Assessment of Relationship Between Expression of Survivin Protein and Histopathology Diagnosis and Malignancy Severity in Colon Specimen.

BACKGROUND: Survivin is a member of the inhibitor of an apoptosis protein family that has been shown to inhibit apoptosis, promote cell proliferation and enhance angiogenesis. In this study, the survivin protein expression in normal, colon polyp, and adenocarcinoma tissues was investigated. METHODS: Immunohistochemical staining for nuclear survivin was carried out on 45 normal colon tissue samples, 38 samples of a colonic polyp, and 37 cases of colon adenocarcinoma operated by colonoscopy or colectomy. The percentages of cells that expressed survivin were classified qualitatively into four categories (0, 1+, 2+, and 3+) based on the intensity of staining and the percentage of cells. An area of samples with colon polyp diagnosis or colon adenocarcinoma that had no microscopic pathology was considered as normal tissues. RESULTS: Survivin protein expression was negative in all cases of normal colon tissue samples while it was expressed in 31 out of 38 colon polyp specimens (81.5%) and in 35 out of 37 (94.5%) colon adenocarcinoma samples. Amount of expression in the colon adenocarcinoma (p < 0.001) was significantly higher than the amount of expression in the colon polyp. There was not a significant correlation between the survivin protein expression and the low and high grade adenocarcinoma (p = 0.874). CONCLUSIONS: Survivin protein was not expressed in normal colon tissues and its amount was higher in the colonic adenocarcinoma compared to the colon polyp. Due to the variations in the intensity of expression in colon polyp (changing from negative to + 3), this marker cannot be used for differentiating the polyp from the adenocarcinoma.

Survivin polymorphisms and susceptibility to prostate cancer: A genetic association study and an in silico analysis.

Survivin is a member of the apoptosis inhibitor protein family and its polymorphisms may lead to susceptibility to cancer. The aim of this study was to investigate the possible association of c.-31G>C (rs9904341), c.454G>A (rs2071214), c.*148T>C (rs2239680) and c.*571T>C (rs1042489) polymorphisms of survivin gene with prostate cancer risk and provide some justification using in silico analysis. The 157 men with prostate cancer and 145 healthy controls were included in a case-control study. The studied polymorphisms were genotyped using PCR-RFLP method. An in silico approach was employed to show the possible effects of the polymorphisms on the survivin gene function. The study revealed that there are significant associations between c.-31CC genotype (OR= 2.29, 95 % CI= 1.20-4.37, p= 0.012), c.-31C allele (OR= 1.62, 95 % CI= 1.17-2.26, p= 0.004), c.454AG genotype (OR= 2.03, 95 % CI= 1.02-4.04, p= 0.043), and c.*148C allele (OR= 1.49, 95 % CI= 1.04-2.15, p= 0.031) with prostate cancer. Using stratified analysis, we found also significant effects of age distribution on the association of c.-31G>C with prostate cancer risk (OR= 2.10, 95 % CI= 1.08-4.10, p= 0.030). Also as a preliminary study, it was shown that smoking status has significant effects on the association of c.-31G>C (OR= 1.94, 95 % CI= 1.08-3.49, p= 0.027) and c.*148T>C (OR= 2.60, 95 % CI= 1.47-4.60, p= 0.001) polymorphisms with prostate cancer risk. Finally, in silico analysis revealed that c.-31G>C, which is located in a CpG island of the promoter may change transcriptional regulation of survivin gene and c.454G>A and *148T>C could affect protein structure and possible miRNA interaction with 3'-UTR of survivin transcript respectively. According to the results, c.-31G>C, c.454G>A, and c.*148T>C polymorphisms could be genetic risk factors for prostate cancer in an Iranian population. However, further studies with larger sample size and different ethnicities are required to obtain more comprehensive results.

Association of Regulatory T Cells with Diabetes Type-1 and Its Renal and Vascular Complications Based on the Expression of Forkhead Box Protein P3 (FoxP3), Helios and Neurophilin-1.

In recent years, it has been recognized that regulatory T cells (Tregs) play a critical role in maintaining immune tolerance. Moreover, the expression of two markers named Helios and neurophilin-1 (NRP-1) has been highlighted in such cells. Helios, an intracellular transcription marker, largely differentiates twomost operative sub group of Tregs, namely naturally occurring (nTreg) and induced (iTreg) Tregs, and NRP-1 is reckoned as a membranous activity marker of Tregs. We aimed to count peripheral mononuclear cells expressing such markers in a group of type 1 diabetes patients to elucidate the possible role of Tregs in the pathogenesis of such disease and its complications. Blood samples from 61 adult patients with type 1 diabetes and 61 sex and age-matched healthy controls were tested to count two types of Tregs, namely naturally occurring and inducible types, according to the expression of cell surface markers of CD4/CD25/CD47-FITC/PE/APC and intracellular markers of FoxP3/Helios-PE-CY5/eFlour450 by flow cytometry, respectively.We also investigated the relation between expression of such markers with HbA1c, urine albumin/creatinine ratio (UACR), and common carotid intima thickness (CIMT). The circulatory frequency of both Helios+ and Helios- T-cells were significantly decreased in patients compared to those in healthy controls (p<0.001). There was also a significant decrease in circulatory frequency of Helios+ NRP-1+ and Helios- NRP-1+ cells in the patients compared to controls (p=0.029). According to expression of Helios and NRP-1 markers, the number and function of both Tregs were decreased in diabetic patients. Moreover, the neurophilin expression was inversely associated with complications of type 1 diabetes.

The Wound Healing Effects of Herbal Cream Containing Oliveria Decumbens and Pelargonium Graveolens Essential Oils in Diabetic Foot Ulcer Model.

BACKGROUND: The number of diabetic patients in adult population is increasing. All this population are at risk of developing diabetic foot ulcers (DFUs) that are associated with unwanted ailments and high mortality. In spite of current therapies for DFUs, further therapies are needed to help the patients. METHODS: The efficacy of herbal cream containing Pelargonium graveolens and Oliveria decombens essential oils was evaluated topically for treatment of DFUs in rat animal model in comparison with two other herbal formulas containing each essential oil alone, placebo (the basic formula without active ingredients) and normal saline as control groups. After anesthesia of diabetic rats (n=75) induced by streptozotocin (STZ), diabetic wounds were visible on the hind dorsal surface of the foot. The treatments were initiated on Day 1 and repeated 3 times a day for thirteen consecutive days. On day 1, 3, 5, 8 and 13, the wound sizes were determined and assessed histologically. RESULTS: Three herbal formulations reduced the size of wounds in rats with DFUs, while the cream containing combined herbals of O. decumbens and P. graveolens essential oils had the highest tissue repair in DFU rat models. CONCLUSION: Due to better wound healing effects of combined herbal cream containing O. decumbens and P. graveolens essential oils, it can be recommended in treatment of DFUs.

The Effect of Oliveria Decumbens and Pelargonium Graveolens on Healing of Infected Skin Wounds in Mice.

BACKGROUND: Staphylococcus aureus is one of the most causative organisms in the skin wound infections. Development of resistant S. aureus to current treatments in individuals with low immunity is a global concern. The aim of this study was to evaluate the efficacy of herbal formulation against skin wound infection. METHODS: The efficacy of herbal formulation containing Oliveria decumbens and Pelargonium graveolens essential oils was evaluated in comparison to mupirocin against Methicillin Resistant S. aureus (MRSA) related skin wound infection in mice animal model. RESULTS: The herbal cream and mupirocin decreased the log CFU by 2.5±0.26 and 2.46±0.32, respectively, while the log CFU of S. aureus from wound skin were 5.9±0.26 and 5.65±0.23 for placebo and control groups, respectively. Moreover, the histological examinations showed that this cream improved the wound healing and increased the collagen deposition and wound contraction. CONCLUSION: This natural new formulation with O. decumbens and P. graveolens essential oils could be recommended as a new candidate for wound healing.

Variations in Intraplatelet Phospho-VASP Expression Due to Pre-analytical Sample Preparations, Illustration of a Quality Control Issue in Platelet Pharmacology.

Intraplatelet vasodilator-stimulated phosphoprotein (VASP) analysis is a commonly used laboratory approach for monitoring of the anti-platelet therapy with adenosine diphosphate (ADP) receptor blocking agents; however, it's testing in clinical laboratory needs a high level of experience and proficiency. The ability to recognize how the pre-analytical variations can change the results would be helpful for the interpretation of data from intraplatelet VASP analysis. The aim of this study was to describe the possible differences of intraplatelet phospho-VASP expression between washed and platelet rich plasma (PRP) samples, both at baseline levels and following experimentally induction of VASP phosphorylation. PRP and washed platelet samples were treated with different inducers of VASP phosphorylation, including forskolin (10 µM), prostaglandin E1 (PGE1) (50 nM) and sodium nitro-prusside (SNP) (100 µM). Untreated PRP and washed platelet samples were also included in study as baseline controls. After labeling of platelets with either anti P-Serine(157)-VASP or anti P-Serine(239)-VASP, the samples were subjected to flow cytometric analysis to monitor the levels of intraplatelet phospho-VASP expression. Washed platelet samples tend to show increased expression of intraplatelet P-Serine(157)-VASP at baseline state and also more expression of P-Serine(157)-VASP and P-Serine(239)-VASP in response to forskolin and SNP, compared with PRP samples. Though, reduced levels of PGE1-induced VASP phosphorylation at both residues were detected for washed platelets. In this study we have provided some background information required for performing of intraplatelet VASP analysis on differently handled platelet samples and interpretation of the obtained results.