Jnk or p38 signaling. In addition, the inactivation of Akt signaling was attributed to the inhibition of ubiquitination mediated by K63-Ub but not K48-Ub. Furthermore, we found that BDMC upregulated the expression of CYLD, leading to Akt deubiquitination and inactivation. CONCLUSION: BDMC inhibited HCC cell proliferation, and that this effect was induced by Akt inactivation via CYLD-mediated deubiquitination.

Study on mechanism of release oxygen by photo-excited hemoglobin in low-level laser therapy.

According to the calculated results on the charge distribution of oxygenated heme and deoxygenated heme, and based on the theory of electron excitations in photo-acceptor molecules and the absorption spectra of hemoglobin, it is found that low-level laser within the waveband of about 800-1060 nm can promote the release of oxygen from oxyhemoglobin and improve the oxygen supply of capillaries to surrounding tissues. Furthermore, the reasons have been explained that why the low-level laser at a wavelength of 830 nm is better in the treatment on burn injury and stimulation of hair growth. We also explained why the near-infrared laser of 1064 nm is applied to the forehead to improve cerebral oxygenation in healthy humans. Finally, according to comparison of atomic charge distribution in heme before and after bound to small molecule of carbon monoxide or nitric oxide, it could be inferred that the low-level laser with an appropriate wavelength can promote the carbon monoxide hemoglobin and nitric oxide hemoglobin to dissociate the carbon monoxide molecules and the nitric oxide molecules. This may be used for adjuvant therapy of carbon monoxide poisoning or nitric oxide poisoning.

Study on the selection of laser wavelengths in the intravascular low-level laser irradiation therapy.

According to the absorption spectra of blood and hemoglobin, a photon-bond energy formula is established using physical methods and the effects on hemoglobin of low-level laser at different wavelengths are analyzed. The results show that lasers with the peak wavelengths of 200∼240, 275, and 342 nm in the whole blood absorption spectra curve are easy to destroy protein molecules and then lead to hemoglobin lose biological activity. While lasers with wavelengths longer than 800 nm will reduce the oxygen carrying capacity of blood, only lasers with wavelengths between 630 and 670 nm have the best efficacy.

Proton-transfer in hydrogenated guanine-cytosine trimer neutral species, cations, and anions embedded in B-form DNA.

The neutral DNA trimers with the hydrogen atom added to the C8 site of the middle guanine-cytosine (GC) base pair, the DNA trimers protonated at the N7 site of the middle GC base pair, and the anionic species resulting from hydride addition to the C6 site of the middle GC base pair are investigated using theoretical methods. The canonical Watson-Crick structures (WC), transition state structures (TS) and proton-transferred structures (PT) of each relevant system are optimized in the gas phase and in aqueous solution, in order to understand the processes of proton transfer. The proton transfer reactions of the DNA trimers are compared with the corresponding isolated hydrogenated GC base pairs to explore the influence of the surrounding molecules and the base sequence. The proton transfer reactions of the neutral species, cations, and anions are compared, aiming to clarify the effects of the system's total charge. The results reveal that the surrounding molecules decrease the reaction energies of proton-transfer in aqueous solution. The structures with the dATGCAT and dGCGCGC sequences facilitate proton H4a transfer, but hinder proton H1 transfer. The structures with the dCGGCCG and dTAGCTA sequences facilitate proton H1 transfer. The net charge on the system plays an important role in determining the single and double proton-transfer patterns. Anions are more likely to experience proton-transfer reactions than neutral species and cations, and all the proton-transfer reactions of the anions are exothermic.

The surface-enhanced Raman spectra of aflatoxins: spectral analysis, density functional theory calculation, detection and differentiation.

High-quality surface-enhanced Raman scattering (SERS) spectra of aflatoxin (AF) B(1), B(2), G(1) and G(2) have been acquired using silver nanorod (AgNR) array substrates fabricated by oblique angle deposition method. Significant vibrational peaks are identified on the argon plasma-cleaned substrates, and those peaks agree very well with the Raman spectra calculated by density function theory (DFT). The concentration-dependent SERS detection is also explored. The relationship between the concentration (C) of different AFs and the SERS intensity (I) of the Raman peak at Δν = 1592 cm(-1) is found to follow the general relationship I = AC(α), with α ranging from 0.32 to 0.46 for the four AFs. The limits of detection (LODs) reach 5 × 10(-5) mol L(-1) for AFB(1), 1 × 10(-4) mol L(-1) for AFB(2), and 5 × 10(-6) mol L(-1) for both AFG(1) and AFG(2) in bulk solution, or 6.17 × 10(-16) mol/1.93 × 10(-4) ng of AFB(1), 1.23 × 10(-15) mol/3.88 × 10(-4) ng for AFB(2), 6.17 × 10(-17) mol/2.03 × 10(-5) ng for AFG(1), and 6.17 × 10(-17) mol/2.04 × 10(-5) ng for AFG(2) per laser spot. Principal component analysis (PCA) is used to successfully differentiate these four different kinds of AFs at different concentrations up to their detection limits. The LODs obtained from PCA agree with the LODs obtained by using peak fitting method. With such a low detection limit and outstanding differentiation ability, we prove the possibility of utilizing the SERS detection system as a platform for highly sensitive mycotoxin detection.

Hydrogen-bonded double-proton transfer in five guanine-cytosine base pairs after hydrogen atom addition.

The double-proton transfer reactions in Watson-Crick guanine-cytosine (GC) base pairs after hydrogen atom addition are studied theoretically. The structural changes and energy differences among the structures are compared to explore the double-proton transfer mechanisms, concerted and stepwise. The concerted mechanism is found in all five radicals (GC+H)(•) considered, while the stepwise mechanism is predicted only for structures G-H(•)C(C6) and H(•)G(N7)-C. The geometrical features have been found to change regularly in the concerted double-proton transfer. This is different from the single-proton transfer, for which the structural perturbations are dispersed throughout the GC base pair. The energy analyses demonstrate that the concerted double-proton transfer mechanism is more favorable in the gas phase, while the stepwise mechanism dominates in water. The structures of proton transfer products become less favored energetically.

Hydrogen-bonded proton transfer in the protonated guanine-cytosine (GC+H)+ base pair.

The single proton transfer at the different sites of the Watson-Crick (WC) guanine-cytosine (GC) DNA base pair are studied here using density functional methods. The conventional protonated structures, transition state (TS) and proton-transferred product (PT) structures of every relevant species are optimized. Each transition state and proton-transferred product structure has been compared with the corresponding conventional protonated structure to demonstrate the process of proton transfer and the change of geometrical structures. The relative energies of the protonated tautomers and the proton-transfer energy profiles in gas and solvent are analyzed. The proton-transferred product structure G(+H(+))-H(+)C(N3)(-H(+))(PT) has the lowest relative energy for which only two hydrogen bonds exist. Almost all 14 isomers of the protonated GC base pair involve hydrogen-bonded proton transfer following the three pathways, with the exception of structure G-H(+)C(O2). When the positive charge is primarily "located" on the guanine moiety (H(+)G-C, G-H(+)C(C4), and G-H(+)C(C6)), the H(1) proton transfers from the N(1) site of guanine to the N(3) site of cytosine. The structures G-H(+)C(C5) and G-H(+)C(C4) involve H(4a) proton transfer from the N(4) of cytosine to the O(6) site of guanine. H(2a) proton transfer from the N(2) site of guanine to the O(2) site of cytosine is found only for the structure G-H(+)C(C4). The structures to which a proton is added on the six-centered sites adjoining the hydrogen bonds are more prone to proton transfer in the gas phase, whereas a proton added on the minor groove and the sites adjoining the hydrogen bonds is favorable to the proton transfer in energy in the aqueous phase.