ABCG2 inhibition as a therapeutic approach for overcoming multidrug resistance in cancer.

Breast cancer resistance protein (BCRP, ABCP or MXR)/ATP-binding cassette subfamily G member 2 (ABCG2) was characterized as a multidrug resistance efflux transporter in 1998. ABCG2 physiologically acts as a part of a selfdefence mechanism for the organism; it enhances eliminating of toxic xenobiotic substances and harmful agents in the intestine, as well as through the blood–brain barrier and placenta. ABCG2 recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and new targeted small therapeutic molecules in clinical usage. Development of ABCG2 inhibitors for clinical usage may allow increased penetration of therapeutic agents into sanctuary sites and increases their intestinal absorption. Here we review the mechanisms that modulate MDR mediated by the ABC transporter ABCG2 in normal and cancer cells by different levels including, epigenetic modifications, transcriptional, post-transcriptional, translation and post-translational regulation. Some clinical applications of ABCG2 inhibitors are also explained.

[Effect of celecoxib on serum visfatin levels in streptozotocin-induced diabetes in male rats: role of nitrergic system]

Background and Aim: Nicotinamide phosphoribosyltransferase [NAMPT]/ [visfatin] have been proposed as proinflammatory cytokine that is influenced by blood glucose or insulin. In diabetes mellitus proinflammatory agents such as prostaglandin E2 and nitric oxide can increase visfatin synthesis and visfatin stimulates their expression. The aim of this study was to determine the effect of cyclooxygenase and nitrergic system on serum visfatin level and some biochemical parameters in diabetic rats

Material and Methods: Male Wistar rats were rendered diabetic by streptozotocin [60 mg/kg, i.p.]. Animals were treated with celecoxib [5 mg/kg] or L-arginine [50 mg/kg] or L-NAME [50 mg/kg] alone or with combinations of celecoxib and L-arginine or celecoxib and L-NAME. Using SPSS software, we used one way analysis of variance followed by tukey test for data analysis

Results: All treated groups showed significant decrease in blood glucose and triglyceride levels [P<0.05]. Treatment with L-NAME decreased serum insulin level significantly [P<0.05], while celecoxib alone [P<0.05] or in combination with L-NAME and L-arginine enhanced its levels significantly [P<0.01]. Serum visfatin level increased in diabetic rats compared to controls [P<0.05]. Treatment with L-arginine had a significant effect on increasing visfatin level [P<0.05]. Celecoxib decreased visfatin level [P<0.01]. Combination of L-NAME or L-arginine with celecoxib caused a greater reduction in visfatin level [P<0.01]

Conclusion: Serum visfatin level increased in streptozotocin- induced diabetes. Inhibition of cyclooxygenase-2 by celecoxib, resulted in decreased visfatin level and part of this effect was due to interaction with nitrergic system. It seems that blood glucose and insulin do not affect visfatin level directly, but proinflammatory cytokines play the main role in its synthesis

The Effects of Crocin on 6-OHDA-Induced Oxidative/Nitrosative Damage and Motor Behaviour in Hemiparkinsonian Rats

Background: Crocin is considered to prevent oxidative stress-related diseases, such as ischemia and Alzheimer's. The aim of the present investigation was to evaluate the effects of crocin on motor behaviour and 6-OHDA-induced oxidative/nitrosative damage to the striatum in an experimental model of Parkinson's disease. Methods: Left medial forebrain bundle was lesioned by microinjection of 6-OHDA (16μg in 0.2% ascorbate-saline). Crocin (30 and 60 mg/kg) was injected intraperitoneally three days before surgery until six weeks. Rotational behaviour and biochemical analysis were used to evaluate the effect of crocin in a unilateral 6-OHDA-induced model of Parkinson's disease. Results: The contralateral rotations induced by apomorphine in 6-OHDA lesioned group were highly significant (P < 0.001) as compared to the sham group. Moreover, chronic administration of crocin at doses of 30 and 60 mg/kg over six weeks did not change the rotations. The TBARS and nitrite levels in the striatum were also significantly (P < 0.05) increased in lesioned group. Treatment with crocin at a dose of 60 mg/kg significantly decreased the nitrite levels (P < 0.05) in the striatum. Conclusion: Crocin at a dose of 60 mg/kg could be effective in preventing the nitrosative damage in the striatum. Further investigations using higher doses of crocin is suggested to get the full neuroprotective effects of crocin in Parkinson's disease.

Analysis of human B cell response to recombinant Leishmania LPG3

Objective: To evaluate the capability of recombinant Leishmania LPG3 and its fragments in the activation of B cells. Methods: In the present study, human B cells were purified from peripheral blood of 10 adult healthy subjects using magnetic-activated cell sorting technique. Subsequently, purified B cells were treated with recombinant LPG3, and its N-terminal and C-terminal fragments at different concentrations (2, 10 and 20 μg/mL). B cell activation was assessed through expression of CD69 molecule by flow cytometry and secretion of IL-6, TNF-α and IL-10 cytokines via enzyme-linked immunosorbent assay following treatment with recombinant antigens. Results: Our results showed that while the recombinant LPG-3 could significantly increase the production of IL-6 and TNF-α (P < 0.05) in B cells, it had no effect on the secretion of IL-10 by B cells. Conclusions: Our study indicated that recombinant LPG-3 and especially its N-terminal fragment could stimulate B cell response as an important immune response component against leishmaniasis. Thus, it seems that it can be considered as an effective adjuvant in vaccine developments against leishmaniasis.

Analysis of human B cell response to recombinant Leishmania LPG3

OBJECTIVE@#To evaluate the capability of recombinant Leishmania LPG3 and its fragments in the activation of B cells.@*METHODS@#In the present study, human B cells were purified from peripheral blood of 10 adult healthy subjects using magnetic-activated cell sorting technique. Subsequently, purified B cells were treated with recombinant LPG3, and its N-terminal and C-terminal fragments at different concentrations (2, 10 and 20 μg/mL). B cell activation was assessed through expression of CD69 molecule by flow cytometry and secretion of IL-6, TNF-α and IL-10 cytokines via enzyme-linked immunosorbent assay following treatment with recombinant antigens.@*RESULTS@#Our results showed that while the recombinant LPG-3 could significantly increase the production of IL-6 and TNF-α (P < 0.05) in B cells, it had no effect on the secretion of IL-10 by B cells.@*CONCLUSIONS@#Our study indicated that recombinant LPG-3 and especially its N-terminal fragment could stimulate B cell response as an important immune response component against leishmaniasis. Thus, it seems that it can be considered as an effective adjuvant in vaccine developments against leishmaniasis.

Philosophy of fasting in Quran and Islamic narratives and its relationship with human health, based on scientific notions

Abstinence from eating and drinking on long hot summer days is no easy task. In fact, it is considered the greatest "Jihad" in Islamic tradition. Here, the main question is concerned with the importance of fasting, its purposes, and advantages for individuals. We need to determine if fasting plays a role in overcoming human problems. This article, by using an analytical approach, states Quranic verses and Hadiths and reviews the philosophy of fasting in response to two questions: 1] What is the philosophy of fasting in Quran and Hadiths?, and 2] What role does it play in maintaining human health? Therefore, Islamic verses and narratives, concerning the importance of fasting in maintaining health, are reviewed, using the opinions of some scientists

Evaluation of fungal contaminations and humidity percent of consumed flour in the bakeries of Tabriz city

Foods contaminations with Mycotoxin producing fungi is the common problem in production and maintenance of foods leads to production and presence of many types of Mycotoxins with extensive clinical effect on human called Mycotoxicosis. The aim of this study is to determine humidity percent and fungal contaminations of flour which is used in bakeries of Tabriz city. From 89 bakeries that were baking every kind of wheat bread, flour samples were collected .At first, humidity percent of samples was measured with standard method; Then experimented with standards of Iran[997 and 2393]:10 gram flour sample were dissolved in 90cc of ¼ sterile Ringer solution; then10-2 ,10-3 ,10-4,10-5and10-6 dilutions were prepared. From each dilution, 1cc were spilled in different sterile plates; afterward, 15-20cc of sterile YCGA culture medium were spilled on the plates and they were shacked slowly; hereafter, they were left until the culture mediums were coagulated. Thereupon, the plates were incubated in 25 degree c for 5 days. Finally, fungi colonies were identified and counted. From 89 samples, 28 samples [31,5%]contain fungi contaminations more than 104 colonies/gram of flour[allowable limit] [p<0.05]. Results showed the most fungi were Aspergillus niger and Acromonium. Mean of humidity percent in samples was12.8+/-0.76 which was in standard level [

Crude and age-specific incidence rate patterns for histopathologic subtypes of ovarian cancer in Iran

The purpose of this study was to report age-specific incidence rates of histopathological subtypes of ovarian cancer in Iran. Data published by the pathology-based Cancer Registry, Iranian Ministry of Health and Medical Education for the year 2004, was utilized. This study included 793 new ovarian cancer cases which were analyzed by SPSS software [version 13]. There were 45 different histologies reported in 793 new cases which were categorized into ten major groups. Epithelial tumors displayed the highest age specific incidence rate, followed by germ cell tumors. Serous epithelial tumors were the most common in the epithelial group. The age-specific incidence rate of ovarian cancer varies based on histolo

Anatomical and visual outcomes of three different scleral buckling techniques

To compare the anatomical and visual outcomes of three different scleral buckling techniques and to explore the effect of cryotherapy and subretinal fluid drainage [SRFD] on outcomes of surgery. This retrospective study was performed on 111 eyes of 109 patients undergoing scleral buckling for rhegmatogenous retinal detachments [RRDs] by a single surgeon. Pre-, intra- and postoperative data were retrieved from hospital records. Buckles were radial in 27 [24.3%], circumferential [segmental] in 16 [14.4%] and encircling in 68 [61.3%] eyes. Anatomical and visual results were comparable with all three buckling techniques. Application of cryotherapy, the spot number, and SRFD did not affect anatomical and visual results. The only preoperative factor associated with poorer anatomical results was the presence of multiple retinal breaks [P=0.006]. The following preoperative factors affected visual outcomes on univariate analysis: extent of retinal detachment [r=0.417, P=0.011] and relative afferent pupillary defect [r=0.423, P=0.02]. Preoperative macular status [attached vs detached] also had a significant effect on visual outcomes [P < 0.001]. Based on multivariate analysis however, only preoperative macular status was significantly correlated with visual results [P=0.022]. Silicone sponges placed for non-encircling surgery were removed due to ocular dysmotility in 4 [3.6%] eyes, cosmetic reasons in 3 [2.7%] cases and extrusion in 2 [1.8%] eyes. One encircling tire was also removed due to extrusion. Surgical technique and performing cryotherapy or SRFD do not seem to influence the anatomical and visual outcomes of scleral buckling. Postoperative complications seem to be more prevalent with non-encircling techniques