Effects of synergistic and non-synergistic anions on the iron binding site from serum transferrin: A molecular dynamic simulation analysis.

The role of the anions in transferrin chemistry highlights the importance of the anion binding site in transferrin family. A synergistic anion as carbonate is an anion that is required for iron binding by transferrin while non-synergistic anions do not act as the synergistic anions to promote iron binding, but affect the iron binding and release. Some questions remain unclear about the difference between synergistic and non-synergistic anion functions. In the present work, molecular dynamic simulation techniques were employed in order to gain access into a molecular level understanding of the iron binding site of the human serum transferrin during the synergistic and non-synergistic anion binding. For this purpose, a comparative analysis was performed to illustrate the observed changes. In addition to the comparison between the synergistic and non-synergistic anions, structural differences between two synergistic anions, Carbonate and Oxalate were studied. Meanwhile,the simulation of the open (Apo), partially closed (Carbonate) and fully closed (Carbonate-Fe) forms of the transferrin structure allows a direct comparison between the iron binding site of these three states.On the basis of results, synergistic anions form high affinity binding site, while non-synergistic anions act like Apo state of the transferrin structure and change the proper conformation of the binding site. In order to act as a synergistic anion and form high affinity binding site, anion stereochemistry and interactions must be able to achieve a Carbonate-like configuration. Carbonate complex showed the highest binding affinity and electrostatic energy is the major favorable contributor to synergistic anion-transferrin interaction. Carbonate and Oxalatecomplexes as synergistic anions have many features in common, without a significant change in the transferrin structure. Only the residues in the vicinity of the binding site showed a little different conformation depending on whether the synergistic anion is Carbonate orOxalate.Finally, the results show thatASP63, GLY65 and HIS249 residues have the maximum displacement during the Carbonate and iron binding. ASP63 and HIS249 are the residues, which are coordinated to the iron and GLY65 is in the second shell residuesof the transferrin structure.

Iranian postmenopausal women's experiences of treatment of symptomatic vulvovaginal atrophy.

OBJECTIVES: Our aim was to explore the experiences of Iranian postmenopausal women who sought medical help for their symptomatic vulvovaginal atrophy (VVA). METHODS: Five focus group discussions (FGDs) were conducted. Participants had to be postmenopausal; had bothersome symptoms of VVA for which they came to the clinic; had previously sought medical help for their VVA; and had confirmed physical signs of VVA upon examination by a gynecologist. RESULTS: Twenty-five women, aged 49-60 years participated in the five FGDs. Twenty women said they currently had >1 VVA symptom at presentation to the clinic. Four major themes emerged from the women's narrative stories: (1) negative impact of VVA on women's life, (2) psychological distress associated with VVA, (3) negative impact of VVA on marriage and relationship, (4) inadequate symptom relief from available treatments due to lack of awareness of VVA treatment options. None of the participants reported ongoing treatment of their VVA with local low-dose estrogen. Women further commented that, although local estrogen products were costly, they would like to use them if they were prescribed. CONCLUSIONS: Considering the negative impact of VVA symptoms on women's lives, health professionals in Iran should be prescribing approved and effective therapies for symptomatic women.

The effect of glycosylation on the transferrin structure: A molecular dynamic simulation analysis.

Transferrins have been defined by the highly cooperative binding of iron and a carbonate anion to form a Fe-CO3-Tf ternary complex. As such, the layout of the binding site residues affects transferrin function significantly; In contrast to N-lobe, C-lobe binding site of the transferrin structure has been less characterized and little research which surveyed the interaction of carbonate with transferrin in the C-lobe binding site has been found. In the present work, molecular dynamic simulation was employed to gain access into the molecular level understanding of carbonate binding site and their interactions in each lobe. Residues responsible for carbonate binding of transferrin structure were pointed out. In addition, native human transferrin is a glycoprotein that two N-linked complex glycan chains located in the C-lobe. Usually, in the molecular dynamic simulation for simplifying, glycan is removed from the protein structure. Here, we explore the effect of glycosylation on the transferrin structure. Glycosylation appears to have an effect on the layout of the binding site residue and transferrin structure. On the other hand, sometimes the entire transferrin formed by separated lobes that it allows the results to be interpreted in a straightforward manner rather than more parameters required for full length protein. But, it should be noted that there are differences between the separated lobe and full length transferrin, hence, a comparative analysis by the molecular dynamic simulation was performed to investigate such structural variations. Results revealed that separation in C-lobe caused a significant structural variation in comparison to N-lobe. Consequently, the separated lobes and the full length one are different, showing the importance of the interlobe communication and the impact of the lobes on each other in the transferrin structure.

Tissue-specific somatic stem-cell isolation and characterization from human endometriosis. Key roles in the initiation of endometrial proliferative disorders.

AIM: The endometrial-proliferation related diseases leads to endometrial hyperplasia, i.e., endometriosis. Endometrial progenitor and stem cells play key roles in the beginning of endometrial proliferative disorders. The purpose of this study was the isolation of stem cells in the endometriosis lesion as well as the evaluation and comparison of the stemness-related target genes in endometriosis endometrial stem cells (EESCs), normal endometrial stem cell (ESCs), endometrial lesions stem cell (ELSCs) and bone marrow mesenchymal stem cells (MSCs). METHODS: EESCs, ESCs, ELSCs and MSCs were isolated. Flowcytometry and real-time PCR were utilized to detect the cell surface marker and expression pattern of 16 stemness genes. The proliferation of all stem cells was observed by MTT assay. The differentiation potential was evaluated by alizarin red, oil red O and RT-PCR method. The karyotyping was performed on EESCs and ELSCs at passage 20. RESULTS: The unique patterns of gene expression were detected although EESCs, ESCs, ELSCs and MSCs have a background expression of stemness-related genes. Spindle-like morphology, normal karyotype, adipogenic and osteogenic potential, significantly expression of Oct4, SALL4, DPPA2, Sox2, Sox17 and also specific surface markers such as CD44, CD105, CD90, CD73 and CD146 in EESCs and ELSCs was observed. CONCLUSION: According to our data, stem cells in endometriosis endometrial and endometriosis are such a informative tools to study of pathogenesis of gynecological diseases. Furthermore, endometrial stem/progenitor cells which easily obtain from tissue may be valuable targets for early diagnosis of endometrial disorders in the future.

Comparison of transobturator tape (TOT) vs Burch method in treatment of stress urinary incontinence.

This study aim was to compare the efficacy of transobturator tape (TOT) as a new sling procedure, and Burch colposuspension as the gold standard surgical technique, in the treatment of stress urinary incontinence (SUI). This prospective randomised clinical trial was conducted on 62 women with SUI diagnosed with urodynamic test in Vali-e-Asr Hospital, Tehran, Iran. Patients were allocated into two surgery groups, randomly; TOT and Burch (31 patients in each group). After treatment, they were followed-up for long-term outcome. The average duration of follow-up was 22 and 28 months in the TOT and Burch group, respectively. Operation duration and hospital stay in the TOT group was significantly less than the Burch group (p=0.001). The rate of complete cure, improvement and failure in the TOT group was 90.3%, 9.7% and 0%, respectively, as well as 74.2%, 19.4% and 6.5% in the Burch group. In the TOT group, 90.3% of patients were very satisfied, 6.5% moderately satisfied and 3.2% were less satisfied; none of them were unsatisfied. It is concluded that the TOT procedure is a safe and effective option with less operation time and shorter in-hospital stay for SUI treatment.