Articles in press have been peer-reviewed and accepted, which are not yet assigned to volumes /issues, but are citable by Digital Object Identifier (DOI).
Display Method:
Butyrate-based ionic liquid for improved oral bioavailability and synergistic anti-colorectal cancer activity of glycyrol
Ziyu Wang, Xingyue Shi, Yikang Shu, Ran Gao, Ting Sun, Mingyue Wu, Mingxin Dong, Weiguo Wu, Ruili Ma, Daoquan Tang, Min Ye, Shuai Ji
 doi: 10.1016/j.jpha.2025.101359
[Abstract](0) [PDF 0KB](0)
Abstract:
Pharmacological mechanisms of natural products with antidepressant effects: A focus on the programmed cell death regulation
Guangheng Zhang, Shimeng Lv, Shengchuan Bao, Weijie Zhao, Yunhao Yi, Haonan Gao, Xia Zhong, Xiangyu Li, Fengzhao Liu, Yitong Lu, Siyuan Sun, Jing Teng
 doi: 10.1016/j.jpha.2025.101356
[Abstract](0) [PDF 1491KB](0)
Abstract:
Depression is a prevalent mental disorder characterized by persistent disinterest and a depressed mood, with severe cases potentially leading to suicide. In recent years, the incidence of depression has steadily increased, making it the second-largest global health burden. The pathogenesis of depression involves a series of complex pathological mechanisms, although the key underlying causes remain unclear. Programmed cell death (PCD), including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, involves highly organized gene expression processes that may influence the occurrence and development of depression by regulating cellular fate. Furthermore, numerous studies have shown that natural products can modulate PCDs through various signaling pathways, presenting significant potential for managing depression. Natural products offer benefits such as cost-effectiveness, fewer side effects, and other advantages, making them viable supplements or alternatives to traditional antidepressant drugs. To explore this potential, we reviewed studies demonstrating the antidepressant effects of natural products through multi-target modulation of PCDs. In addition, we discussed the toxicity and clinical applications of these natural products. This study highlights that diverse core biological pathways and targets are involved in determining the fate of depression-associated brain cells, including the PI3K/Akt signaling pathway, caspase-8, GSDMD, and others. In conclusion, the multi-target mechanisms of PCD regulation by natural products may provide a promising foundation for the future development of novel antidepressant medications.
Ferroptosis and retinal ganglion cell death in glaucoma: Mechanisms and therapeutic approaches
Minggao Qin, Xueqin He, Weiwen Qiu, Yanjing Peng, Yequan Liao, Jusen Zhao, Lianxiang Luo, Qiuli Zhang
 doi: 10.1016/j.jpha.2025.101355
[Abstract](0) [PDF 5840KB](0)
Abstract:
Glaucoma represents a predominant worldwide etiology of permanent vision impairment; it is clinically manifested through progressive neuronal atrophy in retinal ganglion cells (RGCs) and is accompanied by axonal degeneration in the optic pathway. Given the limited efficacy of conventional intraocular pressure-lowering therapies in halting RGC degeneration, the exploration of novel neuroprotective strategies has become imperative. An increasing amount of research emphasizes the pathogenic role of ferroptosis, a metal ion-associated programmed cellular demise mechanism recently implicated in neurodegenerative cascades, as a pivotal executor of RGC demise and putative central mechanism in glaucomatous pathology. This comprehensive review systematically examines the mechanistic interplay between ferroptosis and established contributors to glaucomatous optic neuropathy, including oxidative stress, mitochondrial dysfunction, glutamate excitotoxicity, and neuroinflammation. We provide evidence demonstrating that retinal ferroptosis is associated with the death of RGCs and discuss current therapeutic strategies to mitigate retinal ferroptosis, including treatments with natural products and gene therapy. Furthermore, by understanding ferroptosis, we provide insights into potential therapeutic targets and offer valuable directions for future research and clinical applications.
CXCL8/SDC1 Axis Mediates Tumor Stem Cell Interactions to Drive Remote Transfer in Thyroid Cancer
Wenjuan Wang, Jian Zhou, Baorui Tao, Ning Kong, Jie Shao
 doi: 10.1016/j.jpha.2025.101354
[Abstract](8) [PDF 12845KB](2)
Abstract:
CRISPR screening redefines therapeutic target identification and drug discovery with precision and scalability
Yao He, Xiao Tu, Yuxin Xue, Yuxuan Chen, Bengui Ye, Xiaojie Li, Dapeng Li, Zhihui Zhong, Qixing Zhong
 doi: 10.1016/j.jpha.2025.101357
[Abstract](10) [PDF 5308KB](0)
Abstract:
Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screening technology is redefining the landscape of drug discovery and therapeutic target identification by providing a precise and scalable platform for functional genomics. The development of extensive single-guide RNA (sgRNA) libraries enables high-throughput screening (HTS) that systematically investigates gene-drug interactions across the genome. This powerful approach has found broad applications in identifying drug targets for various diseases, including cancer, infectious diseases, metabolic disorders, and neurodegenerative conditions, playing a crucial role in elucidating drug mechanisms and facilitating drug screening. Despite challenges like off-target effects, data complexity, and ethical or regulatory concerns, ongoing advancements in CRISPR technology and bioinformatics are steadily overcoming these limitations. Additionally, by integrating with organoid models, artificial intelligence (AI), and big data technologies, CRISPR screening expands the scale, intelligence, and automation of drug discovery. This integration boosts data analysis efficiency and offers robust support for uncovering new therapeutic targets and mechanisms. This review outlines the fundamental principles and applications of CRISPR screening technology, delves into specific case studies and technical challenges, and highlights its expanding role in drug discovery and target identification. It also examines the potential for clinical translation and addresses the associated ethical and regulatory considerations.
Development of a dual-chamber derivatization method for the determination of cyanide in sodium nitroprusside and its preparation via HS-GC-ECD
Jinqi Zheng, Xinyu Zhao, Caixia Li, Chenxiao Yan, Pingping Chen, Xiao Gu, Liya Hong, Su Zeng
 doi: 10.1016/j.jpha.2025.101353
[Abstract](7) [PDF 1596KB](1)
Abstract:
The acute toxicity of cyanide and its pharmaceutical residues, has fueled interest in the development of analytical methods for its determination, particularly for sodium nitroprusside (SNP), a widely used vasodilator with potential cyanide residues. In this study, a dual-chamber derivatization bottle was designed to establish an interconnected gas environment, thereby facilitating chloramine T-mediated cyanide conversion to cyanogen chloride (CNCl) without direct contact with SNP. Subsequent determination of the analytes was undertaken using a headspace gas chromatography electron capture detector (HS-GC-ECD). The challenges of analyzing cyanide and the rapid degradation of SNP were addressed simultaneously. The method was subjected to rigorous validation, encompassing specificity, linearity, limits of detection (LOD), limit of quantification (LOQ), accuracy, precision, and robustness. The validation process revealed a notable degree of linearity within the range of 0.012-1.56 μg/mL, with a LOQ of 12.0 ng/mL. The method was found to be both accurate and precise, thus satisfying the requisite criteria. This method facilitates reliable cyanide monitoring in degradation-prone pharmaceuticals.
Export
Original articles
Radiotracer labeled thymohydroquinyl gallate capped gold nanoparticles as a theranostic radiopharmaceutical for targeted antineoplastic and bioimaging
Munaza Batool, Batool Fatima, Dilshad Hussain, Rubaida Mahmood, Muhammad Imran, Saeed Akhter, Muhammad Saqib Khan, Saadat Majeed, Muhammad Najam-ul-Haq
2025, 15(4): 100965.   doi: 10.1016/j.jpha.2024.100965
Abstract(181) HTML Full Text PDF(8)
Abstract:
Thymoquinone (TQ) and gallic acid (GA) are known for counter-tumorigenic characteristics. GA inhibits cancer cell proliferation by interfering with many apoptotic signaling pathways, producing more reactive oxygen species (ROS), focusing on the cell cycle, and suppressing the expression of oncogenes and matrix metalloproteinases (MMPs). In this study, TQ (after reducing to thymohydroquinone) and GA are esterified to form thymohydroquinyl gallate (a prodrug). Thymohydroquinyl gallate (THQG) possesses enhanced antineoplastic efficacy and targeted delivery potential. The chemical and spectroscopic analysis confirms ester synthesis. Gold nanoparticles (AuNPs) are employed as nanocarriers due to their physicochemical and optical characteristics, biocompatibility, and low toxicity. As an efficient drug transporter, (AuNPs shield conjugated drugs from enzymatic digestion. The prodrug acts as a reducing agent for Au metal atoms and is loaded onto it after reduction. The nano drug is radiolabeled with 99mTc and 131I to monitor the drug biodistribution in animals using a gamma camera and single-photon emission computerized tomography (SPECT). 131I is an antineoplastic that helps enhance the drug's efficiency. Chromatographic results reveal promising radiolabeling percentages. In vitro, drug release shows sustained release at pH ~5.8. In vitro 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) cytotoxicity assay reveals drug potency on CAL 27 and MCF 7 cell lines.
A tailored database combining reference compound-derived metabolite, metabolism platform and chemical characteristic of Chinese herb followed by activity screening: Application to Magnoliae Officinalis Cortex
Zhenzhen Xue, Yudong Shang, Lan Yang, Tao Li, Bin Yang
2025, 15(4): 101066.   doi: 10.1016/j.jpha.2024.101066
Abstract(151) HTML Full Text PDF(15)
Abstract:
A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex (MOC) was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine (TCM). The strategy possessed four characteristics: 1) The tailored database consisted of metabolites derived from big data-originated reference compound, metabolites predicted in silico, and MOC chemical profile-based pseudomolecular ions. 2) When profiling MOC-derived metabolites in vivo, attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds, as reported by most papers, but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites. 3) Metabolite traceability was performed, especially to distinguish isomeric prototypes-derived metabolites, prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds. 4) Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification. Using this strategy, 134 metabolites were swiftly characterized after the oral administration of MOC to rats, and several metabolites were reported for the first time. Furthermore, 17 potential active metabolites were discovered by targeting the motilin, dopamine D2, and the serotonin type 4 (5-HT4) receptors, and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model. This study extends the application of mass spectrometry (MS) to rapidly profile TCM-derived metabolites in vivo, which will help pharmacologists rapidly discover potent metabolites from a complex matrix.
Review papers
Pterostilbene: A natural neuroprotective stilbene with anti-Alzheimer's disease properties
Songlan Gao, Honglei Zhang, Na Li, Lijuan Zhang, Zhe Zhu, Changlu Xu
2025, 15(4): 101043.   doi: 10.1016/j.jpha.2024.101043
Abstract(94) HTML Full Text PDF(4)
Abstract:
Alzheimer's disease (AD) is the leading cause of dementia, and no effective treatment has been developed for it thus far. Recently, the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions. Accordingly, the potential therapeutic effect of pterostilbene (PTS) on AD has been demonstrated in multiple in vivo and in vitro experiments. In this study, we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD. Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms, including anti-oxidative damage, anti-neuroinflammation, anti-apoptosis, cholinesterase activity inhibition, attenuation of β-amyloid deposition, and tau protein hyperphosphorylation. Moreover, PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha (PPAR-α), monoamine oxidase B (MAO-B), silent information regulator sirtuin 1 (SIRT1), and phosphodiesterase 4A (PDE4A). Furthermore, to further elucidate the potential therapeutic mechanisms of PTS in AD, we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins, and the obtained binding energies ranged from -2.83 to -5.14 kJ/mol, indicating that these proteins exhibit good binding ability with PTS. Network pharmacology analysis revealed multiple potential mechanisms of action for PTS in AD. In summary, by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD, it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD, either using PTS or other developed drug interventions.
Pharmacological modulation of mitochondrial function as novel strategies for treating intestinal inflammatory diseases and colorectal cancer
Boya Wang, Xinrui Guo, Lanhui Qin, Liheng He, Jingnan Li, Xudong Jin, Dapeng Chen, Guangbo Ge
2025, 15(4): 101074.   doi: 10.1016/j.jpha.2024.101074
Abstract(228) HTML Full Text PDF(12)
Abstract:
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.
View All >
Molecular immune pathogenesis and diagnosis of COVID-19
Xiaowei Li, Manman Geng, Yizhao Peng, Liesu Meng, Shemin Lu
2020, 10(2): 102-108.  
[Abstract](2109) [PDF 2284KB](42)
摘要:
Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coro-navirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.
Structural basis of SARS-CoV-23CLpro and anti-COVID-19 drug discovery from medicinal plants
Muhammad Tahir ul Qamar, Safar M.Alqahtani, Mubarak A.Alamri, Ling-Ling Chen
2020, 10(4): 313-319.  
[Abstract](12505) [PDF 5841KB](133)
摘要:
The recent pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has raised global health concerns. The viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme controls coronavirus replication and is essential for its life cycle. 3CLpro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV. Therefore, herein, we analysed the 3CLpro sequence, constructed its 3D homology model, and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds. Our analyses revealed that the top nine hits might serve as potential anti- SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.
Recent advances and perspectives of nucleic acid detection for coronavirus
Minzhe Shen, Ying Zhou, Jiawei Ye, Abdu Ahmed Abdullah AL-maskri, Yu Kang, Su Zeng, Sheng Cai
2020, 10(2): 97-101.  
[Abstract](1897) [PDF 2697KB](37)
摘要:
The recent pneumonia outbreak caused by a novel coronavirus (SARS-CoV-2) is posing a great threat to global public health. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. It is important to establish a quick standard diagnostic test for the detection of the infectious disease (COVID-19) to prevent subsequent secondary spread. Polymerase chain reaction (PCR) is regarded as a gold standard test for the molecular diagnosis of viral and bacterial infections with high sensitivity and specificity. Isothermal nucleic acid amplification is considered to be a highly promising candidate method due to its fundamental advantage in quick procedure time at constant temperature without thermocycler opera-tion. A variety of improved or new approaches also have been developed. This review summarizes the currently available detection methods for coronavirus nucleic acid. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coro-navirus infection.
Research advances in the detection of miRNA
Jiawei Ye, Mingcheng Xu, Xueke Tian, Sheng Cai, Su Zeng
2019, 9(4): 217-226.  
[Abstract](812) [PDF 6429KB](44)
摘要:
MicroRNAs (miRNAs) are a family of endogenous, small (approximately 22 nucleotides in length), noncoding, functional RNAs. With the development of molecular biology, the research of miRNA bio-logical function has attracted significant interest, as abnormal miRNA expression is identified to contribute to serious human diseases such as cancers. Traditional methods for miRNA detection do not meet current demands. In particular, nanomaterial-based methods, nucleic acid amplification-based methods such as rolling circle amplification (RCA), loop-mediated isothermal amplification (LAMP), strand-displacement amplification (SDA) and some enzyme-free amplifications have been employed widely for the highly sensitive detection of miRNA. MiRNA functional research and clinical diagnostics have been accelerated by these new techniques. Herein, we summarize and discuss the recent progress in the development of miRNA detection methods and new applications. This review will provide guidelines for the development of follow-up miRNA detection methods with high sensitivity and spec-ificity, and applicability to disease diagnosis and therapy.
Application of microfluidic chip technology in pharmaceutical analysis:A review
Ping Cui, Sicen Wang
2019, 9(4): 238-247.  
[Abstract](432) [PDF 5845KB](40)
摘要:
The development of pharmaceutical analytical methods represents one of the most significant aspects of drug development. Recent advances in microfabrication and microfluidics could provide new approaches for drug analysis, including drug screening, active testing and the study of metabolism. Microfluidic chip technologies, such as lab-on-a-chip technology, three-dimensional (3D) cell culture, organs-on-chip and droplet techniques, have all been developed rapidly. Microfluidic chips coupled with various kinds of detection techniques are suitable for the high-throughput screening, detection and mechanistic study of drugs. This review highlights the latest (2010–2018) microfluidic technology for drug analysis and dis-cusses the potential future development in this field.
Carbon nanotubes:Evaluation of toxicity at biointerfaces
Debashish Mohanta, Soma Patnaik, Sanchit Sood, Nilanjan Das
2019, 9(5): 293-300.  
[Abstract](690) [PDF 3216KB](123)
摘要:
Carbon nanotubes (CNTs) are a class of carbon allotropes with interesting properties that make them productive materials for usage in various disciplines of nanotechnology such as in electronics equip-ments, optics and therapeutics. They exhibit distinguished properties viz., strength, and high electrical and heat conductivity. Their uniqueness can be attributed due to the bonding pattern present between the atoms which are very strong and also exhibit high extreme aspect ratios. CNTs are classified as single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) on the basis of number of sidewalls present and the way they are arranged spatially. Application of CNTs to improve the performance of many products, especially in healthcare, has led to an occupational and public exposure to these nanomaterials. Hence, it becomes a major concern to analyze the issues pertaining to the toxicity of CNTs and find the best suitable ways to counter those challenges. This review summarizes the toxicity issues of CNTs in vitro and in vivo in different organ systems (bio interphases) of the body that result in cellular toxicity.
Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase
Muhammad Usman Mirza, Matheus Froeyen
2020, 10(4): 320-328.  
[Abstract](606) [PDF 19436KB](74)
摘要:
Recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear, threatening global health safety. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are under way to test possible therapies. During this urgent situation, computational drug discovery methods provide an alternative to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has indicated the highest potential towards antiviral drug discovery. In this work, we present potential compounds that specifically target SARS-CoV-2 vital proteins, including the main protease, Nsp12 RNA polymerase and Nsp13 helicase. An integrative virtual screening and molecular dynamics simulations approach has facilitated the identifi-cation of potential binding modes and favourable molecular interaction profile of corresponding com-pounds. Moreover, the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural infor-mation obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.
Nanodiamonds with powerful ability for drug delivery and biomedical applications: Recent updates on in vivo study and patents
Swati Chauhan, Neha Jain, Upendra Nagaich
2020, 10(1): 1-12.  
[Abstract](393) [PDF 2643KB](20)
摘要:
Nanodiamonds are novel nanosized carbon building blocks possessing varied fascinating mechanical, chemical, optical and biological properties, making them significant active moiety carriers for biomedical application. These are known as the most'captivating' crystals attributed to their chemical inertness and unique properties posing them useful for variety of applications in biomedical era. Alongside, it becomes increasingly important to find, ascertain and circumvent the negative aspects associated with nano-diamonds. Surface modification or functionalization with biological molecules plays a significant role in managing the toxic behavior since nanodiamonds have tailorable surface chemistry. To take advantage of nanodiamond potential in drug delivery, focus has to be laid on its purity, surface chemistry and other considerations which may directly or indirectly affect drug adsorption on nanodiamond and drug release in biological environment. This review emphasizes on the basic properties, synthesis techniques, surface modification techniques, toxicity issues and biomedical applications of nanodiamonds. For the devel-opment of nanodiamonds as an effective dosage form, researchers are still engaged in the in-depth study of nanodiamonds and their effect on life interfaces.
Progress and prediction of multicomponent quantification in complex systems with practical LC-UV methods
Xi Chen, Zhao Yang, Yang Xu, Zhe Liu, Yanfang Liu, Yuntao Dai, Shilin Chen
2023, 13(2): 142-155.   doi: 10.1016/j.jpha.2022.11.011
[Abstract](2676) [PDF 1336KB](1337)
Abstract:
Complex systems exist widely, including medicines from natural products, functional foods, and biological samples. The biological activity of complex systems is often the result of the synergistic effect of multiple components. In the quality evaluation of complex samples, multicomponent quantitative analysis (MCQA) is usually needed. To overcome the difficulty in obtaining standard products, scholars have proposed achieving MCQA through the “single standard to determine multiple components (SSDMC)” approach. This method has been used in the determination of multicomponent content in natural source drugs and the analysis of impurities in chemical drugs and has been included in the Chinese Pharmacopoeia. Depending on a convenient (ultra) high-performance liquid chromatography method, how can the repeatability and robustness of the MCQA method be improved? How can the chromatography conditions be optimized to improve the number of quantitative components? How can computer software technology be introduced to improve the efficiency of multicomponent analysis (MCA)? These are the key problems that remain to be solved in practical MCQA. First, this review article summarizes the calculation methods of relative correction factors in the SSDMC approach in the past five years, as well as the method robustness and accuracy evaluation. Second, it also summarizes methods to improve peak capacity and quantitative accuracy in MCA, including column selection and two-dimensional chromatographic analysis technology. Finally, computer software technologies for predicting chromatographic conditions and analytical parameters are introduced, which provides an idea for intelligent method development in MCA. This paper aims to provide methodological ideas for the improvement of complex system analysis, especially MCQA.
Celastrol targeting Nedd4 reduces Nrf2-mediated oxidative stress in astrocytes after ischemic stroke
Zexuan Hong, Jun Cao, Dandan Liu, Maozhu Liu, Mengyuan Chen, Fanning Zeng, Zaisheng Qin, Jigang Wang, Tao Tao
2023, 13(2): 156-169.   doi: 10.1016/j.jpha.2022.12.002
[Abstract](607) [PDF 5665KB](295)
Abstract:
Stroke is the second leading cause of death worldwide, and oxidative stress plays a crucial role. Celastrol exhibits strong antioxidant properties in several diseases; however, whether it can affect oxidation in cerebral ischemic-reperfusion injury (CIRI) remains unclear. This study aimed to determine whether celastrol could reduce oxidative damage during CIRI and to elucidate the underlying mechanisms. Here, we found that celastrol attenuated oxidative injury in CIRI by upregulating nuclear factor E2-related factor 2 (Nrf2). Using alkynyl-tagged celastrol and liquid chromatography-tandem mass spectrometry, we showed that celastrol directly bound to neuronally expressed developmentally downregulated 4 (Nedd4) and then released Nrf2 from Nedd4 in astrocytes. Nedd4 promoted the degradation of Nrf2 through K48-linked ubiquitination and thus contributed to astrocytic reactive oxygen species production in CIRI, which was significantly blocked by celastrol. Furthermore, by inhibiting oxidative stress and astrocyte activation, celastrol effectively rescued neurons from axon damage and apoptosis. Our study uncovered Nedd4 as a direct target of celastrol, and that celastrol exerts an antioxidative effect on astrocytes by inhibiting the interaction between Nedd4 and Nrf2 and reducing Nrf2 degradation in CIRI.
Microneedle-based interstitial fluid extraction for drug analysis: Advances, challenges, and prospects
Shuwen Ma, Jiaqi Li, Lixia Pei, Nianping Feng, Yongtai Zhang
2023, 13(2): 111-126.   doi: 10.1016/j.jpha.2022.12.004
[Abstract](822) [PDF 4018KB](403)
Abstract:
Similar to blood, interstitial fluid (ISF) contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis. However, current ISF extraction techniques require bulky instruments and are both time-consuming and complicated, which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles. Currently, microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis. The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring, while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification. Herein, we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.
Identification and characterization of phenolics and terpenoids from ethanolic extracts of Phyllanthus species by HPLC-ESI-QTOF-MS/MS
Sunil Kumar, Awantika Singh, Brijesh Kumar
2017, 7(4): 214-222.  
[Abstract](973) [PDF 3923KB](479)
Abstract:
Phyllanthus species plants are a rich source of phenolics and widely used due to their medicinal properties. A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed using high-pressure liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-QTOF-MS/MS) for the identification and characterization of quercetin, kaempferol, ellagic acid and their derivatives in ethanolic extracts of Phyllanthus species. The chromatographic separation was carried out on Thermo Betasil C8 column (250 mm×4.5 mm, 5 μm) using 0.1% formic acid in water and 0.1% formic acid in methanol as the mobile phase. The identification of diagnostic fragment ions and optimization of collision energies were carried out using 21 reference standards. Totally 51 compounds were identified which include 21 compounds identified and characterized unambiguously by comparison with their authentic standards and the remaining 30 were tentatively identified and characterized in ethanolic extracts of P. emblica, P. fraternus, P. amarus and P. niruri.
Preface for Special Issue: Single-Cell and Spatially Resolved Omics
2023, 13(7): 689-690.   doi: 10.1016/j.jpha.2023.07.005
[Abstract](241) [PDF 229KB](119)
Abstract:
Potential of RP-UHPLC-DAD-MS for the qualitative and quantitative analysis of sofosbuvir in film coated tablets and profiling degradants
María del Mar Contreras, Aránzazu Morales-Soto, Antonio Segura-Carretero, Javier Valverde
2017, 7(4): 208-213.  
[Abstract](217) [PDF 2055KB](103)
Abstract:
Sofosbuvir is one of the new direct-acting antiviral drugs against hepatitis C virus (HCV) infection. This drug has recently been launched into the market, and generic versions of the medication are expected to be produced by local drug producers in some countries. Therefore, new methods are required to control sofosbuvir in pharmaceuticals. In the present study, a new method based on reversed phase (RP)-ultra-high performance liquid chromatography (UHPLC) coupled to diode array detection (DAD) and mass spectrometry (MS) was developed to facilitate the qualitative and quantitative analysis of sofosbuvir in film coated tablets. A wavelength of 260 nm was selected to perform a cost-effective quantification and the method showed adequate linearity, with an R2 value of 0.9998, and acceptable values of accuracy (75%–102%) and precision (residual standard deviation < 5%). The detection and quantification limits were 0.07 μg/mL and 0.36 μg/mL, respectively. Furthermore, the use of high-resolution MS enabled us to ensure the specificity, check impurities and better sensitivity. Therefore, this methodology promises to be suitable not only for the routine analysis of sofosbuvir in pharmaceutical dosage forms, but also for potential degradants.
Editorial Board
2023, 13(2): ii-ii.   doi: 10.1016/S2095-1779(23)00009-6
[Abstract](199) [PDF 64KB](99)
Abstract:
Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs
Qili Liao, Jie Yang, Shengfang Ge, Peiwei Chai, Jiayan Fan, Renbing Jia
2023, 13(2): 127-141.   doi: 10.1016/j.jpha.2022.11.009
[Abstract](695) [PDF 2290KB](352)
Abstract:
The reversible and precise temporal and spatial regulation of histone lysine methyltransferases (KMTs) is essential for epigenome homeostasis. The dysregulation of KMTs is associated with tumor initiation, metastasis, chemoresistance, invasiveness, and the immune microenvironment. Therapeutically, their promising effects are being evaluated in diversified preclinical and clinical trials, demonstrating encouraging outcomes in multiple malignancies. In this review, we have updated recent understandings of KMTs' functions and the development of their targeted inhibitors. First, we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis, tumor suppression, and immune regulation. In addition, we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors. In summary, we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.