Pharmaceutical Science Advances最新文献

{"title":"Conquering viral drug resistance: Structural and mechanistic paradigms for antiresistance drug design","authors":"Mei Wang ,&nbsp;Haiyong Jia ,&nbsp;Xinyong Liu ,&nbsp;Peng Zhan","doi":"10.1016/j.pscia.2025.100094","DOIUrl":"10.1016/j.pscia.2025.100094","url":null,"abstract":"<div><div>Viral drug resistance remains a critical challenge in antiviral therapy. This perspective highlights five studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus type 1 (HIV-1), monkeypox virus (MPXV), influenza A virus (IAV), and Hepatitis B virus (HBV), revealing novel resistance mechanisms and innovative strategies. For SARS-CoV-2, GC376's flexible benzyl group overcomes nirmatrelvir resistance. HIV-1's non-nucleoside reverse transcriptase inhibitors (NNRTIs) 5i3 adapts to resistant mutants via a quinazoline scaffold, while MPXV's tecovirimat acts as a “molecular glue” stabilizing F13 dimers. Expanding these paradigms, we present groundbreaking insights: An indazole-based IAV inhibitor (compound 24) disrupts the conserved PA-PB1 heterodimer, showing sub-micromolar potency against resistant strains. For HBV, a hydrophobic tagging degrader (HyT-S7) induces HBc degradation, bypassing resistance mutations impairing traditional capsid modulators. Key strategies include dynamic flexibility, multivalent interactions, and oligomerization control, integrated with AI-driven design and real-time surveillance. This perspective bridges structural insights with translational applications, offering a roadmap for next-generation, mutation-resilient antivirals.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219487","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":"Research progress of 3D printing technology in the field of oral materials","authors":"Khan Rajib Hossain ,&nbsp;Dipika Ramdas Kalambhe ,&nbsp;M. Abdul Jalil ,&nbsp;Nusrat Tabassum Farah","doi":"10.1016/j.pscia.2025.100093","DOIUrl":"10.1016/j.pscia.2025.100093","url":null,"abstract":"<div><div>The emergence of three-dimensional (3D) printing has represented a significant technological breakthrough, exerting a profound influence across various domains of society in recent times. There has been a noticeable shift in the healthcare industry's dominant paradigm of therapeutic interventions, particularly regarding the utilization of 3D printing technology to mend or replace damaged or missing biological components. Adopting cutting-edge technology can significantly enhance the range of applications within the field of oral healthcare. A significant amount of research is being conducted to leverage the substantial potential of 3D printing in oral applications, with a focus on developing customized treatment plans tailored to specific case scenarios. By building specialized implantology from different biological composite materials layer by layer, 3D printing technology precisely restores the anatomical structure of defects in the mouth and maxillofacial region. This review presents a comprehensive discussion on the history and classification of 3D printing technology, as well as the dynamics of biological materials, cells, and bioactive factors utilized in repairing oral and maxillofacial bone defects. Additionally, this review provides an update on the materials commonly used in typical oral healthcare applications and examines future trends and concerns related to material perspectives in oral healthcare management.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104578","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":"Curative antimalarial efficacy and hepato-renal protective effects of Melochia umbellata leaf extract in rats infected with Plasmodium berghei","authors":"Vincent Ngouana ,&nbsp;Patrick Valere Tsouh Fokou ,&nbsp;Marius Jaures Tsakem Nangap ,&nbsp;Raoul Kemzeu ,&nbsp;Aubin Kamche Youbi ,&nbsp;Fabrice Fekam Boyom","doi":"10.1016/j.pscia.2025.100092","DOIUrl":"10.1016/j.pscia.2025.100092","url":null,"abstract":"<div><div>Malaria remains a major global health issue, particularly in endemic regions. Traditional medicine offers promising remedies, such as <em>Melochia umbellata</em>, a plant used in Cameroonian folk medicine for malaria treatment. While its <em>in vitro</em> antiplasmodial activity has been reported, the safety and curative efficacy of <em>M. umbellata</em> aqueous leaf extract (MULAE) <em>in vivo</em> required further investigation. This study evaluated the curative antimalarial and hepato-renal protective effects of MULAE in a <em>Plasmodium berghei</em>-infected rat model, alongside its phytochemical characterization. Qualitative and quantitative analyses confirmed the presence of pharmacologically active secondary metabolites, including alkaloids, phenols, flavonoids, and saponins. In acute toxicity tests (OECD guideline 423), female rats received single oral doses of MULAE (2000, 5000 ​mg/kg). No mortality or signs of toxicity were observed throughout the 14-day monitoring period, indicating an LD₅₀ greater than 5000 ​mg/kg. For the curative assay, <em>P. berghei</em>-infected rats were treated for five days with MULAE (100, 200, 400 ​mg/kg), chloroquine (10 ​mg/kg), or distilled water. MULAE significantly suppressed parasitemia dose-dependently; the 400 ​mg/kg dose achieved 86.20% chemosuppression. The extract also improved hematological markers (restoring hemoglobin levels to 14.9 ​g/dL at 400 ​mg/kg), mitigated infection-induced weight loss, and reduced organ damage. This organ protection was evidenced by improved blood serum markers (creatinine, ALAT, ASAT, bilirubin, total protein), restored oxidative status, and ameliorated histopathological changes in the liver, kidneys, and spleen. These findings validate the traditional use of <em>M. umbellata</em> and support its potential as a source for novel antimalarial and organ-protective agents.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104587","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":"A biodegradable antimicrobial oligomer-containing hydrogel for drug-resistant bacteria-infected skin wound treatment","authors":"Min Wang ,&nbsp;Xinyun Zeng ,&nbsp;Xiuping Wang ,&nbsp;Zhiyuan Zhang ,&nbsp;Siwei Guo ,&nbsp;Yang Deng ,&nbsp;Xin Li ,&nbsp;Lin Yao ,&nbsp;Jiaqi Li ,&nbsp;Wing-Leung Wong ,&nbsp;Yugang Bai ,&nbsp;Xinxin Feng","doi":"10.1016/j.pscia.2025.100091","DOIUrl":"10.1016/j.pscia.2025.100091","url":null,"abstract":"<div><div>Antibiotic resistance poses a serious global threat, contributing to severe clinical outcomes such as skin and soft tissue infections. Effective treatment of these infections requires both potent antimicrobial activity against resistant pathogens and wound dressings that can conform closely to the wound site. Degradable antimicrobial polymers offer a promising solution to this challenge. Unlike traditional antibiotic-loaded dressings, which often fail against multidrug-resistant (MDR) bacteria, antimicrobial polymers can effectively overcome resistance barriers. Moreover, these polymers can be easily incorporated into wound dressing materials—hydrogels being a particularly advantageous platform due to their biocompatibility and wound-conforming properties. In this study, we developed a modular strategy to integrate a biodegradable cationic antimicrobial oligomer, oligoamidine (<strong>OA1</strong>), into a thermo-responsive hydrogel. <strong>OA1</strong> exerts a triple antibacterial mechanism involving membrane disruption, DNA binding, and ROS generation. The resulting hydrogel system can be conveniently formulated by simple mixing and undergoes a solution-gel transition at body temperature, enabling easy application to infected skin wounds. Importantly, the hydrogel matrix does not impair the bactericidal efficacy of <strong>OA1</strong>, preserving its full antimicrobial potential. This synergistic system offers an effective and user-friendly approach for treating wounds infected with MDR pathogens.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004022","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":"The applications of single-cell multiomics in drug screening","authors":"Qingming Xue ,&nbsp;Hanyu Hu ,&nbsp;Ruogu Wang ,&nbsp;Fei Wu ,&nbsp;Haiqing Xiong","doi":"10.1016/j.pscia.2025.100090","DOIUrl":"10.1016/j.pscia.2025.100090","url":null,"abstract":"<div><div>Single-cell multiomics (scMultiomics) technologies and methods encompassing transcriptomics, genomics, epigenomics, proteomics, and metabolomics, together with associated computational tools have profoundly revolutionized disease research, enabling unprecedented dissection of cellular heterogeneity and dynamic biological responses. The use of scMultiomics technologies to study drug drug screening, actions and responses has not only unlocked novel avenues in precision drug screening but also transformed our understanding of how small molecules target specific cell types in cancer treatment, as well as their connections to disease etiology and progression from a high-resolution view of their functional diversity. In this review, we systematically explore how scMultiomics technologies develop and drive advancements in drug screening. With a specific focus on the applications in target identification, drug response, and drug resistance, we highlight how scMultiomics can link cellular-level insights with individualized drug screening, which in turn promises actionable strategies to improve therapeutic precision in drug development.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903507","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":"Targeted RNA base editing for therapeutic: mechanisms and advances","authors":"Weikai Yan,&nbsp;Xiaocheng Weng","doi":"10.1016/j.pscia.2025.100089","DOIUrl":"10.1016/j.pscia.2025.100089","url":null,"abstract":"<div><div>RNA base editing, which enables RNA base modification through effector proteins guided by targeting systems, is a powerful technology to correct disease-associated point mutations. Although overshadowed by CRISPR-based genome editing, RNA editing has seen rapid development in recent years, with significant improvements in efficiency and precision. In this review, we summarize the core components of RNA base editing systems (RNA-targeting systems and effector proteins) and describe major RNA editing types, including A-to-I, C-to-U, A-to-m⁶A/m⁶A-to-A, and U-to-Ψ base editors, along with their research progress. In addition, we systematically summarize the delivery methods of the developed RNA editors and their initial exploration in treating diseases caused by nonsense mutations. Finally, combining the current development status of the RNA editing related field, we reflect on the problems encountered in the current development of the RNA editing field and offer our own insights on the future development direction.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903972","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":"Enhancing ferroptosis and inhibiting ABCB1 make the novel aldose reductase inhibitor 5F-E a promising sensitizer in liver cancer","authors":"Ziyou Zheng ,&nbsp;Zhenqiang Chen ,&nbsp;Chao Zhang ,&nbsp;Shuling Peng ,&nbsp;Jianling Hu ,&nbsp;Chanxi Wang ,&nbsp;Lujie Liu ,&nbsp;Mao-xun Yang ,&nbsp;Heru Chen","doi":"10.1016/j.pscia.2025.100088","DOIUrl":"10.1016/j.pscia.2025.100088","url":null,"abstract":"<div><div>Multidrug resistance (MDR) poses a critical barrier to chemotherapy efficacy. While the promising agents, aldose reductase inhibitors (ARIs), to overcome multidrug resistance (MDR) has been investigated over recent decades, their underlying mechanisms remain unclear and clinically viable candidates are still lacking. In our study, we identified a novel ARI, 5F-E, which exhibited a more potent sensitizing effect on doxorubicin (DOX) resistant HepG2 cells (HepG2/ADR) compared to epalrestat (EPA). Both <strong>5F-E</strong> and EPA were observed to decrease intracellular GSH levels while elevating reactive oxygen species (ROS), Fe²⁺ and lipid peroxidation; these effects could be reversed by <em>N</em>-acetyl cysteine (NAC), suggesting that enhanced ferroptosis may be involved in restoring DOX sensitivity. Furthermore, inhibition of AKR1B1 by either compound led to marked reductions in <em>p</em>-STAT3 and SLC7A11 expression, an outcome that was recapitulated by AKR1B1 gene knockdown. The results demonstrate that ARIs exert antitumor effects on HepG2/ADR cells by triggering ferroptosis, a process dependent on AKR1B1/STAT3/SLC7A11 signaling. And, 5F-E, but not EPA, was found to increase intracellular DOX accumulation by inhibiting ABCB1. Our integrated experimental approach reveals that 5F-E exhibits strong chemosensitizing effects against multidrug-resistant liver cancer, highlighting its therapeutic promise.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010180","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":"An investigation into the underlying mechanisms of risperidone-induced antinociception through the cholinergic pathway","authors":"Lawrence Adedayo ,&nbsp;Victor Adesoye ,&nbsp;Olubayode Bamidele ,&nbsp;Idris Azeez ,&nbsp;Oyetola Oyebanjo ,&nbsp;Adeshina Adekeye ,&nbsp;Saminu Samaila ,&nbsp;Nimedia Aitokhuehi ,&nbsp;Olusegun Adebayo ,&nbsp;Gideon Ojo","doi":"10.1016/j.pscia.2025.100086","DOIUrl":"10.1016/j.pscia.2025.100086","url":null,"abstract":"<div><div>Pain is a complex phenomenon involving the perception of physical discomfort caused by tissue damage in the body. Risperidone, a neuroleptic with dopamine (D2) and serotonin (5-HT2) receptor antagonistic potentials, also exhibits antinociceptive properties, however, its use in the treatment of peripheral nociception has received little attention. Hence, this study evaluated the antinociceptive effects of risperidone and its possible mechanism of action. Ninety Swiss mice (23–30 ​g) were divided into two phases: antinociceptive and mechanistic. Antinociceptive activity was assessed using acetic acid-induced writhing and formalin-induced paw-licking tests. In each model, mice were grouped (n ​= ​6) and treated with distilled water (control), risperidone (0.5, 1.0, and 1.5 ​mg/kg), or indomethacin (10 ​mg/kg). Mechanistic studies involved atropine, propranolol, or naloxone co-administered with risperidone (1.5 ​mg/kg). The results of the studies showed that risperidone significantly decreased neurogenic and inflammatory pain in the paw licking test while risperidone 1.5 ​mg/kg significantly decreased writhing in the acetic acid-induced writhing test. In the mechanistic studies, atropine co-administered with risperidone group showed significantly reversed anti-nociception when compared with risperidone 1.5 ​mg/kg alone in the paw-licking test model. Histological assessment of the mice paw tissues using Hematoxylin &amp; Eosin, and Giemsa staining techniques revealed improved infiltration of inflammatory cells, which was significantly decreased in mice pre-treated with atropine, further supporting the analgesic potential of risperidone in the study. This study highlights risperidone's antinociceptive potential and suggests its mechanism is mediated via cholinergic pathways, offering insights into its therapeutic applications that can be implore in pain management.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829464","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":"Nanoplatforms in sepsis storm: Multimodal synergy for precision immunomodulation and pathogen neutralizations","authors":"Xinxin Wang ,&nbsp;Xuemei Wang ,&nbsp;Yuxin Cao ,&nbsp;Wenming Wang ,&nbsp;Dandan Liu ,&nbsp;Jingwen Zhang ,&nbsp;Yuxiu Chen ,&nbsp;Daquan Chen","doi":"10.1016/j.pscia.2025.100087","DOIUrl":"10.1016/j.pscia.2025.100087","url":null,"abstract":"<div><div>Sepsis, a severe global health challenge characterized by life-threatening organ dysfunction stemming from a dysregulated immune response to drug-resistant pathogens, imposes a substantial disease burden. The intricate nature of sepsis necessitates meticulous drug administration and underscores the urgency for advanced drug delivery strategies. This paper presents a comprehensive overview of recent advancements in nanotechnology-driven therapeutic interventions for sepsis, emphasizing innovative approaches such as stimulus-responsive and nano-drug delivery systems that have been applied to tackle sepsis and its associated complications. Drawing from various theories and mechanistic insights into sepsis pathogenesis, we explore novel therapeutic avenues and their potential integration with nano-delivery systems, considering factors such as the microenvironment. We demonstrate how these nano-delivery systems can enhance treatment accuracy and diversity. Furthermore, the synergy between nanomedicine and emerging technologies like CRISPR, CAR-T therapy, AI, microfluidics, microbiome research, and immunotherapy holds the promise to revolutionize sepsis diagnosis, treatment, and management strategies. However, overcoming pathogen resistance, precisely modulating excessive immune response/immunosuppression, and achieving efficient targeted delivery of nanocarriers in complex pathological environments remain core challenges. Future research needs to focus on the development of smarter and more responsive nanoplatforms and deeply explore their deep integration with multiple cutting-edge technologies in order to advance the clinical translation of precision sepsis diagnosis and treatment.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829465","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":"Circular RNA: From non-coding regulators to functional protein encoders","authors":"Xinwei Zhang ,&nbsp;Hongyan Wu ,&nbsp;Xuechuan Hong ,&nbsp;Yuling Xiao ,&nbsp;Xiaodong Zeng","doi":"10.1016/j.pscia.2025.100085","DOIUrl":"10.1016/j.pscia.2025.100085","url":null,"abstract":"<div><div>Circular RNAs (circRNAs), a distinct class of non-coding RNAs characterized by a covalently closed circular structure, have gained prominence as a promising research field due to their unique biological properties and functional roles relative to linear RNAs. This review summarizes recent progress in circRNA research, emphasizing fundamental mechanisms and translational potential. We first outline the discovery, biological features, synthesis, and purification of circRNAs. Next, their delivery systems, biological functions, and applications are reviewed. Finally, we discuss challenges and future prospects for clinical translation, with a focus on advancing precision medicine, gene therapy, and personalized vaccines. This review uniquely integrates recent advances in circRNA biology with their translational applications, offering a comprehensive perspective from molecular mechanisms to clinical potential.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004023","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}