Adel Spotin, Soheila Rouhani, Parnazsadat Ghaemmaghami, Ali Haghighi, Mohammad Reza Zolfaghari, Aref Amirkhani, Mahin Farahmand, Ali Bordbar, Parviz Parvizi,
Volume 19, Issue 3 (7-2015)
Abstract
Background: Molecular diversity of Leishmania major and its morphological changes have become a controversial issue among researchers. Some aspects of polymorphic shapes of amastigotes in clinical manifestations along with molecular variation were evaluated among suspected patients of some exceptional zoonotic cutaneous leishmaniasis locations in Northern Khuzestan, Southwestern Iran. Methods: Suspected patients (n = 165) were sampled in zoonotic cutaneous leishmaniasis foci over two consecutive years during 2012-2014. Prepared smears were stained, scaled and measured by ocular micrometer. DNA was extracted from smears ITS-rDNA and Cytochrome b (Cyt b) markers were amplified, and PCR products were digested by BsuR1 restriction enzyme. Then the RFLP and sequencing were employed. Results: Only L. major was identified in patients containing regular amastigotes' shapes (oval or round) with a size of 2-4 µm in each of classical wet, dry, mixed lesions. Meanwhile, irregular shapes (spindle, pear, or cigarette) were observed separately in non-classical wet lesions with more than 4 µm. Interestingly, a few amastigotes with an external flagellum were observed in some lesions. All sequenced ITS-rDNA and Cyt b genes of L. major did not show any molecular variation (&chi 2 P > 0.05), including only one common haplotype (GenBank access no. EF413075). Conclusion: Findings proved that unlike other endemic foci, there is not a meaningful correlation between phenotypic and genotypic features of L. major isolates. This study is considered as the first comprehensive report to incriminate morphometric shapes of L. major amastigotes, which enhances our knowledge concerning their relevance with various clinical appearances and genotypic traits.
Saeide Rouhani, Hajar Yaghoobi,
Volume 28, Issue 0 (Supplementary 2024)
Abstract
Introduction: Cardiovascular diseases (CVDs) are one of the leading causes of death worldwide, placing a significant burden on healthcare systems. Despite advances in medical interventions, there is a growing interest in exploring alternative treatment options, particularly herbal compounds, due to their potential efficacy and minimal side effects. This research aims to investigate the therapeutic role of plant compounds against CVDs using bioinformatics and systems biology approaches and to discover their potential as adjunctive or alternative treatments. Virtual screening to achieve the best therapeutic target of the best herbal combination reduces the cost and time spent on data review.
Methods and Materials: In this study, the names and then the three-dimensional structure of all native plant compounds of the province are extracted using the natural flora of plants using several databases. Plant names were searched in the ChEBI database for compounds. In the following, using the related servers, their potential targets are identified. The PharmMapper website will be used to identify potential target candidates for these compounds. The identified targets are related to diseases, and the best target or targets are determined by drawing biological networks using relevant software. Then, the most effective compounds with the highest impact on the targets are selected by drawing the target-drug network and molecular docking and virtual screening methods. Their structure was retrieved from the protein database in PDB format and converted to pdbqt using AutoDock software. Vina software in PyRx, a virtual screening software, was used for docking. PyMol and DiscoveryStudio were used to analyze the docked complexes.
Results: Herbal medicines were collected using articles and databases, and their effective compounds were extracted from the ChEBI database. The Network Analyser results calculate parameters such as the Betweenness centrality, degrees, and clustering coefficient, which are used to select the best molecular targets. TGFBR1, ADRB1, GATA4, ADRA1D, and CACNA1B were the best potential therapeutic targets. Using docking results, the effective compounds of Zataria multiflora and valerian had good results on target proteins in terms of pharmacodynamic parameters.
Conclusion and Discussion: Network pharmacology analysis showed the key pathways involved in recovering heart diseases caused by natural compounds in medicinal plants. Five pathways were obtained from the drug-target network analysis (TGFBR1, ADRB1, GATA4, ADRA1D, CACNA1B), and molecular docking studies of these pathways revealed that the identified chemical compounds had strong binding affinities with these pathway components. Additional in vitro and in vivo experiments will help validate and optimize the findings of this study.
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