{"title":"Probing the biological efficacy and mechanistic pathways of natural compounds in breast cancer therapy via the Hedgehog signaling pathway.","authors":"Yining Cheng, Wenfeng Zhang, Qi Sun, Xue Wang, Qihang Shang, Jingyang Liu, Yubao Zhang, Ruijuan Liu, Changgang Sun","doi":"10.1016/j.jpha.2024.101143","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101143","url":null,"abstract":"<p><p>Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101143"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040542","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":"Pharmacological modulation of mitochondrial function as novel strategies for treating intestinal inflammatory diseases and colorectal cancer.","authors":"Boya Wang, Xinrui Guo, Lanhui Qin, Liheng He, Jingnan Li, Xudong Jin, Dapeng Chen, Guangbo Ge","doi":"10.1016/j.jpha.2024.101074","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101074","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101074"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063739","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":"New uses of halofuginone to treat cancer.","authors":"Runan Zuo, Xinyi Guo, Xinhao Song, Xiuge Gao, Junren Zhang, Shanxiang Jiang, Vojtech Adam, Kamil Kuca, Wenda Wu, Dawei Guo","doi":"10.1016/j.jpha.2024.101080","DOIUrl":"10.1016/j.jpha.2024.101080","url":null,"abstract":"<p><p>The small-molecule alkaloid halofuginone (HF) is obtained from febrifugine. Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions, which range from parasite infections and fibrosis to autoimmune diseases. In particular, HF is believed to play an excellent anticancer role by suppressing the proliferation, adhesion, metastasis, and invasion of cancers. This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF. In the studies covered in this review, the anticancer molecular mechanisms of HF mainly included transforming growth factor-β (TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2 (Nrf2), serine/threonine kinase proteins (Akt)/mechanistic target of rapamycin complex 1(mTORC1)/wingless/integrated (Wnt)/β-catenin, the exosomal microRNA-31 (miR-31)/histone deacetylase 2 (HDAC2) signaling pathway, and the interaction of the extracellular matrix (ECM) and immune cells. Notably, HF, as a novel type of adenosine triphosphate (ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase (ProRS) and amino acid starvation therapy (AAS) to suppress the formation of ribosome, further exerts a significant effect on the tumor microenvironment (TME). Additionally, the combination of HF with other drugs or therapies obtained universal attention. Our results showed that HF has significant potential for clinical cancer treatment.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 3","pages":"101080"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653105","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 role of mitochondria transfer in cancer biological behavior, the immune system and therapeutic resistance.","authors":"Xintong Lyu, Yangyang Yu, Yuanjun Jiang, Zhiyuan Li, Qiao Qiao","doi":"10.1016/j.jpha.2024.101141","DOIUrl":"10.1016/j.jpha.2024.101141","url":null,"abstract":"<p><p>Mitochondria play a crucial role as organelles, managing several physiological processes such as redox balance, cell metabolism, and energy synthesis. Initially, the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria. Recent scholarly works, however, suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer. This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms. Specifically, we review the role of mitochondria transfer in regulating cellular metabolism restoration, excess reactive oxygen species (ROS) generation, proliferation, invasion, metastasis, mitophagy activation, mitochondrial DNA (mtDNA) inheritance, immune system modulation and therapeutic resistance in cancer. Additionally, we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 3","pages":"101141"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672157","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":"Elucidating the role of artificial intelligence in drug development from the perspective of drug-target interactions.","authors":"Boyang Wang, Tingyu Zhang, Qingyuan Liu, Chayanis Sutcharitchan, Ziyi Zhou, Dingfan Zhang, Shao Li","doi":"10.1016/j.jpha.2024.101144","DOIUrl":"10.1016/j.jpha.2024.101144","url":null,"abstract":"<p><p>Drug development remains a critical issue in the field of biomedicine. With the rapid advancement of information technologies such as artificial intelligence (AI) and the advent of the big data era, AI-assisted drug development has become a new trend, particularly in predicting drug-target associations. To address the challenge of drug-target prediction, AI-driven models have emerged as powerful tools, offering innovative solutions by effectively extracting features from complex biological data, accurately modeling molecular interactions, and precisely predicting potential drug-target outcomes. Traditional machine learning (ML), network-based, and advanced deep learning architectures such as convolutional neural networks (CNNs), graph convolutional networks (GCNs), and transformers play a pivotal role. This review systematically compiles and evaluates AI algorithms for drug- and drug combination-target predictions, highlighting their theoretical frameworks, strengths, and limitations. CNNs effectively identify spatial patterns and molecular features critical for drug-target interactions. GCNs provide deep insights into molecular interactions via relational data, whereas transformers increase prediction accuracy by capturing complex dependencies within biological sequences. Network-based models offer a systematic perspective by integrating diverse data sources, and traditional ML efficiently handles large datasets to improve overall predictive accuracy. Collectively, these AI-driven methods are transforming drug-target predictions and advancing the development of personalized therapy. This review summarizes the application of AI in drug development, particularly in drug-target prediction, and offers recommendations on models and algorithms for researchers engaged in biomedical research. It also provides typical cases to better illustrate how AI can further accelerate development in the fields of biomedicine and drug discovery.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 3","pages":"101144"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653104","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}
Yong Wang, Kewen He, Yang Zhang, Yunhao Chen, Shijie Wang, Kunlong Zhao, Zhiguo Liu, Man Hu
{"title":"Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy.","authors":"Yong Wang, Kewen He, Yang Zhang, Yunhao Chen, Shijie Wang, Kunlong Zhao, Zhiguo Liu, Man Hu","doi":"10.1016/j.jpha.2024.101082","DOIUrl":"10.1016/j.jpha.2024.101082","url":null,"abstract":"<p><p>Real-time, noninvasive programmed death-ligand 1 (PD-L1) testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy. However, the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography (PET/CT) remains limited. This investigation involved the synthesis of [<sup>18</sup>F]AlF-NOTA-PCP2, which is a novel peptide-based radiolabeled tracer that targets PD-L1, and evaluated its imaging capabilities in orthotopic glioblastoma (GBM) models. Using this tracer, we could noninvasively monitor radiation-induced PD-L1 changes in GBM. [<sup>18</sup>F]AlF-NOTA-PCP2 exhibited high radiochemical purity (>95%) and stability up to 4 h after synthesis. It demonstrated specific, high-affinity binding to PD-L1 <i>in vitro</i> and <i>in vivo</i>, with a dissociation constant of 0.24 nM. PET/CT imaging, integrated with contrast-enhanced magnetic resonance imaging, revealed significant accumulation of [<sup>18</sup>F]AlF-NOTA-PCP2 in orthotopic tumors, correlating with blood-brain barrier disruption. After radiotherapy (15 Gy), [<sup>18</sup>F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51% ± 0.73% to 12.04% ± 1.43%, indicating enhanced PD-L1 expression consistent with immunohistochemistry findings. Fractionated radiation (5 Gy × 3) further amplified PD-L1 upregulation (13.9% ± 1.54% ID/cc) compared with a single dose (11.48% ± 1.05% ID/cc). Taken together, [<sup>18</sup>F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 3","pages":"101082"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775218","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":"Unlocking the dual role of autophagy: A new strategy for treating lung cancer.","authors":"Fei Tang, Jing-Nan Zhang, Xiao-Lan Zhao, Li-Yue Xu, Hui Ao, Cheng Peng","doi":"10.1016/j.jpha.2024.101098","DOIUrl":"10.1016/j.jpha.2024.101098","url":null,"abstract":"<p><p>Lung cancer exhibits the highest incidence and mortality rates among cancers globally, with a five-year overall survival rate alarmingly below 20%. Targeting autophagy, though a controversial therapeutic strategy, is extensively employed in clinical practice. Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy. Nevertheless, the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention. This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer. It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells. Notably, most autophagy-targeting drugs, primarily natural small molecules, have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer, as opposed to inhibiting protective autophagy. These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies, offering promising approaches to combat this disease.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 3","pages":"101098"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660279","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":"Advanced treatment strategies for high-altitude pulmonary hypertension employing natural medicines: A review.","authors":"Zahra Batool, Mohammad Amjad Kamal, Bairong Shen","doi":"10.1016/j.jpha.2024.101129","DOIUrl":"10.1016/j.jpha.2024.101129","url":null,"abstract":"<p><p>High-altitude pulmonary hypertension (HAPH) occurs when blood pressure in the pulmonary arteries rises due to exposure to high altitudes above 2,500 m. At these elevations, reduced atmospheric pressure leads to lower oxygen levels, triggering a series of physiological responses, including pulmonary artery constriction, which elevates blood pressure. This review explored the complex pathophysiological mechanisms of HAPH and reviewed current pharmaceutical interventions for its management. Meanwhile, this review particularly emphasized on the emerging research concerning Chinese medicinal plants as potential treatments for HAPH. Traditional Chinese medicines are rich in diverse natural ingredients that show significant promise in alleviating HAPH symptoms. We reviewed both <i>in vitro</i> and <i>in vivo</i> studies to assess the efficacy, safety, and mechanisms of these natural medicines, along with their potential adverse effects. Additionally, this review highlighted new alternative natural remedies, underscoring the need for ongoing research to expand available treatment options for HAPH.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 3","pages":"101129"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756717","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":"Rapid enrichment and SERS differentiation of various bacteria in skin interstitial fluid by 4-MPBA-AuNPs-functionalized hydrogel microneedles.","authors":"Ying Yang, Xingyu Wang, Yexin Hu, Zhongyao Liu, Xiao Ma, Feng Feng, Feng Zheng, Xinlin Guo, Wenyuan Liu, Wenting Liao, Lingfei Han","doi":"10.1016/j.jpha.2024.101152","DOIUrl":"10.1016/j.jpha.2024.101152","url":null,"abstract":"<p><p>Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10<sup>7</sup> to 1 × 10<sup>10</sup> colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 3","pages":"101152"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672154","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}