Advanced pharmaceutical bulletin最新文献

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Purinergic Signaling in Ovarian Carcinoma. 卵巢癌中的嘌呤能信号传导。
IF 4.1
Advanced pharmaceutical bulletin Pub Date : 2025-10-25 eCollection Date: 2025-11-01 DOI: 10.34172/apb.025.46032
Angélica Sofía Martínez-Ramírez, José David Nuñez-Ríos, Ana Patricia Juárez-Mercado, Anaí Del Rocío Campos-Contreras, Francisco G Vázquez-Cuevas
{"title":"Purinergic Signaling in Ovarian Carcinoma.","authors":"Angélica Sofía Martínez-Ramírez, José David Nuñez-Ríos, Ana Patricia Juárez-Mercado, Anaí Del Rocío Campos-Contreras, Francisco G Vázquez-Cuevas","doi":"10.34172/apb.025.46032","DOIUrl":"10.34172/apb.025.46032","url":null,"abstract":"<p><p>Ovarian carcinoma (OC) is the most lethal gynecological cancer worldwide. Around 95% of patients exhibit recurrence five years after treatment; 80% experience recurrence within 18 months after first-line treatment, and progression-free survival rates have not changed over the past 40 years. New therapeutic approaches are imperative to face this complex disease. The purinergic system is a newly recognized element of the tumor microenvironment (TME), as it exhibits a pro-tumor role. Tumor cells release adenosine triphosphate (ATP) into the TME, where it exerts autocrine-paracrine actions that regulate several processes, including the induction of a metastatic phenotype, cell proliferation, and metabolic adaptations. In the extracellular milieu, ATP is converted to adenosine (ADO) by ectonucleotidases (CD39 and CD73), thereby significantly blocking the anti-tumor immune response through interactions with various immune cells. Recent analyses have focused on the diversity and plasticity of purinergic signaling in OC. This review outlines the disease, explains basic concepts of purinergic signaling, and summarizes experimental evidence that indicates purinergic elements may serve as potential targets for novel therapies to overcome OC.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"779-792"},"PeriodicalIF":4.1,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462613","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}
引用次数: 0
Delivery Systems of mRNA Vaccines in the Treatment of Infectious Diseases: From Lipid Nanoparticles to Next-Generation Platforms. mRNA疫苗在感染性疾病治疗中的递送系统:从脂质纳米颗粒到下一代平台
IF 4.1
Advanced pharmaceutical bulletin Pub Date : 2025-10-20 eCollection Date: 2025-11-01 DOI: 10.34172/apb.025.46087
Chou-Yi Hsu, Abdulsalam Abdulsattar Abdulazez, Yasir Qasim Almajidi, A K Kareem, Abdullah A Aseeri, Kdv Prasad, Zahraa Khudhair Al-Khafaji, Zuhair I Al-Mashhadani, Sami Najaf Bokhoor, Raad N Hasan
{"title":"Delivery Systems of mRNA Vaccines in the Treatment of Infectious Diseases: From Lipid Nanoparticles to Next-Generation Platforms.","authors":"Chou-Yi Hsu, Abdulsalam Abdulsattar Abdulazez, Yasir Qasim Almajidi, A K Kareem, Abdullah A Aseeri, Kdv Prasad, Zahraa Khudhair Al-Khafaji, Zuhair I Al-Mashhadani, Sami Najaf Bokhoor, Raad N Hasan","doi":"10.34172/apb.025.46087","DOIUrl":"10.34172/apb.025.46087","url":null,"abstract":"<p><p>The historic accomplishment of mRNA vaccines against SARS-CoV-2 has provided a massive shift in vaccinology, providing a quick, nimble, and powerful platform for infectious disease prevention. This success, however, does not simply stem from the mRNA sequence but equally depends on the delivery vehicle-the lipid nanoparticle (LNP). The delivery system has evolved from a passive transporter into an active immunomodulatory component, a critical component that (1) protects the inherently fragile mRNA payload, (2) allows cellular uptake and endosomal escape, and (3) adds its own inherent adjuvant properties to shape the immune response. This review provides a comprehensive summary of the current advancements in mRNA vaccine delivery technologies. We first deconstruct the structure, mechanisms, advantages, and disadvantages of the clinically validated LNP platform. Following this discussion, we highlight the emerging landscape of new systems, including chemically diverse polymeric nanoparticles, biologically-inspired peptide-based carriers, and endogenous extracellular vesicles, potentially overcome current limitations in these delivery systems, including issues with thermostability and targeted delivery. After this, we summarize how these new delivery technologies are being leveraged clinically for a continuum of high-priority infectious diseases, including influenza, RSV, CMV, HIV, Zika, and Rabies. This discussion also illustrates how the design of vaccine prototypes is being rational to address the immune-mediated strategies exploited by each distinct pathogen.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"717-734"},"PeriodicalIF":4.1,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462542","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}
引用次数: 0
Deep Learning-Based Drug Half-Life Classification to Enhance Drug Development and Pharmacokinetics. 基于深度学习的药物半衰期分类促进药物开发和药代动力学。
IF 4.1
Advanced pharmaceutical bulletin Pub Date : 2025-10-19 eCollection Date: 2025-11-01 DOI: 10.34172/apb.025.45420
Affaf Khaouane, Hadjer Barki, Samira Ferhat
{"title":"Deep Learning-Based Drug Half-Life Classification to Enhance Drug Development and Pharmacokinetics.","authors":"Affaf Khaouane, Hadjer Barki, Samira Ferhat","doi":"10.34172/apb.025.45420","DOIUrl":"10.34172/apb.025.45420","url":null,"abstract":"<p><strong>Purpose: </strong>Predicting drug half-life is essential in pharmacokinetics (PK), influencing dosing strategies and guiding drug development. Traditional regression models estimate exact half-life values but are sensitive to pharmacokinetic variability, limiting their practical use. This study introduces a classification-based approach that separates drugs into short and long half-life groups using a 12-hour threshold, offering clearer clinical interpretability.</p><p><strong>Methods: </strong>Molecular structures were processed using a convolutional neural network (CNN), specifically a fine-tuned AlexNet, to extract high-level features. These extracted features served as inputs for a neural network classifier. A holdout validation strategy was applied, with data split into 70% for training, 15% for validation, and 15% for testing. Model performance was assessed based on classification accuracy and F1-score.</p><p><strong>Results: </strong>The model achieved an F1-score of 90.9% at the optimal feature dimension of 10. Accuracy reached 96.2% on validation data and 92.3% on test data, demonstrating strong generalization capabilities. Compared to regression-based methods, this framework better accounts for variability in drug half-life and yield results that are easier to interpret in clinical contexts.</p><p><strong>Conclusion: </strong>This work proposes an efficient method for drug half-life classification, supporting drug formulation and dosing strategies. The findings highlight the value of classification in early drug development and provide a robust, scalable tool for pharmacokinetic research.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"836-843"},"PeriodicalIF":4.1,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462535","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}
引用次数: 0
Investigating the Role of Empagliflozin in the Pathological Progress of Ischemia-Reperfusion Injury in Rat Kidneys: The Involvement of Nitric Oxide. 恩格列净在大鼠肾缺血再灌注损伤病理过程中的作用:一氧化氮的参与。
IF 4.1
Advanced pharmaceutical bulletin Pub Date : 2025-10-19 eCollection Date: 2025-11-01 DOI: 10.34172/apb.025.46028
Amin Hasanvand, Abdolreza Tajdar, Azita Zafar Mohtashami, Zahra Haghighatian, Elham Goodarzi, Peyman Amanolahi Baharvand, Babak Hadian
{"title":"Investigating the Role of Empagliflozin in the Pathological Progress of Ischemia-Reperfusion Injury in Rat Kidneys: The Involvement of Nitric Oxide.","authors":"Amin Hasanvand, Abdolreza Tajdar, Azita Zafar Mohtashami, Zahra Haghighatian, Elham Goodarzi, Peyman Amanolahi Baharvand, Babak Hadian","doi":"10.34172/apb.025.46028","DOIUrl":"10.34172/apb.025.46028","url":null,"abstract":"<p><strong>Purpose: </strong>Renal ischemia-reperfusion (RIR) is a pathological condition that can lead to severe outcomes due to damage to kidney structures. Additionally, oxidative stress is triggered by mitochondrial disruption during reperfusion, potentially resulting in necrosis and, ultimately, cell death through the destruction of cellular membranes.</p><p><strong>Methods: </strong>Thirty rats were included in this study and divided into the following groups: healthy rats, an ischemia-reperfusion (I/R) group, an I/R group treated with empagliflozin, an I/R group treated with empagliflozin plus L-NAME, and an I/R group treated with empagliflozin plus L-arginine. The drugs were administered from three days before I/R induction to one day post-operation. Blood samples were collected 24 hours after I/R induction to evaluate renal function, inflammatory markers, and oxidative stress. Subsequently, the right kidney was harvested for nitric oxide (NO) measurement, while the left kidney was used for histological analysis.</p><p><strong>Results: </strong>Empagliflozin administration significantly reduced creatinine, urea, inflammatory markers, and oxidative stress levels. Moreover, empagliflozin increased the levels of antioxidant enzymes and NO. Histopathological analysis indicated that empagliflozin mitigated ischemia-reperfusion injury in renal tissue. The protective effects were further enhanced with the co-administration of empagliflozin and L-arginine. In contrast, simultaneous treatment with empagliflozin and L-NAME led to pathological changes associated with ischemia-reperfusion and attenuated the beneficial effects of empagliflozin.</p><p><strong>Conclusion: </strong>The findings of this study suggest that empagliflozin exerts protective effects against ischemia-reperfusion injury, likely through the NO pathway.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"939-947"},"PeriodicalIF":4.1,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462586","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}
引用次数: 0
The Art of Nanoimmunobiotechnomedicine in Depression Management. 纳米免疫生物技术在抑郁症治疗中的应用。
IF 4.1
Advanced pharmaceutical bulletin Pub Date : 2025-10-18 eCollection Date: 2025-11-01 DOI: 10.34172/apb.025.42757
Dito Anurogo, Ririn Tri Ratnasari, Novi Irmania, Muhammad Sobri Maulana, Kholis Abdurachim Audah, Novi Sekar Sari, Maratu Soleha, Amir Su'udi, Ahmad Hafidul Ahkam, Andi Weri Sompa, Riswal Nafi' Siregar, Maulida Mazaya, Riri Rimbun Anggih Chaidir, Azzah Khoridah Maulidiya, Suryani As'ad, Ami Febriza Achmad, Nur Rahmah Awaliah, Gangga Anuraga, Waode Fifin Ervina, Noorman Rinanto, Era Catur Prasetya, Tzu-Jen Kao, Tria Astika Endah Permatasari, Arli Aditya Parikesit, Nguyen Quoc Khanh Le, Nadhirah Nordin
{"title":"The Art of Nanoimmunobiotechnomedicine in Depression Management.","authors":"Dito Anurogo, Ririn Tri Ratnasari, Novi Irmania, Muhammad Sobri Maulana, Kholis Abdurachim Audah, Novi Sekar Sari, Maratu Soleha, Amir Su'udi, Ahmad Hafidul Ahkam, Andi Weri Sompa, Riswal Nafi' Siregar, Maulida Mazaya, Riri Rimbun Anggih Chaidir, Azzah Khoridah Maulidiya, Suryani As'ad, Ami Febriza Achmad, Nur Rahmah Awaliah, Gangga Anuraga, Waode Fifin Ervina, Noorman Rinanto, Era Catur Prasetya, Tzu-Jen Kao, Tria Astika Endah Permatasari, Arli Aditya Parikesit, Nguyen Quoc Khanh Le, Nadhirah Nordin","doi":"10.34172/apb.025.42757","DOIUrl":"10.34172/apb.025.42757","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the role of nanoimmunobiotechnomedicine in depression management, emphasizing how nanotechnology and immunobiology offer innovative approaches to understanding and treating depression. We investigated the molecular mechanisms underlying depression and integrated multi-omics approaches such as genomics, epigenomics, and bioinformatics to advance therapeutic strategies.</p><p><strong>Methods: </strong>An interdisciplinary approach was applied, synthesizing data from epigenetics, nutrigenomics, and advanced bioinformatics. Furthermore, molecular and cellular neuroscience techniques were utilized alongside pharmacogenomics to deepen the understanding of depression.</p><p><strong>Results: </strong>Findings highlight the effectiveness of nano-based interventions, like targeted drug delivery systems and anti-inflammatory treatments, in reducing neuroinflammation and enhancing neuroplasticity. Multi-omics data show the importance of neurotrophic factors and gut-brain axis interactions in depression management. Additionally, pharmacogenetics suggests personalized treatment strategies, tailoring therapeutic responses based on individual genetic profiles.</p><p><strong>Conclusion: </strong>Nanoimmunobiotechnomedicine represents a frontier for personalized depression therapies. The integration of nanotechnology and immunobiology enhances bioavailability and specificity in targeting depressive disorders at the molecular level. This convergence of molecular biology, and bioinformatics studies holds significant potential to revolutionize depression treatment, offering more effective and individualized solutions for better mental health outcomes.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"750-765"},"PeriodicalIF":4.1,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462381","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}
引用次数: 0
Diabetes and NAFLD: A Synergistic Threat to Metabolic Health. 糖尿病和NAFLD:对代谢健康的协同威胁。
IF 4.1
Advanced pharmaceutical bulletin Pub Date : 2025-10-18 eCollection Date: 2025-11-01 DOI: 10.34172/apb.025.44094
Shilpa Chaudhary, Keerti Manocha, Praveen Malik, Monica Aggarwal, Rekha Rao, Minakshi Garg
{"title":"Diabetes and NAFLD: A Synergistic Threat to Metabolic Health.","authors":"Shilpa Chaudhary, Keerti Manocha, Praveen Malik, Monica Aggarwal, Rekha Rao, Minakshi Garg","doi":"10.34172/apb.025.44094","DOIUrl":"10.34172/apb.025.44094","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2Dm) are increasingly recognized as interrelated metabolic disorders, each contributing to the other's progression. NAFLD, a leading cause of chronic liver disease globally, is often underdiagnosed due to its asymptomatic nature. The startlingly high frequency of NAFLD, especially in those with T2Dm, emphasizes the need of thorough screening in high-risk groups. In the setting of T2Dm, the pathophysiology of NAFLD comprises intricate metabolic pathways that exacerbate the disease's progression. These pathways include insulin resistance, lipotoxicity, and chronic inflammation. Early diagnosis and timely intervention are crucial to prevent the advancement of NAFLD to more severe stages, such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Current guidelines advocate for routine NAFLD screening in patients with T2Dm, emphasizing the importance of early detection. Therapeutic approaches have evolved that are pivotal in managing these intertwined conditions. Each of these treatments offers unique benefits, from improving glycemic control to mitigating liver fat accumulation and reducing cardiovascular risks. This review highlights the pathophysiological linkages, clinical implications, and therapeutic advancements in managing these conditions. By exploring global prevalence, emerging diagnostic tools, and novel therapies, we propose an integrative framework for improved patient outcomes.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"766-778"},"PeriodicalIF":4.1,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462583","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}
引用次数: 0
Ozonated Oil for Rheumatic Diseases. 臭氧油用于风湿病。
IF 4.1
Advanced pharmaceutical bulletin Pub Date : 2025-10-15 eCollection Date: 2025-11-01 DOI: 10.34172/apb.025.44040
Jozélio Freire de Carvalho, Ana Tereza Amoedo Martinez
{"title":"Ozonated Oil for Rheumatic Diseases.","authors":"Jozélio Freire de Carvalho, Ana Tereza Amoedo Martinez","doi":"10.34172/apb.025.44040","DOIUrl":"10.34172/apb.025.44040","url":null,"abstract":"","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"689-690"},"PeriodicalIF":4.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462523","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}
引用次数: 0
Hyaluronic Acid-Functionalized Liposomes for Co-delivery of 5-Fluorouracil and Cannabidiol Against Colorectal Cancer. 透明质酸功能化脂质体联合递送5-氟尿嘧啶和大麻二酚抗结直肠癌。
IF 4.1
Advanced pharmaceutical bulletin Pub Date : 2025-10-15 eCollection Date: 2025-11-01 DOI: 10.34172/apb.025.43401
Soheil Abbaspour-Ravasjani, Mahdi Zeinali, Leila Asadollahi, Malahat Safavi, Amin Mahoutforoush, Mehdi Talebi, Hamed Hamishehkar
{"title":"Hyaluronic Acid-Functionalized Liposomes for Co-delivery of 5-Fluorouracil and Cannabidiol Against Colorectal Cancer.","authors":"Soheil Abbaspour-Ravasjani, Mahdi Zeinali, Leila Asadollahi, Malahat Safavi, Amin Mahoutforoush, Mehdi Talebi, Hamed Hamishehkar","doi":"10.34172/apb.025.43401","DOIUrl":"10.34172/apb.025.43401","url":null,"abstract":"<p><strong>Purpose: </strong>Colorectal cancer (CRC) is a formidable global health challenge, ranking as the third most prevalent cancer. Conventional treatments like surgery, radiation, and chemotherapy are limited by adverse effects, driving the search for more effective alternatives.</p><p><strong>Methods: </strong>This study investigates the synergistic potential of co-delivering 5-fluorouracil (5-FU) and cannabidiol (CBD) using hyaluronic acid (HA)-decorated liposomes. While 5-FU is a cornerstone of CRC treatment, CBD offers promise as an anti-tumor agent. The HA-decorated liposomes enable potential targeted drug delivery to CD44 receptors, which are overexpressed in CRC, while minimizing systemic toxicity by reducing the concentrations of anticancer drugs required.</p><p><strong>Results: </strong>The liposomal formulation displays optimal physicochemical properties (a sub100nm size and an appropriate negative zeta potential) and acceptable encapsulation and loading efficiencies, ensuring effective drug release. In vitro studies demonstrate that the targeted liposomes have superior anticancer effects, inducing apoptosis (up to 59.1%), cell cycle arrest in the Sub-G1 and G0-G1 phases, reduction of cell viability to 6.98% in human colorectal adenocarcinoma (HT-29) cells, induction of oxidative stress, and inhibition of colony formation. Additionally, HepG2 (non-CD44-expressing) cells were used as a control to evaluate CD44-targeting efficiency. Gene expression analysis by real-time PCR indicates modulation of key genes associated with cell cycle progression and apoptosis.</p><p><strong>Conclusion: </strong>This multifaceted approach presents a promising strategy for CRC therapy, but requires additional optimization and rigorous in vivo investigations to facilitate successful clinical translation. In particular, optimization of drug-release kinetics and thorough in vivo validation are essential to advance this platform toward clinical application.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"819-835"},"PeriodicalIF":4.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462528","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}
引用次数: 0
MUC1-Driven Guanylin Gene Delivery via Succinylated PEI-9 Nanocarrier for Colorectal Cancer Treatment: An in Silico and In vitro Study. 通过琥珀酰化PEI-9纳米载体传递muc1驱动的观观林基因治疗结直肠癌:一个在硅和体外的研究。
IF 4.1
Advanced pharmaceutical bulletin Pub Date : 2025-10-15 eCollection Date: 2025-11-01 DOI: 10.34172/apb.025.45741
Pouria Samadi, Fatemeh Rahbarizadeh, Fatemeh Nouri, Meysam Soleimani, Rezvan Najafi, Akram Jalali
{"title":"MUC1-Driven Guanylin Gene Delivery via Succinylated PEI-9 Nanocarrier for Colorectal Cancer Treatment: An in Silico and In vitro Study.","authors":"Pouria Samadi, Fatemeh Rahbarizadeh, Fatemeh Nouri, Meysam Soleimani, Rezvan Najafi, Akram Jalali","doi":"10.34172/apb.025.45741","DOIUrl":"https://doi.org/10.34172/apb.025.45741","url":null,"abstract":"<p><strong>Purpose: </strong>Addressing colorectal cancer (CRC) poses a significant challenge, demanding the precise delivery of therapeutic agents to eliminate cancer cells while minimizing the impact on healthy cells. The strategic selection of therapeutic targets, the utilization of nanocarriers with optimal efficacy and low toxicity, and the development of gene constructs with targeted expression in cancer cells are crucial aspects of this pursuit.</p><p><strong>Methods: </strong>This study employed a systems biology approach to comprehensively investigate the guanylin hormone-encoding gene (GUCA2A). Exploration encompassed expression patterns across tissues and single cells, clinical endpoints, methylation profiles, mutations, and immune and functional analyses. Subsequently, GUCA2A was identified as a potential target for gain of function studies, leading to its amplification and cloning into gene constructs featuring both a robust CMV promoter and a cancer-specific MUC1 promoter. The succinylated PEI-9, characterized by low toxicity and high gene transfer efficiency, was then fabricated and characterized on HCT-116 cancer cells and normal Vero cell lines.</p><p><strong>Results: </strong>systems biology studies revealed guanylin's aberrant expression patterns, methylation variations, and mutational changes as well as its remarkable association with immune engagement and poor survival outcomes in CRC. Moreover, SPEI-9 was introduced as a highly efficient and safe nanocarrier for gene delivery purposes. Additionally, in vitro studies revealed that both guanylin-expressing gene constructs exhibited the potential to inhibit cell growth and proliferation, inducing apoptosis, suppressing cell migration, and curtailing colony formation. Notably, these effects were more robust but non-specific in cancer cells treated with constructs containing the CMV general promoter, while induction via the MUC1 promoter was more specific.</p><p><strong>Conclusion: </strong>A genetic construct featuring strong universal CMV and specific MUC1 promoter, expressing the guanylin peptide hormone, demonstrated highly effective and specific anticancer effects when transfected with nanocarriers characterized by high efficiency and low cytotoxicity. This nano-system holds promising implications for future targeted CRC therapy clinical trials.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"844-870"},"PeriodicalIF":4.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643779","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}
引用次数: 0
Mebendazole-Treated Human Monocyte-Derived Dendritic Cells Represent Promoted Immunogenic Phenotype with Augmented Expression of Inflammatory Markers. 甲苯达唑处理的人单核细胞来源的树突状细胞通过增强炎症标志物的表达来促进免疫原性表型。
IF 4.1
Advanced pharmaceutical bulletin Pub Date : 2025-10-11 eCollection Date: 2025-11-01 DOI: 10.34172/apb.025.43394
Shiva Alipour, Sepideh Sohrabi, Amirhossein Mardi, Negin Karamali, Elham Baghbani, Vahid Khaze, Behzad Baradaran
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