The clinical signature of genetic variants and serum levels of macrophage migration inhibitory factor in Egyptian breast cancer patients.

PURPOSE: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC. METHODS: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case-control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay. RESULTS: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk. CONCLUSIONS: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC.

Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking.

In an effort to discover potent anticancer agents, 2-thiouracil-5-sulfonamides derivatives were designed and synthesized. The cytotoxic activity of all synthesized compounds was investigated against four human cancer cell lines viz A-2780 (ovarian), HT-29 (colon), MCF-7 (breast), and HepG2 (liver). Compounds 6b,d-g, and 7b showed promising anticancer activity and significant inhibition of CDK2A. Moreover, they were all safe when tested on WI38 normal cells with high selectivity index for cancer cells. Flow cytometric analysis for the most active compound 6e displayed induction of cell growth arrest at G1/S phase (A-2780 cells), S phase (HT-29 and MCF-7 cells), and G2/M phase (HepG2 cells) and stimulated the apoptotic death of all cancer cells. Moreover, 6e was able to cause cycle arrest indirectly through enhanced expression of cell cycle inhibitors p21 and p27. Finally, molecular docking of compound 6e endorsed its proper binding to CDK2A, which clarifies its potent anticancer activity.

Antioxidant and anti-proliferative activities of Acalypha fruticosa: Possible elucidated mechanism.

This study aimed to investigate the potential anti-oxidant activity of methanol (Aca-M) extract and n-hexane (Aca-H), chloroform (Aca-Ch), ethyl acetate (Aca-E), n-butanol (Aca-B) and aqueous (Aca-A) fractions obtained from the aerial parts of Acalypha fruticosa (Aca) using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Data obtained revealed that A. fruticosa methanol extract and different fractions inhibited the DPPH radicals in the following descending order: Aca-E >Aca-B >Aca-M >Aca-A >Aca-Ch >Aca-H compared to ascorbic acid. Additionally, in vitro 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium (MTT) assay against MCF-7, HCT-116, HepG-2 and non-cancerous MRC-5 cell lines was performed to determine their selective anti-cancer activity. The Aca-Ch fraction exhibited remarkable cytotoxic activity against all tested cancerous cell lines with IC50 4.81- 12.2µg/mL, while both Aca-Ch and Aca-H fractions possessed potent cytotoxic activities on HCT-116 (IC50 4.81 and 10.1, respectively) with negligible harm but selective effect on non-cancerous MRC-5 cells (IC50 20.4 and 85.2, respectively).

Homocysteine as a predictive biomarker in early diagnosis of renal failure susceptibility and prognostic diagnosis for end stages renal disease.

Glomerular filtration rate and/or creatinine are not accurate methods for renal failure prediction. This study tested homocysteine (Hcy) as a predictive and prognostic marker for end stage renal disease (ESRD). In total, 176 subjects were recruited and divided into: healthy normal group (108 subjects); mild-to-moderate impaired renal function group (21 patients); severe impaired renal function group (7 patients); and chronic renal failure group (40 patients) who were on regular hemodialysis. Blood samples were collected, and serum was separated for analysis of total Hcy, creatinine, high sensitive C-reactive protein (CRP), serum albumin, and calcium. Data showed that Hcy level was significantly increased from normal-to-mild impairment then significantly decreases from mild impairment until the patient reaches severe impairment while showing significant elevation in the last stage of chronic renal disease. Creatinine level was increased in all stages of kidney impairment in comparison with control. CRP level was showing significant elevation in the last stage. A significant decrease in both albumin and calcium was occurred in all stages of renal impairment. We conclude Hcy in combination with CRP, creatinine, albumin, and calcium can be used as a prognostic marker for ESRD and an early diagnostic marker for the risk of renal failure.

Mechanism of endothelial cyto-protective and thrombo-resistance effects of sildenafil, vardenafil and tadalafil in male rabbit.

INTRODUCTION: PDE5 inhibitors (PDE5inhs) have proven to be of great impact in the treatment of numerous human extra-sexual diseases and their chronic use may induce endothelial rehabilitation. This study aimed to assess the effects of PDE5inhs at chronic administration to explore the possible endothelial cyto-protective and thrombo-resistance effects. MATERIAL AND METHODS: One hundred New Zealand white male rabbits were divided into four groups. The first group (control, C) received 1 ml saline/kg, the second group (S) received 10 mg/kg sildenafil, the third group (V) received 2 mg/kg vardenafil, and the fourth group (T) received 2 mg/kg tadalafil in saline I.P. three times weekly for 4 weeks. Blood samples were collected and plasma was isolated for determination of 2,3-dinor-6-keto-prostaglandin F-1α (PGF1α), 11-dehydro-TXB2 (TXB2), fibrinogen, calcium levels, prothrombin (PT), and thrombin times (TT). RESULTS: PDE5inhs significantly increase PGF1α, calcium levels, PT and TT (p < 0.001) when compared with baseline data or with the saline group at the end of treatment. In contrast, PDE5inhs significantly decrease TXB2 and fibrinogen levels (p < 0.001) when compared either with their baseline data or with the saline group at the end of treatment. The tadalafil group showed a lower increase in PGF1α (p < 0.001), lower decrease in TXB2 (p < 0.001), and higher increase in calcium levels (p < 0.01, p < 0.05), lower increase in PT and TT levels (p < 0.001) when compared with sildenafil or vardenafil. CONCLUSIONS: The prolonged use of PDE5inhs has time-dependent mild to moderate endothelial cyto-protective, thrombo-resistance anti-inflammatory and anti-nociception effects via activation of endothelial NOS (eNOS), increase of PGI2 synthesis and decrease of fibrinogen with significant increase in PT and TT.

Effects of Portulaca oleracea L. seeds in treatment of type-2 diabetes mellitus patients as adjunctive and alternative therapy.

UNLABELLED: ETHNPHARMACOLOGICAL RELEVANCE: To investigate antidiabetic activity of purslane seeds on type-2 diabetic subjects and to provide scientific basis for the clinical use of Portulaca oleracea (PO). MATERIALS AND METHODS: A thirty subject with type-2 diabetes divided into two groups, to receive 5 g of PO seeds twice daily while in the second group, their participants receive 1,500 mg of metformin/day. All participants were requested to report the effects of treatments on diabetic manifestations, their weights, body mass index (BMI), adverse effects, fasting and post-prandial blood glucose during treatment schedule. Blood samples from participants before and after treatment were taken for serum separation, which are used for measurement of serum lipids, liver enzymes, total and direct bilirubin, albumin, and insulin. RESULTS: It showed a significant decrease in serum levels of triglycerides (TGs), total cholesterol (T(C)), low density lipoprotein cholesterol (LDL(C)), liver alanine-, aspartate- and gamma glutamyl transaminase (ALT, AST, and GGT), total and direct bilirubin, fasting and post-prandial blood glucose, insulin, body weight and BMI while a significant increase in high density lipoprotein cholesterol (HDL(C)) and albumin but non-significant change of alkaline phosphatase (ALP) in PO seeds treated subjects. Metformin (M) group has the same results of PO group except in high density lipoprotein cholesterol (HDL(C)), LDL(C), and ALP levels had a different pattern. CONCLUSIONS: PO seeds could be effective and safe as adjuvant therapy for Type-2 diabetic subjects. These results demonstrated that PO seeds possessed notable hypoglycaemic, hypolipidaemic and insulin resistance reducer effects; possibly due to its contents of polyunsaturated fatty acids, flavonoids, and polysaccharides.