Integrative Bioinformatics Analysis Reveals Potential Target Genes and PTEN Signaling in Breast Cancer and Effect of Zingiber officinale (Ginger) and Allium sativum (Garlic) extract on It.

INTRODUCTION: Breast cancer is the most common type of cancer in women. The construction of a competing gene network is an important step in the identification of the role of hub genes in breast cancers. In the current research, we used a number of bioinformatics tools to construct this network in breast cancer and investigated the combined effect of garlic and ginger on mice model of breast cancer. MATERIALS AND METHODS: We chose female mice weighing 18-20 g that were divided into 7 groups including; the cancer group receiving normal saline, different doses of ginger extract (100 and 500 mg/kg), different doses of garlic (50 and 100 mg/kg), tamoxifen (10 mg/ kg) and simultaneous garlic (100 mg/kg) and ginger (500 mg/kg) for 3 weeks intraperitoneal. Then we anesthetized the mice, isolated the tumor, and determined its size. Glutathione reductase and peroxidase levels and HER2, PTEN, and Cullin3 genes expression were measured. RESULTS: We identified 20 hub genes for breast cancer. In animal phase we found that tumor size in all mice receiving garlic and ginger showed a significant decrease compared to the control. Glutathione reductase showed a significant increase in all groups, especially in ginger 500 and combined groups. Glutathione peroxidase increased almost in all groups, especially in ginger 500. Expression of HER2 decreased in all treated groups. Expression of PTEN increased just in the combined group. CONCLUSION: Taken together, we introduce a number of novel promising diagnostic biomarkers for breast cancer. The use of garlic and ginger in the treatment of cancer can be useful. This action is probably through the antioxidant mechanism, and regulation of the expression of cancer related genes such as PTEN.

Evaluation of the Anti-Metastatic Effect of Foeniculum Vulgare on the Protein Expression of HSP 70 & 90 in Balb/c Mice with 4t1 Model of Breast Cancer.

INTRODUCTION: Breast cancer is one of the important factors of cancer-related deaths. Considering the drug resistance, special attention has been paid to natural compounds. This study aimed at evaluating the anti-metastatic activity of fennel in a breast cancer mouse model. METHODS: A total of 35 adult female BALB/C mice were used in this study. Breast cancer was induced by subcutaneous injection of 4T1 cells in the right lower flank. The mice received fennel extracts daily via intraperitoneal injection for two weeks. Meanwhile, tumor volume was measured every day using calipers. After two weeks, each animal was anesthetized. The protein expression of HSP 70 & 90 was measured in liver tissue and ovary. The expression of her2 was measured in tumor tissue. The activity of Glutathione peroxidase and reductase as anti-oxidant agents were measured in serum. RESULTS: Tumor size significantly decreased after nine days' treatment of the fennel. The expression of HER2 increased in the tumor tissue and decrease with different dose of fennel. Fennel treatment caused a decrease in the protein expression of HSP 70 & 90 in the liver tissues. CONCLUSION: Based on our findings, fennel has anti-tumor and anti-metastatic activities against aggressive cancers.

Beneficial effects of Se/Zn co-supplementation on body weight and adipose tissue inflammation in high-fat diet-induced obese rats.

This research investigated the effect of co-supplementation of selenium with zinc on weight control and the inflammatory and oxidative status in relation to obesity. Male Wistar rats (N = 32) were randomly divided into four groups after induction of obesity model: 1) "Zn" was supplemented with zinc sulfate (15 mg/kg BW), 2) "Se" supplemented with selenium as sodium selenate (0.5 mg/kg BW), 3) "Zn + Se" which received Zn (15 mg/kg BW) + Se (0.5 mg/kg BW), and 4) "HFD" as the control group. The intervention was done for eight weeks. At the end of treatment, serum and tissue level of Zn, Se, SOD, GSH-Px, MDA, leptin, TNF-α, and IL-6 was evaluated. Weight and food intake were significantly reduced in the Se group(p < .001), while in the Zn group, weight gain due to obesity was prevented compared to the control group (p = .48). There was a significant and stronger increase in SOD, GSH-Px levels and a remarkable decrease in MDA, leptin, TNF-α, and IL-6 in the group receiving the combination of two supplements than either alone(p < .001). Leptin had a positive correlation with inflammatory factors and lipid peroxidation marker and showed an inverse relationship with Zn and Se levels and anti-oxidative enzymes(p < .05). The analysis showed the mediating role of leptin in the effects of zinc. Co-supplementation of selenium and zinc may have a synergistic effect in reduction of oxidative and inflammatory markers. Regarding the effect of zinc on inflammatory factors and lipid peroxidation, leptin can play a mediating role.

A randomized controlled trial on the coloprotective effect of coenzyme Q10 on immune-inflammatory cytokines, oxidative status, antimicrobial peptides, and microRNA-146a expression in patients with mild-to-moderate ulcerative colitis.

PURPOSE: Coenzyme Q10 (CoQ10), having potent antioxidant and anti-inflammatory pharmacological properties, has recently been shown to be a safe and promising agent in maintaining remission of ulcerative colitis (UC). This trial was, therefore, designed to determine CoQ10 efficacy on inflammation and antioxidant status, antimicrobial peptides, and microRNA-146a expression in UC patients. METHODS: In this randomized double-blind controlled trial, 88 mild-to-moderate UC patients were randomly allocated to receive CoQ10 (200 mg/day) or placebo (rice flour) for 2 months. At the baseline and at an 8-week follow-up, serum levels of Nrf2, cathelicidin LL-37, ß-defensin 2, IL-10, IL-17, NF-κB p65 activity in peripheral blood mononuclear cells (PBMCs), simple clinical colitis activity index questionnaire (SCCAIQ), and quality of life (IBDQ-32 score), as well as an expression rate of microRNA-146a were measured. RESULTS: A significant reduction was detected in the serum IL-17 level, activity of NF-κB p65 in PBMCs, and also SCCAI score in the CoQ10 group compared to the placebo group, whereas IL-10 serum concentrations and IBDQ-32 score of the CoQ10 group considerably increased versus the control group; the changes of these variables were also significantly different within and between groups at the end of the study. Furthermore, CoQ10 remarkably increased serum levels of cathelicidin LL-37. A significant change in serum cathelicidin LL-37 levels was also observed between the two groups. No statistical difference, however, was seen between the two groups in terms of the serum levels of Nrf2 and ß-defensin 2 and the relative expression of microRNA-146a. CONCLUSIONS: Our results indicate that CoQ10 supplementation, along with drug therapy, appears to be an efficient reducer of inflammation in patients with mild-to-moderate UC at a remission phase. TRIAL REGISTRATION: The research has also been registered at the Iranian Registry of Clinical Trials (IRCT): IRCT20090822002365N17.

The effects of curcumin supplementation on oxidative stress, Sirtuin-1 and peroxisome proliferator activated receptor γ coactivator 1α gene expression in polycystic ovarian syndrome (PCOS) patients: A randomized placebo-controlled clinical trial.

BACKGROUND & AIMS: Curcumin is a biologically active phytochemical ingredient found in turmeric and has antioxidant pharmacologic actions that may benefit patients with polycystic ovarian syndrome (PCOS). The aim in this trial was to evaluate the efficacy of curcumin supplementation on oxidative stress enzymes, sirtuin-1 (SIRT1) and Peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) gene expression in PCOS patients. METHODS: Seventy-two patients with PCOS were recruited for this randomized, double-blinded, clinical trial. Thirty-six patients received curcumin, 1500 mg (three times per day), and 36 patients received placebo for 3 months. Gene expression of SIRT1, PGC1α and serum activity of glutathione peroxidase (Gpx) and superoxide dismutase (SOD) enzymes were evaluated at the beginning of trial and at 3-month follow-up. RESULTS: Sixty-seven patients with PCOS completed the trial. Curcumin supplementation significantly increased gene expression of PGC1α (p = 0.011) and activity of the Gpx enzyme (p = 0.045). Curcumin also non-significantly increased gene expression of SIRT1 and activity of the SOD enzyme. CONCLUSIONS: Curcumin seems to be an efficient reducer of oxidative stress related complications in patients with PCOS. Further studies on curcumin should strengthen our findings.

Low, but not high, dose triptolide controls neuroinflammation and improves behavioral deficits in toxic model of multiple sclerosis by dampening of NF-κB activation and acceleration of intrinsic myelin repair.

Cuprizone (Cup) is a copper chelating agent frequently used to study factors that affect oligodendrocytes (OLGs) death and acute demyelination. Triptolide (TP), a nuclear factor-kappaB (NF-κB) blocker, is a major bioactive component of Tripterygium wilfordii Hook f. (TWHf) with various therapeutic activities. In this study, we examined the effects of TP on neuroglia activation, inflammation, apoptosis, demyelination, and behavioral deficits in the Cup-induced toxic model of multiple sclerosis (MS). C57BL/6 J mice were fed with chow containing 0.2% Cup for 6 weeks to induce detectable neuroinflammation and myelin loss. TP was administered intraperitoneally at different doses (125, 250 or 500 µg/kg/day) during the last week of the Cup challenge. Although TP substantially decreased Cup-induced NF-κB extra activation, TNF-α and IL-1 over expression, and gliosis in a dose-dependent manner, only low dose of TP (TP-125) was able to raise the number of OLGs precursor cells (NG-2+/O4+), reduce Bax/Bcl-2 ratio and improve behavioral deficits. In addition, TP-125 decreased NF-κB activation on GFAP+ astrocytes more than MAC-3+ microglial and MOG+ oligodendrocytes which suggested the possibility of specific dampening of NF-κB signaling in reactive astrocytes. Behavioral assessments by open-field and rota-rod tests showed that only TP-125 notably improved motor function and motor coordination compared to the Cup group. These findings highlight the pivotal role of NF-κB signaling in the oligodendrogenesis and lesion reduction in demyelination diseases such as MS.

Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis.

CONTEXT: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions. OBJECTIVE: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated. MATERIAL AND METHODS: C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p.) from the first day of cup diet. Oligodendrocytes apoptosis [TUNEL assay and myelin oligodendrocyte glycoprotein (MOG+)/caspase-3+ cells), gliosis (H&E staining, glial fibrillary acidic protein (GFAP+) and macrophage-3 (Mac-3+) cells) and inflammatory markers (interleukin 17 (IL-17), interleukin 11 (IL-11) and stromal cell-derived factor 1 α (SDF-1α) or CXCL12] during cup intoxication were examined. RESULTS: High dose of EA (EA-80) increased mature oligodendrocytes population (MOG+ cells, p < 0.001), and decreased apoptosis (p < 0.05) compared with the cup mice. Treatment with both EA doses did not show any considerable effects on the expression of CXCL12, but significantly down-regulated the expression of IL-17 and up-regulated the expression of IL-11 in mRNA levels compared with the cup mice. Only treatment with EA-80 significantly decreased the population of active macrophage (MAC-3+ cells, p < 0.001) but not reactive astrocytes (GFAP+ cells) compared with the cup mice. DISCUSSION AND CONCLUSION: In this model, EA-80 effectively reduces lesions via reduction of neuroinflammation and toxic effects of cup on mature OLGs. EA is a suitable therapeutic agent for moderate brain damage in neurodegenerative diseases such as multiple sclerosis.