Background: Neuroinflammation and oxidative stress are critical factors involved in the pathogenesis of Parkinson's disease (PD), the second most common progressive neurodegenerative disease. Additionally, lipid peroxidation end products contribute to inflammatory responses by activating pro-inflammatory genes. Lipid peroxidation occurs as a result of either the overproduction of intracellular reactive oxygen species (ROS) or the reaction of cyclooxygenases (COXs).
Objectives: In this study, we examined the role of 1,5-diaryl pyrrole derivatives against the neurotoxic effects of 6-hydroxydopamine (6-OHDA) in a cellular model of PD.
Methods: PC12 cells were pre-treated with compounds 2-(4-chlorophenyl)-5-methyl-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrole (A), 2-(4-chlorophenyl)-1-(4-methoxyphenyl)-5-methyl-1H-pyrrole (B), and 1-(2-chlorophenyl)-2-(4-chlorophenyl)-5-methyl-1H-pyrrole (C), respectively, 24 h before exposure to 6-OHDA. We conducted various assays, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT), ROS, and lipid peroxidation assays, Hoechst staining, Annexin V/PI, Western blotting analysis and ELISA method, to assess the neuroprotective effects of pyrrole derivatives on 6-OHDA-induced neurotoxicity.
Results: Our results demonstrated that apoptosis induction was inhibited by controlling the lipid peroxidation process in the in vitro model following pre-treatment with compounds A, B, and, somehow, C. Furthermore, compounds A and C likely act by suppressing the COX-2/PGE2 pathway, a mechanism not attributed to compound B.
Conclusions: These findings suggest that the novel synthetic pyrrolic derivatives may be considered promising neuroprotective agents that can potentially prevent the progression of PD.
{"title":"Biological Activity of Novel Pyrrole Derivatives as Antioxidant Agents Against 6-OHDA Induced Neurotoxicity in PC12 Cells.","authors":"Hanieh Javid, Ebrahim Saeedian Moghadam, Maryam Farahmandfar, Mahboubeh Manouchehrabadi, Mohsen Amini, Mona Salimi, Anahita Torkaman-Boutorabi","doi":"10.5812/ijpr-140450","DOIUrl":"10.5812/ijpr-140450","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation and oxidative stress are critical factors involved in the pathogenesis of Parkinson's disease (PD), the second most common progressive neurodegenerative disease. Additionally, lipid peroxidation end products contribute to inflammatory responses by activating pro-inflammatory genes. Lipid peroxidation occurs as a result of either the overproduction of intracellular reactive oxygen species (ROS) or the reaction of cyclooxygenases (COXs).</p><p><strong>Objectives: </strong>In this study, we examined the role of 1,5-diaryl pyrrole derivatives against the neurotoxic effects of 6-hydroxydopamine (6-OHDA) in a cellular model of PD.</p><p><strong>Methods: </strong>PC12 cells were pre-treated with compounds 2-(4-chlorophenyl)-5-methyl-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrole (A), 2-(4-chlorophenyl)-1-(4-methoxyphenyl)-5-methyl-1H-pyrrole (B), and 1-(2-chlorophenyl)-2-(4-chlorophenyl)-5-methyl-1H-pyrrole (C), respectively, 24 h before exposure to 6-OHDA. We conducted various assays, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT), ROS, and lipid peroxidation assays, Hoechst staining, Annexin V/PI, Western blotting analysis and ELISA method, to assess the neuroprotective effects of pyrrole derivatives on 6-OHDA-induced neurotoxicity.</p><p><strong>Results: </strong>Our results demonstrated that apoptosis induction was inhibited by controlling the lipid peroxidation process in the in vitro model following pre-treatment with compounds A, B, and, somehow, C. Furthermore, compounds A and C likely act by suppressing the COX-2/PGE2 pathway, a mechanism not attributed to compound B.</p><p><strong>Conclusions: </strong>These findings suggest that the novel synthetic pyrrolic derivatives may be considered promising neuroprotective agents that can potentially prevent the progression of PD.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"22 1","pages":"e140450"},"PeriodicalIF":1.6,"publicationDate":"2023-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-12eCollection Date: 2023-01-01DOI: 10.5812/ijpr-141920
Fariba Fathi, Maryam Ghobeh, Farshad H Shirazi, Maryam Tabarzad
Background: Infections caused by pathogenic microorganisms have increased the need for hospital care and have thus represented a public health problem and a significant financial burden. Classical treatments consisting of traditional antibiotics face several challenges today. Anti-microbial peptides (AMPs) are a conserved characteristic of the innate immune response among different animal species to defend against pathogenic microorganisms.
Objectives: In this study, a new peptide sequence (mCHTL131-140) was designed using the in silico approach.
Methods: Cathelicidin-2 (UniprotID: Q2IAL7) was used as a potential antimicrobial protein, and a novel 10 - 12 amino acids sequence AMP was designed using bioinformatics tools and the AMP databases. Then, the anti-bacterial, anti-biofilm, and anti-fungal properties of the peptide, as well as its hemolytic activity and cytotoxicity towards human fibroblast (HDF) cells, were investigated in vitro.
Results: Online bioinformatics tools indicated that the peptide sequence could have anti-bacterial, anti-viral, anti-fungal, and anti-biofilm properties with little hemolytic properties. The experimental tests confirmed that mCHTL131-140 exhibited the best anti-bacterial properties against Acinetobacter baumannii and had fair anti-fungal properties. Besides, it did not cause red blood cell lysis and showed no cytotoxicity towards HDF cells.
Conclusions: In general, the designed peptide can be considered a promising AMP to control hospital-acquired infections by A. baumannii.
{"title":"Design and Evaluation of a Novel Anti-microbial Peptide from Cathelicidin-2: Selectively Active Against <i>Acinetobacter baumannii</i>.","authors":"Fariba Fathi, Maryam Ghobeh, Farshad H Shirazi, Maryam Tabarzad","doi":"10.5812/ijpr-141920","DOIUrl":"10.5812/ijpr-141920","url":null,"abstract":"<p><strong>Background: </strong>Infections caused by pathogenic microorganisms have increased the need for hospital care and have thus represented a public health problem and a significant financial burden. Classical treatments consisting of traditional antibiotics face several challenges today. Anti-microbial peptides (AMPs) are a conserved characteristic of the innate immune response among different animal species to defend against pathogenic microorganisms.</p><p><strong>Objectives: </strong>In this study, a new peptide sequence (mCHTL131-140) was designed using the in silico approach.</p><p><strong>Methods: </strong>Cathelicidin-2 (UniprotID: Q2IAL7) was used as a potential antimicrobial protein, and a novel 10 - 12 amino acids sequence AMP was designed using bioinformatics tools and the AMP databases. Then, the anti-bacterial, anti-biofilm, and anti-fungal properties of the peptide, as well as its hemolytic activity and cytotoxicity towards human fibroblast (HDF) cells, were investigated in vitro.</p><p><strong>Results: </strong>Online bioinformatics tools indicated that the peptide sequence could have anti-bacterial, anti-viral, anti-fungal, and anti-biofilm properties with little hemolytic properties. The experimental tests confirmed that mCHTL131-140 exhibited the best anti-bacterial properties against <i>Acinetobacter baumannii</i> and had fair anti-fungal properties. Besides, it did not cause red blood cell lysis and showed no cytotoxicity towards HDF cells.</p><p><strong>Conclusions: </strong>In general, the designed peptide can be considered a promising AMP to control hospital-acquired infections by <i>A. baumannii</i>.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"22 1","pages":"e141920"},"PeriodicalIF":1.6,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10909124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nafiseh Shafiei, H. Mahmoodzadeh Hosseini, Jafar Amani, Ali Mirhosseini, H. Jafary
Background: Epsilon toxin (ETX), produced by Clostridium perfringens, is one of the most potent toxins known, with a lethal potency approaching that of botulinum neurotoxins. Epsilon toxin is responsible for enteritis. Therefore, the development of rapid and simple methods to detect ETX is imperative. Aptamers are single-stranded oligonucleotides that can bind tightly to specific target molecules with an affinity comparable to that of monoclonal antibodies (mAbs). DNA aptamers can serve as tools for the molecular identification of organisms, such as pathogen subspecies. Objectives: This study aimed to isolate high-affinity single-stranded DNA (ssDNA) aptamers against ETX. Methods: This study identified aptamers using the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method, enzyme-linked apta-sorbent assay (ELASA), and surface plasmon resonance (SPR) to determine the affinity and specificity of the newly obtained aptamers targeting ETX. Results: Several aptamers obtained through the SELEX process were studied. Among them, 2 aptamers, ETX clone 3 (ETX3; dissociation constant [Kd] = 8.4 ± 2.4E-9M) and ETX11 (Kd = 6.3 ± 1.3E-9M) had favorable specificity for ETX. The limits of detection were 0.21 and 0.08 μg/mL for ETX3 and ETX11, respectively. Conclusions: The discovered aptamers can be used in various aptamer-based rapid diagnostic tests for the detection of ETX.
{"title":"Screening and Identification of DNA Nanostructure Aptamer Using the SELEX Method for Detection of Epsilon Toxin","authors":"Nafiseh Shafiei, H. Mahmoodzadeh Hosseini, Jafar Amani, Ali Mirhosseini, H. Jafary","doi":"10.5812/ijpr-140505","DOIUrl":"https://doi.org/10.5812/ijpr-140505","url":null,"abstract":"Background: Epsilon toxin (ETX), produced by Clostridium perfringens, is one of the most potent toxins known, with a lethal potency approaching that of botulinum neurotoxins. Epsilon toxin is responsible for enteritis. Therefore, the development of rapid and simple methods to detect ETX is imperative. Aptamers are single-stranded oligonucleotides that can bind tightly to specific target molecules with an affinity comparable to that of monoclonal antibodies (mAbs). DNA aptamers can serve as tools for the molecular identification of organisms, such as pathogen subspecies. Objectives: This study aimed to isolate high-affinity single-stranded DNA (ssDNA) aptamers against ETX. Methods: This study identified aptamers using the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method, enzyme-linked apta-sorbent assay (ELASA), and surface plasmon resonance (SPR) to determine the affinity and specificity of the newly obtained aptamers targeting ETX. Results: Several aptamers obtained through the SELEX process were studied. Among them, 2 aptamers, ETX clone 3 (ETX3; dissociation constant [Kd] = 8.4 ± 2.4E-9M) and ETX11 (Kd = 6.3 ± 1.3E-9M) had favorable specificity for ETX. The limits of detection were 0.21 and 0.08 μg/mL for ETX3 and ETX11, respectively. Conclusions: The discovered aptamers can be used in various aptamer-based rapid diagnostic tests for the detection of ETX.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"34 25","pages":""},"PeriodicalIF":1.6,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138589097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Osouli, H. Yazdanpanah, J. Salamzadeh, S. Eslamizad
Background: Wheat grains are susceptible to mycotoxins, toxic natural secondary metabolites generated by certain fungi on agricultural produce in the field during growth, harvest, transportation, or storage. Therefore, wheat flour can be contaminated with mycotoxins, which seriously threaten human health. Methods: A rapid method for screening seven mycotoxins in wheat flour was validated in accordance with Commission Decision 2002/657/EC. With this multi-analytical screening method, 7 prevalent mycotoxins (fumonisin B1, ochratoxin A, aflatoxin G1, deoxynivalenol, T-2 toxin, aflatoxin B1, and zearalenone) can be determined simultaneously. The method’s applicability was demonstrated by screening 7 mycotoxins in 39 wheat flour samples collected from different bakeries in Tehran province, Iran. Results: The validation results indicated that for all 7 mycotoxins, the positivity threshold (T) was above the cut-off value (Fm), and no false positive results were obtained for any of the mycotoxins. The screening results of 12 packaged and 27 bulk wheat flour samples indicated that the concentrations of all mentioned mycotoxins were higher than the cut-off (in the relative light unit [RLU]), and all the samples were compliant. Conclusions: The present study revealed that the biochip-based technique is valid for identifying and assessing the levels of 7 mycotoxins in grain samples, such as wheat flour, at the measured validation concentrations. The method was simple, fast, and able to screen 7 mycotoxins simultaneously. The test process of the kit is easy to conduct, and the results are straightforward to interpret.
{"title":"Performance Evaluation of Biochip Chemiluminescent Immunoassay for Screening Seven Mycotoxins in Wheat Flour Simultaneously","authors":"M. Osouli, H. Yazdanpanah, J. Salamzadeh, S. Eslamizad","doi":"10.5812/ijpr-140356","DOIUrl":"https://doi.org/10.5812/ijpr-140356","url":null,"abstract":"Background: Wheat grains are susceptible to mycotoxins, toxic natural secondary metabolites generated by certain fungi on agricultural produce in the field during growth, harvest, transportation, or storage. Therefore, wheat flour can be contaminated with mycotoxins, which seriously threaten human health. Methods: A rapid method for screening seven mycotoxins in wheat flour was validated in accordance with Commission Decision 2002/657/EC. With this multi-analytical screening method, 7 prevalent mycotoxins (fumonisin B1, ochratoxin A, aflatoxin G1, deoxynivalenol, T-2 toxin, aflatoxin B1, and zearalenone) can be determined simultaneously. The method’s applicability was demonstrated by screening 7 mycotoxins in 39 wheat flour samples collected from different bakeries in Tehran province, Iran. Results: The validation results indicated that for all 7 mycotoxins, the positivity threshold (T) was above the cut-off value (Fm), and no false positive results were obtained for any of the mycotoxins. The screening results of 12 packaged and 27 bulk wheat flour samples indicated that the concentrations of all mentioned mycotoxins were higher than the cut-off (in the relative light unit [RLU]), and all the samples were compliant. Conclusions: The present study revealed that the biochip-based technique is valid for identifying and assessing the levels of 7 mycotoxins in grain samples, such as wheat flour, at the measured validation concentrations. The method was simple, fast, and able to screen 7 mycotoxins simultaneously. The test process of the kit is easy to conduct, and the results are straightforward to interpret.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"93 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138595868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Somayeh Soleymanzadeh, R. Hosseini Doust, Ali Majidpour, Mahdi Adabi, Sara Minaeian
Background: The emergence of multidrug resistance among nosocomial pathogens has prompted researchers to look for new antibacterial sources. Metal nanoparticles and probiotic products have attracted the attention of researchers. However, combination therapy is an attractive alternative in this field. Objectives: This study evaluated the antibacterial activity and toxicity of Zinc Oxide nanoparticles (ZnO-NPs) combined with Cell-free Supernatant (CFS) of Lactobacillus plantarum (L. plantarum) and Lactobacillus acidophilus (L. acidophilus) alone and in a novel mixture. Methods: Antibacterial effects and cytotoxic properties of ZnO-NPs, CFS of L. plantarum (SLP), and CFS of L. acidophilus (SLA) were determined alone and in a mixture against ESKAPE strains. In addition, the viability percentage of the cells was evaluated after exposure to these agents. Results: Antibacterial mixtures (ZnO-NPs with SLP or ZnO-NPs with SLA) demonstrated synergistic and additive effects against Pseudomonas aeruginosa (FIC≤0.75), Acinetobacter baumannii (FIC = 1), and Escherichia coli (FIC≤0.75). The viability percentage of the cells after 24 h of exposure to a mixture of ZnO-NPs and SLA (about 50%) was more than when the cells were exposed to ZnO-NPs alone (about 30%) at the same concentration. Conclusions: A mixture of ZnO-NPs and CFS of probiotics can be an alternative to antibiotics, with more effectiveness and fewer side effects.
{"title":"Antibacterial Activity and Toxicity of Zinc Oxide Nanoparticles Combined with Supernatants of Lactobacillus spp. Against ESKAPE Bacteria: A Novel Mixture","authors":"Somayeh Soleymanzadeh, R. Hosseini Doust, Ali Majidpour, Mahdi Adabi, Sara Minaeian","doi":"10.5812/ijpr-139222","DOIUrl":"https://doi.org/10.5812/ijpr-139222","url":null,"abstract":"Background: The emergence of multidrug resistance among nosocomial pathogens has prompted researchers to look for new antibacterial sources. Metal nanoparticles and probiotic products have attracted the attention of researchers. However, combination therapy is an attractive alternative in this field. Objectives: This study evaluated the antibacterial activity and toxicity of Zinc Oxide nanoparticles (ZnO-NPs) combined with Cell-free Supernatant (CFS) of Lactobacillus plantarum (L. plantarum) and Lactobacillus acidophilus (L. acidophilus) alone and in a novel mixture. Methods: Antibacterial effects and cytotoxic properties of ZnO-NPs, CFS of L. plantarum (SLP), and CFS of L. acidophilus (SLA) were determined alone and in a mixture against ESKAPE strains. In addition, the viability percentage of the cells was evaluated after exposure to these agents. Results: Antibacterial mixtures (ZnO-NPs with SLP or ZnO-NPs with SLA) demonstrated synergistic and additive effects against Pseudomonas aeruginosa (FIC≤0.75), Acinetobacter baumannii (FIC = 1), and Escherichia coli (FIC≤0.75). The viability percentage of the cells after 24 h of exposure to a mixture of ZnO-NPs and SLA (about 50%) was more than when the cells were exposed to ZnO-NPs alone (about 30%) at the same concentration. Conclusions: A mixture of ZnO-NPs and CFS of probiotics can be an alternative to antibiotics, with more effectiveness and fewer side effects.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"64 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138606405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zahra Karimi Majd, N. Yousefi, M. Peikanpour, Mohammad Sistanizad, Ghader Mohammadnezhad, Behniya Azadmehr, F. Peiravian
Background: In addition to clinical and technical considerations, patients’ preferences are essential for evaluating interventions such as precision medicine (PM). Objectives: This study aimed to identify and prioritize attributes of precision oncology that are important for patients to develop and validate a standard stated preference instrument. Methods: The key attributes of precision oncology and their related levels were extracted from the systematic literature review and were presented on a validated 5-point Likert scale questionnaire to experts (n = 35). In two rounds of Delphi, participants scored and prioritized the attributes through this personally administered questionnaire to identify the five most important ones to develop a discrete choice experiment (DCE) instrument. The developed DCE questionnaire was subsequently validated, providing a robust and standard instrument for evaluating patients’ preferences for precision oncology. Results: Based on the consensus criteria, the final DCE included four attributes and a total of 14 levels, which were access to treatment (easy/not easy), out-of-pocket (OOP) expenditures (four levels according to treatment costs in the country), change in life expectancy (LE, six levels from an average gain of three months to four years), and change in quality of life (QoL, improvement or no change). Conclusions: The above-mentioned attributes represent patients’ main preferences from the views of the Iranian experts. The developed DCE questionnaire can be used to assess patients’ preferences and willingness to pay (WTP) in precision oncology.
{"title":"Developing a Discrete Choice Experiment Instrument for Evaluating Patients’ Preferences in Precision Oncology","authors":"Zahra Karimi Majd, N. Yousefi, M. Peikanpour, Mohammad Sistanizad, Ghader Mohammadnezhad, Behniya Azadmehr, F. Peiravian","doi":"10.5812/ijpr-141797","DOIUrl":"https://doi.org/10.5812/ijpr-141797","url":null,"abstract":"Background: In addition to clinical and technical considerations, patients’ preferences are essential for evaluating interventions such as precision medicine (PM). Objectives: This study aimed to identify and prioritize attributes of precision oncology that are important for patients to develop and validate a standard stated preference instrument. Methods: The key attributes of precision oncology and their related levels were extracted from the systematic literature review and were presented on a validated 5-point Likert scale questionnaire to experts (n = 35). In two rounds of Delphi, participants scored and prioritized the attributes through this personally administered questionnaire to identify the five most important ones to develop a discrete choice experiment (DCE) instrument. The developed DCE questionnaire was subsequently validated, providing a robust and standard instrument for evaluating patients’ preferences for precision oncology. Results: Based on the consensus criteria, the final DCE included four attributes and a total of 14 levels, which were access to treatment (easy/not easy), out-of-pocket (OOP) expenditures (four levels according to treatment costs in the country), change in life expectancy (LE, six levels from an average gain of three months to four years), and change in quality of life (QoL, improvement or no change). Conclusions: The above-mentioned attributes represent patients’ main preferences from the views of the Iranian experts. The developed DCE questionnaire can be used to assess patients’ preferences and willingness to pay (WTP) in precision oncology.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"44 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139199457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Polycystic ovary syndrome (PCOS) affects women of reproductive age globally with an incidence rate of 5% - 26%. Growing evidence reports important roles for microRNAs (miRNAs) in the pathophysiology of granulosa cells (GCs) in PCOS.
Objectives: The objectives of this study were to identify the top differentially expressed miRNAs (DE-miRNAs) and their corresponding targets in hub gene-miRNA networks, as well as identify novel DE-miRNAs by analyzing three distinct microarray datasets. Additionally, functional enrichment analysis was performed using bioinformatics approaches. Finally, interactions between the 5 top-ranked hub genes and drugs were investigated.
Methods: Using bioinformatics approaches, three GC profiles from the gene expression omnibus (GEO), namely gene expression omnibus series (GSE)-34526, GSE114419, and GSE137684, were analyzed. Targets of the top DE-miRNAs were predicted using the multiMiR R package, and only miRNAs with validated results were retrieved. Genes that were common between the "DE-miRNA prediction results" and the "existing tissue DE-mRNAs" were designated as differentially expressed genes (DEGs). Gene ontology (GO) and pathway enrichment analyses were implemented for DEGs. In order to identify hub genes and hub DE-miRNAs, the protein-protein interaction (PPI) network and miRNA-mRNA interaction network were constructed using Cytoscape software. The drug-gene interaction database (DGIdb) database was utilized to identify interactions between the top-ranked hub genes and drugs.
Results: Out of the top 20 DE-miRNAs that were retrieved from the GSE114419 and GSE34526 microarray datasets, only 13 of them had "validated results" through the multiMiR prediction method. Among the 13 DE-miRNAs investigated, only 5, namely hsa-miR-8085, hsa-miR-548w, hsa-miR-612, hsa-miR-1470, and hsa-miR-644a, demonstrated interactions with the 10 hub genes in the hub gene-miRNA networks in our study. Except for hsa-miR-612, the other 4 DE-miRNAs, including hsa-miR-8085, hsa-miR-548w, hsa-miR-1470, and hsa-miR-644a, are novel and had not been reported in PCOS pathogenesis before. Also, GO and pathway enrichment analyses identified "pathogenic E. coli infection" in the Kyoto encyclopedia of genes and genomes (KEGG) and "regulation of Rac1 activity" in FunRich as the top pathways. The drug-hub gene interaction network identified ACTB, JUN, PTEN, KRAS, and MAPK1 as potential targets to treat PCOS with therapeutic drugs.
Conclusions: The findings from this study might assist researchers in uncovering new biomarkers and potential therapeutic drug targets in PCOS treatment.
{"title":"Unveiling Key Biomarkers and Therapeutic Drugs in Polycystic Ovary Syndrome (PCOS) Through Pathway Enrichment Analysis and Hub Gene-miRNA Networks.","authors":"Roozbeh Heidarzadehpilehrood, Maryam Pirhoushiaran, Malina Binti Osman, King-Hwa Ling, Habibah Abdul Hamid","doi":"10.5812/ijpr-139985","DOIUrl":"10.5812/ijpr-139985","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) affects women of reproductive age globally with an incidence rate of 5% - 26%. Growing evidence reports important roles for microRNAs (miRNAs) in the pathophysiology of granulosa cells (GCs) in PCOS.</p><p><strong>Objectives: </strong>The objectives of this study were to identify the top differentially expressed miRNAs (DE-miRNAs) and their corresponding targets in hub gene-miRNA networks, as well as identify novel DE-miRNAs by analyzing three distinct microarray datasets. Additionally, functional enrichment analysis was performed using bioinformatics approaches. Finally, interactions between the 5 top-ranked hub genes and drugs were investigated.</p><p><strong>Methods: </strong>Using bioinformatics approaches, three GC profiles from the gene expression omnibus (GEO), namely gene expression omnibus series (GSE)-34526, GSE114419, and GSE137684, were analyzed. Targets of the top DE-miRNAs were predicted using the multiMiR R package, and only miRNAs with validated results were retrieved. Genes that were common between the \"DE-miRNA prediction results\" and the \"existing tissue DE-mRNAs\" were designated as differentially expressed genes (DEGs). Gene ontology (GO) and pathway enrichment analyses were implemented for DEGs. In order to identify hub genes and hub DE-miRNAs, the protein-protein interaction (PPI) network and miRNA-mRNA interaction network were constructed using Cytoscape software. The drug-gene interaction database (DGIdb) database was utilized to identify interactions between the top-ranked hub genes and drugs.</p><p><strong>Results: </strong>Out of the top 20 DE-miRNAs that were retrieved from the GSE114419 and GSE34526 microarray datasets, only 13 of them had \"validated results\" through the multiMiR prediction method. Among the 13 DE-miRNAs investigated, only 5, namely <i>hsa-miR-8085</i>, <i>hsa-miR-548w</i>, <i>hsa-miR-612</i>, <i>hsa-miR-1470</i>, and <i>hsa-miR-644a</i>, demonstrated interactions with the 10 hub genes in the hub gene-miRNA networks in our study. Except for <i>hsa-miR-612</i>, the other 4 DE-miRNAs, including <i>hsa-miR-8085</i>, <i>hsa-miR-548w</i>, <i>hsa-miR-1470</i>, and <i>hsa-miR-644a</i>, are novel and had not been reported in PCOS pathogenesis before. Also, GO and pathway enrichment analyses identified \"pathogenic <i>E. coli</i> infection\" in the Kyoto encyclopedia of genes and genomes (KEGG) and \"regulation of Rac1 activity\" in FunRich as the top pathways. The drug-hub gene interaction network identified <i>ACTB</i>, <i>JUN</i>, <i>PTEN</i>, <i>KRAS</i>, and <i>MAPK1</i> as potential targets to treat PCOS with therapeutic drugs.</p><p><strong>Conclusions: </strong>The findings from this study might assist researchers in uncovering new biomarkers and potential therapeutic drug targets in PCOS treatment.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"22 1","pages":"e139985"},"PeriodicalIF":1.6,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abbas Ranjbar, Mohsen Soltanshahi, Saeid Taghiloo, Hossein Asgarian-Omran
Background: Metabolism reprogramming is a survival mechanism in acute myeloid leukemia (AML) cells in the tumor microenvironment. Therefore, we investigated the effect of signaling pathway inhibitors on the expression of genes rewired in the metabolic pathway of AML cells. Methods: HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, which respectively are selective inhibitors of phosphatidylinositol-3-kinase (PI3K), AKT, and the mammalian target of rapamycin (mTOR), either individually or in combination. The relative expressions of Glucose Transporter 1, Hexokinase 2, Pyruvate Kinase, Pyruvate Dehydrogenase E1, Citrate synthase, Isocitrate Dehydrogenase 2, and Hypoxia Inducible Factor 1 Subunit Alpha were determined by real-time PCR. Results: The combined treatment of HL-60 cells with Idelalisib, MK-2206, and Everolimus decreased the expression of Glucose Transporter 1, Hexokinase 2, Pyruvate Kinase M2, Pyruvate Dehydrogenase E1, Citrate synthase, Isocitrate Dehydrogenase 2, and Hypoxia Inducible Factor 1 Subunit Alpha. Conclusions: A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, Pyruvate Dehydrogenase Complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells. Combinational therapy approaches to block these pathways might be a promising and novel therapeutic strategy for targeting the metabolic requirements of AML cells.
{"title":"Glucose Metabolism in Acute Myeloid Leukemia Cell Line Is Regulated via Combinational PI3K/AKT/mTOR Pathway Inhibitors","authors":"Abbas Ranjbar, Mohsen Soltanshahi, Saeid Taghiloo, Hossein Asgarian-Omran","doi":"10.5812/ijpr-140507","DOIUrl":"https://doi.org/10.5812/ijpr-140507","url":null,"abstract":"Background: Metabolism reprogramming is a survival mechanism in acute myeloid leukemia (AML) cells in the tumor microenvironment. Therefore, we investigated the effect of signaling pathway inhibitors on the expression of genes rewired in the metabolic pathway of AML cells. Methods: HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, which respectively are selective inhibitors of phosphatidylinositol-3-kinase (PI3K), AKT, and the mammalian target of rapamycin (mTOR), either individually or in combination. The relative expressions of Glucose Transporter 1, Hexokinase 2, Pyruvate Kinase, Pyruvate Dehydrogenase E1, Citrate synthase, Isocitrate Dehydrogenase 2, and Hypoxia Inducible Factor 1 Subunit Alpha were determined by real-time PCR. Results: The combined treatment of HL-60 cells with Idelalisib, MK-2206, and Everolimus decreased the expression of Glucose Transporter 1, Hexokinase 2, Pyruvate Kinase M2, Pyruvate Dehydrogenase E1, Citrate synthase, Isocitrate Dehydrogenase 2, and Hypoxia Inducible Factor 1 Subunit Alpha. Conclusions: A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, Pyruvate Dehydrogenase Complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells. Combinational therapy approaches to block these pathways might be a promising and novel therapeutic strategy for targeting the metabolic requirements of AML cells.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"50 20","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134902809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Fatigue is one of the most prevalent symptoms, increasing worldwide with no specific medication for fatigue. Iranian traditional medicine (ITM), or Persian medicine, is a reliable source for discovering natural medicine for diseases and their symptoms. Myrtus communis L. (Myrtle), Malus domestica Borkh. (Apple), and Syzygium aromaticum (L.) Merr. & L. M. Perry (Clove) have been utilized as brain and heart tonics in ITM. Based on ITM, cardiac tonics decrease fatigue by enhancing heart function and increasing blood flow to tissues. These plants, particularly myrtle berries, have been utilized as potent enlivening agents that reduce mental fatigue. Objectives: This study aims to investigate the effects of aqueous extracts of these plants on weight-loaded forced swimming (WLFS) tests and three doses of aqueous myrtle extract in an animal model of chronic sleep deprivation-induced fatigue. Methods: Five groups of rats (n = 6) were evaluated: sham, control, apple-treated, clove-treated, and myrtle-treated groups. After 28 days of treatment, the WLFS test was performed, and swimming time was recorded. Subsequently, central fatigue was induced in rats by chronic sleep deprivation for 21 days. Five groups of rats (n = 6) were evaluated: sham, control (sleep-deprived, which received water), and three sleep-deprived + treatment groups, which received aqueous myrtle extract (350, 700, and 1000 mg/kg). An open field test on the 20th day and a WLFS test on the 21st day were performed. Results: The myrtle berries significantly increased glucose, reduced lactate dehydrogenase (LDH) levels, and enhanced swimming time. Fatigue caused by chronic sleep deprivation increased malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and LDH while decreased superoxide dismutase (SOD), glucose, and swimming time. In all treatment groups, SOD levels and swimming time were increased, whereas MDA, IL-1β, and TNF-α levels were decreased significantly. Only the 1000 mg/kg dose significantly reduced LDH levels (P < 0.001). The treatment significantly improved the velocity and the total distance moved in the open-field test. Conclusions: According to the results, the myrtle berries reduced fatigue in two animal models, probably due to its phenolic compounds, flavonoids, and polysaccharides.
背景:疲劳是最普遍的症状之一，在世界范围内增加，没有特定的药物治疗疲劳。伊朗传统医学(ITM)或波斯医学是发现治疗疾病及其症状的天然药物的可靠来源。桃金娘(Myrtus communis L.);(苹果)和Syzygium aromaticum (L.)稳定。,L. M. Perry(丁香)在ITM中被用作大脑和心脏的滋补品。根据ITM，心脏补药通过增强心脏功能和增加组织血流量来减少疲劳。这些植物，特别是桃金娘浆果，已经被用作有效的提神剂，减少精神疲劳。目的:本研究旨在探讨这些植物的水提取物对慢性睡眠剥夺性疲劳动物模型负重强迫游泳(WLFS)试验和三种剂量的桃金娘水提取物的影响。方法:将大鼠分为5组(n = 6):假手术组、对照组、苹果组、丁香组、桃金娘组。治疗28 d后进行WLFS试验，记录游泳时间。随后，慢性睡眠剥夺大鼠21天诱导中枢疲劳。评估五组大鼠(n = 6):假手术组、对照组(剥夺睡眠，给予水)和3个剥夺睡眠+治疗组，给予桃金娘水提取物(350、700和1000 mg/kg)。第20天进行野外试验，第21天进行WLFS试验。结果:桃金娘果实显著提高葡萄糖，降低乳酸脱氢酶(LDH)水平，延长游泳时间。慢性睡眠剥夺引起的疲劳增加丙二醛(MDA)、肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)和LDH，降低超氧化物歧化酶(SOD)、葡萄糖和游泳时间。在所有治疗组中，SOD水平和游泳时间均升高，MDA、IL-1β和TNF-α水平均显著降低。只有1000mg /kg剂量显著降低LDH水平(P <0.001)。该处理显著提高了裸地试验中的速度和总移动距离。结论:桃金娘果实具有明显的抗疲劳作用，可能与桃金娘果实中的酚类化合物、黄酮类化合物和多糖有关。
{"title":"Antifatigue Effects of the Aqueous Extracts of Myrtle Berries, Apple and Clove: An Animal Study","authors":"Akram Alembagheri, Homa Hajimehdipour, Mona Khoramjouy, Somayeh Esmaeili, Mehrdad Faizi","doi":"10.5812/ijpr-140323","DOIUrl":"https://doi.org/10.5812/ijpr-140323","url":null,"abstract":"Background: Fatigue is one of the most prevalent symptoms, increasing worldwide with no specific medication for fatigue. Iranian traditional medicine (ITM), or Persian medicine, is a reliable source for discovering natural medicine for diseases and their symptoms. Myrtus communis L. (Myrtle), Malus domestica Borkh. (Apple), and Syzygium aromaticum (L.) Merr. & L. M. Perry (Clove) have been utilized as brain and heart tonics in ITM. Based on ITM, cardiac tonics decrease fatigue by enhancing heart function and increasing blood flow to tissues. These plants, particularly myrtle berries, have been utilized as potent enlivening agents that reduce mental fatigue. Objectives: This study aims to investigate the effects of aqueous extracts of these plants on weight-loaded forced swimming (WLFS) tests and three doses of aqueous myrtle extract in an animal model of chronic sleep deprivation-induced fatigue. Methods: Five groups of rats (n = 6) were evaluated: sham, control, apple-treated, clove-treated, and myrtle-treated groups. After 28 days of treatment, the WLFS test was performed, and swimming time was recorded. Subsequently, central fatigue was induced in rats by chronic sleep deprivation for 21 days. Five groups of rats (n = 6) were evaluated: sham, control (sleep-deprived, which received water), and three sleep-deprived + treatment groups, which received aqueous myrtle extract (350, 700, and 1000 mg/kg). An open field test on the 20th day and a WLFS test on the 21st day were performed. Results: The myrtle berries significantly increased glucose, reduced lactate dehydrogenase (LDH) levels, and enhanced swimming time. Fatigue caused by chronic sleep deprivation increased malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and LDH while decreased superoxide dismutase (SOD), glucose, and swimming time. In all treatment groups, SOD levels and swimming time were increased, whereas MDA, IL-1β, and TNF-α levels were decreased significantly. Only the 1000 mg/kg dose significantly reduced LDH levels (P < 0.001). The treatment significantly improved the velocity and the total distance moved in the open-field test. Conclusions: According to the results, the myrtle berries reduced fatigue in two animal models, probably due to its phenolic compounds, flavonoids, and polysaccharides.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135041799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iman Ansari, Ezzatalsadat Hajiseid Javadi, Hamideh Pakniat, Ali Emami, Fatemeh Ranjkesh, Simindokht Molaverdikhani
Background: A significant number of pregnancies are at risk of threatened abortion (TA). Different types of progesterone are used to treat TA. Objectives: In this study, the effects of 2 forms of progesterone on the continuation of pregnancy and TA-caused pregnancy outcomes were compared. Methods: A total of 190 women with a gestational age of 6 - 13 weeks presenting with uterine bleeding, closed cervix, and absence of fetal heart rate diagnosed by vaginal examination and ultrasound were allocated into 2 groups and treated with either (D) dydrogesterone (10 mg twice a day) or (M) micronized progesterone (200 mg, twice a day) for beyond 2 weeks after the cessation of uterine bleeding to ensure that bleeding would not recur. The participants were followed up and received prenatal care until the end of pregnancy. The outcomes of pregnancy were recorded and compared between the 2 groups. Results: The incidence of preeclampsia, gestational diabetes, cesarean section, intrauterine fetal death (IUFD), placenta previa, and abortion was not significantly different between the 2 groups. However, the prevalence of preterm labor and low birth weight (LBW) was significantly lower in M-treated women (P < 0.001 and P = 0.007, respectively). The baby’s weight and gestational age at delivery were significantly higher in the M group than in the D group (P < 0.001). No serious drug side effects were observed in the 2 groups throughout the study. Conclusions: The results of this study showed that the incidence of preterm labor and LBW was significantly lower in the patients treated with micronized progesterone than in patients treated with dydrogesterone; however, the prevalence of preeclampsia, gestational diabetes, cesarean section, IUFD, and abortion was not significantly different between the 2 groups.
{"title":"Micronized Progesterone or Dydrogesterone? A Comparative Study on the Effects of Two Forms of Progesterone on Pregnancy Outcomes After Threatened Abortion","authors":"Iman Ansari, Ezzatalsadat Hajiseid Javadi, Hamideh Pakniat, Ali Emami, Fatemeh Ranjkesh, Simindokht Molaverdikhani","doi":"10.5812/ijpr-136320","DOIUrl":"https://doi.org/10.5812/ijpr-136320","url":null,"abstract":"Background: A significant number of pregnancies are at risk of threatened abortion (TA). Different types of progesterone are used to treat TA. Objectives: In this study, the effects of 2 forms of progesterone on the continuation of pregnancy and TA-caused pregnancy outcomes were compared. Methods: A total of 190 women with a gestational age of 6 - 13 weeks presenting with uterine bleeding, closed cervix, and absence of fetal heart rate diagnosed by vaginal examination and ultrasound were allocated into 2 groups and treated with either (D) dydrogesterone (10 mg twice a day) or (M) micronized progesterone (200 mg, twice a day) for beyond 2 weeks after the cessation of uterine bleeding to ensure that bleeding would not recur. The participants were followed up and received prenatal care until the end of pregnancy. The outcomes of pregnancy were recorded and compared between the 2 groups. Results: The incidence of preeclampsia, gestational diabetes, cesarean section, intrauterine fetal death (IUFD), placenta previa, and abortion was not significantly different between the 2 groups. However, the prevalence of preterm labor and low birth weight (LBW) was significantly lower in M-treated women (P < 0.001 and P = 0.007, respectively). The baby’s weight and gestational age at delivery were significantly higher in the M group than in the D group (P < 0.001). No serious drug side effects were observed in the 2 groups throughout the study. Conclusions: The results of this study showed that the incidence of preterm labor and LBW was significantly lower in the patients treated with micronized progesterone than in patients treated with dydrogesterone; however, the prevalence of preeclampsia, gestational diabetes, cesarean section, IUFD, and abortion was not significantly different between the 2 groups.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135042607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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