Curcumin and ustekinumab cotherapy alleviates induced psoriasis in rats through their antioxidant, anti-inflammatory, and antiproliferative effects.

INTRODUCTION: Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects. OBJECTIVE: The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model. MATERIALS AND METHODS: Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis. RESULTS: Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant (p < 0.05) reductions in the levels of antioxidant biomarkers (SOD, GPx, and CAT) with significant (p < 0.05) elevations in psoriasis-related cytokines (TNF-α, IL-17A, IL-12P40, and IL-23). In contrast, CUC alleviated the psoriatic changes in G4 better than ustekinumab monotherapy in G3. CONCLUSIONS: Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC.HighlightsIQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CATUstekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levelsCUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effectsCUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels.

Methanolic Fenugreek Seed Extract Induces p53-Dependent Mitotic Catastrophe in Breast Cancer Cells, Leading to Apoptosis.

PURPOSE: The plant Trigonella foenum-graecum, well-known as fenugreek, has been shown to control type-2 diabetes, the level of cholesterol, inflammation of wounds, disorders related to gastrointestinal tracts, and cancer as well. The present study aimed to evaluate the anti-cancer potential of methanolic fenugreek seed extract (FSE) and its possible molecular mechanism of action in breast cancer cells. METHODS: The anticancer potential of FSE was evaluated in MCF-7 and SK-BR3 breast cancer cells through various cellular assays after selecting the IC10, IC25, IC35, and IC50 doses by the cell cytotoxicity assay. Furthermore, the oral acute toxicity of FSE was examined in mice, according to the guidelines of the Organization for Economic Co-operation and Development (OECD). RESULTS: FSE exhibited dose-dependent cytotoxicity, as the IC50 was found to be 150 and 40 µg/mL for MCF-7 and SK-BR3 breast cancer cells, respectively. The cytological observations showed the typical apoptotic morphology in both of the breast cancer cells upon treatment with FSE, as it inhibited the migration and adhesion, in a dose-dependent manner. The flow cytometry analysis revealed that FSE induced a significant shift from G2/M, and polyploidy (>G) at higher concentrations that suggested the activation of p53-mediated mitotic catastrophe, consequently leading to apoptosis. FSE induced a significant increase in the mitochondrial depolarization, ROS as well as a Bax/Bcl-2 ratio, and also exhibited the mitochondrial associated p53 signaling pathway. The in vivo acute toxicity data revealed that the oral administration of FSE did not induce any toxic effect in mice. CONCLUSION: This study, for the first time, reports the mechanistic details of the anti-cancer potential of FSE. It requires a detailed analysis to understand the effect of FSE to induce the apoptosis through the multiple signaling pathways at varying concentrations. The nontoxic effect of FSE in mice suggests to utilize it safely for pharmaceutical formulations in different cancer systems.

Thymoquinone Augments Cyclophosphamide-Mediated Inhibition of Cell Proliferation in Breast Cancer Cells

Objective: Cancer chemotherapy at the recommended doses is largely associated with toxicity, and also it is not effective enough to reduce the advancement of the disease at lower doses. Thymoquinone (TQ) is an active compound derived from black seeds (Nigella sativa) which exhibits anticancer activities. The aim of the present study was to investigate the synergistic effect of TQ alone and in combination with cyclophosphamide (cyclo), and to unravel the role of TQ in fatty acid synthase (FASN) mediated molecular signaling in Her2 + and Her2- breast cancer cell lines. Methods: The effect of TQ on the growth of Her2+ SKBR-3 and Her2- MDA-231 breast cancer lines were evaluated as percent cell viability by cytotoxicity-based MTT assay. The analysis of cell cycle arrest was done through flowcytometry followed by Western blot and RT-PCR to detect signaling events in the cells. Results: The data showed that TQ-cyclo (0.5mM-10µM) combination significantly inhibited the proliferation through the 5.49% and 57.72% accumulation of cells in sub-G1 and G1 respectively as 12% cells were shifted from G2/M phase in Her2+ breast cancer cells. Similarly, TQ-cyclo (0.5mM-20µM) combination exhibited that the 16.6% cells were arrested in Sub-G1 and only 3.54% cells were remained in G2/M phase as it was 22.89% in DMSO control in Her-2- breast cancers cells. Though TQ alone or in combination with cyclo alleviated the PI3K/Akt signaling by downregulating the phosphorylation of Akt and upregulating the PTEN, no changes was observed in FASN and Her-2 as well in both type of cells. The significant decreased expression of cyclin D1 was found in TQ-cyclo combinations. Conclusion: The current findings suggested that TQ can alter the cell cycle progression and induce cell death independent of FASN mediated signaling. In terms of clinical perspective, the present study clearly showed that TQ can broadly augment the effect of cyclo in breast cancer cases irrespective of Her-2+ or Her-.

Therapeutic potential of thymoquinone liposomes against the systemic infection of Candida albicans in diabetic mice.

The present study was aimed to develop a liposomal formulation of thymoquinone (Lip-TQ) to treat Candida albicans infection in diabetic mice. Streptozotocin (STZ) was injected to induce hyperglycemia and on day 3 post STZ administration, mice were intravenously infected with C. albicans. Various doses (2, 5 and 10 mg/kg) of Free or Lip-TQ were administered in C. albicans infected diabetic mice. The effect of Lip-TQ was also determined on the organ indices, liver and kidney function parameters. Lip-TQ at a dose of 10 mg/kg significantly reduced the level of the blood glucose and alleviated the systemic C. albicans infection in diabetic mice. C. albicans infected diabetic mice treated with Lip-TQ at a dose of 10 mg/kg showed the survival rate of 70% as compared to that of 20% in the group treated with free TQ. The treatment with Lip-TQ resulted in the recovery of the organ indices, liver inflammation, kidney functioning and pancreas regeneration in diabetic mice. Moreover, TQ formulations also showed the direct therapeutic effect against candidiasis in the untreated or metformin-treated diabetic mice. Therefore, the findings of the present study support the use of Lip-TQ in the treatment of candidiasis in the diabetic patients.

Histopathological Pattern and Age Distribution, of Malignant Ovarian Tumor among Sudanese Ladies.

INTRODUCTION: Ovarian cancer is the cause of a high case-fatality ratio, and most of the cases are diagnosed in late stages. OBJECTIVES: To determine the histopathological types, age distribution, and ovarian tumour stages among diagnosed with ovarian cancer at Al - Amal Tower a multi-referral polyclinic of Radiology & Isotope Center Khartoum (RICK), Sudan. METHODS: All histopathology reports patients' case from January to June 2015 were reviewed. The cancers classified according to federation international of Obstetrics and Gynecology (FIGO). RESULTS: There were 127 cases of ovarian cancers. Surface epithelial cancers were the most common 77.7% (n = 98), followed by sex cord-stromal cancers 11.23% (n = 14), Germ cell tumor 1.6% (n = 2). Metastatic cancers were seen from colon and breast in 6.3% and 3.9 % of cases respectively. Few cases (14%) of ovarian cancers were reported before 40 years of age, after the age of 50 is a sharp increase in the incidence of a tumour. The mean age at presentation was 52.36 ± 14.210 years, there is mean age of menarche 13.59 ± 2.706 years. Very few patients used HRT (1.6%) or had been on ovulation induction treatment (8.7%). Most of patients 39 (30.7%) presented in stage IIIC, and stage 1V 32 (25.2%) indicating a poor prognosis. CONCLUSION: The incidence of different types of ovarian cancers in the present study is similar to worldwide incidence. The surface epithelial tumour is the commonest ovarian cancer, of which serous adenocarcinoma is the commonest and most of our patients present in late stages.

Protective potential of thymoquinone against peroxynitrite induced modifications in histone H2A: In vitro studies.

Peroxynitrite (ONOO-) is a reactive oxidant involved in numerous pathological conditions. Thymoquinone (TQ) is an active constituent of Nigella sativa and is reported to have anti-disease activities, but its role on ONOO- has never been investigated. This study was undertaken to investigate the role of TQ on ONOO--induced damage of histone-H2A. Our novel data showed TQ significantly inhibited ONOO--induced oxidative damage in histone-H2A. ONOO- induces UV-hypochromicity of histone-H2A, whereas TQ reversed this effect to hyperchromicity. Tyrosine fluorescence was significantly reduced by ONOO- and was significantly increased upon TQ treatment. TQ reduces ONOO--induced hydrophobicity in histone-H2A and also reduces thermal stability of ONOO--histone H2A complex. SDS-PAGE of native histone-H2A showed a single band, which disappeared when treated with ONOO- alone. This changed was retained when protein samples were treated with TQ. Similar protective effects of TQ were found when protein carbonyl contents were estimated. In conclusion, this is the first study that shows the potential of TQ against ONOO--induced damaged of histone-H2A. TQ inhibits oxidative modification of tyrosine, lysine, arginine, proline and threonine in histone-H2A. These results have importance for the development of novel therapeutic strategies for the treatment of disorders, where ONOO- plays a role.