Introduction: Medications used to treat oral ulcers include corticosteroids, anesthetics, and antihistamines. These can be used as gels, mouthwashes, pastes, ointments, etc. Diphenhydramine hydrochloride (DPH) has local anesthetic properties that can help treat the aphthae. One of the drawbacks of the delivery to the transmucosal is the quick turnaround time of the gel, a mucous form that is located on the epithelial film surface.
Methods: Therefore, it seems that the preparation of a carrier that has the characteristics of adhesive mucus can increase the duration of drug retention on the mucous surface. To solve this problem, mesoporous silica nanoparticles (MSNPs) were synthesized and functionalized with amino and thiol groups and suggested as a system of drug delivery. The properties and structure of MSNPs were investigated by dynamic light scattering (DLS), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), thermal gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and nitrogen adsorption-desorption isotherms (BET).
Results: Our outcomes indicated that the average sizes of bare MSNPs (MSN), amino modified MSNPs (MSN-NH2), and thiol modified MSNPs (MSN-SH) were obtained to be 611, 655, and 655 nm respectively and the average pore size of MSN, MSN-NH2, and MSN-SH were about 2.42 nm, 2.42 nm, and 2.44 nm, respectively, according to the BJH (Barrett-Joyner-Halenda) pore size distribution. The release kinetics and release of DPH from mesoporous silica carriers were evaluated.
Conclusion: Eventually, the mucoadhesive study and DPH-loaded particles were investigated. Also, the MSN-SH exhibited a high mucoadhesive capacity for buccal mucosa compared with MSN-NH2 and MSN.
{"title":"Synthesis and functionalization of mucoadhesive mesoporous silica particles containing diphenhydramine for treatment of aphthous ulcers.","authors":"Azadeh Vaezi Moghaddam, Seyed Alireza Mortazavi, Farzad Kobarfard, Reza Bafkary, Behzad Darbasizadeh","doi":"10.34172/bi.2023.27548","DOIUrl":"10.34172/bi.2023.27548","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Medications used to treat oral ulcers include corticosteroids, anesthetics, and antihistamines. These can be used as gels, mouthwashes, pastes, ointments, etc. Diphenhydramine hydrochloride (DPH) has local anesthetic properties that can help treat the aphthae. One of the drawbacks of the delivery to the transmucosal is the quick turnaround time of the gel, a mucous form that is located on the epithelial film surface.</p><p><strong>Methods: </strong>Therefore, it seems that the preparation of a carrier that has the characteristics of adhesive mucus can increase the duration of drug retention on the mucous surface. To solve this problem, mesoporous silica nanoparticles (MSNPs) were synthesized and functionalized with amino and thiol groups and suggested as a system of drug delivery. The properties and structure of MSNPs were investigated by dynamic light scattering (DLS), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), thermal gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and nitrogen adsorption-desorption isotherms (BET).</p><p><strong>Results: </strong>Our outcomes indicated that the average sizes of bare MSNPs (MSN), amino modified MSNPs (MSN-NH2), and thiol modified MSNPs (MSN-SH) were obtained to be 611, 655, and 655 nm respectively and the average pore size of MSN, MSN-NH2, and MSN-SH were about 2.42 nm, 2.42 nm, and 2.44 nm, respectively, according to the BJH (Barrett-Joyner-Halenda) pore size distribution. The release kinetics and release of DPH from mesoporous silica carriers were evaluated.</p><p><strong>Conclusion: </strong>Eventually, the mucoadhesive study and DPH-loaded particles were investigated. Also, the MSN-SH exhibited a high mucoadhesive capacity for buccal mucosa compared with MSN-NH2 and MSN.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48008928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2022-08-13DOI: 10.34172/bi.2022.24256
Behnaz Ahrabi, Hojjat Allah Abbaszadeh, Abbas Piryaei, Faezeh Shekari, Navid Ahmady Roozbahany, Mahya Rouhollahi, Forough Azam Sayahpour, Mahnaz Ahrabi, Hadi Azimi, Reza Moghadasali
Introduction: Chronic and progressive damage to the kidney by inflammatory processes, may lead to an increase in the extracellular matrix production, a condition known as renal fibrosis. The current study aims to evaluate if the extracellular vesicles (EVs) derived from autophagic adipose-derived mesenchymal stem cells (ADMSCs) can reduce the inflammation and extracellular matrix accumulation in damaged kidney tissue.
Methods: Autophagy was induced in ADMSCs using 2µM concentration curcumin and was confirmed by evaluating LC3B, ATG7, and Beclin1 using real-time polymerase chain reaction (PCR) and Western blot. An in vitro renal fibrotic model was established in HEK-293 cells exposed to H2O2 (0.8mM) for 24 and 72 hours. The fibrotic model was confirmed through evaluation of collagen I, transforming growth factor-beta 1 (TGF-β1), E-cadherin, and vimentin genes expression using real-time PCR, collagen I protein by ELISA. After induction of fibrosis for 24 and 72 hours, the HEK cells were treated with NEVs (non-autophagy EVs) (50µM) or AEVs (autophagy EVs) (50µM) at 48, 96, and 124 hours, and then the samples were collected at 72 and 148 hours. Expression of collagen I, TGF-β1, E-cadherin, and vimentin Genes was evaluated via RT-PCR, and protein levels of IL1, TNF-α, IL4, IL10 using ELISA.
Results: Induction of autophagy using curcumin (2µM) for 24 hours significantly increased LC3B, Beclin1, and ATG7 in the ADMSCs. Upregulation in anti-fibrotic (E-cadherin) and anti-inflammatory (IL4, IL10) gene expression was significantly different in the fibrotic model treated by AEVs compared to NEVs. Also, the downregulation of fibrotic (TGF-β1, vimentin, collagen I) and pro-inflammatory (IL1, TNFα) gene expression was significantly different in AEVs compared with those treated by NEVs.
Conclusion: Our findings suggest that AEVs can be considered as a therapeutic modality for renal fibrosis in the future.
{"title":"Autophagy-induced mesenchymal stem cell-derived extracellular vesicles ameliorated renal fibrosis in an <i>in vitro</i> model.","authors":"Behnaz Ahrabi, Hojjat Allah Abbaszadeh, Abbas Piryaei, Faezeh Shekari, Navid Ahmady Roozbahany, Mahya Rouhollahi, Forough Azam Sayahpour, Mahnaz Ahrabi, Hadi Azimi, Reza Moghadasali","doi":"10.34172/bi.2022.24256","DOIUrl":"https://doi.org/10.34172/bi.2022.24256","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Chronic and progressive damage to the kidney by inflammatory processes, may lead to an increase in the extracellular matrix production, a condition known as renal fibrosis. The current study aims to evaluate if the extracellular vesicles (EVs) derived from autophagic adipose-derived mesenchymal stem cells (ADMSCs) can reduce the inflammation and extracellular matrix accumulation in damaged kidney tissue.</p><p><strong>Methods: </strong>Autophagy was induced in ADMSCs using 2µM concentration curcumin and was confirmed by evaluating LC3B, ATG7, and Beclin1 using real-time polymerase chain reaction (PCR) and Western blot. An in vitro renal fibrotic model was established in HEK-293 cells exposed to H2O2 (0.8mM) for 24 and 72 hours. The fibrotic model was confirmed through evaluation of collagen I, transforming growth factor-beta 1 (TGF-β1), E-cadherin, and vimentin genes expression using real-time PCR, collagen I protein by ELISA. After induction of fibrosis for 24 and 72 hours, the HEK cells were treated with NEVs (non-autophagy EVs) (50µM) or AEVs (autophagy EVs) (50µM) at 48, 96, and 124 hours, and then the samples were collected at 72 and 148 hours. Expression of collagen I, TGF-β1, E-cadherin, and vimentin Genes was evaluated via RT-PCR, and protein levels of IL1, TNF-α, IL4, IL10 using ELISA.</p><p><strong>Results: </strong>Induction of autophagy using curcumin (2µM) for 24 hours significantly increased LC3B, Beclin1, and ATG7 in the ADMSCs. Upregulation in anti-fibrotic (E-cadherin) and anti-inflammatory (IL4, IL10) gene expression was significantly different in the fibrotic model treated by AEVs compared to NEVs. Also, the downregulation of fibrotic (TGF-β1, vimentin, collagen I) and pro-inflammatory (IL1, TNFα) gene expression was significantly different in AEVs compared with those treated by NEVs.</p><p><strong>Conclusion: </strong>Our findings suggest that AEVs can be considered as a therapeutic modality for renal fibrosis in the future.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/3d/bi-13-359.PMC10509741.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41173079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fatima Molavi, Mohammad Barzegar-Jalali, Hamed Hamishehkar
Introduction: Glatiramer acetate (GA) is a newly emerged therapeutic peptide to reduce the frequency of relapses in multiple sclerosis (MS). Despite its good performance in controlling MS, it is not widely used due to daily or biweekly subcutaneous injections due to rapid degradation and body clearance. Therefore, implant design with sustained release leads to prolonged biological effects by gradually increasing drug exposure and protecting GA from rapid local degradation. Methods: Different emulsion methods, PLGA type, surfactant concentration, drug/polymer ratio, drying processes, stirring method, and other variables in preliminary studies modified the final formulation. The release kinetics were studied through mechanistic kinetic models such as zero-order, Weibull, Higuchi, etc. In this study, all challenges for easy scale-up, methodological detail, and a simple, feasible setup in mass production were discussed. Results: The optimized formulation was obtained by 1:6 drug/PLGA, 0.5% w/w polyvinyl alcohol, and 0.75% w/w NaCl in the external aqueous phase, 1:10 continuous phase to dispersed phase ratio, and without any surfactant in the primary emulsion. The final freeze-dried particles presented a narrow distributed size of 1-10 µm with 7.29% ± 0.51 drug loading and zero-order release behavior with appropriate regression correlation (R2 98.7), complete release, and only 7.1% initial burst release. Conclusion: Therefore, to achieve improvement in patient compliance through better and longer efficacy, designing the parenteral sustained release microspheres (MPSs) of this immune modulator is a promising approach that should be considered.
{"title":"Changing the daily injection of glatiramer acetate to a monthly long acting product through designing polyester-based polymeric microspheres.","authors":"Fatima Molavi, Mohammad Barzegar-Jalali, Hamed Hamishehkar","doi":"10.34172/bi.2022.23733","DOIUrl":"https://doi.org/10.34172/bi.2022.23733","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> Glatiramer acetate (GA) is a newly emerged therapeutic peptide to reduce the frequency of relapses in multiple sclerosis (MS). Despite its good performance in controlling MS, it is not widely used due to daily or biweekly subcutaneous injections due to rapid degradation and body clearance. Therefore, implant design with sustained release leads to prolonged biological effects by gradually increasing drug exposure and protecting GA from rapid local degradation. <i><b>Methods:</b></i> Different emulsion methods, PLGA type, surfactant concentration, drug/polymer ratio, drying processes, stirring method, and other variables in preliminary studies modified the final formulation. The release kinetics were studied through mechanistic kinetic models such as zero-order, Weibull, Higuchi, etc. In this study, all challenges for easy scale-up, methodological detail, and a simple, feasible setup in mass production were discussed. <i><b>Results:</b></i> The optimized formulation was obtained by 1:6 drug/PLGA, 0.5% w/w polyvinyl alcohol, and 0.75% w/w NaCl in the external aqueous phase, 1:10 continuous phase to dispersed phase ratio, and without any surfactant in the primary emulsion. The final freeze-dried particles presented a narrow distributed size of 1-10 µm with 7.29% ± 0.51 drug loading and zero-order release behavior with appropriate regression correlation (R2 98.7), complete release, and only 7.1% initial burst release. <i><b>Conclusion:</b></i> Therefore, to achieve improvement in patient compliance through better and longer efficacy, designing the parenteral sustained release microspheres (MPSs) of this immune modulator is a promising approach that should be considered.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2d/95/bi-12-501.PMC9809140.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10536384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2021-12-07DOI: 10.34172/bi.2021.23522
Mohammad Azadbakht, Ali Sayadmanesh, Naghme Nazer, Amirhossein Ahmadi, Sara Hemmati, Hoda Mohammadzade, Marzieh Ebrahimi, Hossein Baharvand, Babak Khalaj, Mahmoud Reza Aghamaali, Mohsen Basiri
Introduction: B lymphocyte-induced maturation protein 1 (BLIMP1) encoded by the positive regulatory domain 1 gene (PRDM1), is a key regulator in T cell differentiation in mouse models. BLIMP1-deficiency results in a lower effector phenotype and a higher memory phenotype. Methods: In this study, we aimed to determine the role of transcription factor BLIMP1 in human T cell differentiation. Specifically, we investigated the role of BLIMP1 in memory differentiation and exhaustion of human T cells. We used CRISPR interference (CRISPRi) to knock-down BLIMP1 and investigated the differential expressions of T cell memory and exhaustion markers in BLIMP1-deficient T cells in comparison with BLIMP1-sufficient ex vivo expanded human T cells. Results: BLIMP1-deficiency caused an increase in central memory (CM) T cells and a decrease in effector memory (EM) T cells. There was a decrease in the amount of TIM3 exhaustion marker expression in BLIMP1-deficient T cells; however, there was an increase in PD1 exhaustion marker expression in BLIMP1-deficient T cells compared with BLIMP1-sufficient T cells. Conclusion: Our study provides the first functional evidence of the impact of BLIMP1 on the regulation of human T cell memory and exhaustion phenotype. These findings suggest that BLIMP1 may be a promising target to improve the immune response in adoptive T cell therapy settings.
{"title":"CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in <i>ex vivo</i>-expanded human T cells.","authors":"Mohammad Azadbakht, Ali Sayadmanesh, Naghme Nazer, Amirhossein Ahmadi, Sara Hemmati, Hoda Mohammadzade, Marzieh Ebrahimi, Hossein Baharvand, Babak Khalaj, Mahmoud Reza Aghamaali, Mohsen Basiri","doi":"10.34172/bi.2021.23522","DOIUrl":"https://doi.org/10.34172/bi.2021.23522","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> B lymphocyte-induced maturation protein 1 (BLIMP1) encoded by the positive regulatory domain 1 gene (<i>PRDM1</i>), is a key regulator in T cell differentiation in mouse models. BLIMP1-deficiency results in a lower effector phenotype and a higher memory phenotype. <i><b>Methods:</b> </i> In this study, we aimed to determine the role of transcription factor BLIMP1 in human T cell differentiation. Specifically, we investigated the role of BLIMP1 in memory differentiation and exhaustion of human T cells. We used CRISPR interference (CRISPRi) to knock-down BLIMP1 and investigated the differential expressions of T cell memory and exhaustion markers in BLIMP1-deficient T cells in comparison with BLIMP1-sufficient ex vivo expanded human T cells. <i><b>Results:</b> </i> BLIMP1-deficiency caused an increase in central memory (CM) T cells and a decrease in effector memory (EM) T cells. There was a decrease in the amount of TIM3 exhaustion marker expression in BLIMP1-deficient T cells; however, there was an increase in PD1 exhaustion marker expression in BLIMP1-deficient T cells compared with BLIMP1-sufficient T cells. <i><b>Conclusion:</b> </i> Our study provides the first functional evidence of the impact of BLIMP1 on the regulation of human T cell memory and exhaustion phenotype. These findings suggest that BLIMP1 may be a promising target to improve the immune response in adoptive T cell therapy settings.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/3c/bi-12-337.PMC9376159.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40420451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-06-30DOI: 10.34172/bi.2022.23877
Aleksandr L Urakov, Natalya A Urakova, Ilnur I Yagudin, Milena D Svetova, Darya O Suntsova
COVID-19 causes non-specific pneumonia, which has become a new cause of hypoxia, leading to the death of many patients. Today, there are no effective drugs that provide an urgent increase in blood oxygenation. Therefore, it is urgently necessary to develop drugs to increase blood oxygenation in order to save the lives of patients with the new coronavirus infection. Since hypoxia develops in this disease due to the blockage of respiratory tract with viscous mucus and sputum, an appropriate experimental model is needed for screening and finding new drugs. However this model is yet missing. Therefore, the development of an experimental model of respiratory obstruction by sputum with traces of blood can accelerate the discovery of drugs that eliminate hypoxia and prevent the death of patients with nonspecific pneumonia complicated by respiratory obstruction. The purpose of this letter was to present a model for evaluating the biological activity of drugs, which can become a new vector for the development of effective ways to increase blood oxygenation across pulmonary and save the lives of patients with severe atypical pneumonia complicated by respiratory obstruction in COVID-19.
{"title":"COVID-19: Artificial sputum, respiratory obstruction method and screening of pyolitic and antihypoxic drugs.","authors":"Aleksandr L Urakov, Natalya A Urakova, Ilnur I Yagudin, Milena D Svetova, Darya O Suntsova","doi":"10.34172/bi.2022.23877","DOIUrl":"https://doi.org/10.34172/bi.2022.23877","url":null,"abstract":"<p><p>COVID-19 causes non-specific pneumonia, which has become a new cause of hypoxia, leading to the death of many patients. Today, there are no effective drugs that provide an urgent increase in blood oxygenation. Therefore, it is urgently necessary to develop drugs to increase blood oxygenation in order to save the lives of patients with the new coronavirus infection. Since hypoxia develops in this disease due to the blockage of respiratory tract with viscous mucus and sputum, an appropriate experimental model is needed for screening and finding new drugs. However this model is yet missing. Therefore, the development of an experimental model of respiratory obstruction by sputum with traces of blood can accelerate the discovery of drugs that eliminate hypoxia and prevent the death of patients with nonspecific pneumonia complicated by respiratory obstruction. The purpose of this letter was to present a model for evaluating the biological activity of drugs, which can become a new vector for the development of effective ways to increase blood oxygenation across pulmonary and save the lives of patients with severe atypical pneumonia complicated by respiratory obstruction in COVID-19.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7e/7d/bi-12-393.PMC9376158.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40420453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yosef Masoudi-Sobhanzadeh, Hosein Esmaeili, Ali Masoudi-Nejad
Introduction: COVID-19 has spread out all around the world and seriously interrupted human activities. Being a newfound disease, not only many aspects of the disease are unknown, but also there is not an effective medication to cure the disease. Besides, designing a drug is a time-consuming process and needs large investment. Hence, drug repurposing techniques, employed to discover the hidden benefits of the existing drugs, maybe a useful option for treating COVID-19. Methods: The present study exploits the drug repositioning concepts and introduces some candidate drugs which may be effective in controlling COVID-19. The suggested method consists of three main steps. First, the required data such as the amino acid sequences of targets and drug-target interactions are extracted from the public databases. Second, the similarity score between the targets (protein/enzymes) and genome of SARS-COV-2 is computed using the proposed fuzzy logic-based method. Since the classical approaches yield outcomes which may not be useful for the real-world applications, the fuzzy technique can address the issue. Third, after ranking targets based on the obtained scores, the usefulness of drugs affecting them is examined for managing COVID-19. Results: The results indicate that antiviral medicines, designed for curing hepatitis C, may also cure COVID-19. According to the findings, ribavirin, simeprevir, danoprevir, and XTL-6865 may be helpful in controlling the disease. Conclusion: It can be concluded that the similarity-based drug repurposing techniques may be the most suitable option for managing emerging diseases such as COVID-19 and can be applied to a wide range of data. Also, fuzzy logic-based scoring methods can produce outcomes which are more consistent with the real-world biological applications than others.
{"title":"A fuzzy logic-based computational method for the repurposing of drugs against COVID-19.","authors":"Yosef Masoudi-Sobhanzadeh, Hosein Esmaeili, Ali Masoudi-Nejad","doi":"10.34172/bi.2021.40","DOIUrl":"https://doi.org/10.34172/bi.2021.40","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> COVID-19 has spread out all around the world and seriously interrupted human activities. Being a newfound disease, not only many aspects of the disease are unknown, but also there is not an effective medication to cure the disease. Besides, designing a drug is a time-consuming process and needs large investment. Hence, drug repurposing techniques, employed to discover the hidden benefits of the existing drugs, maybe a useful option for treating COVID-19. <i><b>Methods:</b> </i> The present study exploits the drug repositioning concepts and introduces some candidate drugs which may be effective in controlling COVID-19. The suggested method consists of three main steps. First, the required data such as the amino acid sequences of targets and drug-target interactions are extracted from the public databases. Second, the similarity score between the targets (protein/enzymes) and genome of SARS-COV-2 is computed using the proposed fuzzy logic-based method. Since the classical approaches yield outcomes which may not be useful for the real-world applications, the fuzzy technique can address the issue. Third, after ranking targets based on the obtained scores, the usefulness of drugs affecting them is examined for managing COVID-19. <i><b>Results:</b> </i> The results indicate that antiviral medicines, designed for curing hepatitis C, may also cure COVID-19. According to the findings, ribavirin, simeprevir, danoprevir, and XTL-6865 may be helpful in controlling the disease. <i><b>Conclusion:</b> </i> It can be concluded that the similarity-based drug repurposing techniques may be the most suitable option for managing emerging diseases such as COVID-19 and can be applied to a wide range of data. Also, fuzzy logic-based scoring methods can produce outcomes which are more consistent with the real-world biological applications than others.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/90/ce/bi-12-315.PMC9376160.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10842223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wael A Mahdi, Mohammad S Absar, Suna Choi, Victor C Yang, Young M Kwon
Introduction: In targeted enzyme prodrug constructs, it is critical to control the bioactivity of the drug in its prodrug form. The preparation of such constructs often involves conjugation reactions directed to functional groups on amino acid side chains of the protein, which result in random conjugation and incomplete control of bioactivity of a prodrug, which may result in significant nontarget effect. Thus, more specific method of modification is desired. If the drug is a glycoprotein, enzymatic oxidation may offer an alternative approach for therapeutic glycoproteins. Methods: Tissue plasminogen activator (tPA), a model glycoprotein enzyme, was treated with galactose oxidase (GO) and horseradish peroxidase, followed by thiolation reaction and conjugation with low molecular weight heparin (LMWH). The LMWH-tPA conjugate was isolated by ion-exchange chromatography followed by centrifugal filtration. The conjugate was characterized for its fibrinolytic activity and for its plasminogen activation through an indirect amidolytic assay with a plasmin-specific substrate S-2251 when LMWH-tPA conjugate is complexed with protamine-albumin conjugate, followed by triggered activation in the presence of heparin. Results: LMWH-tPA conjugate prepared via enzymatic oxidation retained ~95% of its fibrinolytic activity with respect to native tPA. Upon complexation with protamine-albumin conjugate, the activity of LMWH-tPA was effectively inhibited (~90%) whereas the LMWH-tPA prepared by random thiolation exhibited ~55% inhibition. Addition of heparin fully generated the activities of both conjugates. Conclusion: The tPA was successfully modified via enzymatic oxidation by GO, resulting in enhanced control of its activity in the prodrug construct. This approach can be applied to other therapeutic glycoproteins.
{"title":"Enhanced control of bioactivity of tissue plasminogen activator (tPA) through domain-directed enzymatic oxidation of terminal galactose.","authors":"Wael A Mahdi, Mohammad S Absar, Suna Choi, Victor C Yang, Young M Kwon","doi":"10.34172/bi.2022.23477","DOIUrl":"https://doi.org/10.34172/bi.2022.23477","url":null,"abstract":"<p><p><b><i>Introduction:</i> </b> In targeted enzyme prodrug constructs, it is critical to control the bioactivity of the drug in its prodrug form. The preparation of such constructs often involves conjugation reactions directed to functional groups on amino acid side chains of the protein, which result in random conjugation and incomplete control of bioactivity of a prodrug, which may result in significant nontarget effect. Thus, more specific method of modification is desired. If the drug is a glycoprotein, enzymatic oxidation may offer an alternative approach for therapeutic glycoproteins. <i><b>Methods:</b> </i> Tissue plasminogen activator (tPA), a model glycoprotein enzyme, was treated with galactose oxidase (GO) and horseradish peroxidase, followed by thiolation reaction and conjugation with low molecular weight heparin (LMWH). The LMWH-tPA conjugate was isolated by ion-exchange chromatography followed by centrifugal filtration. The conjugate was characterized for its fibrinolytic activity and for its plasminogen activation through an indirect amidolytic assay with a plasmin-specific substrate S-2251 when LMWH-tPA conjugate is complexed with protamine-albumin conjugate, followed by triggered activation in the presence of heparin. <i><b>Results:</b> </i> LMWH-tPA conjugate prepared via enzymatic oxidation retained ~95% of its fibrinolytic activity with respect to native tPA. Upon complexation with protamine-albumin conjugate, the activity of LMWH-tPA was effectively inhibited (~90%) whereas the LMWH-tPA prepared by random thiolation exhibited ~55% inhibition. Addition of heparin fully generated the activities of both conjugates. <i><b>Conclusion:</b> </i> The tPA was successfully modified via enzymatic oxidation by GO, resulting in enhanced control of its activity in the prodrug construct. This approach can be applied to other therapeutic glycoproteins.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5e/b6/bi-12-479.PMC9809136.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10536385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2021-09-25DOI: 10.34172/bi.2021.23499
Sepideh Sheshpari, Mahnaz Shahnazi, Shahin Ahmadian, Mohammad Nouri, Mehran Mesgari Abbasi, Rahim Beheshti, Reza Rahbarghazi, Ali Honaramooz, Mahdi Mahdipour
Introduction: Cell-based therapies with certain cell types are touted as novel and hopeful therapeutic intervention in the clinical setting. Here, we aimed to assess the regenerative potential of c-Kit+ cells in the rejuvenation of ovarian tissue and fertility rate in rat model of premature ovarian failure (POF). Methods: Rats were treated with 160 mg/kg/BW of 4-vinylcyclohexene dioxide for 15 days. Freshly enriched rat bone marrow-derived c-Kit+ (MACS) and c-Kit- cells (4×105 cells/10 µL) were transplanted into the ovaries of treatment and control animals. Prior to transplantation as well as 2, 4, 6, and 8 weeks post-transplantation, randomly-selected rats were euthanized and ovarian tissues were subjected to pathophysiological examinations and real-time PCR analyses. Results: POF status was confirmed by the presence of pathological features and a decreased number of immature and mature follicles compared with the control group (P < 0.05). Histological examination revealed a substantial reduction of atretic follicles in POF rats receiving c-Kit+ cells in comparison with POF rats that did not receive these cells (P < 0.05). Compared with the control samples, angiogenesis-related genes, Angpt2 and KDR, showed increased and decreased expressions in POF ovaries, respectively (P < 0.05). c-Kit+ cells had potential to restore angiogenesis in the ovarian tissue within normal ranges. Systemic levels of FSH did not significantly change in pre- or post-transplantation time points for any group (P > 0.05). Notable reduction of collagen deposition was found in c-Kit-treated rats. Transplantation of c-Kit+ cells also restored the reduced fertility rate (P < 0.05). Conclusion: The administration of c-Kit+ cells can modulate angiogenesis and pathological changes, leading to the rejuvenation of ovarian function of a rat model of premature menopause.
{"title":"Intra-ovarian injection of bone marrow-derived c-Kit<sup>+</sup> cells for ovarian rejuvenation in menopausal rats.","authors":"Sepideh Sheshpari, Mahnaz Shahnazi, Shahin Ahmadian, Mohammad Nouri, Mehran Mesgari Abbasi, Rahim Beheshti, Reza Rahbarghazi, Ali Honaramooz, Mahdi Mahdipour","doi":"10.34172/bi.2021.23499","DOIUrl":"https://doi.org/10.34172/bi.2021.23499","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> Cell-based therapies with certain cell types are touted as novel and hopeful therapeutic intervention in the clinical setting. Here, we aimed to assess the regenerative potential of c-Kit<sup>+</sup> cells in the rejuvenation of ovarian tissue and fertility rate in rat model of premature ovarian failure (POF). <i><b>Methods:</b> </i> Rats were treated with 160 mg/kg/BW of 4-vinylcyclohexene dioxide for 15 days. Freshly enriched rat bone marrow-derived c-Kit<sup>+</sup> (MACS) and c-Kit<sup>-</sup> cells (4×10<sup>5</sup> cells/10 µL) were transplanted into the ovaries of treatment and control animals. Prior to transplantation as well as 2, 4, 6, and 8 weeks post-transplantation, randomly-selected rats were euthanized and ovarian tissues were subjected to pathophysiological examinations and real-time PCR analyses. <i><b>Results:</b> </i> POF status was confirmed by the presence of pathological features and a decreased number of immature and mature follicles compared with the control group (<i>P </i>< 0.05). Histological examination revealed a substantial reduction of atretic follicles in POF rats receiving c-Kit<sup>+</sup> cells in comparison with POF rats that did not receive these cells (<i>P </i>< 0.05). Compared with the control samples, angiogenesis-related genes, <i>Angpt2</i> and <i>KDR</i>, showed increased and decreased expressions in POF ovaries, respectively (<i>P </i>< 0.05). c-Kit<sup>+</sup> cells had potential to restore angiogenesis in the ovarian tissue within normal ranges. Systemic levels of FSH did not significantly change in pre- or post-transplantation time points for any group (<i>P </i>> 0.05). Notable reduction of collagen deposition was found in c-Kit-treated rats. Transplantation of c-Kit<sup>+</sup> cells also restored the reduced fertility rate (<i>P </i>< 0.05). <i><b>Conclusion:</b> </i> The administration of c-Kit<sup>+</sup> cells can modulate angiogenesis and pathological changes, leading to the rejuvenation of ovarian function of a rat model of premature menopause.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/24/13/bi-12-325.PMC9376162.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40420449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Hypoxia context is highly specific for tumors and represents a unique niche which is not found elsewhere in the body. Clostridium novyi is an obligate anaerobic bacterium. It has a potential to treat tumors. The aim of this study was to produce the C. novyi nontoxic spores and to investigate its oncolytic effect on breast cancer in mice model. Methods: Primarily, the lethal toxin gene in C. novyi type B was removed. Colonies were isolated using PCR testing. To assure the removal of alpha-toxin, plasmid extraction and in vivo assay were conducted. Next, to treat breast cancer model in different sizes of tumors, a single dose of spores of C. novyi nontoxic was tested. Results: The results denoted that C. novyi nontoxic lost lethal toxin and a--ppeared to be safe. For smaller than 1000 mm3 tumors, a single dose of C. novyi nontoxic was able to cure 100% of mice bearing breast tumors. Hence the mice remained free of tumor relapse. Tumors larger than 1000 mm3 were not cured by a single dose- of C. novyi nontoxic treatment. Conclusion: The experiment concluded that the C. novyi nontoxic might be a suitable and safe candidate, a novel therapeutic approach to encounter such hypoxic regions in the center of tumors. Research also showed that bacteriolytic therapy by C. novyi nontoxic could lead to regression in small tumor.
{"title":"The oncolytic activity of <i>Clostridium novyi</i> nontoxic spores in breast cancer.","authors":"Fatemeh Abedi Jafari, Asghar Abdoli, Reza Pilehchian, Neda Soleimani, Seyed Masoud Hosseini","doi":"10.34172/bi.2021.25","DOIUrl":"https://doi.org/10.34172/bi.2021.25","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> Hypoxia context is highly specific for tumors and represents a unique niche which is not found elsewhere in the body. <i>Clostridium novyi</i> is an obligate anaerobic bacterium. It has a potential to treat tumors. The aim of this study was to produce the <i>C. novyi</i> nontoxic spores and to investigate its oncolytic effect on breast cancer in mice model. <i><b>Methods:</b> </i> Primarily, the lethal toxin gene in <i>C. novy</i>i type B was removed. Colonies were isolated using PCR testing. To assure the removal of alpha-toxin, plasmid extraction and in vivo assay were conducted. Next, to treat breast cancer model in different sizes of tumors, a single dose of spores of <i>C. novyi</i> nontoxic was tested. <b><i>Results:</i></b> The results denoted that <i>C. novyi</i> nontoxic lost lethal toxin and a--ppeared to be safe. For smaller than 1000 mm<sup>3</sup> tumors, a single dose of <i>C. novyi</i> nontoxic was able to cure 100% of mice bearing breast tumors. Hence the mice remained free of tumor relapse. Tumors larger than 1000 mm<sup>3</sup> were not cured by a single dose- of <i>C. novyi</i> nontoxic treatment. <i><b>Conclusion:</b> </i> The experiment concluded that the <i>C. novyi</i> nontoxic might be a suitable and safe candidate, a novel therapeutic approach to encounter such hypoxic regions in the center of tumors. Research also showed that bacteriolytic therapy by <i>C. novyi</i> nontoxic could lead to regression in small tumor.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/68/38/bi-12-405.PMC9596882.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40476936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Inflammation is one of the most important mechanisms involved in cisplatin-induced acute kidney injury (AKI). Mesenchymal stromal/stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory abilities. Human endometrial stromal/stem cells (hEnSCs) exhibit similar properties to MSCs. These cells secrete immunoregulators, so we investigated the inflammatory aspect of hEnSCs in the treatment of cisplatin-induced AKI in Wistar rats. Methods: Each group consisted of 6 male Wistar rats. Groups were as follows: sham, model (5 mg/kg cisplatin, IP), and treatment (1 million hEnSCs, IV, 3 hours after cisplatin). Renal function, histopathology, proliferation rate, infiltration of CD3+ T cell, and expression of Il-10 and cystatin c (Cst3) were assessed on day 5. DiI-labeled cells were tracked in kidney and liver on days 4 and 14. Results: HEnSC transplantation improved cisplatin-induced injuries such as renal dysfunction and tissue damage. The highest levels of pathologic scores and hyaline cast formation were observed in the model group while hEnSCs transplantation resulted in their reduction (154.00 ± 14.95, 8.00 ± 1.41 vs. 119.40 ± 5.43, 2.50 ± 1.05). The percentage of Ki-67 positive cells in the treatment group increased while cisplatin decreased proliferation (39.91 ± 5.33 vs. 23.91 ± 3.57 in glomeruli and 39.07 ± 2.95 vs. 16.61 ± 3.25 in tubules). The expression of Cst3 and Il-10 was higher in the model and treatment groups, respectively. DiI-labeled cells were observed in the renal tubules and liver lobes on days 4 and 14. Conclusion: HEnSCs may ameliorate cisplatin-induced AKI through anti-inflammatory and immunomodulatory effects and/or through paracrine effects.
{"title":"Reduced inflammation following human endometrial stromal/stem cell injection into male Wistar rats with cisplatin-induced acute kidney injury.","authors":"Hadis Zeinali, Mahnaz Azarnia, Peyman Keyhanvar, Reza Moghadasali, Somayeh Ebrahimi-Barough, Majid Marandi-Kouchaki","doi":"10.34172/bi.2022.22132","DOIUrl":"https://doi.org/10.34172/bi.2022.22132","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> Inflammation is one of the most important mechanisms involved in cisplatin-induced acute kidney injury (AKI). Mesenchymal stromal/stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory abilities. Human endometrial stromal/stem cells (hEnSCs) exhibit similar properties to MSCs. These cells secrete immunoregulators, so we investigated the inflammatory aspect of hEnSCs in the treatment of cisplatin-induced AKI in Wistar rats. <i><b>Methods:</b> </i> Each group consisted of 6 male Wistar rats. Groups were as follows: sham, model (5 mg/kg cisplatin, IP), and treatment (1 million hEnSCs, IV, 3 hours after cisplatin). Renal function, histopathology, proliferation rate, infiltration of CD3<sup>+</sup> T cell, and expression of <i>Il-10</i> and cystatin c (<i>Cst3</i>) were assessed on day 5. DiI-labeled cells were tracked in kidney and liver on days 4 and 14. <i><b>Results:</b> </i> HEnSC transplantation improved cisplatin-induced injuries such as renal dysfunction and tissue damage. The highest levels of pathologic scores and hyaline cast formation were observed in the model group while hEnSCs transplantation resulted in their reduction (154.00 ± 14.95, 8.00 ± 1.41 vs. 119.40 ± 5.43, 2.50 ± 1.05). The percentage of Ki-67 positive cells in the treatment group increased while cisplatin decreased proliferation (39.91 ± 5.33 vs. 23.91 ± 3.57 in glomeruli and 39.07 ± 2.95 vs. 16.61 ± 3.25 in tubules). The expression of <i>Cst3</i> and <i>Il-10</i> was higher in the model and treatment groups, respectively. DiI-labeled cells were observed in the renal tubules and liver lobes on days 4 and 14. <i><b>Conclusion:</b> </i> HEnSCs may ameliorate cisplatin-induced AKI through anti-inflammatory and immunomodulatory effects and/or through paracrine effects.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/d0/bi-12-439.PMC9596877.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40465663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}