Oxidative stress and female infertility: the role of follicular fluid soluble receptor of advanced glycation end-products (sRAGE) in women with endometriosis.

Oxidative Stress (OS) relates to the pathophysiology of endometriosis by activation of the inflammation process in the ovary, abdomen, peritoneum and endometrium. Advanced Glycation end-products (AGEs) cause oxidative damage to the follicles of the ovary. This study aims to investigate the correlation of follicular fluid soluble receptor of AGEs (FF sRAGE) with fertility-related parameters in infertile women with endometriosis. From January 2012 to July 2015 twenty-four women diagnosed with mild to moderate endometriosis aged 28-38 years underwent assisted reproduction. sRAGE levels measured in FF were related to lifestyle factors, sociodemographic characteristics, gynaecological and obstetric parameters, hormonal status and fertilization. sRAGE was inversely associated with BMI (r = -0.503, p = 0.012). No significant association of sRAGE with age (p = 0.714) or alcohol consumption (p = 0.882) was found. Pearson's r correlation coefficient revealed that sRAGE was positively associated with serum AMH (r = 0.518, p = 0.009), FF AMH (r = 0.630, p = 0.001), number of follicles >15mm (r = 0.601, p = 0.002), total number of follicles aspirated (r = 0.698, p < 0.001), total number of MII oocytes obtained, (r = 0.757, p < 0.001) and the number of embryos with good embryo scoring (suitable for ET) (r = 0.522, p = 0.009). It seems that measurement of FF RAGE might be a useful predictive marker for IVF success in infertile women with endometriosis undergoing assisted reproduction.

Assessment of the Immunomodulatory Properties of the Probiotic Strain Lactobacillus paracasei K5 in vitro and In Vivo.

Lactobacillus paracasei K5 is a lactic acid bacteria (LAB) strain that has been isolated from dairy products. Previous studies have established its probiotic potential in a series of in vitro tests, including molecular characterization, safety profiling, and tolerability of the gastrointestinal tract conditions. To characterize its beneficial actions on the host, we have shown previously that L. paracasei K5 adheres to Caco-2 cells and exerts anti-proliferative effects through the induction of apoptosis. In the present study, we focused on the immunomodulatory potential of this strain. We employed the dorsal-air-pouch mouse model of inflammation and recorded an eight-fold increase in the recruitment of immune cells in mice treated with the probiotic strain, compared to the control group. Analysis of the exudates revealed significant changes in the expression of pro-inflammatory mediators on site. Treatment of Caco-2 cells with L. paracasei K5 induced significant upregulation of cytokines interleukin-1α (IL-1α), ΙL-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), the chemokine C-X-C motif ligand 2 (CXCL2), and the inflammation markers soluble intercellular adhesion molecule (sICAM) and metallopeptidase inhibitor-1 (TIMP-1). Transient induction of the Toll-like receptors (TLRs) 2, 4, 6, and 9 expression levels was recorded by real-time PCR analysis. These results highlight the immunomodulatory potential of this strain and further support its probiotic character.

Evaluation of Antioxidant and Antiproliferative Properties of Cornus mas L. Fruit Juice.

Cornus mas L. (Cornelian cherry) is a flowering plant indigenous to Europe and parts of Asia, mostly studied for the antimicrobial activity of its juice. In this report, we investigated the composition and the in vitro antioxidant capacity of Cornus mas L. fruit juice from Greece, as well as its antiproliferative properties in vitro and in vivo. The fruits showed a high content of citric, malic, and succinic acid, in contrast to their juice, which had a low concentration of organic acids. The juice demonstrated significant antioxidant activity against the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and modest antiproliferative potential against four human cancer cells lines and one murine: mammary adenocarcinoma MCF-7, hepatocellular carcinoma HepG2 and colon adenocarcinomas Caco2, HT-29, as well as murine colon carcinoma CT26. Cell viability was reduced by 40-50% following incubation of the cells with the highest concentration of the juice. Although Cornelian cherry juice exhibited in vitro growth inhibitory effects against colon carcinoma cells, no tumor growth inhibition was observed in an in vivo experimental colon carcinoma model in mice following prophylactic oral administration of a daily dose of 100 L juice for a period of 10 days. Thus, our findings raise interesting questions for further research on Cornus mas L. fruit juice, and in parallel, the strong antioxidant potential implies that the plant could be further explored and exploited for its protective effect against oxidative damage.

Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma.

BACKGROUND: Several studies have highlighted hyperthermia's ability to enhance the effectiveness of radiation and chemotherapy in various in vitro and in vivo cancer models. MATERIALS AND METHODS: In vivo murine models of malignant melanoma and colon carcinoma were utilized for demonstrating hyperthermia's therapeutic effectiveness by examining levels of caspase 3, COX-2 and phospho-H2A.X (Ser139) as endpoints of apoptosis, proliferation and DNA damage respectively. RESULTS: Hyperthermia induced in vitro cytotoxicity in malignant melanoma (B16-F10) and colon carcinoma (CT26) cell lines. In addition, it reduced post-in vitro proliferation and suppression of tumor growth by inducing the expression of caspase-3 and phospho-H2A.X (Ser139) while reducing the expression of COX-2 in both murine cancer models. CONCLUSION: Hyperthermia can exert therapeutic effectiveness against melanoma and colon carcinoma by inhibiting a number of critical cellular cascades including apoptosis, proliferation and DNA damage.

Dietary mastic oil extracted from Pistacia lentiscus var. chia suppresses tumor growth in experimental colon cancer models.

Plant-derived bioactive compounds attract considerable interest as potential chemopreventive anticancer agents. We analyzed the volatile dietary phytochemicals (terpenes) present in mastic oil extracted from the resin of Pistacia lentiscus var. chia and comparatively investigated their effects on colon carcinoma proliferation, a) in vitro against colon cancer cell lines and b) in vivo on tumor growth in mice following oral administration. Mastic oil inhibited - more effectively than its major constituents- proliferation of colon cancer cells in vitro, attenuated migration and downregulated transcriptional expression of survivin (BIRC5a). When administered orally, mastic oil inhibited the growth of colon carcinoma tumors in mice. A reduced expression of Ki-67 and survivin in tumor tissues accompanied the observed effects. Notably, only mastic oil -which is comprised of 67.7% α-pinene and 18.8% myrcene- induced a statistically significant anti-tumor effect in mice but not α-pinene, myrcene or a combination thereof. Thus, mastic oil, as a combination of terpenes, exerts growth inhibitory effects against colon carcinoma, suggesting a nutraceutical potential in the fight against colon cancer. To our knowledge, this is the first report showing that orally administered mastic oil induces tumor-suppressing effects against experimental colon cancer.

Development of a Novel Experimental In Vitro Model of Isothiocyanate-induced Apoptosis in Human Malignant Melanoma Cells.

BACKGROUND: Isothiocyanates are constituents of cruciferous vegetables which have been associated with reduced cancer risk partially through their ability to induce apoptosis in malignant cells including melanoma. MATERIALS AND METHODS: We have utilized human malignant melanoma (A375), epidermoid carcinoma (A431) and immortalized keratinocyte (HaCaT) cells exposed to various isothiocyanates, under different experimental conditions. RESULTS: An experimental in vitro model utilizing low isothiocyanate concentrations (0.1-5 µM for 48 h with all treatments being refreshed after 24h) was shown to be (i) most efficient in exerting an anti-cancer effect when compared to higher concentrations (5-100 µM for 24 or 48 h added as a single bolus) and (ii) specific to A375 cells while A431 and HaCaT cells remained unaffected. Such effect involved the activation of several caspases including (iii) initiator caspases 8, 9, 4 (indicating the involvement of intrinsic, extrinsic and endoplasmic reticulum-based pathways) and (iv) effector caspases 3, 7 and 6. CONCLUSION: Utilization of low isothiocyanate concentrations (under the conditions described herein) exerts an anti-cancer effect specific to human malignant melanoma cells thus providing a therapeutic basis for their utilization in management of the disease.