Bioimpacts最新文献

{"title":"Functionality of immune cells in COVID-19 infection: development of cell-based therapeutics.","authors":"Maryam Sayahinouri,&nbsp;Sahar Mashayekhi Firouz,&nbsp;Amin Ebrahimi Sadrabadi,&nbsp;Mina Masoudnia,&nbsp;Mahnaz Abdolahi,&nbsp;Fatemeh Jafarzadeh,&nbsp;Meshkat Nouripour,&nbsp;Sana Mirzazadeh,&nbsp;Nazanin Zangeneh,&nbsp;Arsalan Jalili,&nbsp;Nasser Aghdami","doi":"10.34172/bi.2023.23839","DOIUrl":"https://doi.org/10.34172/bi.2023.23839","url":null,"abstract":"<p><p><i><b>Introduction:</b></i> In late December 2019, a sudden severe respiratory illness of unknown origin was reported in China. In early January 2020, the cause of COVID-19 infection was announced a new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Examination of the SARS-CoV-2 genome sequence revealed a close resemblance to the previously reported SARS-CoV and coronavirus Middle East respiratory syndrome (MERS-CoV). However, initial testing of drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. One of the key strategies to fight the virus is to look at how the immune system works against the virus, which has led to a better understanding of the disease and the development of new therapies and vaccine designs. <i><b>Methods:</b></i> This review discussed the innate and acquired immune system responses and how immune cells function against the virus to shed light on the human body's defense strategies. <i><b>Results:</b></i> Although immune responses have been revealed critical to eradicating infections caused by coronaviruses, dysregulated immune responses can lead to immune pathologies thoroughly investigated. Also, the benefit of mesenchymal stem cells, NK cells, Treg cells, specific T cells, and platelet lysates have been submitted as promising solutions to prevent the effects of infection in patients with COVID-19. <i><b>Conclusion:</b></i> It has been concluded that none of the above has undoubtedly been approved for the treatment or prevention of COVID-19, but clinical trials are underway better to understand the efficacy and safety of these cellular therapies.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 2","pages":"159-179"},"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/6b/0e/bi-13-159.PMC10182441.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9485467","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}

{"title":"Mode of binding, kinetic and thermodynamic properties of a lipid-like drug (Fingolimod) interacting with Human Serum Albumin.","authors":"Samira Gholizadeh,&nbsp;Hossein Haghaei,&nbsp;Hosna Karami,&nbsp;Somaieh Soltani,&nbsp;Mostafa Zakariazadeh,&nbsp;Javad Shokri","doi":"10.34172/bi.2022.23383","DOIUrl":"https://doi.org/10.34172/bi.2022.23383","url":null,"abstract":"<p><p><i><b>Introduction:</b></i> Fingolimod is a drug that is used to treat multiple sclerosis (MS). It has pH-dependent solubility and low solubility when buffering agents are present. Multi-spectroscopic and molecular modeling methods were used to investigate the molecular mechanism of Fingolimod interaction with human serum albumin (HSA), and the resulting data were fitted to the appropriate models to investigate the molecular mechanism of interaction, binding constant, and thermodynamic properties. <i><b>Methods:</b></i> The interaction of Fingolimod with HSA was investigated in a NaCl aqueous solution (0.1 mM). The working solutions had a pH of 6.5. Data was collected using UV-vis, fluorescence quenching titrations, FTIR, and molecular modeling methods. <i><b>Results:</b></i> According to the results of the fluorescence quenching titrations, the quenching mechanism is static. The apparent binding constant value (K_A = 4.26×10³) showed that Fingolimod is a moderate HSA binder. The reduction of the K_A at higher temperatures could be a result of protein unfolding. Hydrogen bonding and van der Waals interactions are the main contributors to Fingolimod-HSA complex formation. FTIR and CD characterizations suggested a slight decrease in the α-helix and β-sheets of the secondary structure of HSA due to Fingolimod binding. Fingolimod binds to the binding site II, while a smaller tendency to the binding site I was observed as well. The results of the site marker competitive experiment and the thermodynamic studies agreed with the results of the molecular docking. <i><b>Conclusion:</b></i> The pharmacokinetic properties of fingolimod can be influenced by its HSA binding. In addition, considering its mild interaction, site II binding drugs are likely to compete. The methodology described here may be used to investigate the molecular mechanism of HSA interaction with lipid-like drugs with low aqueous solubility or pH-dependent solubility.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 2","pages":"109-121"},"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/db/fd/bi-13-109.PMC10182447.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9479085","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}

{"title":"Diagnosis of acute myocardial infarction: highlighting cardiac troponins as vital biomarkers.","authors":"Ali Pourali,&nbsp;Yadollah Omidi","doi":"10.34172/bi.2023.22023","DOIUrl":"https://doi.org/10.34172/bi.2023.22023","url":null,"abstract":"<p><p>The molecular marker, cardiac troponin (cTn) is a complex protein that is attached to tropomyosin on the actin filament. It is an essential biomolecule in terms of the calcium-mediated regulation of the contractile apparatus in myofibrils, the release of which is an indication of the dysfunction of cardiomyocytes and hence the initiation of ischemic phenomena in the heart tissue. Fast and accurate analysis of cTn may help the diagnosis and management of acute myocardial infarction (AMI), for which electrochemical biosensors and microfluidics devices can be of great benefit. This editorial aims to highlight the importance of cTn as vital biomarkers in AMI diagnosis.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 2","pages":"85-88"},"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/73/13/bi-13-85.PMC10182445.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9485463","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}

{"title":"Bone marrow mesenchymal stem cells improve cognitive impairments induced by methamphetamine in rats and reduce relapse.","authors":"Raheleh Rafaiee,&nbsp;Naghmeh Ahmadiankia,&nbsp;Seyed Abbas Mousavi,&nbsp;Behnaz Jafari,&nbsp;Hamid Kalalian Moghaddam","doi":"10.34172/bi.2022.23329","DOIUrl":"https://doi.org/10.34172/bi.2022.23329","url":null,"abstract":"<p><p><i><b>Introduction:</b></i> Chronic exposure to methamphetamine (Meth) results in permanent central nervous system damage and learning and memory dysfunction. This study aimed at investigating the therapeutic effects of bone marrow mesenchymal stem cells (BMMSCs) on cognitive impairments in Meth addicted rats and comparing intravenous (IV) delivery with intranasal (IN) delivery of BMMSCs. <i><b>Methods:</b></i> Adult Wistar rats were randomly divided into 6 groups; Control; Meth-addicted; IV-BMMSC (Meth administered and received IV BMMSCs); IN-BMMSC (Meth administered and received IN BMMSCs); IV-PBS (Meth administered and received IV Phosphate-buffered saline (PBS); IN-PBS (Meth administered and received IN PBS). BMMSCs were isolated, expanded in vitro, immunophenotyped, labeled, and administered to BMMSCs-treated groups (2 × 10⁶ cells). The therapeutic effect of BMMSCs was measured using Morris water maze and Shuttle Box. Moreover, relapse-reduction was evaluated by conditioning place preference after 2 weeks following BMMSCs administration. The expression of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) in rat hippocampus was assessed using immunohistochemistry method. <i><b>Results:</b></i> Administration of BMMSCs caused a significant improvement in the learning and memory functions of Meth-addicted rats and reduced the relapse (<i>P</i><0.01). In behavioral tests, comparison of IV and IN BMMSC-treated groups did not show any significant difference. Administration of BMMSCs improved the protein level of BDNF and GDNF in the hippocampus, as well as causing behavioral improvement (<i>P</i><0.001). <i><b>Conclusion:</b></i> BMMSC administration might be a helpful and feasible method to treat Meth-induced brain injuries in rats and to reduce relapse. BMMSCs were significantly higher in IV-treated group compared to the IN route. Moreover, the expression of BDNF and GDNF was higher in IN-treated rats compared with IV treated group.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 2","pages":"97-108"},"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/9a/7c/bi-13-97.PMC10182440.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9485468","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}

{"title":"Evaluation of osteogenic differentiation of human mesenchymal stem cells (hMSCs) on random and aligned polycaprolactone-polyaniline-gelatin scaffolds.","authors":"Ali KarbalaeiMahdi,&nbsp;Kaykhosro Moridi,&nbsp;Marzieh Ghollasi","doi":"10.34172/bi.2022.23713","DOIUrl":"https://doi.org/10.34172/bi.2022.23713","url":null,"abstract":"<p><p><i><b>Introduction:</b></i> Biocompatible and biodegradable scaffolds have gained tremendous attention because of their potential in tissue engineering. In this study, the aim was to reach a feasible setup from a ternary hybrid of polyaniline (PANI), gelatin (GEL), and polycaprolactone (PCL) to fabricate aligned and random nanofibrous scaffolds by electrospinning for tissue engineering purposes. <i><b>Methods:</b></i> Different setups of PANI, PCL, and GEL were electrospun. Then, the best aligned and random scaffolds were chosen. SEM imaging was done to observe nanoscaffolds before and after stem cell differentiation. Mechanical properties of the fibers were tested. Their hydrophilicity was measured using the sessile drop method. SNL Cells were then seeded onto the fiber, and MTT was performed to assess its toxicity. The cells were then differentiated. After osteogenic differentiation, alkaline phosphatase activity, calcium content assay, and alizarin red staining were done to check the validity of osteogenic differentiation. <i><b>Results:</b></i> The two chosen scaffolds had an average diameter of 300 ± 50 (random) and 200 ± 50 (aligned). MTT was performed and its results showed that the scaffolds were non-toxic to cells. After stem cell differentiation, alkaline phosphatase activity was performed, confirming differentiation on both types of scaffolds. Calcium content and alizarin red staining also confirmed stem cell differentiation. Morphological analysis showed no difference regarding differentiation on either type of scaffold. However, unlike on the random fibers, cells followed a specific direction and had a parallel-like growth pattern on aligned fibers. <i><b>Conclusion:</b></i> All in all, PCL-PANI-GEL fibers showed to be capable candidates for cell attachment and growth. Furthermore, they proved to be of excellent use in bone tissue differentiation.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 2","pages":"123-132"},"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/a4/44/bi-13-123.PMC10182442.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9490721","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}

{"title":"Synthesis and characterization of actively HER-2 Targeted Fe₃O₄@Au nanoparticles for molecular radiosensitization of breast cancer.","authors":"Behnaz Babaye Abdollahi,&nbsp;Marjan Ghorbani,&nbsp;Hamed Hamishehkar,&nbsp;Reza Malekzadeh,&nbsp;Alireza Farajollahi","doi":"10.34172/bi.2022.23682","DOIUrl":"https://doi.org/10.34172/bi.2022.23682","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> The present study was done to assess the effect of molecularly-targeted core/shell of iron oxide/gold nanoparticles (Fe₃O₄@AuNPs) on tumor radiosensitization of SKBr-3 breast cancer cells. <i><b>Methods:</b></i> Human epidermal growth factor receptor-2 (HER-2)-targeted Fe₃O₄@AuNPs were synthesized by conjugating trastuzumab (TZ, Herceptin) to PEGylated (PEG)-Fe₃O₄@AuNPs (41.5 nm). First, the Fe₃O₄@Au core-shell NPs were decorated with PEG-SH to synthesize PEG-Fe₃O₄@AuNPs. Then, the TZ was reacted to OPSS-PEG-SVA to conjugate with the PEG-Fe₃O₄@AuNPs. As a result, structure, size and morphology of the developed NPs were assessed using Fourier-transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM), and ultraviolet-visible spectroscopy. The SKBr-3 cells were treated with different concentrations of TZ, Fe₃O₄@Au_, and TZ-PEG-Fe₃O₄@AuNPs for irradiation at doses of 2, 4, and 8 Gy (from X-ray energy of 6 and 18 MV). Cytotoxicity was assessed by MTT assay, BrdU assay, and flow cytometry. <i><b>Results:</b> </i> Results showed that the targeted TZ-PEG-Fe₃O₄@AuNPs significantly improved cell uptake. The cytotoxic effects of all the studied groups were increased in a higher concentration, radiation dose and energy-dependent manner. A combination of TZ, Fe₃O₄@Au, and TZ-PEG-Fe₃O₄@AuNPs with radiation reduced cell viability by 1.35 (<i>P</i>=0.021), 1.95 (<i>P</i>=0.024), and 1.15 (<i>P</i>=0.013) in comparison with 8 Gy dose of 18 MV radiation alone, respectively. These amounts were obtained as 1.27, 1.58, and 1.10 for 8 Gy dose of 6 MV irradiation, respectively. <i><b>Conclusion:</b></i> Radiosensitization of breast cancer to mega-voltage radiation therapy with TZ-PEG-Fe₃O₄@AuNPs was successfully obtained through an optimized therapeutic approach for molecular targeting of HER-2.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 1","pages":"17-29"},"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/ad/7a/bi-13-17.PMC9923814.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10767204","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}

{"title":"Autophagy-induced mesenchymal stem cell-derived extracellular vesicles ameliorated renal fibrosis in an <i>in vitro</i> model.","authors":"Behnaz Ahrabi,&nbsp;Hojjat Allah Abbaszadeh,&nbsp;Abbas Piryaei,&nbsp;Faezeh Shekari,&nbsp;Navid Ahmady Roozbahany,&nbsp;Mahya Rouhollahi,&nbsp;Forough Azam Sayahpour,&nbsp;Mahnaz Ahrabi,&nbsp;Hadi Azimi,&nbsp;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":"13 5","pages":"359-372"},"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}

{"title":"Chemo-immune cell therapy by intratumoral injection of adoptive NK cells with capecitabine in gastric cancer xenograft model.","authors":"Zeinab Ghazvinian,&nbsp;Shahrokh Abdolahi,&nbsp;Mohammad Ahmadvand,&nbsp;Amir Hossein Emami,&nbsp;Samad Muhammadnejad,&nbsp;Hamid Asadzadeh Aghdaei,&nbsp;Jafar Ai,&nbsp;Mohammad Reza Zali,&nbsp;Iman Seyhoun,&nbsp;Javad Verdi,&nbsp;Kaveh Baghaei","doi":"10.34172/bi.2022.26386","DOIUrl":"https://doi.org/10.34172/bi.2022.26386","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Gastric cancer is one of the most commonly known malignancies and is the fifth cancer-related death globally. Whereas natural killer (NK) cells play a critical role in tumor elimination; therefore, adoptive NK cell therapy has become a promising approach in cancer cytotherapy. Hence, this study investigated the chemo-immune cell therapy in MKN-45 derived xenograft gastric cancer model.</p><p><strong>Methods: </strong>Three groups of animals have received the following treatments separately: activated NK cells, capecitabine, the combination of capecitabine and activated NK cells, and one was considered as the control group. Morphometric properties of tumor samples were evaluated at the end of the study. NK cells infiltration was evaluated by immunohistochemistry (IHC) of hCD56. Mitotic count and treatment response was assessed by hematoxylin and eosin (H&E) staining. The proliferation ratio to apoptosis was determined by IHC assessment of Ki67 and caspase 3.</p><p><strong>Results: </strong>The results indicated that the NK cell therapy could effectively decrease the mitotic count in pathology assessment, but the tumor was not completely eradicated. In combination with metronomic chemotherapy (MC) of capecitabine, NK cell therapy demonstrated a significant difference in tumor morphometric properties compared to the control group. The proliferation ratio to apoptosis was also in line with pathology data.</p><p><strong>Conclusion: </strong>Although NK cell therapy could effectively decrease the mitotic count <i>in vivo</i>, the obtained findings indicated lesser potency than MC despite <i>ex vivo</i> activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 5","pages":"383-392"},"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/2a/ed/bi-13-383.PMC10509737.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41136384","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}

{"title":"Changing the daily injection of glatiramer acetate to a monthly long acting product through designing polyester-based polymeric microspheres.","authors":"Fatima Molavi,&nbsp;Mohammad Barzegar-Jalali,&nbsp;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":"12 6","pages":"501-513"},"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}

{"title":"Enhanced control of bioactivity of tissue plasminogen activator (tPA) through domain-directed enzymatic oxidation of terminal galactose.","authors":"Wael A Mahdi,&nbsp;Mohammad S Absar,&nbsp;Suna Choi,&nbsp;Victor C Yang,&nbsp;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":"12 6","pages":"479-486"},"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}