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).
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Targeting SH3GL1 for Prognosis and Immune Response in Breast Cancer
Si Si, Hong Yu, Hao Zhang, Jianqiao Yin, Ziwei Li, Ning Wang, Xiaopeng Yu
 doi: 10.1016/j.jpha.2025.101377
[Abstract](0) [PDF 0KB](0)
Abstract:
The cuproptosis-related gene (CRG) SH3GL1 is identified as a pivotal regulator in breast cancer (BRCA) progression and immune regulation in this study. Through gene expression profiling and meta-analysis of public datasets, SH3GL1 was found to be overexpressed in BRCA tumor tissues and correlated with poor prognosis. Single-cell RNA sequencing pinpointed SH3GL1's expression in epithelial cells and its critical interactions with immune cells, particularly T cells and monocytes. Functional experiments confirmed SH3GL1’s role in promoting immune cell migration and modulating drug sensitivity. Moreover, high SH3GL1 expression was linked to reduced immunotherapy response, as revealed by TIDE scoring, suggesting its contribution to the immune microenvironment complexity in high-risk BRCA groups. These results emphasize SH3GL1's dual role as a prognostic biomarker and a target for therapeutic intervention in BRCA, providing new insights into personalized cancer treatment approaches.
Antimicrobial sonodynamic therapy: recent advances and challenges in new therapeutic approaches to antimicrobials
Linyu Xue, Shidian Ran, Jindie Huang, Xiaorui Wei, Xingrui Yan, Tongchuan He, Hongmei Zhang, Mengqin Gu
 doi: 10.1016/j.jpha.2025.101375
[Abstract](0) [PDF 2560KB](0)
Abstract:
Pathogenic microorganisms pose significant threat to global health. In particular, conventional antibiotic treatments run the risk of exacerbating bacterial resistance. Antimicrobial sonodynamic therapy (aSDT), which combines sonosensitizers and low-intensity ultrasound (US), has opened up new avenues for the treating drug-resistant bacteria. The appeal of this therapy lies in its ability to focus US energy toward the deep-seated site of bacterial infection sites, it locally activates sonosensitizers and generates cytotoxic reactive oxygen species (ROS), which ultimately induces bacterial death. In the last decade, aSDT has been rapidly developed due to its good penetrative, biocompatibility and targeting properties. This paper highlights the recent aSDT advances in antimicrobial applications. We review aSDT mechanisms and sonosensitizers types, and propose relevant strategies to improve aSDT effects in terms of improving hypoxia and combining applications with other therapies. Furthermore, we summarize the potential obstacles and opportunities for the advancement of aSDT, and provide a deeper understanding of sonodynamic therapy (SDT) for antimicrobial applications, thereby promoting further innovation and clinical application.
Validation of breast cancer as a risk factor for anxiety and depression: insights from mendelian randomization analysis
Guannan He, Man Xi, Tianhao Zhang, Shuang Wang, Gang Liu
 doi: 10.1016/j.jpha.2025.101378
[Abstract](0) [PDF 27022KB](0)
Abstract:
This study employed Mendelian randomization (MR) analysis to confirm the association between breast cancer and the risk of anxiety and depression, and to explore the molecular mechanisms by which lipid nanoparticles of ketamine (LNP@Ket) modulate these behaviors in a mouse model of breast cancer. Through single-cell transcriptomic analysis, the study aimed to clarify nuclear factor erythroid 2-related factor 2 (Nrf2)'s role in the development of anxiety and depression in these mice. Analysis of patient data from genome-wide association study (GWAS) databases supported the link between breast cancer, anxiety, and depression. In vivo experiments demonstrated that treating breast cancer mice with LNP@Ket significantly reduced anxiety and depression behaviors. The synthesis of LNP@Ket and its subsequent analysis highlighted its inhibitory effects on these behaviors. Single-cell transcriptomic sequencing identified key cells and genes affected by LNP@Ket treatment, particularly emphasizing Nrf2. Upregulation of Nrf2 in astrocytes increased the expression of antioxidant enzymes and reduced pro-inflammatory cytokines, alleviating anxiety and depression symptoms by inhibiting neuroinflammation and neurodegeneration. This comprehensive study highlights the pivotal role of Nrf2 in the therapeutic efficacy of LNP@Ket for treating anxiety and depression in breast cancer mice.
Synergistic antibacterial and anti-inflammatory potentials of dual-loaded self-healing hydrogel for methicillin-resistant Staphylococcus aureus-infected wound healing
Sangyu Hu, Weigang Zhong, Yuzhu Pei, Yutong Zhou, Jianfeng Wang, Xuming Deng, Zihao Teng, Lei Xu
 doi: 10.1016/j.jpha.2025.101376
[Abstract](0) [PDF 35179KB](0)
Abstract:
The emergence of drug-resistant bacterial infection and persistent biofilm colonization pose a rigorous challenge to effective wound healing and regeneration, necessitating the innovative therapeutic strategies to combat these pressing clinical crises. Herein, nortriptyline, a novel FDA-approved tricyclic antidepressant was uncovered to effectively potentiate bactericidal activities of β-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA). Mechanistically, nortriptyline functions by disrupting the microbial iron homeostasis and potentiation of Fenton chemistry-mediated oxidative stress, concomitant with metabolic reprogramming via TCA cycle dysregulation and membrane destabilization. To enhance combination therapy-mediated therapeutic potential in wound management, the dual-loaded self-healing hydrogel OHA-PLL@AN was engineered to exhibit excellent biocompatibility and antibacterial potentials through molecular cross-linking of oxidized hyaluronic acid (OHA) and ε-polylysine (PPL). The therapeutic efficacy of OHA-PLL@AN was further validated in a murine model with MRSA-infected cutaneous wounds. OHA-PLL@AN therapy significantly attenuated the inflammatory response, concurrently promoting angiogenesis and accelerating the cutaneous wounds healing. Collectively, these findings underscore the dual drug-loaded self-healing hydrogel OHA-PLL@AN with anti-infection and anti-inflammatory properties as a novel therapeutic strategy for drug-resistant bacterial infected wounds therapy.
Luteolin attenuates RA-associated chronic pain by targeting the LDHA/H3K9la/NFATC2 axis to suppress Th17 cell differentiation and central infiltration
Yuepeng Jiang, Yang Zhao, Xiao Ma, Xiaoxuan Zhao, Mengjia Zheng, Junjun Wen, Cunrui Yuan, Xinyi Ding, Chengping Wen
 doi: 10.1016/j.jpha.2025.101373
[Abstract](0) [PDF 35093KB](0)
Abstract:
Chronic joint pain in rheumatoid arthritis (RA) represents a persistent therapeutic challenge, and although luteolin (LUT) exhibits established anti-inflammatory properties, its precise mechanism for alleviating RA-associated chronic pain remains undefined. Through systematic investigation in collagen-induced arthritis (CIA) mice, we demonstrated that LUT administration effectively attenuated chronic pain by modulating spinal cluster of differentiation 4 positive T (CD4+ T) cell dynamics and suppressing microglial activation. Integrated multi-omics profiling (cleavage under targets and tagmentation, RNA sequencing (RNA-seq), and metabolomics) coupled with functional validation revealed nuclear factor of activated T cells 2 (NFATC2) as the central transcriptional regulator governing T helper 17 (Th17) cell differentiation and spinal infiltration through protein kinase C epsilon (PRKCE)-signal transducer and activator of transcription 3 (STAT3) signaling transduction. Significantly, our mechanistic studies uncovered a previously unrecognized epigenetic cascade: LUT-mediated suppression of lactate dehydrogenase A (LDHA) activity disrupts glycolysis-fueled histone h3 lysine 9 lactylation (H3K9la), thereby epigenetically silencing NFATC2 transcription. Translational studies using RA patient-derived CD4+ T cells confirmed LUT's capacity to normalize pathological hyperactivity of the LDHA/H3K9la/NFATC2 axis, concomitantly regulating CD4+ T dynamics. Biophysical validation through molecular docking, surface plasmon resonance, and molecular dynamics simulations established LUT's direct binding to LDHA with high affinity. Collectively, these findings delineate a novel therapeutic paradigm wherein LUT alleviates RA-associated chronic pain by orchestrating Th17 differentiation and migratory capacity through coordinated blockade of the LDHA-H3K9la-NFATC2 signaling network, highlighting its potential as a disease-modifying agent for chronic pain management in RA.
A comprehensive narrative review of Epimedium and its bioactive compounds in respiratory diseases
Lanlan Song, Changyu Lei, Cheng Zheng, Yichen Liu, Jian Liu, Dan Yao, Xiaoying Huang
 doi: 10.1016/j.jpha.2025.101374
[Abstract](0) [PDF 7800KB](0)
Abstract:
Respiratory diseases pose a significant global health challenge due to their high morbidity and mortality rates. Traditional Chinese medicine (TCM), particularly the herb Epimedium, has demonstrated therapeutic potential in managing these diseases. This review systematically evaluates evidence from both in vitro and in vivo studies to assess the effects of Epimedium and its bioactive compounds, including Icariin (ICA), Icariside I (ICS I), Icariside II (ICS II), Icaritin (ICT), and others, on respiratory diseases. The synthesis of current literature reveals that these compounds exhibit anti-inflammatory, antioxidant, and immunomodulatory activities, as well as other effects crucial for the management of respiratory diseases. Further research is needed to fully understand and harness the therapeutic potential of Epimedium and its bioactive compounds in respiratory diseases.
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The biological roles of exosome-encapsulated traditional Chinese medicine monomers in neuronal disorders
Chen Pang, Jie Zhang, Yujin Gu, Qili Zhang, Yanfang Zhao
2025, 15(5): 101131.   doi: 10.1016/j.jpha.2024.101131
Abstract(114) HTML Full Text PDF(5)
Abstract:

A traditional Chinese medicine (TCM) monomer is a bioactive compound extracted from Chinese herbal medicines possessing determined biological activity and pharmacological effects, and has gained much attention for treating neuronal diseases. However, the application of TCM monomers is limited by their low solubility and poor ability to cross the blood-brain barrier (BBB). Exosomes are small extracellular vesicles (EVs) ranging in size from 30 to 150 nm in diameter and can be used as drug delivery carriers that directly target cells or tissues with unique advantages, including low toxicity, low immunogenicity, high stability in blood, and the ability to cross the BBB. This review discusses the biogenesis, components, stability, surface modification, isolation technology, advantages, and disadvantages of exosomes as drug carriers and compares exosomes and other similar drug delivery systems. Furthermore, exosome-encapsulated TCM monomers exert neuroprotective roles, such as anti-inflammation, anti-apoptosis, anti-mitophagy, and anti-oxidation, in various neuronal diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and cerebral ischemia and reperfusion (CI/R) injury, as well as anti-drug resistance, anti-tumorigenesis, anti-angiogenesis, and promotion of apoptosis in brain tumors, providing more inspiration to promote the development of an exosome-based delivery tool in targeted therapy for neuronal diseases.

A review of research methods for elucidating the microstructure of pharmaceutical preparations
Peng Yan, Zhiyuan Hou, Jinsong Ding
2025, 15(5): 101156.   doi: 10.1016/j.jpha.2024.101156
Abstract(85) HTML Full Text PDF(6)
Abstract:

The microstructures of pharmaceutical preparations play a pivotal role in determining their critical quality attributes (CQAs), such as drug release, content uniformity, and stability, which greatly impact the safety and efficacy of drugs. Unlike the inherent molecular structures of active pharmaceutical ingredients (APIs) and excipients, the microstructures of pharmaceutical preparations are developed during the formulation process, presenting unique analytical challenges. In this review, we primarily focus on presenting the research methods used to elucidate the microstructures of pharmaceutical preparations, including X-ray imaging (XRI), scanning electron microscopy (SEM), atomic force microscopy (AFM), Raman spectroscopy, infrared (IR) spectroscopy, and rheometer technology. Subsequently, we highlight the applications, advantages, and limitations of these methods. Finally, we discuss the current challenges and future perspectives in this field. This review aims to provide a comprehensive reference for understanding the microstructures of pharmaceutical preparations, offering new insights and potential advancements in their development.

Lycium barbarum's diabetes secrets: A comprehensive review of cellular, molecular, and epigenetic targets with immune modulation and microbiome influence
Zeshan Ali, Aqsa Ayub, Yawen Lin, Sonam Anis, Ishrat Khan, Shoaib Younas, Rana Adnan Tahir, Shulin Wang, Jianrong Li
2025, 15(5): 101130.   doi: 10.1016/j.jpha.2024.101130
Abstract(97) HTML Full Text PDF(3)
Abstract:

Diabetes, a metabolic disease stemming from impaired or defective insulin secretion, ranks among the most severe chronic illnesses globally. While several approved drugs exist for its treatment, they often come with multiple side effects. Therefore, there is a pressing need for safe and effective anti-diabetic medications. Traditional Chinese medicine has recognized Lycium barbarum (LB; goji berry) plant, commonly known as “wolfberry fruit” in China, for over 2,000 years. Natural compounds derived from LB show promise in reducing diabetes levels. Although research on the impact of LB on diabetes is still limited, our review aims to explore the potential of LB in reducing the risk of diabetes and examine the underlying mechanisms involved. LB can modulate diabetes through various pathways, such as inhibiting α-amylase and α-glucosidase activities, promoting β-cell proliferation, stimulating insulin secretion, inhibiting glucagon secretion, improving insulin resistance and glucose tolerance, and enhancing antioxidant and anti-inflammatory activities. Additionally, LB improves gut flora and immunomodulation, further aiding diabetes management. These findings highlight the potential clinical utility of LB in managing diabetes and its complications within the framework of evidence-based modern medicine.

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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](2178) [PDF 2284KB](43)
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](12990) [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](1928) [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](837) [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](441) [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](709) [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](613) [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](401) [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](2697) [PDF 1336KB](1348)
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](614) [PDF 5665KB](299)
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](847) [PDF 4018KB](415)
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](1011) [PDF 3923KB](497)
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](259) [PDF 229KB](129)
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](226) [PDF 2055KB](107)
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](207) [PDF 64KB](103)
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](704) [PDF 2290KB](357)
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.