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Aim: Despite the various studies done in the field of cutaneous leishmaniasis treatment, there is still no perfect and safe drug for definite treatment of this disease. Therefore, the quest to find an appropriate drug continues. Previous studies have shown that auranofin has anti-leishmanial activity; therefore, in this study; the effect of auranofin on Leishmania major was studied. Materials and Methods: Effectiveness of four concentrations (1, 2, 4, and 8 μg/ml) of auranofin on L. major was studied. After culturing amastigotes and promastigotes of the parasite, IC50 was calculated. The ability of auranofin to induce apoptosis in promastigotes was evaluated, and the degree of fragmentation of promastigotes DNA after treatment with auranofin was studied. Subsequently, the ultrastructural changes induced by treatment with auranofin in promastigotes were studied. Using the obtained results, IC50 of auranofin against amastigotes and promastigotes was calculated as 1.007 and 2.38 μg/ml, respectively. Findings: Showed that auranofin induce apoptosis in L. major. The highest rate of apoptosis (%80.1) occurred at the concentration of 8 μg/ml and also auranofin-induced fragmentation of DNA. Considerable changes occurred in the shape of body and free flagellum of the L. major promastigotes after treatment with auranofin. Conclusion: Based on the results, it can be concluded that auranofin has a considerable anti-leishmanial activity and additional studies in this field will be based on the results. [ABSTRACT FROM AUTHOR]

Cancer is a disease advanced via surplus angiogenesis. The development of new anti-angiogenic therapeutic agents with more efficacy and fewer side effects is still quite necessary. Conventional therapies saving the life of many cancer patients but due to drug resistance and lack of specificity utilizing these methods is faced with limits. Recently, new therapeutic agents have been developed and used to treat cancers such as scaffold proteins, monoclonal antibodies, tyrosine kinase inhibitors, and peptides. In antiangiogenic drug development, anti-angiogenic peptides design is a significant aim. Peptides have developed as substantial therapeutics that are being carefully investigated in angiogenesis-dependent diseases because of their high penetrating rate into the cancer cells, high specificity, and low toxicity. In this review, we focus on anti-angiogenic peptides in the field of cancer therapy that are designed, screened, or derived from nanobodies, mimotopes, phage displays, and natural resources. [ABSTRACT FROM AUTHOR]

Background: Inhibition of angiogenesis using monoclonal antibodies is an effective strategy in cancer therapy. However, they could not penetrate sufficiently into solid tumors. Antibody fragments have solved this issue. However, they suffer from short in vivo half-life. In the current study, a tandem bivalent strategy was used to enhance the pharmacokinetic parameters of an anti-VECFl65 nanobody. Methods: Homology modeling and MD simulation were used to check the stability of protein. The cDNA was cloned into pHEN6C vector and the expression was investigated in WK6 Escherichia coli(E. coli) cells by SDS-PACE and western blot. After purification, the size distribution of tandem bivalent nanobody was investigated by dynamic light scattering. Moreover, in vitro antiproliferative activity and pharmacokinetic study were studied in HUVECs and Balb/c mice, respectively. Results: RMSD analysis revealed the tandem bivalent nanobody had good structural stability after 50 ns of simulation. A hinge region of llama IgC2 was used to fuse the domains. The expression was induced by 1 mMIPTC at 25 °C for overnight. A 30 bDa band in 12% polyacrylamide gel and nitrocellulose paper has confirmed the expression. The protein was successfully purified using metal affinity chromatography. MTT assay revealed there is no significant difference between the antiproliferative activity of tandem bivalent nanobody and the native protein. The hydrodynamic radius and terminal half-life of tandem bivalent nanobody increased approximately 2-fold by multivalency compared to the native protein. Conclusion: Our data revealed that the physicochemical as well as in vivo pharmaco- kinetic parameters of tandem bivalent nanobody was significantly improved. [ABSTRACT FROM AUTHOR]

Nowadays, proteins are frequently administered as therapeutic agents in human diseases. However, the main challenge regarding the clinical application of therapeutic proteins is short circulating plasma half-life that leads to more frequent injections for maintaining therapeutic plasma levels, increased therapy costs, immunogenic reactions, and low patient compliance. So, the development of novel strategies to enhance the pharmacokinetic profile of therapeutic proteins has attracted great attention in pharmaceuticals. So far, several techniques, each with their pros and cons, have been developed including chemical bonding to polymers, hyper glycosylation, Fc fusion, human serum albumin fusion, and recombinant PEG mimetics. These techniques mainly classify into three strategies; (i) the endosomal recycling of neonatal Fc receptor which is observed for immunoglobulins and albumin, (ii) decrease in receptor-mediated clearance, and (iii) increase in hydrodynamic radius through chemical and genetic modifications. Recently, novel PEG mimetic peptides like proline/alanine/serine repeat sequences are designed to overcome pitfalls associated with the previous technologies. Biodegradability, lack of or low immunogenicity, product homogeneity, and a simple production process, currently make these polypeptides as the preferred technology for plasma half-life extension of therapeutic proteins. In this review, challenges and pitfalls in the pharmacokinetic enhancement of therapeutic proteins using PEG-mimetic peptides will be discussed in detail. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer has been growing rapidly during the last decades. Radioiodine-131 (I-131) as an appropriate therapy modality is currently using in the treatment of cancer and hyperthyroidism diseases. This radiotracer is considered as a cause of oxidative DNA damage in nontarget cells and tissues. The aim of this study was to investigate the effects of curcumin and trehalose on the level of DNA double-strand breaks (DSBs) caused by I-131 in human lymphocytes. Materials and Methods: First, 6-mL blood samples were taken from each of the five volunteers. After 1 h of preincubation with the antioxidants, a total of 20 µCi I-131/2 mL (blood + NaCl) was added to each sample, and then, the samples were reincubated for 1 h. Lymphocytes were separated and the mean DSB levels were measured for each sample through γ-H2AX assay to evaluate the effects of antioxidants. Results: After 1-h incubation with I-131, the DSBs increased by 102.9% compared to the control group (0.343 vs. 0.169 DSB/cell; P = 0.00). Furthermore, compared to the control + I-131 group, curcumin and trehalose reduced the DSBs by 42% and 38%, respectively. There was a significant decrement (P = 0.00) in the levels of DSBs of the curcumin + I-131 and trehalose + I-131 subgroups compared to the control + I-131 subgroup. Furthermore, there was no significant relationship between the radioprotective effect of curcumin and trehalose (P = 0.95). Conclusion: The use of curcumin and trehalose as antioxidant can reduce the numbers of DSBs caused by I-131. Meanwhile, the radioprotective effect of curcumin was more than trehalose. [ABSTRACT FROM AUTHOR]

BACKGROUND: The effects of high intensity interval training (HIIT) on inflammatory markers and endothelial function have been extensively shown. However, the acute effect of HIIT on platelet activation and function in patients with recent revascularization is unclear. OBJECTIVE: The purpose of present study was to compare the responses of platelet activation (CD62P) and function (platelet aggregation) to high intensity interval exercise (HIIE) and moderate continuous exercise (MCE) in coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI) patients. METHODS: Thirty patients who had CABG or PCI were randomly divided into HIIE, MCE and control groups. After determining the VO2peak, subjects in the MCE group carried out 30 min of continuous exercise at 60% of VO2peak, whereas, the subjects in HIIE group performed an interval protocol consisted of 8 repetitions of 2 min activity (running on treadmill) at 90% of VO2peak interspersed by 2 min of active recovery between repetitions at 30% of VO2peak. Subjects in control group were seated and had no activity for the same period of time. Two blood samples were collected before and immediately after exercise and were analyzed for markers of platelet activation and function. RESULTS: Data analyzes revealed that increases in platelet aggregation induced by ADP and corrected for increases in platelet count in response to MCE trial was significantly lower than HIIE group (P < 0.05). In addition, responses of CD62P to MCE trial was significantly lower compared to HIIE group (P < 0.05). Changes in plateletcrit and platelet distribution width were significantly different among the three trials where the PCT and PDWfollowing the HIIE were higher than MCE. Platelet count increased significantly (P < 0.05) by 13% following HIIE trial. CONCLUSIONS:Based on the findings of the present study it could be concluded that the risk of exercise-induced thrombosis is higher during HIIE than MCE in patients with recent revascularization. [ABSTRACT FROM AUTHOR]

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-Serine157-VASP or anti P-Serine239-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-Serine157- VASP at baseline state and also more expression of P-Serine157-VASP and P-Serine239-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. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a complex, heterogeneous disease and one of the most common malignancies in women worldwide. The efficacy of chemotherapy as an important breast cancer treatment option has been severely limited because of the inherent or acquired resistance of cancer cells. The molecular chaperone heat shock protein 90 (HSP90) upregulated in response to cellular stress is required for functions such as conformational maturation, activation and stability in more than 200 client proteins, mostly of the signaling type. In this study, the expression of HSP90 isoforms including HSP90α and HSP90 β in breast cancer cell lines before and after treatment with doxorubicin (DOX) was assessed., Material and Methods: The cell cytotoxicity of DOX in MDA-MB-231 and MCF-7 cell lines was determined using the MTT assay. Immunofluorescence and western blotting techniques were used to determine the expression of HSP90 β in the cell lines before and after DOX treatment. Immunofluorescence was also conducted to ascertain the expression of HSP90α., Results: The MTT assay results showed that the MDA-MB- 231 cells (IC 50 =14.521 μM) were more sensitive than the MCF-7 cells (IC 50 =16.3315 μM) to DOX. The immunofluorescence results indicated that the expression of HSP90α in both cell lines decreased after exposure to DOX. The western blot and immunofluorescence analyses showed that HSP90 β expression decreased in the MCF-7 cells but increased in the MDA-MB- 231 cells after DOX treatment. Conclusion: The obtained results suggested that HSP90α and HSP90 β expression levels were reduced in the MCF-7 cells after exposure to DOX. In the MDA-MB-231 cells, HSP90α expression was reduced while HSP90 β was found to be overexpressed following DOX treatment., Competing Interests: Conflict of interest The authors declare no conflict of interest.

Computed tomography (CT) is one of the most important diagnostic X-ray procedures which plays an important role in increasing the patient dose values. The purpose of this clinical study was to evaluate the efficacy of vitamins E and C in lowering down the level of DNA double strand break (DSB) caused by CT scan. Sixty patients for abdomen/pelvic enhanced CT scan were randomly assigned to placebo (control), vitamin C, and vitamin E groups. The patient blood samples were taken before and immediately after the CT scan. Counting the number of DSB was performed using γ-H2AX method as a sensitive biomarker. Immediately after the CT scan, the mean number of DSBs/cell increased in all three groups of control (131%, P<0.001), vitamin C (103%, P <0.001), and vitamin E (66%, P<0.001) compared to their mean before the CT scan. Furthermore, the results showed that vitamin E decreased the mean number of DSBs/cell by 22% in comparison with the control group (P =0.023), whereas vitamin C had no significant effect on reducing the DSB (<3%, P =0.741). It is concluded that the administration of vitamin E one hour before the CT scan, significantly decreases DSB levels., Competing Interests: The authors declare that they have no conflict of interest.

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.