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Exosomes in ovarian cancer: impact on drug resistance and advances in SERS detection techniques
Biqing Chen, Xiaohong Qiu, Yang Li
 doi: 10.1016/j.jpha.2024.101170
[Abstract](0) [PDF 0KB](0)
Abstract:
Ovarian cancer is a prevalent gynecological malignancy with high mortality and low survival rates. The absence of specific symptoms in early stages often leads to late-stage diagnoses. Standard treatment typically includes surgery followed by platinum and paclitaxel chemotherapy. Exosomes, nanoscale vesicles released by various cell types, are key in intercellular communication, carrying biologically active molecules like proteins, lipids, enzymes, mRNA, and miRNAs. They are involved in tumor microenvironment remodeling, angiogenesis, metastasis, and chemoresistance in ovarian cancer. Emerging research highlights exosomes as drug carriers and therapeutic targets to suppress anti-tumor immune responses. Surface-Enhanced Raman Scattering (SERS) enables multiplexed, sensitive, and rapid detection of exosome surface proteins, offering advantages such as low background noise, no photobleaching, robustness, and high sensitivity over other detection methods. This review explores the relationship between exosomes and chemoresistance in ovarian cancer, examining the mechanisms by which exosomes contribute to drug resistance and their clinical implications. The goal is to provide new insights into chemoresistance mechanisms, improve diagnosis and intervention strategies, and enhance chemotherapy sensitivity in clinical treatments. In addition, the prospects of exosomes as drug carriers to resist chemical resistance and improve the survival of ovarian cancer patients are summarized. This article emphasizes the role of SERS in detecting ovarian cancer exosomes and advances in exosome detection.
Aldolase A accelerates hepatocarcinogenesis by refactoring c-Jun transcription
Xin Yang, Guang-Yuan Ma, Xiao-Qiang Li, Na Tang, Yang Sun, Xiao-Wei Hao, KeHan Wu, Yu-Bo Wang, Wen Tian, Xin Fan, Zezhi Li, Caixia Feng, Xu Chao, Yu-Fan Wang, Yao Liu, Di Li, Wei Cao
 doi: 10.1016/j.jpha.2024.101169
[Abstract](14) [PDF 8516KB](0)
Abstract:
Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c- Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of ALDOA strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.
Advances and challenges in drug design against dental caries: application of in silico approaches
Zhongxin Chen, Xinyao Zhao, Hanyu Zheng, Yufei Wang, Linglin Zhang
 doi: 10.1016/j.jpha.2024.101161
[Abstract](8) [PDF 10078KB](2)
Abstract:
Dental caries, a chronic disease characterized by tooth decay, occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria, especially Streptococcus mutans, because of its acidogenic, aciduric, and biofilm-forming capabilities. Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents. The current study represents an up-to-date review of in silico approaches of drug design against dental caries, which have emerged more and more powerful complementary to biochemical attempts. Firstly, we categorize the in silico approaches into computer-aided drug design (CADD) and AI-assisted drug design (AIDD) and highlight the specific methods and models they contain respectively. Subsequently, we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S. mutans, such as glucosyltransferases (Gtfs), antigen I/II (AgI/II), sortase A (SrtA), the VicRK signal transduction system and superoxide dismutases (SODs). Finally, we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.
The integration of artificial intelligence into traditional Chinese medicine
Yanfeng Hong, Sisi Zhu, Yuhong Liu, Chao Tian, Hongquan Xu, Gongxing Chen, Lin Tao, Tian Xie
 doi: 10.1016/j.jpha.2024.101157
[Abstract](20) [PDF 3837KB](5)
Abstract:
Traditional Chinese medicine (TCM) is an ancient medical system distinctive and effective in treating cancer, depression, coronavirus disease 2019 (COVID-19), and other diseases. However, the relatively abstract diagnostic methods of TCM lack objective measurement, and the complex mechanisms of action are difficult to comprehend, which hinders the application and internationalization of TCM. Recently, while breakthroughs have been made in utilizing methods such as network pharmacology and virtual screening for traditional Chinese medicine research, the rise of machine learning (ML) has significantly enhanced their integration with TCM. This article introduces representative methodological cases in quality control, mechanism research, diagnosis, and treatment processes of TCM, revealing the potential applications of ML technology in TCM. Furthermore, the challenges faced by ML in TCM applications are summarized, and future directions are discussed.
Unveiling the role of Pafah1b3 in liver fibrosis: A novel mechanism revealed
Lifan Lin, Shouzhang Yang, Xinmiao Li, Weizhi Zhang, Jianjian Zheng
 doi: 10.1016/j.jpha.2024.101158
[Abstract](10) [PDF 34859KB](1)
Abstract:
Liver fibrosis is a common outcome of various chronic hepatic insults, characterized by excessive extracellular matrix (ECM) deposition. The precise mechanisms, however, remain largely undefined. This study identified an elevated expression of Platelet-activating factor acetylhydrolase 1B3 (Pafah1b3) in liver tissues from both carbon tetrachloride (CCl4)-treated mice and patients with cirrhosis. Deletion of Pafah1b3 significantly attenuated CCl4-induced fibrosis, hepatic stellate cell (HSC) activation, and activation of transforming growth factor-β (TGF-β) signaling. Mechanistically, PAFAH1B3 binds to mothers against decapentaplegic homolog 7 (SMAD7), disrupting SMAD7’s interaction with TGF-β receptor 1 (TβR1), which subsequently decreases TβR1 ubiquitination and degradation. Pharmacological inhibition using 3-IN-P11, a specific Pafah1b3 inhibitor, conferred protective effects against CCl4-induced fibrosis in mice. Furthermore, Pafah1b3 deficiency reduced hepatic inflammation. Overall, these results establish a pivotal role for Pafah1b3 in modulating TGF-β signaling and driving HSC activation.
RCAN-DDI: Relation-aware Cross Adversarial Network for Drug-Drug Interaction Prediction
Yuanyuan Zhang, Xiaoyu Xu, Baoming Feng, Haoyu Zheng, Ci'ao Zhang, Wentao Xu, Zengqian Deng
 doi: 10.1016/j.jpha.2024.101159
[Abstract](8) [PDF 1688KB](1)
Abstract:
Drug-drug interaction (DDI) refers to the interaction between two or more drugs in the body, altering their efficacy or pharmacokinetics. Fully considering and accurately predicting DDI has become an indispensable part of ensuring safe medication for patients. In recent years, many deep learning-based methods have been proposed to predict DDI. However, most existing computational models tend to oversimplify the fusion of drug structural and topological information, often relying on methods such as splicing or weighted summation, which fail to adequately capture the potential complementarity between structural and topological features. This loss of information may lead to models that do not fully leverage these features, thus limiting their performance in DDI prediction. To address these challenges, we propose a Relation-aware Cross Adversarial Network for predicting DDI, named RCAN-DDI, which combines a relationship-aware structure feature learning module and a topological feature learning module based on DDI networks to capture multimodal features of drugs. To explore the correlations and complementarities among different information sources, the cross-adversarial network is introduced to fully integrate features from various modalities, enhancing the predictive performance of the model. The experimental results demonstrate that the RCAN-DDI method outperforms other methods. Even in cases of labeled DDI scarcity, the method exhibits good robustness in the DDI prediction task. Furthermore, the effectiveness of the cross-adversarial module is validated through ablation experiments, demonstrating its superiority in learning multimodal complementary information.
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Review papers
Advances in surface plasmon resonance for analyzing active components in traditional Chinese medicine
Jing Xie, Xian-Deng Li, Mi Li, Hong-Yan Zhu, Yan Cao, Jian Zhang, A-Jing Xu
2024, 14(10): 100983.   doi: 10.1016/j.jpha.2024.100983
Abstract(221) HTML Full Text PDF(22)
Abstract:

The surface plasmon resonance (SPR) biosensor technology is a novel optical analysis method for studying intermolecular interactions. Owing to in-depth research on traditional Chinese medicine (TCM) in recent years, comprehensive and specific identification of components and target interactions has become key yet difficult tasks. SPR has gradually been used to analyze the active components of TCM owing to its high sensitivity, strong exclusivity, large flux, and real-time monitoring capabilities. This review sought to briefly introduce the active components of TCM and the principle of SPR, and provide historical and new insights into the application of SPR in the analysis of the active components of TCM.

miR-135b: An emerging player in cardio-cerebrovascular diseases
Yingchun Shao, Jiazhen Xu, Wujun Chen, Minglu Hao, Xinlin Liu, Renshuai Zhang, Yanhong Wang, Yinying Dong
2024, 14(10): 100997.   doi: 10.1016/j.jpha.2024.100997
Abstract(200) HTML Full Text PDF(6)
Abstract:

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b. Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases. It is involved in regulating the pathological process of myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, atrial fibrillation, diabetic cardiomyopathy, atherosclerosis, pulmonary hypertension, cerebral ischemia/reperfusion injury, Parkinson's disease, and Alzheimer's disease. Obviously, miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases. However, the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed. Therefore, in this review, we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases. Drugs targeting miR-135b for the treatment of diseases and related patents, highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases, have been discussed.

Epigenetic regulation of targeted ferroptosis: A new strategy for drug development
Shengli Ouyang, Zeyao Zeng, Jieyi He, Lianxiang Luo
2024, 14(10): 101012.   doi: 10.1016/j.jpha.2024.101012
Abstract(126) HTML Full Text PDF(17)
Abstract:

Ferroptosis is a newly discovered form of cell death that is influenced by iron levels and is triggered by cellular metabolism and excessive lipid peroxidation. Epigenetic regulation plays a crucial role in the development and progression of diseases, making it essential to understand these mechanisms in order to identify potential targets for drug development and clinical treatment. The intersection of ferroptosis and epigenetics has opened up new avenues for research in drug development, offering innovative strategies for combating diseases. Recent studies have shown that epigenetic modifications can impact pathways related to ferroptosis, potentially leading to organ dysfunction. Despite the increasing focus on this relationship, the role of epigenetic regulation in drug development remains largely unexplored. This article explores current research on the interplay between epigenetic regulation and ferroptosis, delving into their regulatory mechanisms and discussing the effects of existing epigenetic modification regulators on diseases. Additionally, we highlight ongoing research on epigenetic factors involved in targeting ferroptosis in cancer, providing new insights for the development of cancer treatments.

Original articles
“Small is beautiful”—Examining reliable determination of low-abundant therapeutic antibody glycovariants
Katharina Böttinger, Christof Regl, Veronika Schäpertöns, Erdmann Rapp, Therese Wohlschlager, Christian G. Huber
2024, 14(10): 100982.   doi: 10.1016/j.jpha.2024.100982
Abstract(123) HTML Full Text PDF(8)
Abstract:

Glycans associated with biopharmaceutical drugs play crucial roles in drug safety and efficacy, and therefore, their reliable detection and quantification is essential. Our study introduces a multi-level quantification approach for glycosylation analysis in monoclonal antibodies (mAbs), focusing on minor abundant glycovariants. Mass spectrometric data is evaluated mainly employing open-source software tools. Released N-glycan and glycopeptide data form the basis for integrating information across different structural levels up to intact glycoproteins. Comprehensive comparison showed that indeed, variations across structural levels were observed especially for minor abundant species. Utilizing modification finder (MoFi), a tool for annotating mass spectra of intact proteins, we quantify isobaric glycosylation variants at the intact protein level. Our workflow's utility is demonstrated on NISTmAb, rituximab and adalimumab, profiling their minor abundant variants for the first time across diverse structural levels. This study enhances understanding and accessibility in glycosylation analysis, spotlighting minor abundant glycovariants in therapeutic antibodies.

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Molecular immune pathogenesis and diagnosis of COVID-19
Xiaowei Li, Manman Geng, Yizhao Peng, Liesu Meng, Shemin Lu
2020, 10(2): 102-108.  
[Abstract](1084) [PDF 2284KB](20)
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](1558) [PDF 5841KB](34)
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](1232) [PDF 2697KB](18)
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.
Application of microfluidic chip technology in pharmaceutical analysis:A review
Ping Cui, Sicen Wang
2019, 9(4): 238-247.  
[Abstract](370) [PDF 5845KB](19)
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.
Research advances in the detection of miRNA
Jiawei Ye, Mingcheng Xu, Xueke Tian, Sheng Cai, Su Zeng
2019, 9(4): 217-226.  
[Abstract](599) [PDF 6429KB](18)
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.
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](492) [PDF 19436KB](12)
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.
Carbon nanotubes:Evaluation of toxicity at biointerfaces
Debashish Mohanta, Soma Patnaik, Sanchit Sood, Nilanjan Das
2019, 9(5): 293-300.  
[Abstract](463) [PDF 3216KB](14)
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.
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](274) [PDF 2643KB](7)
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.
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](701) [PDF 3923KB](350)
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.
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](2326) [PDF 1336KB](1158)
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.
Preface for Special Issue: Single-Cell and Spatially Resolved Omics
2023, 13(7): 689-690.   doi: 10.1016/j.jpha.2023.07.005
[Abstract](179) [PDF 229KB](91)
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](147) [PDF 2055KB](72)
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
2021, 11(6).  
[Abstract](211) [PDF 64KB](105)
Abstract:
Natural Product Virtual-Interact-Phenotypic Target Characterization: A Novel Approach Demonstrated with Salvia Miltiorrhiza Extract
Rui Xu, Hengyuan Yu, Yichen Wang, Boyu Li, Yong Chen, Xuesong Liu, Tengfei Xu
doi: 10.1016/j.jpha.2024.101101
[Abstract](383) [PDF 4176KB](186)
Abstract:
Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative Natural Product Virtual screening-Interaction-Phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high- confidence targets, including Poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.
Single-cell RNA-sequencing and subcellular spatial transcriptomics facilitate the translation of liver microphysiological systems for regulatory application
Dan Li, Zhou Fang, Qiang Shi, Nicholas Zhang, Binsheng Gong, Weida Tong, Ahmet F. Coskun, Joshua Xu
2023, 13(7): 691-693.   doi: 10.1016/j.jpha.2023.06.013
[Abstract](683) [PDF 707KB](332)
Abstract:
Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer
Xiaofan Sun, Lisha Zhou, Yi Wang, Guoliang Deng, Xinran Cao, Bowen Ke, Xiaoqi Wu, Yanhong Gu, Haibo Cheng, Qiang Xu, Qianming Du, Hongqi Chen, Yang Sun
2023, 13(7): 726-744.   doi: 10.1016/j.jpha.2023.04.013
[Abstract](551) [PDF 9014KB](272)
Abstract:
Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy. Cannabidiol (CBD) is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects, including neuroprotective, antiemetic, anti-inflammatory, and antineoplastic activities. This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) technologies. Here, we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment (TME). Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity. Furthermore, CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages, thereby preventing tumor progression. Mechanistically, CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways. We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes. Furthermore, CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1 (PD-1) immunotherapy in xenografted mice. Taken together, we provide new insights into the anti-tumor effects of CBD.