Evaluation of Oxidative Stress, Antioxidant Status and Serum Vitamin C Levels in Cancer Patients

Taking into account the importance role of lipid peroxidation and antioxidants in the prevention and incidence of cancer, the present study was carried out to determine oxidative stress, serum total antioxidant (TAS), and vitamin C levels in cancer patients. Malondialdehyde(MDA), total antioxidant status, and vitamin C levels of 57cancer patients aged 19–80 years and 22 healthy subjects (control group) aged 22–76 years were evaluated. Serum concentrations of MDA as thiobarbitaric acid complexes were measured by fluorometry method, the serum TAS by using commercial test kits from Randox Laboratories, and vitamin C by using spectrocolorimetric method. The mean serum MDA concentrations of all cancer groups except lung cancer were significantly higher than control group (P < 0.004). The mean total antioxidant status was insignificantly higher than control group. The mean serum vitamin C level was significantly lower in patients as compared to the healthy subjects (PV < 0.0001). In conclusion, an alteration in the lipid peroxidation with concomitant changes in antioxidant defense system in cancer patients may be due to excessive oxidative stress. Serum low levels of vitamin C in the different type of cancer patients in spite of adequate daily intake may be due to increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells.     

Biophysical,Rheological, and Functional Properties of Complex of Sodium Caseinate and Olive Leaf Aqueous Polyphenolic Extract Obtained Using Ultrasound-Assisted Extraction

Food Biophysics - This study demonstrated the use of ultrasound-assisted extraction to render aqueous extract polyphenolic compounds from olive leaves. Sodium caseinate-olive leaf extract complexes...     

The effect of terminal groups and halogenation of KLVFF peptide on its activity as an inhibitor of β‐amyloid aggregation

The aggregation of Aβ peptide into amyloid fibrils in the brain is associated with Alzheimer's disease (AD). Inhibition of Aβ aggregation seemed a potential treatment for AD. It was previously shown that a short fragment of Aβ peptide (KLVFF, 16‐20) bound Aβ inhibited its aggregation. In this work, using KLVFF peptide, we synthesized two peptide families and then evaluated their inhibitory capacities by conventional assays such as thioflavin T (ThT) fluorescence spectroscopy, turbidity measurement, and the 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS). The effect of peptide terminal groups on its inhibitory activity was first studied. Subsequently, the influence of halogenated amino acids on peptide anti‐aggregation properties was investigated. We found that iodinated peptide with amine in the N and amide in the C termini, respectively, was the best inhibitor of Aβ fibers formation. Halogenated peptides seemed to decrease the number of Aβ fibrils; however, they did not reduce Aβ cytotoxicity. The data obtained in this work seemed promising in developing potential peptide drugs for treatment of AD.     

Mitochondrial DNA 4977-bp deletion in endometriosis

Endometriosis is a multifactorial gynecological condition characterized by the presence of ectopic endometrial and stromal tissue outside the uterus. Free radicals and Oxidative stress have been proposed to be involved in the pathogenesis of the endometriosis. It has been shown that mitochondrial DNA (mtDNA) is particularly susceptible to oxidative damage and mutations due to the high rate of reactive oxygen species production and limited DNA repair capacity in mitochondria. While a number of deletions can occur, the most commonly studied in human is a 4977-bp deletion that removes all or parts of the genes for NADH dehydrogenase subunits 3, 4, 4L and 5, cytochrome C oxidase subunit III and ATP synthase subunits 6 and 8.” We evaluated whether mtDNA common deletion is related with the susceptibility to endometriosis in northern Iran. In this study 80 endometriosis cases and 100 controls were enrolled. Total DNA was extracted from endometrial tissue samples. The mitochondrial common deletion was determined by Gap- polymerase chain reaction (Gap-PCR). It was found that the mitochondrial common deletion was more likely to be present in patients with endometriosis. Assessing indicate that 60 % of patients and 8 % of controls show mtDNA 4977-bp deletion (Odds Ratio [OR] = 17.25, P < 0.0001, confidence interval [CI] = 5.18–57.36). The mtDNA 4977 deletion may play a role in endometriosis. Further studies with larger numbers of patients are required for further evaluation and confirmation of our finding.     

2,6-Disubstituted pyrazines and related analogs as NR2B site antagonists of the NMDA receptor with anti-depressant activity

Herein we describe the discovery of compounds that are competitive antagonists of the CP101-606 binding site within the NR2B subtype of the NMDA receptor. The compounds identified do not possess phenolic functional groups such as those in ifenprodil and related analogs. Initial identification of hits in this series focused on a basic, secondary amine side chain which led to good potency, but also presented a hERG liability. Further modifications led to examples of non-basic replacements which demonstrated much less liability in this regard. Finally, one compound in the series, 6a, was tested in the mouse forced swim depression assay and found to show activity (sc 60 mg/kg).     

Improved cellular response on functionalized polypyrrole interfaces

Neuroregeneration strategies involve multiple factors to stimulate nerve regeneration. Neural support with chemical and physical cues to optimize neural growth and replacing the lesion neuron and axons are crucial for designing neural scaffolds, which is a promising treatment approach. In this study, polypyrrole polymerization and its functionalization at the interface developed by glycine and gelatin for further optimization of cellular response. Nanofibrous scaffolds were fabricated by electrospinning of polyvinyl alcohol and chitosan solutions. The electrospun scaffolds were polymerized on the surface by pyrrole monomers to form an electroactive interface for further applications in neural tissue engineering. The polymerized polypyrrole showed a positive zeta potential value of 57.5 ± 5.46 mV. The in vitro and in vivo biocompatibility of the glycine and gelatin-functionalized polypyrrole-coated scaffolds were evaluated. No inflammatory cells were observed for the implanted scaffolds. Further, DAPI nucleus staining showed a superior cell attachment on the gelatin-functionalized polypyrrole-coated scaffolds. The topography and tuned positively charged polypyrrole interface with gelatin functionalization is expected to be particularly efficient physical and chemical simultaneous factors for promoting neural cell adhesion.     

Therapeutic potency of oncolytic virotherapy in breast cancer targeting,current status and perspective

Breast cancer is the most common cause of cancer death in women and presents a serious therapeutic challenge worldwide. Traditional treatments are less successful at targeting cancer tumors, leading to recurrent treatment-resistant secondary malignancies. Oncolytic virotherapy (OV) is a novel anticancer strategy with therapeutic implications at targeting cancer cells by using mechanisms that differ from conventional therapies. Administration of OVs either alone or in combination with standard therapies provide new insights regarding the effectiveness and improvement of treatment responses for breast cancer patients. This review summarizes cellular, animal and clinical studies investigating therapeutic potency of oncolytic virotherapy in breast cancer treatment for a better understanding and hence a better management of this disease.     

Regulatory T Cells Negatively Affect IL-2 Production of Effector T Cells through CD39/Adenosine Pathway in HIV Infection

The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human Treg expresses the ectoenzyme CD39, which in association with CD73 converts ATP/ADP/AMP to adenosine. We show here that Treg/CD39+ suppress IL-2 expression of activated CD4+ T-cells more efficiently than Treg/CD39−. This inhibition is due to the demethylation of an essential CpG site of the il-2 gene promoter, which was reversed by an anti-CD39 mAb. By recapitulating the events downstream CD39/adenosine receptor (A2AR) axis, we show that A2AR agonist and soluble cAMP inhibit CpG site demethylation of the il-2 gene promoter. A high frequency of Treg/CD39+ is associated with a low clinical outcome in HIV infection. We show here that CD4+ T-cells from HIV-1 infected individuals express high levels of A2AR and intracellular cAMP. Following in vitro stimulation, these cells exhibit a lower degree of demethylation of il-2 gene promoter associated with a lower expression of IL-2, compared to healthy individuals. These results extend previous data on the role of Treg in HIV infection by filling the gap between expansion of Treg/CD39+ in HIV infection and the suppression of CD4+ T-cell function through inhibition of IL-2 production.