Effects of electroacupuncture on conjunctival cell apoptosis and the expressions of apoptosis-related proteins Caspase-3, Fas and Bcl-2 in rabbits with dry eye syndrome / 针灸推拿医学（英文版）

Objective: By observing the effects of electroacupuncture (EA) on the apoptosis of conjunctival cells of rabbits with dry eye syndrome (DES) and the expressions of apoptosis-related proteins Caspase-3, Fas and Bcl-2, to discuss the mechanism of EA in the treatment of DES from the perspective of cell apoptosis. Methods: Male New Zealand rabbits were randomly divided into a normal group (NG), a model group (MG), an EA group (EAG) and a sham EA group (SEAG). DES rabbit model was developed by eye drop of 0.1％ benzalkonium chloride. The rabbit tear secretion and tear film break-up time (BUT) were measured; terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL) assay was used to detect the apoptosis of conjunctival cells; the expressions of Caspase-3, Fas and Bcl-2 proteins in conjunctival cells were detected by immunohistochemistry. Results: Compared with the NG, the rabbit tear secretion decreased and the BUT was shortened in the MG (both P<0.01); compared with the MG and the SEAG, the rabbit tear secretion increased and the BUT was prolonged in the EAG (all P<0.05). Compared with the NG, the apoptosis of rabbit conjunctival cells increased (P<0.01), the expressions of Caspase-3 and Fas proteins increased (both P<0.05), and the expression of Bcl-2 protein decreased (P<0.01) in the MG; compared with the MG and the SEAG, the apoptosis of rabbit conjunctival cells decreased (both P<0.01), the expressions of Caspase-3 and Fas proteins decreased (all P<0.05), and the expression of Bcl-2 protein increased (both P<0.01) in the EAG. Conclusion: EA can inhibit the apoptosis of rabbit conjunctival cells, down-regulate the expressions of apoptosis-related proteins Caspase-3 and Fas, and up-regulate the expression of Bcl-2 protein, which may be one of the mechanisms of EA in treatment of DES.

Stealth tanshinone IIA-loaded solid lipid nanoparticles: effects of poloxamer 188 coating on in vitro phagocytosis and in vivo pharmacokinetics in rats / 药学学报

Stealth tanshinone IIA-loaded solid lipid nanoparticles (TA-SSLNs) have been prepared and the influence of poloxamer 188 coating on in vitro phagocytosis and in vivo pharmacokinetics in rats were evaluated. TA-SSLNs have been prepared by a nanoprecipitation/solvent diffusion method. Poloxamer 188 was used as a stealth agent. The physicochemical parameters of TA-SSLNs were characterized in terms of particle size, zeta potential, transmission electron microscopy and stability. In vitro, phagocytosis was investigated by incubating TA-SSLNs and non-stealth tanshinone IIA-loaded solid lipid nanoparticles (TA-NSLNs) with murine macrophages. In vivo, pharmacokinetics of TA-SSLNs and TA-NSLNs after a single dose intravenous injection to rat has been studied. The control was tanshinone IIA solution (TA-SOL). The results showed that TA-SSLNs had an average diameter of (91.3 +/- 3.4) nm, zeta potential of (-19.7 +/- 1.6) mV, drug loading of (4.7 +/- 0.5) % and entrapment efficiency of (92.5 +/- 2.1) %. Phagocytosis studies showed significant differences between TA-SSLNs and TA-NSLNs and demonstrated that the poloxamer 188 coating could decrease the macrophage uptake. In vivo experiments showed that the plasma concentration data of TA-SSLNs, TA-NSLNs and TA-SOL were all fitted to a two-compartment model. Areas under curve (AUCs) of TA-NSLNs and TA-SSLNs were 1.28 and 3.70 times than that of TA-SOL, respectively. TA-SSLNs had generated a long circulating time in blood with a mean residence time (MRT) of 5.286 h, compared to 3.051 h of TA-NSLNs and 0.820 h of TA-SOL. Poloxamer 188 modification on solid lipid nanoparticles (SLNs) reduced opsonization by serum proteins and the macrophage uptake. AUC of tanshinone IIA increased as a function of SLNs. In addition, TA-SSLNs exhibited much longer circulation lifetimes for tanshinone IIA than TA-NSLNs. The pharmacokinetic behavior of the incorporated drug can be modified by changing the surface characteristics of SLNs with the use of poloxamer 188.

Apoptotic mechanism of gastric carcinoma cells induced by matrine injection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of gastric carcinoma cells apoptosis induced by matrine injection in vitro.</p><p><b>METHODS</b>Effects of 24, 48, 72, 96 h incubation with different concentrations (0.25-1.5 g/L) of matrine injection on proliferation of SGC-7901 cells were evaluated using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The cellular morphology of SGC-7901 cells was observed by transmission electron microscope (EM). Flow cytometry was used to analyze the apoptosis of SGC-7901 cells by staining with annexin V-FITC/PI. The expression of Fas/FasL was examined by flow cytometry using specific antibody. The activity of caspase-3 was measured by spectrofluorometry.</p><p><b>RESULTS</b>Matrine injection could inhibit the proliferation of SGC-7901 cells in a dose- and time-dependent manner. The typical morphological changes of apoptosis were observed after incubation with 1.0 g/L matrine injections for 48 h. The apoptosis rates of 0.5 g/L, 1.0 g/L and 1.5 g/L groups were 39.80%, 58.11% and 79.00% respectively. The apoptotic cells in matrine injection group were mainly early apoptotic cells, and those in 5-FU group were mainly late apoptotic cells and necrotic cells. Spectrofluorometry revealed FI levels of Fas and FasL were equal, which were both correlated with apoptosis rate. The activity of caspase-3 increased with the elevation of matrine concentration, and was correlated with the apoptosis rate.</p><p><b>CONCLUSION</b>Matrine injection can induce apoptosis of SGC-7901 cells through the up-regulation of Fas/FasL expression and activation of caspase-3.</p>

Antitumor and immune-modulating effects of Scutellaria barbata extract in mice bearing hepatocarcinoma H22 cells-derived tumor / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of Scutellaria barbata extract (ESB) in suppressing tumor growth and modulating the immune functions in mice bearing tumors derived from hepatocarcinoma H22 cells.</p><p><b>METHODS</b>Fifty mice inoculated subcutaneously with H22 cells were equally divided into the model group, high-, moderate-, and low-dose ESB groups, and 5-Fu group, with corresponding treatments for 10 days. Another 10 mice with only saline injection served as the normal control group. The body weight, tumor mass, thymus index and spleen index of the mice were measured, and the lymphocyte proliferation activity, NK cell activity and interleukin-2 (IL-2) production by the splenocytes were detected.</p><p><b>RESULTS</b>Moderate- and high-dose ESB significantly suppressed the tumor growth with tumor inhibition rate of 28.68% and 36.98%, respectively. ESB treatment at moderate and high doses significantly increased the thymus index and spleen index (P < 0.01), which were decreased significantly in 5-Fu group. The lymphocyte proliferation activity, NK cell activity and IL-2 production by the splenocytes were significantly lower in the model group than in the normal group (P < 0.05). Compared with the model group, ESB at the high dose obviously increased the three indexes above mentioned. The NK cell activity was also significantly improved in moderate-dose ESB group (P < 0.05).</p><p><b>CONCLUSION</b>ESB can suppress the growth of H22 implant tumor and enhance the immune function of the tumor-bearing mice.</p>

HER-2 expression in local advanced breast cancer and the efficacy of neoadjuvant chemotherapy regimens / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between HER-2 expression and the efficacy of neoadjuvant chemotherapy in local advanced breast cancer.</p><p><b>METHODS</b>Different neoadjuvant chemotherapy regimens, namely CMF, CEF, and NEF, were administered in 132 patients with local advanced breast cancer for 2 cycles, each lasting for 28 days. According to the criteria recommended by WHO, the efficacy and safety of the regimens were evaluated after two cycles of neoadjuvant chemotherapy. HER-2 expression was examined by immunohistochemistry using specific monoclonal antibodies before chemotherapy and after surgery.</p><p><b>RESULTS</b>The overall response rate (RR) of CMF, CEF, and NEF regimens were 39.5% (17/43), 54.3% (25/46) and 72.1% (31/43), with incidence of leukopenia of 34.9% (15/43), 58.7% (27/46) and 60.5% (26/43), respectively. Other adverse effects including decreased hemoglobin (Hb) level, thrombocytopenia, gastrointestinal irritation and alopecia were similar between the 3 groups (P>0.05). No significant variation in HER-2 expression occurred after administration of the 3 regimens. The overall RR to CMF regimen in HER-2-negative breast cancer patients was significantly higher than that in HER-2-positive patients, but showed no significant difference with CEF and NEF regimens.</p><p><b>CONCLUSION</b>HER-2 expression is not decreased after neoadjuvant chemotherapy in breast cancer patients, and HER-2-positive breast cancer can be resistant to CMF regimen, but not to CEF and NEF regimens.</p>

Chemopreventive effect of celecoxib against DMBA-induced breast cancer and its mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the chemopreventive effect of celecoxib, a specific cyclooxegenease-2 (COX-2) inhibitor, on chemically induced breast cancer of rats and its effect on COX-2 expression.</p><p><b>METHODS</b>7, 12-dimethylbenz anthracene (DMBA) was administered intragastrically in SD female rats to establish breast cancer models, which were divided subsequently into control group, tamoxifen group and celecoxib group to receive different treatments accordingly. The occurrence rate of breast cancer was observed and the effect of celecoxib on COX-2 and vascular endothelial growth factor (VEGF) expressions assayed by immunohistochemical SP method.</p><p><b>RESULTS</b>The incidence of breast cancer in tamoxifen group (48.15%) and celecoxib group (50.00%) were both significantly lower than that in the control group (85.71%; P=0.003 and P=0.004, respectively). The positivity rate of COX-2 expression in celecoxib group (28.57%) was significantly lower than those of tamoxifen group (48.15%) and control group (83.33%; P=0.001 and P=0.035, respectively). The positivity rate of VEGF expression in celecoxib group (42.86%) was significantly lower than that of control group (79.17%, P=0.023), but comparable with that in tamoxifen group (46.15%, P=0.863).</p><p><b>CONCLUSION</b>Celecoxib can significantly suppress DMBA-induced breast cancer in female rats possibly through down-regulation of COX-2 and VEGF expressions.</p>