Advanced pharmaceutical bulletin最新文献

{"title":"Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19.","authors":"Elnaz Shaseb,&nbsp;Saba Ghaffary,&nbsp;Alireza Garjani,&nbsp;Elnaz Zoghi,&nbsp;Nasrin Maleki Dizaji,&nbsp;Somaieh Soltani,&nbsp;Parvin Sarbakhsh,&nbsp;Mohammad Hossein Somi,&nbsp;Parya Valizadeh,&nbsp;Ali Taghizadieh,&nbsp;Masood Faghihdinevari,&nbsp;Mojtaba Varshochi,&nbsp;Behrooz Naghily,&nbsp;Zhinous Bayatmakoo,&nbsp;Parviz Saleh,&nbsp;Sepehr Taghizadeh,&nbsp;Mehdi Haghdoost,&nbsp;Hamid Owaysi,&nbsp;Fatemeh Ravanbakhsh Ghavghani,&nbsp;Mohammad Kazem Tarzamni,&nbsp;Rojin Moradi,&nbsp;Fateme Javan Ali Azar,&nbsp;Saeid Shabestari Khiabani,&nbsp;Ardavan Ghazanchaei,&nbsp;Sana Hamedani,&nbsp;Shahabeddin Hatefi","doi":"10.34172/apb.2023.066","DOIUrl":"https://doi.org/10.34172/apb.2023.066","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19.</p><p><strong>Methods: </strong>This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality.</p><p><strong>Results: </strong>Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (<i>P</i>=0.014) and 4.9% vs. 23.9% (<i>P</i>≤0.001), respectively). Admission time characteristics were the same for both groups except for diabetes and hyperlipidemia, which were significantly different between the two groups. Observations of naproxen consumption on endpoints, duration of hospitalization, and the levels of spO₂ did not show any significant differences between the intervention and the control group. The adjusted OR for intubation in the intervention group versus the control group was 0.21 [95% CI, 0.04-0.99 (<i>P</i>=0.047)].</p><p><strong>Conclusion: </strong>In this trial, metformin consumption had no effect on mortality and ICU admission rates in non-diabetic patients. However, metformin improved COVID-19 complications in diabetic patients who had been receiving metformin prior to COVID-19 infection, and it significantly lowered the intubation rates.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 3","pages":"621-626"},"PeriodicalIF":3.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of a Self-microemulsifying Drug Delivery System for Oral Administration of the Lipophilic Drug, Resveratrol: Enhanced Intestinal Permeability in Rat.","authors":"Shahla Mirzaeei,&nbsp;Negar Tahmasebi,&nbsp;Ziba Islambulchilar","doi":"10.34172/apb.2023.054","DOIUrl":"https://doi.org/10.34172/apb.2023.054","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to formulate Resveratrol, a practically water-insoluble antioxidant in a self-microemulsifying drug delivery system (SMEDDS) to improve the solubility, release rate, and intestinal permeability of the drug.</p><p><strong>Methods: </strong>The suitable oil, surfactant, and co-surfactant were chosen according to the drug solubility study. Utilizing the design of experiment (DoE) method, the pseudo-ternary phase diagram was plotted based on the droplet size. <i>In vitro</i> dissolution study and the single-pass intestinal perfusion were performed for the investigation of <i>in vitro</i> and <i>in-situ</i> permeability for drugs formulated as SMEDDS in rat intestine using High-Performance Liquid Chromatography.</p><p><strong>Results: </strong>Castor oil, Cremophor^® RH60, and PEG 1500 were selected as oil, surfactant, and co-surfactant. According to the pseudo-ternary phase diagram, nine formulations developed microemulsions with sizes ranging between 145-967 nm. Formulations passed the centrifuge and freeze-thaw stability tests. The optimum formulation possessed an almost 2.5-fold higher cumulative percentage of <i>in vitro</i> released resveratrol, in comparison to resveratrol aqueous suspension within 120 minutes. The results of the <i>in-situ</i> permeability study suggested a 2.6-fold higher intestinal permeability for optimum formulation than that of the resveratrol suspension.</p><p><strong>Conclusion: </strong>SMEDDS can be considered suitable for the oral delivery of resveratrol according to the observed increased intestinal permeability, which could consequently enhance the bioavailability and therapeutic efficacy of the drug.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 3","pages":"521-531"},"PeriodicalIF":3.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10121085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tau Protein Biosensors in the Diagnosis of Neurodegenerative Diseases.","authors":"Jafar Sadeghzadeh,&nbsp;Parviz Shahabi,&nbsp;Mehdi Farhoudi,&nbsp;Abbas Ebrahimi-Kalan,&nbsp;Ahmad Mobed,&nbsp;Kourosh Shahpasand","doi":"10.34172/apb.2023.061","DOIUrl":"https://doi.org/10.34172/apb.2023.061","url":null,"abstract":"<p><p>Tau protein plays a crucial role in diagnosing neurodegenerative diseases. However, performing an assay to detect tau protein on a nanoscale is a great challenge for early diagnosis of diseases. Enzyme-linked immunosorbent assay (ELISA), western-blotting, and molecular-based methods, e.g., PCR and real-time PCR, are the most widely used methods for detecting tau protein. These methods are subject to certain limitations: the need for advanced equipment, low sensitivity, and specificity, to name a few. With the above said, it is necessary to discover advanced and novel methods for monitoring tau protein. Counted among remarkable approaches adopted by researchers, biosensors can largely eliminate the difficulties and limitations associated with conventional methods. The main objective of the present study is to review the latest biosensors developed to detect the tau protein. Furthermore, the problems and limitations of conventional diagnosis methods were discussed in detail.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 3","pages":"502-511"},"PeriodicalIF":3.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Treatment of Dendrosomal-Curcumin and Daunorubicin Synergistically Inhibit Cell Proliferation, Migration and Induce Apoptosis in A549 Lung Cancer Cells.","authors":"Seyed Sadegh Eslami,&nbsp;Davod Jafari,&nbsp;Abbas Ghotaslou,&nbsp;Moein Amoupour,&nbsp;Amir Asri Kojabad,&nbsp;Rasool Jafari,&nbsp;Navid Mousazadeh,&nbsp;Parastoo Tarighi,&nbsp;Majid Sadeghizadeh","doi":"10.34172/apb.2023.050","DOIUrl":"https://doi.org/10.34172/apb.2023.050","url":null,"abstract":"<p><strong>Purpose: </strong>Chemotherapy drugs used to treat lung cancer are associated with drug resistance and severe side effects. There have been rising demands for new therapeutic candidates and novel approaches, including combination therapy. Here, we aimed to investigate the combinatorial effect of a dendrosomal formulation of curcumin (DNC) and daunorubicin (DNR) on the A549 lung cancer cell line.</p><p><strong>Methods: </strong>We performed cytotoxicity, apoptosis, cell migration, colony-formation capacity, and gene expression analysis to interpret the mechanism of action for a combination of DNC and DNR on A549 cells.</p><p><strong>Results: </strong>Our results revealed that the combination of DNC and DNR could synergistically inhibit the A549 cells' growth. This synergistic cytotoxicity was further approved by flow cytometry, migration assessment, colony-forming capacity and gene expression analysis. DNR combination with DNC resulted in increased apoptosis to necrosis ratio compared to DNR alone. In addition, the migration and colony-forming capacity were at the minimal range when DNC was combined with DNR. Combined treatment decreased the expression level of <i>MDR-1, hTERT</i> and <i>Bcl-2</i> genes significantly. In addition, the ratio of <i>Bax/Bcl2</i> gene expression significantly increased. Our analysis by free curcumin, dendrosomes and DNC also showed that dendrosomes do not have any significant cytotoxic effect on the A549 cells, suggesting that this carrier has a high potential for enhancing the curcumin's biological effects.</p><p><strong>Conclusion: </strong>Our observations suggest that the DNC formulation of curcumin synergistically enhances the antineoplastic effect of DNR on the A549 cell line through the modulation of apoptosis/necrosis ratio, as well as <i>Bax/Bcl2</i> ratio, <i>MDR-1</i> and <i>hTERT</i> gene expression.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 3","pages":"539-550"},"PeriodicalIF":3.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Anti-cancer Potency Using a Combination of Oleanolic Acid and Maslinic Acid to Control Treatment Resistance in Breast Cancer.","authors":"Cigir Biray Avcı,&nbsp;Fatma Sogutlu,&nbsp;Neslihan Pinar Ozates,&nbsp;Behrouz Shademan,&nbsp;Cumhur Gunduz","doi":"10.34172/apb.2023.057","DOIUrl":"https://doi.org/10.34172/apb.2023.057","url":null,"abstract":"<p><strong>Purpose: </strong>The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/ mTOR) pathway is a complex intracellular metabolic pathway that leads to cell growth and tumor proliferation and plays a key role in drug resistance in breast cancer. Therefore, the anti-cancer effects of oleanolic acid (OA), maslinic acid (MA), and their combination were investigated to improve the performance of the treatment strategy.</p><p><strong>Methods: </strong>We investigated the effect of OA and MA on cell viability using the WST-1 method. The synergistic effect of the combination was analyzed by isobologram analysis. In addition, the effects of the two compounds, individually and in combination, on apoptosis, autophagy, and the cell cycle were investigated in MCF7 cells. In addition, changes in the expression of PI3K/AKT/mTOR genes involved in apoptosis, cell cycle and metabolism were determined by quantitative RT-PCR.</p><p><strong>Results: </strong>MA, OA, and a combination of both caused G0/G1 arrest. Apoptosis also increased in all treated groups. The autophagosomal LC3-II formation was induced 1.74-fold in the MA-treated group and 3.25-fold in the MA-OA-treated group. The combination treatment resulted in increased expression of genes such as GSK3B, PTEN, CDKN1B and FOXO3 and decreased expression of IGF1, PRKCB and AKT3 genes.</p><p><strong>Conclusion: </strong>The results showed that the combination of these two substances showed the highest synergistic effect at the lowest dose and using MA-OA caused cancer cells to undergo apoptosis. The use of combination drugs may reduce the resistance of cancer cells to treatment.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 3","pages":"611-620"},"PeriodicalIF":3.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Refined Edible Oils on Neurodegenerative Disorders.","authors":"Fataneh Hashempour-Baltork,&nbsp;Parastou Farshi,&nbsp;Adel Mirza Alizadeh,&nbsp;Sevda Eskandarzadeh,&nbsp;Solmaz Abedinzadeh,&nbsp;Sodeif Azadmard-Damirchi,&nbsp;Mohammadali Torbati","doi":"10.34172/apb.2023.060","DOIUrl":"https://doi.org/10.34172/apb.2023.060","url":null,"abstract":"<p><p>Neurodegenerative diseases are comprise a prominent class of neurological diseases. Generally, neurodegenerative diseases cannot be cured, and the available treatments can only regulate the symptoms or delay the disease progression. Among the several factors which could clarify the possible pathogenesis of neurodegenerative diseases, next to aging as the main risk, the dietary related diseases are the most important. Vegetable oils, which are composed of triacyclglycerols as the main components and several other components in a trace amount, are the main part of our diet. This review aims to study the effect of refined or unrefined vegetable oil consumption as a preventive or aiding strategy to slow or halt the progression of neurodegenerative diseases. In the refining process, owing to the chemical materials or severe temperatures of the refining process, removal of the desirable minor components is sometimes unavoidable and thus a worrisome issue affecting physical and neurological health.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 3","pages":"461-468"},"PeriodicalIF":3.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10121089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-Specific Growth Factor (TSGF): A Futuristic Tumor Biomarker in Early Diagnosis of Cancer.","authors":"Bhagyalakshmi Nair,&nbsp;Anisha Kuriakose,&nbsp;Bilha Baby,&nbsp;Lekshmi R Nath","doi":"10.34172/apb.2023.051","DOIUrl":"https://doi.org/10.34172/apb.2023.051","url":null,"abstract":"<p><p>Despite the significant improvement in the treatment modalities, cancer is one of the fastest-growing chronic disease conditions all over the world. Genetic and Epigenetic alterations in the normal physiology of the cell are the key factor for tumor development. These changes can trigger the production of abnormal protein expressions through stimulation of different signaling pathways and can deeply affect normal cell growth and proliferation. Any altered protein expression, genetic variation, micro-RNA or post-translational protein modifications that indicate tumorigenesis can act as an early signal termed as biomarker. Cancer, being a multistep process with accumulating genetic and epigenetic alterations, could be detected early with suitable biomarkers. There are several proteins such as AFP, CA-125, PSA, troponin, CEA, osteopontin, CA 19-9 that act as biomarkers which help in early detection, prognosis, and monitoring of disease progression, a hunt for newer biomarkers with higher specificity and sensitivity is still ongoing. Tumor-specific growth factor (TSGF) is one such budding and prevailing tumor biomarker used for the early-stage detection of several types of carcinomas. TSGF is a gene that helps in tumor angiogenesis and gets released during the preliminary stages from cancer cells that ensure the vascular proliferation of the same. In this review, the clinical investigations of TSGF in different kinds of malignancy is discussed in detail and suggests the possibility of using TSGF as a biomarker in early diagnosis of cancer.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 3","pages":"483-488"},"PeriodicalIF":3.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cooperative Treatment of Gastric Cancer Using B7-H7 siRNA and Docetaxel; How Could They Modify Their Effectiveness?","authors":"Nadia Bolandi,&nbsp;Mohammad Hassan Khadem Ansari,&nbsp;Yousef Rasmi,&nbsp;Behzad Baradaran","doi":"10.34172/apb.2023.055","DOIUrl":"https://doi.org/10.34172/apb.2023.055","url":null,"abstract":"<p><strong>Purpose: </strong>Despite the high prevalence of gastric cancer (GC), drug resistance is a major problem for effective chemotherapy. B7-H7 is a novel member of the B7 superfamily and is expressed in most common cancers. However, the role of B7-H7 on the aggressiveness of GC and chemosensitivity has remained unknown. Therefore, this study was designed to assess the effect of B7-H7 suppression using small interference RNA (siRNA) in combination with docetaxel on GC cells.</p><p><strong>Methods: </strong>MTT test was applied to determine the IC50 of docetaxel and the combined effect of B7-H7 siRNA and docetaxel on the viability of the MKN-45 cells. To determine B7-H7, BCL-2, BAX, and caspase-3-8-9 genes expression, qRT-PCR was performed. Furthermore, flow cytometry was applied to evaluate apoptosis and the cell cycle status. Finally, to evaluate the effect of this combination therapy on migratory capacity and colony-forming ability, wound healing assay and colony formation test were employed, respectively.</p><p><strong>Results: </strong>B7-H7 suppression increased the chemo-sensitivity of MKN-45 cells to docetaxel. The expression of B7-H7 mRNA was reduced after using B7-H7 siRNA and docetaxel in MKN-45 GC cells. Also, B7-H7 suppression alongside docetaxel reduced cell migration and colony formation rate, arrested the cell cycle at the G2-M phase, and induced apoptosis by modulating the expression of apoptotic target genes.</p><p><strong>Conclusion: </strong>B7-H7 plays a significant role in the chemo-sensitivity and pathogenesis of GC. Therefore, B7-H7 suppression, in combination with docetaxel, may be a promising therapeutic approach in treating GC.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 3","pages":"573-582"},"PeriodicalIF":3.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In Vitro</i> Efficacy of Curcumin-Loaded Amine-Functionalized Mesoporous Silica Nanoparticles against MCF-7 Breast Cancer Cells.","authors":"Zahra Mohebian,&nbsp;Mirzaagha Babazadeh,&nbsp;Nosratollah Zarghami","doi":"10.34172/apb.2023.035","DOIUrl":"https://doi.org/10.34172/apb.2023.035","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Mesoporous silica nanoparticles (MSNs) have drawn substantial interest as drug nanocarriers for breast cancer therapy. Nevertheless, because of the hydrophilic surfaces, the loading of well-known hydrophobic polyphenol anticancer agent curcumin (Curc) into MSNs is usually very low. <b><i>Methods:</i></b> For this purpose, Curc molecules were loaded into amine-functionalized MSNs (MSNs-NH₂ -Curc) and characterized using thermal gravimetric analysis (TGA), Fourier-transform infrared (FTIR), field emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), Brunauer-Emmett-Teller (BET). MTT assay and confocal microscopy, respectively, were used to determine the cytotoxicity and cellular uptake of the MSNs-NH₂ - Curc in the MCF-7 breast cancer cells. Besides, the expression levels of apoptotic genes were evaluated via quantitative polymerase chain reaction (qPCR) and western blot. <b><i>Results:</i></b> It was revealed that MSNs-NH₂ possessed high values of drug loading efficiency and exhibited slow and sustained drug release compared to bare MSNs. According to the MTT findings, while the MSNs-NH₂ -Curc were nontoxic to the human non-tumorigenic MCF-10A cells at low concentrations, it could considerably decrease the viability of MCF-7 breast cancer cells compared to the free Curc in all concentrations after 24, 48 and 72 hours exposure times. A cellular uptake study using confocal fluorescence microscopy confirmed the higher cytotoxicity of MSNs-NH₂ -Curc in MCF-7 cells. Further, it was found that the MSNs-NH₂ -Curc could drastically affect the mRNA and protein levels of Bax, Bcl-2, caspase 3, caspase 9, and hTERT relative to the free Curc treatment. <b><i>Conclusion:</i></b> Taken together, these preliminary results suggest the amine-functionalized MSNs-based drug delivery platform as a promising alternative approach for Curc loading and safe breast cancer treatment.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"317-327"},"PeriodicalIF":3.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9764057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoring the Angiogenic Capacity of the Human Diabetic Adipose-derived mesenchymal stem cells Primed with Deferoxamine as a Hypoxia Mimetic Agent: Role of HIF-1α.","authors":"Raziye Tajali,&nbsp;Akram Eidi,&nbsp;Hosein Ahmadi Tafti,&nbsp;Abdolreza Pazouki,&nbsp;Ali Mohammad Sharifi","doi":"10.34172/apb.2023.021","DOIUrl":"https://doi.org/10.34172/apb.2023.021","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Insufficient angiogenesis is associated with serious diabetic complications. Recently, adipose-derived mesenchymal stem cells (ADScs) are known to be a promising tool causing therapeutic neovascularization. However, the overall therapeutic efficacy of these cells is impaired by diabetes. This study aims to investigate whether in vitro pharmacological priming with deferoxamine, a hypoxia mimetic agent, could restore the angiogenic potential of diabetic human ADSCs. <b><i>Methods:</i></b> Diabetic human ADSCs were treated with deferoxamine and compared to normal and nontreated diabetic ADSCs for the expression of hypoxia inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and stromal cell-derived factor-1α (SDF-1α), at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activities of matrix metalloproteinases (MMPs)-2 and -9 were measured using a gelatin zymography assay. Angiogenic potentials of conditioned media derived from normal, Deferoxamine treated, and non-treated ADSCs were determined by in vitro scratch assay and also three-dimensional tube formation assay. <b><i>Results:</i></b> It is demonstrated that deferoxamine (150 and 300 μM) stabilized HIF-1α in primed diabetic ADSCs. At the concentrations used, deferoxamine did not show any cytotoxic effects. In deferoxamine treated ADSCs, expression of VEGF, SDF-1α, FGF-2 and the activity of MMP-2 and MMP-9 were significantly increased compared to nontreated ADSCs. Moreover, deferoxamine increased the paracrine effects of diabetic ADSCs in promoting endothelial cell migration and tube formation. <b><i>Conclusion:</i></b> Deferoxamine might be an effective drug for pharmacological priming of diabetic ADSCs to enhance the expression of proangiogenic factors noted via HIF-1α accumulation. In addition, impaired angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by deferoxamine.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"350-360"},"PeriodicalIF":3.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9764062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}