Advanced pharmaceutical bulletin最新文献

{"title":"Dual Modulation of Senescence and Immune Checkpoints by Metformin and Dapagliflozin Attenuates Liver Fibrosis in a Thioacetamide-Induced Rat Model.","authors":"Asmaa Ramadan, Ahmed A Shaaban, Mohammad E Rabeh, Ahmad M Rabi, Eslam E Abd El-Fattah, Amal K Seleem, Ibrahim Osman, Ayman Salama, Noha M Gamil, Ahmed S G Srag El-Din","doi":"10.34172/apb.025.46231","DOIUrl":"10.34172/apb.025.46231","url":null,"abstract":"<p><strong>Introduction: </strong>Liver fibrosis, characterized by excessive extracellular matrix accumulation, reflects a maladaptive repair response to persistent hepatic injury. Recent studies implicate cellular senescence and immune checkpoint dysregulation as pivotal drivers of fibrogenesis, yet these pathways remain underutilized in therapeutic development. This study evaluates the anti-fibrotic efficacy of metformin and dapagliflozin, two metabolic modulators, in a thioacetamide (TAA)-induced rat model, emphasizing their impact on senescence and immune regulation.</p><p><strong>Methods: </strong>Male albino rats (N=6/group) were assigned to five groups: control, TAA (200 mg/kg, i.p., thrice weekly for 4 weeks), TAA+metformin (300 mg/kg/day), TAA+dapagliflozin (1 mg/kg/day), and TAA+combination therapy. Liver tissues underwent histopathological examination and SMAD-3 mRNA quantification via qRT-PCR. Protein levels of TGF-β1, PD-1, p16, NF-κB, α-SMA, fibronectin, collagen-I, and sirtuin-1 were assessed, alongside serum oxidative stress markers (MDA, SOD) and liver enzymes (ALT, AST).</p><p><strong>Results: </strong>All treatments significantly reduced fibrosis, collagen deposition and improved liver architecture. Mechanistically, both drugs suppressed fibrotic and senescence markers, downregulated PD-1, enhanced sirtuin-1, and mitigated oxidative stress. Notably, combination therapy yielded synergistic anti-fibrotic effects.</p><p><strong>Conclusions: </strong>These findings highlight a dual-pathway therapeutic strategy targeting senescence and immune imbalance, with relevance to metabolic liver disease.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"16 1","pages":"166-178"},"PeriodicalIF":4.7,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617956","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":"Biomimetic Scaffold of Chitosan from <i>Litopenaeus vannamei</i> Shrimp Shells Incorporated with Collagen and Hydroxyapatite for Bone Tissue Regeneration.","authors":"Cheryn Ivana, Hendrik Satria Dwi Putra, Nyoman Bayu Wisnu Kencana, Agustina Setiawati","doi":"10.34172/apb.025.45909","DOIUrl":"10.34172/apb.025.45909","url":null,"abstract":"<p><strong>Introduction: </strong>The goal of this study was to create a biocompatible bone tissue engineering scaffold from <i>Litopenaeus vannamei</i> shrimp shell chitosan with hydroxyapatite (HAP) and collagen type I (COL I), and to investigate its physicochemical and biological properties relative to commercial chitosan scaffolds.</p><p><strong>Methods: </strong>The chitosan was extracted by following steps: deproteination, demineralization, and deacetylation processes, further characterizing it through composite FTIR spectroscopy. The scaffolds were fabricated using lyophilization, followed by the evaluation of their morphology, porosity, swelling ratio, degradation rate, and compressive strength. The scaffold morphology and porosity were observed using Scanning Electron Microscopy (SEM) and the solvent displacement method. Swelling and degradation ratio were investigated in phosphate buffer saline, while compressive strength was investigated with the Universal Testing Method. For the assessment of cytocompatibility, MG-63 osteoblast-like cells were subjected to the MTT assay, and cell morphology on the scaffold was observed under SEM.</p><p><strong>Results: </strong>As shown in the FTIR results, the derived chitosan exhibited comparable functional groups to those of commercial chitosan, confirming its successful extraction. Both scaffolds exhibited interconnected pores and suitable diameters and porosity for bone scaffold tissue engineering. Chitosan from shrimp shells showed a reduction in swelling (278.55±36.49% at 24h) and a slower degradation rate (41.87±7.27% at 4 weeks) compared to commercial scaffolds, possibly due to higher residual minerals and a lower degree of deacetylation. However, compressive strength 0.991±0.01 MPa and attachment and proliferation of MG-63 cells were similar, suggesting good osteoconductivity of the biomaterials.</p><p><strong>Conclusion: </strong>Chitosan-derived shrimp shells are a sustainable biomaterial candidate for bone tissue engineering. The scaffold based on shrimp shells exhibited relatively lower degradation and moderate swelling, adequate mechanical stability, and bioactivity to support osteoblast-like cell adhesion and viability, suggesting it is adequate for bone tissue engineering applications.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"16 1","pages":"52-61"},"PeriodicalIF":4.7,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597652","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":"Eplerenone Attenuates Hepatic Oxidative Stress and Mitochondrial Dysfunction Following Renal Ischemia-Reperfusion Injury in Rats.","authors":"Alireza Barati, Seyed Mohammadmahdi Meybodi, Kimia Moradi, Sana Nouraei, Mohammad Bakhshi, Soheila Montazersaheb, Sepideh Zununi Vahed","doi":"10.34172/apb.025.45926","DOIUrl":"10.34172/apb.025.45926","url":null,"abstract":"<p><strong>Purpose: </strong>Acute kidney injury (AKI) is frequently complicated by systemic manifestations, including hepatic dysfunction, largely due to ischemia-reperfusion (I/R) injury. This study investigated the hepatoprotective effects of eplerenone, a selective aldosterone receptor antagonist, in a rat model of renal I/R.</p><p><strong>Methods: </strong>Male Wistar rats (n=24) were randomly divided into four groups: sham, I/R, eplerenone+I/R, and eplerenone alone. A single intraperitoneal dose of eplerenone (100 mg/kg) was administered one hour before ischemia induction. Hepatic injury was evaluated by histopathology, liver function enzymes (ALT, AST, ALP), oxidative stress parameters, sirtuins, and key mitochondrial and apoptotic signaling proteins.</p><p><strong>Results: </strong>Renal I/R resulted in significant hepatic injury, characterized by histological alterations, increased liver enzymes, oxidative stress, and activation of inflammatory and apoptotic pathways. Pretreatment with eplerenone markedly improved hepatic outcomes by lowering ALT, AST, and ALP levels, preserving liver morphology, suppressing NF-κB and caspase-3 expression, and enhancing antioxidant and mitochondrial protective mechanisms, particularly through Nrf2 and Sirt-3/PGC-1α/Opa-1 pathways. The results indicated that eplerenone administration significantly improved liver function and histology following kidney I/R injury. Caspase-3 and NF-κB levels were downregulated following eplerenone administration. It also elevated the antioxidant capacity and protein levels of Nrf-2, HSP-70 (<i>P</i><0.001), mitochondrial biogenesis factor (PGC-1α), sirtuin-1 (<i>P</i><0.05), and dynamics factor (Opa-1, <i>P</i><0.001), while decreasing Drp-1 levels (<i>P</i><0.05) in the liver after kidney I/R injury.</p><p><strong>Conclusion: </strong>Eplerenone demonstrated strong hepatoprotective effects against renal I/R-induced liver injury. Its antioxidant, anti-inflammatory, and mitochondria-stabilizing actions highlight its potential as a therapeutic agent for preventing hepatic dysfunction associated with AKI and underline the importance of targeting distant organ injury in acute renal pathophysiology.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"16 1","pages":"139-148"},"PeriodicalIF":4.7,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617889","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":"Galangin's Therapeutic Potential in Retinoblastoma: Inducing Apoptosis and Modulating RB Protein and Some MicroRNAs.","authors":"Maryam Zamani Sani, Mohammad Mirzaei, Ali Mota, Effat Alizadeh, Maryam Ghasemi, Elmira Aboutalebi Vand Beilankouhi, Niloufar Kheradi, Mohammad Rahmati","doi":"10.34172/apb.025.46369","DOIUrl":"10.34172/apb.025.46369","url":null,"abstract":"<p><strong>Introduction: </strong>Retinoblastoma is a type of cancer that develops in the retina, mainly affecting infants and young children under five years old. Research indicates that microRNAs (miRNAs) can either promote or suppress cancer, significantly impacting its development. Galangin exhibits potential anticancer effects, but further research is necessary to confirm its benefits.</p><p><strong>Methods: </strong>In this study, the MTT assay was used to assess cell viability. Changes in microRNA expression were analyzed using real-time PCR. The apoptotic effect of galangin was determined using flow cytometry. Changes in RB protein expression due to galangin treatment were determined using Western blotting. A t-test and 2-ΔΔCT were used for data analysis. Statistical significance was considered at <i>P</i><0.05.</p><p><strong>Results: </strong>An IC50 of 13.08 μM was determined for the 48-hour MTT assay. Galangin treatment decreased the expression of miR-106a-5p by about 1.41-fold (<i>P</i> value: 0.0375). An about 1.11-fold increase was also observed for mir-519a-3p (<i>P</i> value: 0.0207). The change in miR-192-5p expression was insignificant (<i>P</i> value: 0.4677). A decrease of approximately 1.87-fold was also shown for miR-21-5p (<i>P</i> value: 0.0072). The apoptotic effect of galangin at the IC50 concentration and a dose of 26 µM was 34.30% and 26.70%, respectively. RB protein expression increased 2.66-fold approximately (<i>P</i> value: 0.0045).</p><p><strong>Conclusion: </strong>Our study showed that galangin has an apoptosis-inducing effect in Y79 cell lines. The apoptosis-inducing effect can be dose-dependent and can be reduced by increasing the dose. The increase in RB protein due to galangin treatment is accompanied by an increase in apoptosis. Galangin also affects the expression of miR-106a-5p, miR-519a-3p, and miR-21-5p.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"16 1","pages":"179-188"},"PeriodicalIF":4.7,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617919","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":"Histone Deacetylase Inhibitor Combined with Rosiglitazone Improves Cognitive Function Via Microglial Polarization and Increased Mature/Pro-BDNF in Alzheimer's Disease.","authors":"Melina Rafiey, Rahim Nosrati, Arash Pourgholaminejad, Saba Ahangaran, Parvin Babaei","doi":"10.34172/apb.025.46129","DOIUrl":"10.34172/apb.025.46129","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is characterized by diminished brain metabolism, cognitive impairments, neural loss, astrogliosis, and microgliosis. We hypothesized that co-administration of a peroxisome proliferator-activated receptor gamma (PPARγ) agonist and a histone deacetylase (HDAC) inhibitor would enhance cognitive function in an AD model of rats.</p><p><strong>Methods: </strong>Forty adult male Wistar rats were randomly assigned into five groups (n=8 per group): (1) Control group receiving saline, (2) AD model group (induced by i.c.v injection of Streptozocin), (3) AD+Rosiglitazone (ROSI) (4) AD+MS-275, and (5) AD+combined ROSI and MS-275 group. Cognitive functions were evaluated using the passive avoidance test and the Morris water maze (MWM). Microglial polarization was assessed by flow cytometry, and protein expression was analyzed by western blotting.</p><p><strong>Results: </strong>Data analyzed by one-way ANOVA and post hoc Tukey for (MWM) showed a significant decrease in latency to the target quadrant both in working and reference memories, and a significant increase in total time spent (TTS) in the target quadrant for reference memory in the group of STZ+ROSI+MS-275 (<i>P</i><0.000). Kruskal-Wallis H test revealed a significant increase in the M2/M1 ratio for ROSI+MS-275+STZ group compared with the STZ+Saline group (<i>P</i>=0.001). Also an increased mature brain-derived neurotrophic factor (BDNF)/pro-BDNF ratio was found in treated groups compared with STZ+saline (<i>P</i><0.001).</p><p><strong>Conclusion: </strong>These findings suggest that co-administration of Rosiglitazone and MS-275 improves cognitive function in AD rats, potentially through shifting microglial polarization from the M1 to the M2 phenotype and enhancing synaptic strength via an increased mature BDNF/pro-BDNF ratio.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"16 1","pages":"157-165"},"PeriodicalIF":4.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617887","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":"Development of AS1411 Aptamer-Targeted Solid Lipid Nanoparticles to Improve Anticancer Efficiency of Lawsone.","authors":"Sara Gheshlaghi, Armita Sedighidarijani, Afsaneh Maali, Maryam Hashemi, Shiva Golmohammadzadeh, Zahra Salmasi","doi":"10.34172/apb.025.45553","DOIUrl":"10.34172/apb.025.45553","url":null,"abstract":"<p><strong>Introduction: </strong>Lawsone (LWS), a naphthoquinone dye known for its anticancer properties, faces challenges with aqueous solubility, which restricts its therapeutic use. Solid lipid nanoparticles (SLNs) are recognized for enhancing the bioavailability of poorly soluble drugs, supporting in targeted drug delivery and reducing toxicity to normal tissues. The purpose of this study was to develop chitosan-coated solid lipid nanoparticles that were loaded with lawsone and conjugated with the AS1411 aptamer (LWS-SLN-Chit-Apt) for evaluating the cytotoxic effects on mouse colon adenocarcinoma cells (C26).</p><p><strong>Methods: </strong>High-shear homogenization and ultrasound methods were used for producing the LWS-SLNs nanoparticles. Several considerations, including dynamic light scattering (DLS), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR), were directed to characterize the properties of the nanoparticles. Next, the nanoparticles were coated with chitosan, then conjugated to AS1411 aptamer, which was confirmed with DLS and gel electrophoresis. Additionally, the encapsulation efficiency of LWS and its release profile were investigated. Cytotoxicity and cellular uptake were evaluated on C26 cells and Chinese hamster ovary (CHO) cells.</p><p><strong>Results: </strong>The LWS-SLNs and LWS-SLN-Chit-Apt formulations revealed particle sizes of 160±14.8 nm and 350±22.5 nm, with encapsulation efficiencies of 70.72±2.64% and 70.00±4.3%, respectively. Both formulations exhibited a sustained drug release profile over 120 hours. Targeted nanoparticles displayed higher cellular uptake and cytotoxicity in nucleolin-positive cells (C26 cells) compared to nucleolin-negative cells (CHO cells), with no substantial differences observed.</p><p><strong>Conclusion: </strong>These results illustrated that LWS-SLN-Chit-Apt could be considered as a great candidate for further studies and <i>in vivo</i> trials.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"16 1","pages":"38-51"},"PeriodicalIF":4.7,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597621","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":"GAS2 Co-Expression Networks in Breast Cancer: Identification of Potential Biomarkers and Therapeutic Targets.","authors":"Samin Rahimi, Mehdi Haghi, Dariush Najarzadeh, Mohammad Ali Hosseinpour Feizi","doi":"10.34172/apb.025.46055","DOIUrl":"10.34172/apb.025.46055","url":null,"abstract":"<p><strong>Introduction: </strong>Breast Cancer (BCa) remains the leading cause of cancer-related mortality among women, underscoring the need for developing more effective novel biomarkers. This study investigated the role of Growth Arrest-Specific 2 (GAS2) and its co-expressed genes in breast cancer.</p><p><strong>Methods: </strong>RNA-Seq data from 60 matched normal and malignant breast tissue samples (GSE183947) were analyzed. Expression values were normalized using FPKM, and GAS2 co-expression networks were constructed with SUM Lasso and linear regression. Gene-gene interaction networks were examined using Gephi software.</p><p><strong>Results: </strong>GAS2 expression was significantly reduced in tumors compared with normal tissues (<i>P</i><0.01). Distinct sets of GAS2-associated genes were identified in cancer versus normal tissues, with tumor-associated partners (TAS2R14, PHF21B, CNTN5, UGT2B15) linked to drug metabolism and signaling, and normal-associated partners (DCC, STAT5A, ZCRB1) linked to transcriptional and cytoskeletal regulation. Network analysis revealed substantial differences in gene expression patterns between tumor and normal tissues, indicating GAS2's involvement in cancer-specific signaling pathways.</p><p><strong>Conclusion: </strong>GAS2 displays context-dependent gene interactions and reduced expression in BCa, suggesting potential relevance to tumor biology. While these findings support its value as a candidate biomarker, experimental validation is required before translational applications can be established.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"16 1","pages":"129-138"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617869","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":"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":4.7,"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}

{"title":"The Effect of Glycosylation on Biodistribution and Cytotoxicity of ⁹⁹mTc-Radiolabeled Luteolin.","authors":"Mostafa Pirali Hamedani, Mohammad Seyedhamzeh, Mohammad H Ghahremani, Abbas Hadjiakhoondi, Morteza Pirali Hamedani, Mehdi Shafiee Ardestani, Zahra Tofighi","doi":"10.34172/apb.025.46124","DOIUrl":"10.34172/apb.025.46124","url":null,"abstract":"<p><strong>Introduction: </strong>Luteolin (Lu) and its glycosylated derivative, luteolin-7-O-glucoside (LuG), are the main bioactive flavonoids reported in the <i>Scutellaria</i> genus. Still, in vivo biodistribution and cytotoxic effects on cancer cells remain unrevealed. This study investigated the biodistribution and cytotoxic effects of Lu and LuG on cancer cell lines, particularly hepatic carcinoma (HepG2).</p><p><strong>Methods: </strong>Lu and LuG were isolated from <i>S. pinnatifida</i> extracts, and the structures were confirmed by ¹H-NMR spectroscopy. Radiolabeling was performed to assess their biodistribution in Wistar-Albino rats using SPECT imaging and organ radioactivity was measured. Organs were harvested and radioactivity quantified to determine tissue accumulation. Cytotoxicity was evaluated via MTT assay on normal (HUVEC) and cancer (HepG2, SW480) cell lines. Flow cytometry analyzed apoptosis/necrosis and cell cycle arrest after treatment.</p><p><strong>Results: </strong>LuG exhibited preferential accumulation in the liver (~28.7%) and significant cytotoxicity on HepG2 cells. Flow cytometry indicated non-apoptotic cell death and G1/S phase cell cycle arrest in HepG2 cells treated with LuG, whereas Lu showed less accumulation and cytotoxicity. Biodistribution data revealed lower accumulation in other organs, and LuG had negligible toxicity on non-hepatic cells (HUVEC, SW480). Overall biodistribution analysis revealed lower off-target accumulation, further supporting the hepatic selectivity of LuG.</p><p><strong>Conclusion: </strong>This study provides the first integrated evidence of the liver-targeted biodistribution and selective anticancer effects of LuG. These findings demonstrate LuG as a candidate therapeutic for hepatocellular carcinoma. These results emphasize the importance of pharmacological evaluation of flavonoid glycosides and support preclinical development of LuG as a targeted anticancer agent.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"16 1","pages":"110-118"},"PeriodicalIF":4.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617952","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":"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":4.7,"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}