EPA is More Effective than DHA to Improve Depression-Like Behavior, Glia Cell Dysfunction and Hippcampal Apoptosis Signaling in a Chronic Stress-Induced Rat Model of Depression.

Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1ß were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-α levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-κB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-κB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment.

Clinical evaluation of neoadjuvant chemotherapy followed by radical surgery in the management of stage IB2-IIB cervical cancer.

OBJECTIVE: To evaluate clinical efficacy, toxicity, and survival outcomes of neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) among patients with cervical cancer stage IB2-IIB. METHODS: In a retrospective clinical study at West China Second Hospital, Chengdu, data were analyzed from 414 patients who underwent NACT followed by radical surgery (NACT-RS) or RS alone between January 2008 and November 2009. RESULTS: The clinical response for NACT was 90%. Lymph node metastasis (25% versus 48%, P<0.05) and deep cervical stromal invasion more than 0.5, (68% versus 91%, P<0.05) were significantly lower among responders than among non-responders, respectively, in the NACT-RS group. The 2-year progression-free survival and 2-year overall survival were 93.0% and 95.5% in the NACT-RS group, and 94.5% and 97.1% in the RS group (P>0.05). Parametric infiltration (hazard ratio [HR], 7.668; P<0.05) and lymph node metastasis (HR, 7.714; P<0.05) were independent risk factors for all study patients. CONCLUSION: Compared with RS, NACT-RS did not show a significant advantage for patients with locally advanced cervical cancer. However, the data provide the rationale for assessing NACT-RS in a multicenter randomized clinical trial setting. NACT may be considered as an alternative treatment when radiotherapy is not available.

[Comparative study of that synergistic effect of cisplatin combined with compound herbal medicinal prescription for tonic quality and activating blood circulation is on SKOV3 cell proliferation and apoptosis].

OBJECTIVE: To investigate the synergistic effects on cell apoptosis and growing restriction of SKOV3 cells by the combination of compound herbal medicinal prescription (CHMP) with cisplatin (DDP). METHODS: Cisplatin and two CHMP for tonic quality(CHMP1) and activating blood circulation (CHMP2), which was medicated serum, were prepared and used to treat the human ovarian carcinoma cell line SKOV3. By serum pharmacologic method, the growth and apoptosis of SKOV3 cell were observed at different time points(24,48,72, 96 h) with different concentrations of medicated serum. Coefficient of drug interaction (CDI) between CHMP, and CHMP2 was studied by MTT method. The effects of control group(A group),CHMP1 group(B group),CHMP2 group (C group), DDP group(D group), CHMP1 + DDP group(E group), CHMP2 + DDP group(Fgroup)to SKOV3 cell were studied by flow cytometry; and the cell apoptosis was observed by agarose electrophoresis; the expressions of TNFR1, caspase-8 on each group were analyzed by Western blot method. RESULTS: Synergistic effects were found between herbal medicinal mixtures and DDP, Restraining rate of SKOV3 and CHMP serum concentration was not in a dose-dependent manner as DDP was. CDI between CHMPI and CHMPS was found to be significant difference (CDI of CHMP1, CHMP2 and DDPwas 0.66, 0.58 respectively). It showed that the combined treatment was able to get better effect than single drug treatment. The performed agarose electrophoresis revealed the extracted DNA to show a typical ladder patterns for cell apoptosis. The analysis results of western blot showed the increased expressions of TNFR1 and caspase-8 after combined using of medicine, which were accord to the rates of apoptosis. CONCLUSIONS: CHMP drug granules show the synergistic effects with DDP, and the suppressing functions in the course of cell proliferation, and the inducing effect on apoptosis of human ovarian carcinoma cell line SKOV3 in vitro. And this mechanism is showed to be sponsored by the activation of TNFR1 and Caspase-8.