CeO2@CuS@PDA-FA as targeted near-infrared PTT/CDT therapeutic agents for cancer cells.

Single tumor treatment method usually has some defects, which makes it difficult to achieve good therapeutic effect. The ingenious combination of multiple tumor treatment methods on a single nanoplatform to achieve multifunctional treatment can effectively improve the efficiency of treatment. The targeted modification of nanomaterials can augment the precision of nanotherapeutic drugs in tumor treatment. Herein, a multifunctional nanoplatform (CeO2@CuS@PDA-FA) based on cerium dioxide nanoparticles engineered with copper sulfide (CeO2@CuS) has been constructed for synergistic photothermal therapy (PTT) and chemodynamic therapy (CDT). The CeO2@CuS were coated using polydopamine (PDA), and the modification of PDA surface by folic acid, in order to achieve the targeted effect for tumors. The localized hyperthermia induced by PTT can further improve the CDT efficiency of the nanoplatform, leading to a PTT/CDT synergistic effect. The nanoplatform possessed the capability of cancer cell-targeted and achieved better therapeutic efficacyin vitro. This work provided a new strategy for combined multifunctional theranostic platform and shows strong potential in practical applications.

[Design, manufacture and evaluation of a multi-parameter controllable automatic fire-acupuncture instrument].

A multi-parameter controllable automatic fire-acupuncture instrument was developed by integrating traditional fire needling with modern medical device technology. A gun-like appearance was designed for easy hand-held operation, the electromagnetic induction was for heating needle body, a scale knob was for controlling the needle insertion depth, the combination of electromagnetic ejection and spring return was for the precise control of the needle retention time; and the changeable single ste-rile needle or multiple needles were adopted to meet individual demand, obtain high efficiency and prevent infection. All of these designs are associated with the overall process control system to ensure the exact controllability of needle body temperature, needling density, insertion depth and needle retention time. Besides, this device is advantageous at handy and aseptic operation with high efficiency, conformability and visualization. In this research, this instrument was tested in animals for the impacts of automatic fire needling on skin damage and fur growth. It is found that the accurate control of each parameter is of the significant advantage in the safety and effectiveness of treatment, which lays a solid foundation for the subsequent systematic review on safety and effectiveness.

New C21-steroidal aglycones from the roots of Cynanchum otophyllum and their anticancer activity.

Naturally occurring C21-steroidal aglycones from Cynanchum exhibit significant antitumor effects. To expand the chemical diversity and get large scale C21-steroidal aglycones, the extracts of the roots of Cynanchum otophyllum were treated with 5% HCl in aqueous and the resulting hydrolysate was investigated. Nine new C21-steroidal aglycones (1-9) namely cynotogenins A-I, along with seventeen known analogous (10-26), were isolated from the hydrolysate. The structures of compounds 1-9 were elucidated by spectroscopic analysis (IR, HR-ESI-MS, 1D and 2D NMR) and comparison of observed spectroscopic data with those of reported in the literature. Aglycones 2-5 with rare cis-cinnamoyl group as well as 8 and 9 with 5ß,6ß-epoxy group were found from the genus of Cynanchum for the first time. The cytotoxicities of compounds 1-26 toward human cancer HeLa, H1299, HepG2, and MCF-7 cells were evaluated and preliminary structure-activity relationship (SAR) was discussed. Moreover, compound 20 inhibits HepG2 cell apoptosis and induces of G0/G1 phase arrest in a dose dependent manner.

Potential Role of Hypothalamic and Plasma Ghrelin in the Feeding Behavior of Obese Type 2 Diabetic Rats with Intraventricular Glucagon-Like Peptide-1 Receptor Agonist Intervention.

OBJECTIVE: To investigate the relationship of central and peripheral ghrelin during an exendin-4 (Ex-4) intervention to feeding in obese type 2 diabetic rodents. METHODS: Animal models of diet-induced obesity (DIO) and type 2 diabetes were developed using male Sprague-Dawley rats fed with a high-fat diet and induced into DIO-streptozotocin diabetic rats. Ex-4 or the glucagon-like peptide-1 (GLP-1) receptor agonist exendin fragment-[9-39] (Ex-9) was intracerebroventricularly (ICV) administered. Multivariate linear regression analysis was performed to investigate potential predictors of food intake after Ex-4 administration. RESULTS: ICV administration of Ex-4 significantly inhibited feeding and decreased weight, plasma active ghrelin, hypothalamic ghrelin, and gastric ghrelin levels. The changes in hypothalamic ghrelin and plasma ghrelin could predict the amount of 8-h average food intake. Central preadministration of Ex-9 followed by treatment with Ex-4 could inhibit the decrease in feeding at 0.5, 2, and 8 h. It could also inhibit the decrease in hypothalamic ghrelin at 0.5, 2, and 8 h, as well as in plasma and gastric ghrelin at 2 and 8 h. CONCLUSIONS: In a GLP-1 receptor-dependent manner, central and peripheral ghrelin play a vital role in the inhibition of feeding by Ex-4 administration. Hypothalamic ghrelin, but not plasma ghrelin, may be involved in central Ex-4 inhibition of feeding in the very early feeding period.

Magnolol prevents ovariectomy­induced bone loss by suppressing osteoclastogenesis via inhibition of the nuclear factor­κB and mitogen­activated protein kinase pathways.

Magnolol is the active component of the traditional Chinese medicine Magnolia officinalis, and has antioxidant, anti­inflammatory and anticancer activities, as well as an effect on bone metabolism in vitro. In the present study, it is reported that magnolol suppresses osteoclastogenesis in vivo and in vitro. Magnolol prevented ovariectomy­induced bone loss and osteoclastogenesis in vivo, and decreased the serum levels of C­terminal telopeptide of type 1 collagen, interleukin­6, tumor necrosis factor (TNF)­α and tartrate­resistant acid phosphatase 5B. In vitro, magnolol inhibited the osteoclastogenesis induced by the receptor activator for nuclear factor­κB ligand, and impaired the osteoclast function in bone marrow monocytes and RAW264.7 cells in a dose­dependent manner. Furthermore, magnolol suppressed the expression levels of the osteoclastogenesis markers cathepsin K, calcitonin receptor, matrix metalloproteinase 9, TNF receptor­associated factor 6 and tartrate­resistant acid phosphatase by inhibiting the nuclear factor­κB and mitogen­activated protein kinase pathways. Therefore, magnolol is a promising agent for the treatment of osteoporosis and associated disorders.

Potent antirheumatic activity of a new DNA vaccine targeted to B7-2/CD28 costimulatory signaling pathway in autoimmune arthritis.

Rheumatoid arthritis is a proinflammatory autoimmune disease attributed to failure of both CD4(+)CD25(+) regulatory T (Tr) and CD8(+)CD28(-) suppressor T (Ts) cells to control autoreactive CD4(+)CD28(+) Th1 (Th1) and autoantibody-producing B cells. Here we show a single intramuscular injection of our novel targeted DNA vaccine encoding Pseudomonas exotoxin A and costimulatory molecule B7-2 without autoantigens in a collagen-induced arthritis model simultaneously increased Tr and Ts cells and selectively decreased autoreactive Th1 cells. The vaccine induced a shift from Th1 to Th2 and Th3 cellular and cytokine profiles and a decrease in CD4(+)/CD8(+) cell ratios. Importantly, the vaccine showed potent antirheumatic activity by clinical and other examinations such as X-ray, histopathology, and anti-type II collagen IgG levels and was comparable to methotrexate, the current "gold standard" treatment. As an effective stimulator of both Tr and Ts cells and a specific suppressor of autoreactive Th1 cells, this vaccine is a promising therapeutic approach for rheumatoid arthritis.

[Arginine supplementation in total parenteral nutrition improves postoperative cellular immune function of patients with hepatocellular carcinoma after operation].

OBJECTIVE: To explore the effect of total parenteral nutrition (TPN) supplemented with arginine on cellular immune function of patients with hepatocellular carcinoma (HCC) after radical tumor resection. METHODS: Fifty-six HCC patients undergoing radical surgery received fat-free TPN support, routine TPN or TPN with arginine supplementation, and their clinical data were analyzed prospectively. The percentages of T lymphocyte subpopulation and national killer (NK) cells in peripheral blood are determined, and the levels of interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma) were measured. RESULTS: No marked changes were noted in peripheral blood CD4+, CD8+ T cells and NK cells, or in IL-2, IL-4 and IFN-gamma levels after fat-free TPN and routine TPN support. TPN supplemented with arginine resulted in significant increase in CD4+ T cells, NK cells and CD4+/CD8+ T cell ratio in the peripheral blood, as well as in IL-2 and IFN-gamma levels. Peripheral blood IL-4 level was decreased significantly. CONCLUSION: TPN with arginine supplementation can augment the percentages of CD4+ T lymphocytes and NK cells, and increase IL-2 and IFN-gamma levels, suggesting that arginine can enhance cell-mediated immunity in postoperative patients with HCC.

Arginine supplementation in total parenteral nutrition improves postoperative cellular immune function of patients with hepatocellular carcinoma after operation / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of total parenteral nutrition (TPN) supplemented with arginine on cellular immune function of patients with hepatocellular carcinoma (HCC) after radical tumor resection.</p><p><b>METHODS</b>Fifty-six HCC patients undergoing radical surgery received fat-free TPN support, routine TPN or TPN with arginine supplementation, and their clinical data were analyzed prospectively. The percentages of T lymphocyte subpopulation and national killer (NK) cells in peripheral blood are determined, and the levels of interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma) were measured.</p><p><b>RESULTS</b>No marked changes were noted in peripheral blood CD4+, CD8+ T cells and NK cells, or in IL-2, IL-4 and IFN-gamma levels after fat-free TPN and routine TPN support. TPN supplemented with arginine resulted in significant increase in CD4+ T cells, NK cells and CD4+/CD8+ T cell ratio in the peripheral blood, as well as in IL-2 and IFN-gamma levels. Peripheral blood IL-4 level was decreased significantly.</p><p><b>CONCLUSION</b>TPN with arginine supplementation can augment the percentages of CD4+ T lymphocytes and NK cells, and increase IL-2 and IFN-gamma levels, suggesting that arginine can enhance cell-mediated immunity in postoperative patients with HCC.</p>

Green tea polyphenol epigallocatechin-3-gallate suppresses rat hepatic stellate cell invasion by inhibition of MMP-2 expression and its activation.

AIM: Epigallocatechin-3-gallate (EGCG) is the major component of green tea polyphenols, whose wide range of biological properties includes anti-fibrogenic activity. Matrix metalloproteinases (MMP) that participate in extracellular matrix degradation are involved in the development of hepatic fibrosis. The present study investigates whether EGCG inhibits activation of the major gelatinase matrix metalloproteinase-2 (MMP-2) in rat hepatic stellate cells (HSC). METHODS: The expression of MMP-2, tissue inhibitors of metalloproteinases-2 (TIMP-2), and membrane-type 1-MMP (MT1-MMP) was assessed by RT-PCR and Western blot analyses. MMP-2 activity was evaluated by zymography and MT1-MMP activity was assessed by an enzymatic assay. HSC migration was measured by a wound healing assay and cell invasion was performed using Transwell cell culture chambers. RESULTS: The expression of MMP-2 mRNA and protein in HSC was substantially reduced by EGCG treatment. EGCG treatment also reduced concanavalin A (ConA)-induced activation of secreted MMP-2 and reduced MT1-MMP activity in a dose-dependent manner. In addition, EGCG inhibited either HSC migration or invasion. CONCLUSION: The abilities of EGCG to suppress MMP-2 activation and HSC invasiveness suggest that EGCG may be useful in the treatment and prevention of hepatic fibrosis.

[Study on optimizing extraction process of root of Polygonum multiflorum].

OBJECTIVE: To optimize the extraction process of root of Polygoni multflori and validate the interrelation between antioxdative capacity and the content of 2,3,4,5-tetrahydroxystilbene-2-O-beta-D-glucoside in root of P. multiflori. METHOD: The optimum extraction was abserved with the orthogonal design; 2,3,4,5-tetrahydroxystilbene-2-O-beta-D-glucoside was determined by HPLC and the antioxidative capacity by using photochemiluminescence detection method with the Photochem supplied by Analytik Jena AG; the concentration of ethanol, amount of ethanol, extraction time and extraction times were the four factors in the extraction. RESULT: The concentration of ethanol and extraction times had significant effect on the content of 2,3,4,5-tetrahydroxystilbene-2-O-beta-D-glucoside and the antioxidative capacity of the crude extract. CONCLUSION: The best extraction process is to extract three times by using 10 fold EtOH(60%), refluxing at 85 degrees C and to extract one and half hours each time.