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Fulltext Germline RET mutations in exons 10 and 11: an Iranian survey of 57 medullary thyroid carcinoma cases

Hedayati M, Nabipour I, Rezaei-Ghaleh N, Azizi F

Med J Malaysia, 2006 Dec;61(5):564-9.
PMID: 17623957

The susceptibility gene for hereditary Medullary Thyroid Carcinoma (MTC) is the RET proto-oncogene. The aim of this study was to evaluate the prevalence of common germline RET mutations in exons 10 and 11 among Iranian MTC patients. Fifty-seven non-related MTC patients were examined in this study (Females: Males =1.2:1.0, Mean age = 40.0 +/- 11.5 years) and the existence of mutations was assessed through the PCR-RFLP technique. The only Multiple Endocrine Neoplasia type 2A (MEN2A) patient displayed a C634W mutation in exon 11. Among 53 apparently sporadic MTC patients, one patient showed a C620R mutation in exon 10 and two other patients displayed C624Y mutations in exon 11 of RET proto-oncogene. Neither the only Multiple Endocrine Neoplasia type 2B (MEN2B) patient nor two Familial MTC patients was found to carry germline mutations in exons 10 and 11. This study reports, for the first time, the prevalence of common RET mutations among Iranian, apparently sporadic MTC patients, underlining the critical importance of screening for RET mutations in such patients.
In-vitro and in-silico anti-HSV-1 activity of a marine steroid from the jellyfish Cassiopea andromeda venom

Shamsian S, Nabipour I, Mohebbi G, Baghban N, Zare M, Zandi K, et al.

Microb Pathog, 2024 Jan;186:106486.
PMID: 38056601 DOI: 10.1016/j.micpath.2023.106486

In this study, we investigated the potential in vitro anti-HSV-1 activities of the Cassiopea andromeda jellyfish tentacle extract (TE) and its fractions, as well as computational work on the thymidine kinase (TK) inhibitory activity of the identified secondary metabolites. The LD50, secondary metabolite identification, preparative and analytical chromatography, and in silico TK assessment were performed using the Spearman-Karber, GC-MS, silica gel column chromatography, RP-HPLC, LC-MS, and docking methods, respectively. The antiviral activity of TE and the two purified compounds Ca2 and Ca7 against HSV-1 in Vero cells was evaluated by MTT and RT-PCR assays. The LD50 (IV, mouse) values of TE, Ca2, and Ca7 were 104.0 ± 4, 5120 ± 14, and 197.0 ± 7 (μg/kg), respectively. They exhibited extremely effective antiviral activity against HSV-1. The CC50 and MNTD of TE, Ca2, and Ca7 were (125, 62.5), (25, 12.5), and (50, 3.125) μg/ml, respectively. GC-MS analysis of the tentacle extract revealed seven structurally distinct chemical compositions. Four of the seven compounds had a steroid structure. According to the docking results, all compounds showed binding affinity to the active sites of both thymidine kinase chains. Among them, the steroid compound Pregn-5-ene-3,11-dione, 17,20:20,21 bis [methylenebis(oxy)]-, cyclic 3-(1,2-ethane diyl acetal) (Ca2) exhibited the highest affinity for both enzyme chains, surpassing that of standard acyclovir. In silico data confirmed the experimental results. We conclude that the oxosteroid Ca2 may act as a potent agent against HSV-1.
Fulltext Evaluation of the performance of osteoporosis/fracture screening models to identify high-risk women for osteoporosis: Bushehr elderly health (BEH) program

Sani MP, Fahimfar N, Panahi N, Mansournia MA, Sanjari M, Khalagi K, et al.

J Diabetes Metab Disord, 2022 Dec;21(2):1609-1617.
PMID: 36404865 DOI: 10.1007/s40200-022-01110-3

PURPOSE: This study aimed to evaluate the performance of valid risk assessment models developed for osteoporosis/ fracture screening to identify women in need of bone density measurement in a population of Iranian elderly women.
METHODS: This study was performed using the data of Bushehr Elderly Health (BEH) program, a population-based cohort study of elderly population aged ≥ 60 years. Seven osteoporosis risk assessment tools, including Osteoporosis Risk Assessment Instrument (ORAI), Malaysian Osteoporosis Screening Tool (MOST), Osteoporosis Prescreening Risk Assessment (OPERA), Osteoporosis Prescreening Model for Iranian Postmenopausal women (OPMIP), Osteoporosis Index of Risk (OSIRIS), and Osteoporosis Self-Assessment Tool for Asians (OSTA), as well as Fracture Risk Assessment Tool (FRAX) were included in the study. By using osteoporosis definition based on BMD results, the performance measurement criteria of diagnostic tests such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden index for each model were calculated and the models were compared.
RESULTS: A total of 1237 female participants with the mean age of 69.1 ± 6.3 years were included. Overall, 733 (59%) participants had osteoporosis, and about 80% had no history of fracture. The sensitivity of the seven models ranged from 16.7% (OSIRIS) to 100% (ORAI and MOST) at their recommended cut-off points. Moreover,their specificity ranged from 0.0% (ORAI and MOST) to 78.9% (OSTA). The FRAX and OPERA had the optimal performance with the Youden index of 0.237 and 0.226, respectively. Moreover, after combining these models, the sensitivity of them increased to 85.4%.
CONCLUSION: We found that the FRAX (model with 11 simple variables) and OPERA (model with 5 simple variables) had the best performance. By combining the models, the performance of each was improved. Further studies are needed to adopt the model and to find the best cut-off point in the Iranian postmenopausal women.
Fulltext Molecular interaction of fibrinogen with zeolite nanoparticles

Derakhshankhah H, Hosseini A, Taghavi F, Jafari S, Lotfabadi A, Ejtehadi MR, et al.

Sci Rep, 2019 02 07;9(1):1558.
PMID: 30733474 DOI: 10.1038/s41598-018-37621-4

Fibrinogen is one of the key proteins that participate in the protein corona composition of many types of nanoparticles (NPs), and its conformational changes are crucial for activation of immune systems. Recently, we demonstrated that the fibrinogen highly contributed in the protein corona composition at the surface of zeolite nanoparticles. Therefore, understanding the interaction of fibrinogen with zeolite nanoparticles in more details could shed light of their safe applications in medicine. Thus, we probed the molecular interactions between fibrinogen and zeolite nanoparticles using both experimental and simulation approaches. The results indicated that fibrinogen has a strong and thermodynamically favorable interaction with zeolite nanoparticles in a non-cooperative manner. Additionally, fibrinogen experienced a substantial conformational change in the presence of zeolite nanoparticles through a concentration-dependent manner. Simulation results showed that both E- and D-domain of fibrinogen are bound to the EMT zeolite NPs via strong electrostatic interactions, and undergo structural changes leading to exposing normally buried sequences. D-domain has more contribution in this interaction and the C-terminus of γ chain (γ377-394), located in D-domain, showed the highest level of exposure compared to other sequences/residues.