Autophagy-Targeted Calcium Phosphate Nanoparticles Enable Transarterial Chemoembolization for Enhanced Cancer Therapy.

Transarterial chemoembolization (TACE) is commonly used for treating advanced hepatocellular carcinoma (HCC). However, the instability of lipiodol-drug emulsion and the altered tumor microenvironment (TME, such as hypoxia-induced autophagy) postembolization are responsible for the unsatisfactory therapeutic outcomes. Herein, pH-responsive poly(acrylic acid)/calcium phosphate nanoparticles (PAA/CaP NPs) were synthesized and used as the carrier of epirubicin (EPI) to enhance the efficacy of TACE therapy through autophagy inhibition. PAA/CaP NPs have a high loading capacity of EPI and a sensitive drug release behavior under acidic conditions. Moreover, PAA/CaP NPs block autophagy through the dramatic increase of intracellular Ca2+ content, which synergistically enhances the toxicity of EPI. TACE with EPI-loaded PAA/CaP NPs dispersed in lipiodol shows an obvious enhanced therapeutic outcome compared to the treatment with EPI-lipiodol emulsion in an orthotopic rabbit liver cancer model. This study not only develops a new delivery system for TACE but also provides a promising strategy targeting autophagy inhibition to improve the therapeutic effect of TACE for the HCC treatment.

Chemo-Phototherapy with Carfilzomib-Encapsulated TiN Nanoshells Suppressing Tumor Growth and Lymphatic Metastasis.

The design of nanomedicine for cancer therapy, especially the treatment of tumor metastasis has received great attention. Proteasome inhibition is accepted as a new strategy for cancer therapy. Despite being a big breakthrough in multiple myeloma therapy, carfilzomib (CFZ), a second-in-class proteasome inhibitor is still unsatisfactory for solid tumor and metastasis therapy. In this study, hollow titanium nitride (TiN) nanoshells are synthesized as a drug carrier of CFZ. The TiN nanoshells have a high loading capacity of CFZ, and their intrinsic inhibitory effect on autophagy synergistically enhances the activity of CFZ. Due to an excellent photothermal conversion efficiency in the second near-infrared (NIR-II) region, TiN nanoshell-based photothermal therapy further induces a synergistic anticancer effect. In vivo study demonstrates that TiN nanoshells readily drain into the lymph nodes, which are responsible for tumor lymphatic metastasis. The CFZ-loaded TiN nanoshell-based chemo-photothermal therapy combined with surgery offers a remarkable therapeutic outcome in greatly inhibiting further metastatic spread of cancer cells. These findings suggest that TiN nanoshells act as an efficient carrier of CFZ for realizing enhanced outcomes for proteasome inhibitor-based cancer therapy, and this work also presents a "combined chemo-phototherapy assisted surgery" strategy, promising for future cancer treatment.

Au Nanobottles with Synthetically Tunable Overall and Opening Sizes for Chemo-Photothermal Combined Therapy.

Highly asymmetric Au nanostructures, such as split Au nanorings and Au nanocups, exhibit attractive plasmonic properties because of their asymmetric geometries. To facilitate their plasmonic applications, effective and facile synthetic methods for producing asymmetric Au nanostructures with controllable sizes and uniform shapes are highly desirable. Herein, we report on an approach for the synthesis of largely asymmetric colloidal Au nanobottles with synthetically tunable overall and opening sizes. Au nanobottles with overall sizes in the range of ∼100-230 nm are obtained through sacrificial templating with differently sized PbS nano-octahedra. The opening sizes of the produced Au nanobottles can be tailored from ∼10 to ∼120 nm by either adjusting the Au/PbS molar ratio in the growth process or controlling the oxidation degree. The achieved size tunability allows the plasmon resonance wavelength of Au nanobottles to be varied in the range of ∼600-900 nm. Our uniform Au nanobottles, which possess controllable sizes, large cavity volumes, and tunable plasmon resonance wavelengths in the visible to near-infrared range, have been further applied for anticancer drug delivery and photothermal therapy. The effects of surface coating and the opening size of Au nanobottles on the drug encapsulation efficiency (EE) and initial burst drug release are systemically evaluated. A high doxorubicin EE and low initial burst drug release are realized with the dense silica-coated Au nanobottles having an opening size of 44 nm. In addition, chemo-photothermal combined therapy has been demonstrated with the doxorubicin-loaded Au nanobottles. Our results will be helpful for the design of Au nanobottles with different sizes and plasmonic properties as well as provide ample opportunities for exploring various plasmon-enabled applications of Au nanobottles.

Facile synthesis of acacetin and its derivatives.

Acacetin, a O-methylated bioflavonoid isolated from the traditional Chinese medicine Xuelianhua (Saussurea tridactyla), is a promising orally effective atrium-selective antiarrhythmic agent for the treatment of atrial fibrillation (AF). Here we describe an efficient two-component method for the synthesis of acacetin and its derivatives.

[Anti-depression mechanism of supercritical CO(2) extract from Compound Chaigui Fang based on network pharmacology].

The study was designed to clarify the antidepressant mechanism of supercritical CO(2) extract from Compound Chaigui Fang. We used TCMSP, HIT, Pharm GKB and Gene Cards bioinformatics software to predict and analyze the drug/disease targets and their common targets of compounds in the supercritical CO(2) extract of Compound Chaigui Fang for depression. Chronic unpredictable mild stress（CUMS）was used to induce depressed model in rats. Hippocampus and serum were collected after supercritical CO(2) extract treatment to detect the potential antidepressant targets with enzyme-linked immunosorbent assay（ELISA）. The results predicate that there are 22 chemical compounds and 78 potential therapeutic drug targets for depression. There are 177 disease markers for depression, and 14 common targets for drug intervention of depression, which includes the neurotransmitter transports/metabolic enzyme/receptors, hormone of hypothalamus-pituitary-adrenal/ thyroid/gonad axis, immune-associated factor, etc. ELISA results suggest that depression is associated with the low level of phosphate c AMP responsive element-binding protein in hippocampus and the high levels of corticosterone and interleukin 6 in serum with CUMS rat. Those were restored to normal levels by supercritical CO(2) extract of Compound Chaigui Fang. The study provides an antidepressant mechanism of supercritical CO(2) extract of Compound Chaigui Fang based on the network pharmacology, and a new strategy in the study of the effective extracts of compound Chinese traditional medicine.

[Anti-depressive mechanism of Fufang Chaigui prescription based on neuroendocrine hormone and metabolomic correlation analysis].

To elucidate the anti-depressive effect of Fufang Chaigui prescription and its mechanism and investigate its effect on neuroendocrine hormone, rats were included into a chronic unpredictable mild stress (CUMS) model for 28 d, and drugs were administered at the same time. During the period, rats' behaviors were observed and the blood was collected by using ELISA to determine representative hormone concentrations of HPAA, HPTA and HPGA. The changes in endogenous metabolites were analyzed by using H NMR metabolomics to seek the potential biomarkers. Results showed Fufang Chaigui prescription could improve the behaviors of CUMS rats obviously, increase contents of ACTH, CORT, T3and decrease contents of TSH and TESTO and regulate the levels of lactate, α-glucose, choline, N-acetylglycoprotein, trimethylamine oxide and leucine to get closer to the contents of control group. The results of correlation analysis indicated that HPTA was associated with glycometabolism, amino acid metabolism and choline metabolism. And HPAA was related to glycometabolism and amino acid metabolism. However, HPGA was only correlated with glycometabolism. In conclusion, Fufang Chaigui prescription could show an obvious anti-depressive effect and its underlying mechanism might involve regulations of neuroendocrine function and pathways of glycometabolism, amino acid metabolism and choline metabolism.

Antioxidant properties of Fusarium head blight-resistant and -susceptible soft red winter wheat grains grown in Virginia.

Fusarium head blight (FHB) has emerged as a major threat to wheat crops around the world, and it has been hypothesized that wheat antioxidants may play a role against Fusarium infections. The current study aimed to determine antioxidant properties of FHB-resistant wheat grains as compared to susceptible wheat. The wheat samples were collected from a single growing location (Warsaw, VA) and the same growing season. The results showed that both FHB-resistant and -susceptible wheat grains exerted strong radical scavenging activities against DPPH* radical [0.91-1.53 micromol of Trolox equivalents (TE)/g], peroxyl radical (15.5-24.5 micromol of TE/g), and hydroxyl radical (15.7-35.8 micromol of TE/g). Their total phenolic contents ranged from 888 to 1117 microg of gallic acid equivalents (GAE)/g. Five phenolic acids including ferulic, syringic, vanillic, caffeic, and p-coumaric acids were determined in soluble and insoluble fractions of wheat grains, altogether with a range of 219-389 microg/g. On average, the FHB-resistant wheat group showed significantly higher average values in DPPH* and hydroxyl radicals scavenging activities (30 and 41% higher, respectively) than the FHB-susceptible wheat group.

[Clinical application of acupunctural anesthesia with new combination principle of acupoints in supratentorial craniocerebral operation of tumor in vital functional area or deep site of brain].

OBJECTIVE: To summarize the experience in applying acupunctural anesthesia (AA) with new combination principle (NCP) of acupoints in supratentorial craniocerebral operation of tumor in functional area or deep site of brain. METHODS: With the acupoints selection of AA changed from the previous combination principle of near segmental and peri-operational region to the NCP of near-remote along corresponding meridian, craniotomy was carried out under AA in 23 patients. RESULTS: Operation was performed successfully in all the patients, 82.6% of them with the effectiveness reaching I A grade. In those operated on the vital functional area, such as central anterior/posterior gyrus and language center, the accidental functional injury could be well prevented. CONCLUSION: AA with NCP of acupoints has satisfactory effect in supratentorial craniocerebral operation of functional area or deep site of brain, it is especially valuable in monitoring the effect of operation on function of around normal cerebral area to avoid accident injury.