{"title":"Menadione Sodium Bisulfite Loaded Rhamnolipid Based Solid Lipid Nanoparticle as Skin Lightener Formulation: A Green Production Beside In Vitro/In Vivo Safety Index Evaluation.","authors":"Fatemeh Asadpour Panbehchouleh, Hossein Amani, Majid Saeedi","doi":"10.34172/apb.2024.047","DOIUrl":"10.34172/apb.2024.047","url":null,"abstract":"<p><strong>Purpose: </strong>In the current investigation, an ultrasonic approach was performed to produce menadione sodium bisulfite-loaded solid lipid nanoparticles (MSB-SLNs) with rhamnolipid as bio-surfactant, which aimed to increase the dermal delivery and anti-pigmentation effect.</p><p><strong>Methods: </strong>To achieve optimum delivery for MSB, the impact of the ratio of two surfactants (rhamnolipid: Tween) on nanoparticle attributes and the respective functions were evaluated. In vitro diffusion process, in vitro cytotoxicity assay, determination of melanin content of melanoma cells, L-DOPA auto-oxidation inhibitory test, and skin irritation studies carried out to investigate the suitability of MSB formulation in dermal application.</p><p><strong>Results: </strong>The optimized nanoparticles showed an average particle size, zeta potential, polydispersity index (PDI), and drug entrapment efficiency of 117.26±1.12 nm, -6.28±0.33 mV, 0.262±0.002, 83.34±0.75% respectively in hydrophilic-lipophilic balance (HLB) of 12. The in vitro diffusion process demonstrated that MSB-SLN gel had a prolonged release pattern. The levels of MSB in the cutaneous layers (52.192±2.730% or 961.59±50.313 μg/cm<sup>2</sup> ) and the receiver compartment (23.721±1.803 % or 437.049± 33.236 μg/cm<sup>2</sup> ) for the MSB-SLN gel was higher than MSB simple and showed no cutaneous irritancy and toxicity in rats. MSB-SLN inhibited melanin formation and was remarkably higher than free MSB. MSB-SLN inhibited L-3,4- dihydroxyphenylalanine (L-DOPA) auto-oxidation to a greater extent (95.14±1.46%) than MSB solution (72.28±0.83%).</p><p><strong>Conclusion: </strong>This study's observations revealed that the produced MSB-SLN might be used as a potential nano-vehicle for MSB dermal administration, thereby opening up innovative options for the management of hyper-melanogenesis problems.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566519","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}
Mahrokh Dastmalchi, Maryam Hamzeh-Mivehroud, Hassan Rezazadeh, Mohammad M Farajollahi, Siavoush Dastmalchi
{"title":"Investigating Functional and Folding Stability of an Engineered <i>E. coli</i> L-asparaginase Harboring Y176F/S241C Mutations.","authors":"Mahrokh Dastmalchi, Maryam Hamzeh-Mivehroud, Hassan Rezazadeh, Mohammad M Farajollahi, Siavoush Dastmalchi","doi":"10.34172/apb.2024.048","DOIUrl":"10.34172/apb.2024.048","url":null,"abstract":"<p><strong>Purpose: </strong>L-asparaginase has been widely recognized as a critical component in the treatment of various types of lymphoproliferative disorders, since its introduction in 1960s. However, its use in some cases leads to allergic reactions rendering the continuation of treatment unfeasible. Thus, the development of L-asparaginase from alternative sources or the production of engineered enzymes have always been considered. This study aimed to produce and evaluate a novel enzyme designed based on the sequence of L-asparaginase from <i>Escherichia coli</i> bacteria with Y176F/S241C mutations.</p><p><strong>Methods: </strong>The Y176F/S241C mutant L-asparaginase was successfully expressed as the GST-fusion protein in <i>E. coli</i>, and then was subjected to affinity and size exclusion chromatography. The activity of the purified enzyme was determined based on the released ammonia as the result of substrate hydrolysis using Nessler's reagent. Chemical denaturation experiment in the presence of increasing concentration of guanidinium chloride was applied to determine the folding stability of the purified enzyme.</p><p><strong>Results: </strong>The mutant enzyme was purified with an efficiency of 77-fold but at a low recovery of 0.7%. The determined kinetic parameters Km, Vmax, kcat, specific activity and catalytic efficiency were 13.96 (mM), 2.218 (mM/min), 273.9 (min<sup>-1</sup>), 237.8 (IU/mg) and 19.62 (mM<sup>-1</sup> min<sup>-1</sup>), respectively. Moreover, unfolding free energy determined by guanidinium chloride induced denaturation for mutated and commercial L-asparaginase enzymes were 8421 J/mol and 5274 J/mol, respectively.</p><p><strong>Conclusion: </strong>The mutant enzyme showed improved stability over the wild-type. Although the expression level and recovery were low, the mutant L-asparaginase demonstrated promising activity and stability, with potential clinical and industrial applications.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566327","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}
Fereshteh Asgharzadeh, Maryam Moradi Binabaj, Sahar Fanoudi, William C Cho, Yu-Jeong Yang, Maryam Azarian, Mehdi Shafiee Ardestani, Nasim Nasiri, Marzieh Ramezani Farani, Yun Suk Huh
{"title":"Nanomedicine Strategies Utilizing Lipid-Based Nanoparticles for Liver Cancer Therapy: Exploring Signaling Pathways and Therapeutic Modalities.","authors":"Fereshteh Asgharzadeh, Maryam Moradi Binabaj, Sahar Fanoudi, William C Cho, Yu-Jeong Yang, Maryam Azarian, Mehdi Shafiee Ardestani, Nasim Nasiri, Marzieh Ramezani Farani, Yun Suk Huh","doi":"10.34172/apb.2024.061","DOIUrl":"10.34172/apb.2024.061","url":null,"abstract":"<p><p>Liver cancer, specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related deaths, following pancreatic cancer. The 5-year overall survival rate for HCC remains relatively low. Currently, there are multiple treatment options available for HCC, including systemic drugs, minimally invasive local therapies such as radiofrequency ablation, transarterial chemoembolization (TACE), and arterial radioembolization (TARE), as well as surgical interventions like liver resection or transplantation. However, the effectiveness of drug delivery to the cancerous liver is hindered by pathophysiological changes in the organ. In order to address this challenge, lipid-based nanoparticles (LNPs) have emerged as promising platforms for delivering a diverse range of therapeutic drugs. LNPs offer various structural configurations that enhance their physical stability and enable them to accommodate different types of cargo with varying mechanical properties and degrees of hydrophobicity. In this article, we provide a comprehensive review of the current applications of LNPs in the development of anti-HCC therapies. By examining the existing research, we aim to shed light on the potential future directions and advancements in this field.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566598","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}
Mohammad Shahpouri, Mohammad Amin Adili-Aghdam, Hossein Mahmudi, Saeedeh Ghiasvand, Hamed Dadashi, Aysan Salemi, Sajjad Alimohammadvand, Leila Roshangar, Abolfazl Barzegari, Mehdi Jaymand, Rana Jahanban-Esfahlan
{"title":"Dual-stage Acting Dendrimeric Nanoparticle for Deepened Chemotherapeutic Drug Delivery to Tumor Cells.","authors":"Mohammad Shahpouri, Mohammad Amin Adili-Aghdam, Hossein Mahmudi, Saeedeh Ghiasvand, Hamed Dadashi, Aysan Salemi, Sajjad Alimohammadvand, Leila Roshangar, Abolfazl Barzegari, Mehdi Jaymand, Rana Jahanban-Esfahlan","doi":"10.34172/apb.2024.054","DOIUrl":"10.34172/apb.2024.054","url":null,"abstract":"<p><strong>Purpose: </strong>We report on the design of hypoxia-induced dual-stage acting dendrimeric nanoparticles (NPs) for selective delivery of two chemotherapeutic model drugs doxorubicin (DOX) and tirapazamin (TPZ) for deepened drug delivery into hypoxic tumors <i>in vitro</i>.</p><p><strong>Methods: </strong>PAMAM G5 dendrimers were crosslinked with a hypoxic azo linker, attached to a mPEG to form a detachable corona on the dendrimer surface (PAP NPs). NPs were characterized by Zeta sizer, transmission electron microscope (TEM), Fourier transforms infrared (FTIR) and drug release kinetics. The anti-cancer performance of PAPs was evaluated by numerous tests in 2D and 3D cultured MDA-MB-231 breast cancer cells.</p><p><strong>Results: </strong>MTT assay showed a significant difference between PAP and PAMAMG5 in terms of biocompatibility, and the effect of PAP@DOX was significantly greater than free DOX in hypoxic conditions. The results of DAPI and Annexin V-FITC/PI cell staining also confirmed uniform drug penetration as validated by induction of 90% cell apoptosis in spheroids and a high level of PAP@DOX-induced ROS generation under hypoxia conditions. Mechanistically, PAP@DOX significantly reduced the expression of mTOR, and Notch1, while the expression of Bax and Caspase3 was considerably unregulated, compared to the controls. Importantly, hypoxia-responsive disintegration and hypoxia-induced activation of HAP drug were synergized to promote deep and homogenous HAP distribution in whole microtumor regions to efficiently eliminate residual tumor cells.</p><p><strong>Conclusion: </strong>Our results indicate the safety and high therapeutic potential of PAP system for targeted drug delivery of chemotherapeutics in particular HAPs which show maximum anti-cancer activity against hypoxic solid tumors.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566295","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}
Ramakrishna Gummadi, Nagasen Dasari, D Sathis Kumar, Sai Kiran S S Pindiprolu
{"title":"Evaluating the Accuracy of Large Language Model (ChatGPT) in Providing Information on Metastatic Breast Cancer.","authors":"Ramakrishna Gummadi, Nagasen Dasari, D Sathis Kumar, Sai Kiran S S Pindiprolu","doi":"10.34172/apb.2024.060","DOIUrl":"10.34172/apb.2024.060","url":null,"abstract":"<p><strong>Purpose: </strong>Artificial intelligence (AI), particularly large language models like ChatGPT developed by OpenAI, has demonstrated potential in various domains, including medicine. While ChatGPT has shown the capability to pass rigorous exams like the United States Medical Licensing Examination (USMLE) Step 1, its proficiency in addressing breast cancer-related inquiries-a complex and prevalent disease-remains underexplored. This study aims to assess the accuracy and comprehensiveness of ChatGPT's responses to common breast cancer questions, addressing a critical gap in the literature and evaluating its potential in enhancing patient education and support in breast cancer management.</p><p><strong>Methods: </strong>A curated list of 100 frequently asked breast cancer questions was compiled from Cancer.net, the National Breast Cancer Foundation, and clinical practice. These questions were input into ChatGPT, and the responses were evaluated for accuracy by two primary experts using a four-point scale. Discrepancies in scoring were resolved through additional expert review.</p><p><strong>Results: </strong>Of the 100 responses, 5 were entirely inaccurate, 22 partially accurate, 42 accurate but lacking comprehensiveness, and 31 highly accurate. The majority of the responses were found to be at least partially accurate, demonstrating ChatGPT's potential in providing reliable information on breast cancer.</p><p><strong>Conclusion: </strong>ChatGPT shows promise as a supplementary tool for patient education on breast cancer. While generally accurate, the presence of inaccuracies underscores the need for professional oversight. The study advocates for integrating AI tools like ChatGPT in healthcare settings to support patient-provider interactions and health education, emphasizing the importance of regular updates to reflect the latest research and clinical guidelines.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566303","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}
Mehdi Dadkhah, Mihály Hegedűs, Prema Nedungadi, Raghu Raman, Lóránt Dénes Dávid
{"title":"Unveiling the Hidden Menace: A Topic Modeling Analysis of Hijacked Medical Journals.","authors":"Mehdi Dadkhah, Mihály Hegedűs, Prema Nedungadi, Raghu Raman, Lóránt Dénes Dávid","doi":"10.34172/apb.2024.029","DOIUrl":"10.34172/apb.2024.029","url":null,"abstract":"<p><strong>Purpose: </strong>Nowadays, many studies discuss scholarly publishing and associated challenges, but the problem of hijacked journals has been neglected. Hijacked journals are cloned websites that mimic original journals but are managed by cybercriminals. The present study uses a topic modeling approach to analyze published papers in hijacked versions of medical journals.</p><p><strong>Methods: </strong>A total of 3384 papers were downloaded from 21 hijacked journals in the medical domain and analyzed by topic modeling algorithm.</p><p><strong>Results: </strong>Results indicate that hijacked versions of medical journals are published in most fields of the medical domain and typically respect the primary domain of the original journal.</p><p><strong>Conclusion: </strong>The academic world is faced with the third-generation of hijacked journals, and their detection may be more complex than common ones. The usage of artificial intelligence (AI) can be a powerful tool to deal with the phenomenon.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103249","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}
Joan Onyebuchi Erebor, Elizabeth Oladoyin Agboluaje, Ava M Perkins, Megha Krishnakumar, N. Ngwuluka
{"title":"Targeted Hybrid Nanocarriers as Co-delivery Systems for Enhanced Cancer Therapy","authors":"Joan Onyebuchi Erebor, Elizabeth Oladoyin Agboluaje, Ava M Perkins, Megha Krishnakumar, N. Ngwuluka","doi":"10.34172/apb.2024.046","DOIUrl":"https://doi.org/10.34172/apb.2024.046","url":null,"abstract":"Hybrid nanocarriers have realized a growing interest in drug delivery research because of the potential of being able to treat, manage or cure diseases that previously had limited therapy or cure. Cancer is currently considered the second leading cause of death globally. This makes cancer therapy a major focus in terms of the need for efficacious and safe drug formulations that can be used to reduce the rate of morbidity and mortality globally. The major challenge encountered over the years with cancer chemotherapy is the non-selectivity of anticancer drugs, leading to severe adverse effects in patients. Multidrug resistance has also resulted in treatment failure in cancer chemotherapy over the years. Hybrid nanocarriers can be targeted to the site and offer co-delivery of two or more chemotherapeutics, thus leading to synergistic or additive results. This makes hybrid nanocarriers an extremely attractive type of drug delivery system for cancer therapy. Hybrid nanocarrier systems are also attracting attention as possible non-viral gene vectors that could have a higher level of transfection, and be efficacious, with the added advantage of being safer than viral vectors in clinical settings. An extensive review of various aspects of hybrid nanocarriers was discussed in this paper. It is envisaged that in the future, metastatic cancers, multi-drug resistant cancers, and low prognosis cancers like pancreatic cancers, will have a lasting solution via hybrid nanocarrier formulations with targeted co-delivery of therapeutics.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140974974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saeid Amiri Zadeh Fard, Haniyeh Abuei, Abbas Behzad Behbahani, Gholamreza Rafiei dehbidi, F. Zare, Maryam Nejabat, Alireza Safarpour, Ali Farhadi
{"title":"Unlocking Therapeutic Potential: Enhanced shRNA delivery with Tat peptide in the Human Respiratory Syncytial Virus Treatment","authors":"Saeid Amiri Zadeh Fard, Haniyeh Abuei, Abbas Behzad Behbahani, Gholamreza Rafiei dehbidi, F. Zare, Maryam Nejabat, Alireza Safarpour, Ali Farhadi","doi":"10.34172/apb.2024.045","DOIUrl":"https://doi.org/10.34172/apb.2024.045","url":null,"abstract":"Purpose: This research investigated the development of short hairpin RNA (shRNA) molecules designed to target specific regions of the HRSV M and F genes. The study aimed to assess the therapeutic potential of these shRNAs and evaluate the effectiveness of Tat peptide-mediated delivery in enhancing their functionality. Methods: To investigate the therapeutic potential of short hairpin RNA against HRSV, we acquired isolates from pediatric patients experiencing respiratory illness. These isolates were then cultured in human epidermoid carcinoma cells (HEp-2). To target the M and F genes of HRSV, we constructed plasmids expressing shRNAs. We further investigated the Tat peptide as a facilitator for shRNA plasmid delivery. The cytotoxicity of ribavirin, shRNA constructs, and control agents was assessed using the MTT assay. Next, we compared the transfection efficiency of Tat peptide-mediated shRNA delivery with that of lipofectamine 3000™. Finally, real-time PCR was employed to quantify HRSV replication in the treated cells. Results: Our study successfully demonstrated that Tat peptide-mediated delivery of shRNA plasmids significantly suppressed the expression of the M and F genes of HRSV compared to lipofectamine 3000™. This suppression was evident in both short-term experiments and scenarios involving stable shRNA expression. Furthermore, the combination of ribavirin with shRNA treatment resulted in a substantial reduction in viral load. Notably, the most pronounced antiviral effect was observed when both shRNAs were employed simultaneously. Conclusion: Our findings suggest that Tat peptide-mediated delivery of shRNA plasmids holds significant potential for achieving stable suppression of HRSV genes. This approach warrants further investigation as a potential gene therapy strategy for HRSV. By demonstrating promising results in vitro, this study highlights the need for future in vivo studies to comprehensively evaluate the therapeutic potential of this approach in a clinical setting.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140979031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Behnaz Mokhtari, Amirhossein Jessri, Samad Ghaffari, R. Badalzadeh
{"title":"Superior Anti-Arrhythmogenic Effect of Combined Conditioning with Nicotinamide Mononucleotide and Ubiquinol in Myocardial Ischemia/Reperfusion Injury in Aged Rats","authors":"Behnaz Mokhtari, Amirhossein Jessri, Samad Ghaffari, R. Badalzadeh","doi":"10.34172/apb.2024.044","DOIUrl":"https://doi.org/10.34172/apb.2024.044","url":null,"abstract":"Purpose: Lethal ventricular arrhythmias are a significant clinical concern following reperfusion therapies in elderly patients with myocardial infarction. The combination of multi-target therapies to achieve optimal anti-arrhythmogenesis and improve the chances of successful translation for patient benefit has prompted considerable interest. This study examined the anti-arrhythmic effect of nicotinamide mononucleotide (NMN)/ubiquinol combination treatment following myocardial ischemia/reperfusion (IR) injury in aged rats, with an emphasis on the role of oxidative stress and nitric oxide (NO). Methods: Male Wistar rats (n=30, 22-24 months old, 400-450g) were randomized into five groups with or without IR and/or NMN and ubiquinol, either alone or in combination. NMN (100mg/kg/48hours) was administered intraperitoneally for 28 days before IR, and ubiquinol (30mg/kg) was injected intravenously at early reperfusion. Electrocardiographic signals were recorded during the ischemia and the first 30 minutes of reperfusion. Two hours after reperfusion, myocardial hemodynamic and LDH release were measured, and the left ventricle samples were obtained to evaluate oxidative stress markers and NO levels. Results: NMN/ubiquinol combination treatment significantly minimized the occurrence and severity of IR-induced arrhythmias, improved myocardial function, and reduced LDH release (P<.05). It also decreased MDA content, increased SOD, GPx, and CAT activities, and enhanced NO formation (P<.05). This combined treatment showed greater efficacy than the single treatments. Conclusion: This study revealed the anti-arrhythmic effect of NMN/ubiquinol combination treatment in IR-treated aged rats, which may be associated with reduced oxidative stress and increased NO formation. This combinational approach deserves more investigation due to its potential to confer better anti-arrhythmic effect during aging.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140702987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring a Synergistic Approach: Dual GLP-1 Agonist Combined with Degludec Basal Insulin for Early Type 1 Diabetes Treatment and its Impact on Albumin-Insulin Producing Cells Expression.\"","authors":"A. Ahmed, M. Akl","doi":"10.34172/apb.2024.040","DOIUrl":"https://doi.org/10.34172/apb.2024.040","url":null,"abstract":"This manuscript explores various aspects related to the use of dual GLP-1 agonist with degludec basal insulin as a potential treatment approach for early type 1 diabetes. The background section highlights the destruction of beta cells in type 1 diabetes and the emergence of GLP-1 agonists as a promising option for managing obesity and type 2 diabetes. The authors discuss a retrospective analysis of the efficacy of semaglutide, a GLP-1 agonist, in patients with newly diagnosed type 1 diabetes. The results show the elimination of prandial and basal insulin, increased C-peptide levels, and improved glycemic control. However, the study's retrospective nature and lack of a control group emphasize the need for larger prospective trials. The interpretation section highlights the potential of GLP-1 agonists in protecting residual beta cells, stimulating cell proliferation, and reprogramming liver cells into insulin-producing cells. Moreover, modifying GLP-1 agonists with albumin ligands shows promise in extending their half-life and enhancing their anti-diabetic effects. The perspective section provides a comprehensive overview of the synergistic approach, considering the pharmacokinetic properties of degludec, the plasticity of adult human hepatic tissue, and the benefits of modified GLP-1 derivatives. The conclusion emphasizes the need for further research to explore the full potential of this approach in type 1 diabetes treatment. The proposed approach offers a promising avenue for the treatment of type 1 diabetes, integrating the autoimmune hypothesis, the proliferative effects of GLP-1, and modifications using albumin ligands. By combining these elements, we can strive towards restoring beta cell mass and function, ultimately improving the lives of individuals living with type 1 diabetes. The manuscript is planned to undergo clinical trials in 2024, registered as 'Amr Ahmed, Maher M. Akl, Semaglutide GLP1 Agonists with Degludec Basal-bolus Insulin in Early Type 1 Diabetes to Basal-bolus' with ClinicalTrials.gov Identifier NCT06057077.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140390209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}