Cryptotanshinone-Doped Photothermal Synergistic MXene@PDA Nanosheets with Antibacterial and Anti-Inflammatory Properties for Wound Healing.

Humans are threatened by bacteria and other microorganisms, resulting in countless pathogen-related infections and illnesses. Accumulation of reactive oxygen species (ROS) in infected wounds activates strong inflammatory responses. The overuse of antibiotics has led to increasing bacterial resistance. Therefore, effective ROS scavenging and bactericidal capacity are essential and the advanced development of collaborative therapeutic techniques to combat bacterial infections is needed. Here, this work developes an MXene@polydopamine-cryptotanshinone (MXene@PDA-CPT) antibacterial nanosystem with excellent reactive oxygen and nitrogen species scavenging ability, which effectively inactivates drug-resistant bacteria and biofilms, thereby promoting wound healing. In this system, the adhesion of polydopamine nanoparticles to MXene produced a photothermal synergistic effect and free radical scavenging activity, presenting a promising antibacterial and anti-inflammatory strategy. This nanosystem causes fatal damage to bacterial membranes. The loading of cryptotanshinone further expanded the advantages of the system, causing a stronger bacterial killing effect and inflammation mitigatory effect with desired biosafety and biocompatibility. In addition, combining nanomaterials and active ingredients of traditional Chinese medicine, this work provides a new rationale for the future development of wound dressings, which contributes to eliminating bacterial resistance, delaying disease deterioration, and alleviating the pain of patients.

Revealing the Effect of Photothermal Therapy on Human Breast Cancer Cells: A Combined Study from Mechanical Properties to Membrane HSP70.

Hyperthermia-induced overexpression of heat shock protein 70 (HSP70) leads to the thermoresistance of cancer cells and reduces the efficiency of photothermal therapy (PTT). In contrast, cancer cell-specific membrane-associated HSP70 has been proven to activate antitumor immune responses. The dual effect of HSP70 on cancer cells inspires us that in-depth research of membrane HSP70 (mHSP70) during PTT treatment is essential. In this work, a PTT treatment platform for human breast cancer cells (MCF-7 cells) based on a mPEG-NH2-modified polydopamine (PDA)-coated gold nanorod core-shell structure (GNR@PDA-PEG) is developed. Using the force-distance curve-based atomic force microscopy (FD-based AFM), we gain insight into the PTT-induced changes in the morphology, mechanical properties, and mHSP70 expression and distribution of individual MCF-7 cells with high-resolution at the single-cell level. PTT treatment causes pseudopod contraction of MCF-7 cells and generates a high level of intracellular reactive oxygen species, which severely disrupt the cytoskeleton, leading to a decrease in cellular mechanical properties. The adhesion maps, which are recorded by aptamer A8 functional probes using FD-based AFM, reveal that PTT treatment causes a significant upregulation of mHSP70 expression and it starts to exhibit a partial aggregation distribution on the MCF-7 cell surface. This work not only exemplifies that AFM can be a powerful tool for detecting changes in cancer cells during PTT treatment but also provides a better view for targeting mHSP70 for cancer therapy.

Rectal wall dose-volume effect of pre- or post KUSHEN Ningjiaos relationship with 3D brachytherapy in cervical cancer patients.

BACKGROUND: The present prospective study evaluated the safety and efficacy of the rectum following KUSHEN Ningjiaos in cervical cancer. We compared rectal wall changes during brachytherapy with or without KUSHEN Ningjiaos in cervical cancer patients and analyzed the difference in spatial dose distribution, including whole rectum-wall (R-w), anterior rectum-wall (R-a) and posterior rectum-wall (R-p). METHODS AND MATERIALS: One hundred cervical cancer patients with and without KUSHEN Ningjiaos were treated with brachytherapy (600 cGy). The whole R-w was divided into two areas of R-a and R-p, and R-w dose surface map were constructed. The volume of each R-w was compared in patients pre- and post-KUSHEN Ningjiaos. RESULTS: When the pre- vs. post-KUSHEN groups were compared the volume of R-w increased. In the post-KUSHEN group, a significantly higher proportion of the D2cc of VR-w and VR-a compared with the pre-KUSHEN group showed that the D2ccmean increased from 532.45 cGy to 564.7 cGy and 533.51 cGy to 565.26 cGy, respectively; however, results demonstrated a decrease in the D2ccmean of R-p from 260.5 cGy to 240.0868 cGy (P < 0.05). The insertion of KUSHEN Ningjiaos resulted in a reduction of the relative volume of R-p exposed to high doses, and regressive analysis showed that the DR-p-max correlated most strongly with VR-w and D2ccR-p (P < 0.01 and P < 0.05, respectively). CONCLUSION: The insertion of KUSHEN Ningjiaos can protect the rectum. KUSHEN Ningjiaos appears to be safe and well tolerated; therefore, we believe that there will be fewer adverse events after brachytherapy for patients. TRIAL REGISTRATION: A multi-center, prospective clinical trial for KUSHEN Ningjiaos was inserted into rectum to reduce the rate of radiation proctitis in three-dimensional brachytherapy of cervical cancer. ChiCTR1900021631 . 2 Mar 2019-Retrospectively registered.

Evaluating the protective mechanism of panax notoginseng saponins against oxidative stress damage by quantifying the biomechanical properties of single cell.

Panax notoginseng saponins (PNS) have shown to be the biologically active constituents responsible for the therapeutic action of panax notoginseng. PNS could help to restrain the oxidative stress, however, whether biomechanical properties of the single cell involve in the protective effect exerted by PNS against oxidative stress injury remains unclear. In this work, we investigated the protective mechanism of PNS against oxidative stress based on the PeakForce Tapping technology firstly, focusing on the biomechanical properties of single human umbilical vascular endothelium cell (HUVEC). PNS display distinct inhibition on the reduction of the young's modulus of cells caused by oxidative stress damage. Combining with immunofluorescence assay, it indicates that improving the stability of cytoskeleton is a significant way for PNS to play a protective role in HUVEC cells during oxidative damage. This work provides a new idea for exploring the functional mechanism of traditional Chinese medicine at the single cell level, and reveals great potential of the atomic force microscope in studying the drug mechanism.

A Robust Multiplex Mass Spectrometric Assay for Screening Small-Molecule Inhibitors of CD73 with Diverse Inhibition Modalities.

CD73/Ecto-5'-nucleotidase is a membrane-tethered ecto-enzyme that works in tandem with CD39 to convert extracellular adenosine triphosphate (ATP) into adenosine. CD73 is highly expressed on various types of cancer cells and on infiltrating suppressive immune cells, leading to an elevated concentration of adenosine in the tumor microenvironment, which elicits a strong immunosuppressive effect. In preclinical studies, targeting CD73 with anti-CD73 antibody results in favorable antitumor effects. Despite initial studies using antibodies, inhibition of CD73 catalytic activity using small-molecule inhibitors may be more effective in lowering extracellular adenosine due to better tumor penetration and distribution. To screen small-molecule libraries, we explored multiple approaches, including colorimetric and fluorescent biochemical assays, and due to some limitations with these assays, we developed a mass spectrometry (MS)-based assay. Only the MS-based assay offers the sensitivity and dynamic range required for screening small-molecule libraries at a substrate concentration close to the Km value of substrate and for evaluating the mode of binding of screening hits. To achieve a throughput suitable for high-throughput screening (HTS), we developed a RapidFire-tandem mass spectrometry (RF-MS/MS)-based multiplex assay. This assay allowed a large diverse compound library to be screened at a speed of 1536 reactions per 40-50 min.

Feasibility of lateral dose profile measurements in a small field using TLDs.

The purpose of this work was to study the feasibility of lateral dose profile measurements in a small field using thermoluminescent dosimeters (TLDs) and to evaluate the impact of the field size on the absorbed dose ratio factor fmd of LiF and Al2O3 TLDs. The Monte Carlo package BEAM/EGSNRC was used to simulate the lateral dose profile in solid water phantoms (RW3 slab phantom) with various field sizes beyond the build-up region for 6 MV x-rays, and a LiF : Mg, Cu, P (GR-200) dosimeter with dimensions of 0.1 × 0.1 × 0.1 cm(3) was used to measure the lateral dose profile under the same conditions as the Monte Carlo simulations. To enable comparisons between dosimeters, Gafchromic EBT3 films were used. The results indicate that (1) the measured results are in agreement with the simulated results within the uncertainty of the simulation; (2) the values of fmd for Al2O3 and LiF in a 1 × 1 cm(2) field are 2.8% and 1.6% less, respectively, than those in a 10 × 10 cm(2) field; and (3) within the 80% profile region, the dose differences between TLDs and solid water are less than 1%. In the 80-10% profile region, the TLD results are in agreement with the absorbed doses in the solid water within 1 mm. It is generally acceptable to ignore the impact of field size on the absorbed dose ratio factor fmd when the field sizes are larger than 1 × 1 cm(2) for LiF and 2 × 2 cm(2) for Al2O3. For 6 MV x-rays, the small GR-200 chip can be used to measure the relative lateral dose profiles of small fields.

Detection of anthrax lef with DNA-based photonic crystal sensors.

Bacillus anthracis has posed a threat of becoming biological weapons of mass destruction due to its virulence factors encoded by the plasmid-borne genes, such as lef for lethal factor. We report the development of a fast and sensitive anthrax DNA biosensor based on a photonic crystal structure used in a total-internal-reflection configuration. For the detection of the lef gene, a single-stranded DNA lef probe was biotinylated and immobilized onto the sensor via biotin-streptavidin interactions. A positive control, lef-com, was the complementary strand of the probe, while a negative control was an unrelated single-stranded DNA fragment from the 16S rRNA gene of Acinetobacter baumannii. After addition of the biotinylated lef probe onto the sensor, significant changes in the resonance wavelength of the sensor were observed, resulting from binding of the probe to streptavidin on the sensor. The addition of lef-com led to another significant increase as a result of hybridization between the two DNA strands. The detection sensitivity for the target DNA reached as low as 0.1 nM. In contrast, adding the unrelated DNAs did not cause an obvious shift in the resonant wavelength. These results demonstrate that detection of the anthrax lef by the photonic crystal structure in a total-internal-reflection sensor is highly specific and sensitive.

The adsorption of dopamine on gold and its interactions with iron(III) ions studied by microcantilevers.

The adsorption of dopamine (DA) molecules on gold and their interactions with Fe3+ were studied by a microcantilever in a flow cell. The microcantilever bent toward the Au side with the adsorption of DA due to the change of surface stress induced by the intermolecular hydrogen bonds of DA or the charge transfer effect between adsorbates and the substrate. The interaction process between DA adsorbates and Fe3+ was revealed by the deflection curves of microcantilever. As indicated by the appearance of a variation during the decline of curves, two steps were observed in the curve at relative high concentrations of Fe3+. In this case, Fe3+ reacted with DA molecules only in the outer layers and the complexes removed with solution. Then Fe3+ reacted further with DA molecules forming the surface complex in the first layer next to the gold. At this stage, the stability of surface complexes was time dependent, i.e., unstable initially and stable finally. This may be due to the surface complexes change from mono-dentate to bi-dentate complexes. In another case, i.e., at relative low concentration of Fe3+, only the first step was observed as indicated by the absence of a variation. X-ray photoelectron spectroscopy (XPS) and cycling voltammetry (CV) results provided complementary evidence for the result of microcantilever and proposal. As low as 5 x 10(-10) M Fe3+ was detected by DA modified microcantilever with a good selectivity over other common metal ions.

[The effects of the tangfukang capsules on cytokines of early diabetic nephropathy].

OBJECTIVE: To find out the mechanism of Tangfukang on the diabetic nephropathy(DN). METHOD: A Model of streptorotocin diabetic rats was used. The expressions of the AGEs, ICAM-1, IV-C and FN were observed in renal cortex of diabetic rats with immunohistochemical method. The level of the IL-1 beta in blood serum was measured by radioimmunoassay method and the level of TNF was determined in blood serum by ELISA method. Aminoguanidine was selected as the control medicine which could inhibit the expression of monenzymatic glycosylation end products of protein. All the results were compared to analyze the effect of Tangfukang on monenzymatic glycosylation of protein and cytokine expression in early diabetic nephropathy rats. RESULTS: Both Tangfukang and aminoguanidine significantly decreased the expression of AGEs, but Tangfukang was greatly superior to aminoguanidine in suppressing the expression of cytokine like ICAM-1, IL-1 beta, TNF-alpha and the ingredients of extracellular matrix like IV-C, FN. CONCLUSION: It may be the partical mechanism of Tangfukang to suppress the monenzymatic glycosylation of protein and to reduce the expression of cytokine in diabetes. The effect of Tangfukang is superior to that of aminoguanidine.