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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Biological activity analysis of baicalin nanodrugs: Nanosizing enhances antiviral and anti-inflammatory effects in the treatment of viral pneumonia
Chenqi Chang, Chang Lu, Yu Zheng, Lili Lin, XiuZhen Chen, Linwei Chen, Zhipeng Chen, Rui Chen
 doi: 10.1016/j.jpha.2025.101201
[Abstract](0) [PDF 11662KB](0)
Abstract:
Respiratory syncytial virus (RSV) is a ubiquitous respiratory virus that affects individuals of all ages; however, there is a notable lack of targeted treatments. RSV infection is associated with a range of respiratory symptoms, including bronchiolitis and pneumonia. Baicalin (BA) exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action. Nonetheless, the clinical application of BA is constrained by its low solubility and bioavailability. In this study, we prepared BA nanodrugs (NDs) with enhanced water solubility utilizing the supramolecular self-assembled strategy, and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA. Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA, attributed to prolonged lung retention, improved cellular uptake, and increased targeting affinity. Our study confirms that the nanosizing strategy, a straightforward approach to enhance drug solubility, can also increase biological activity compared to free drugs with the same content, thereby providing a potential ND for RSV treatment. This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.
Greenness evaluation metric for analytical methods and software
Tong Xin, Luyao Yu, Wenying Zhang, Yingxia Guo, Chuya Wang, Zhong Li, Jiansong You, Hongyu Xue, Meiyun Shi, Lei Yin
 doi: 10.1016/j.jpha.2025.101202
[Abstract](0) [PDF 8151KB](0)
Abstract:
The focus of green analytical chemistry (GAC) is to minimize the negative impacts of analytical procedures on human safety, human health, and the environment. Several factors, such as the reagents used, sample collection, sample processing, instruments, energy consumed, and the quantities of hazardous materials and waste generated during analytical procedures, need to be considered in the evaluation of the greenness of analytical assays. In this study, we propose a greenness evaluation metric for analytical methods (GEMAM). The new greenness metric is simple, flexible, and comprehensive. The evaluation criteria are based on both the 12 principles of GAC (SIGNIFICANCE) and the 10 factors of sample preparation, and the results are presented on a 0–10 scale. The GEMAM calculation process is easy to perform, and its results are easy to interpret. The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number
pH-responsive biomimetic zeolitic imidazolate framework-based nanoparticles for co-delivery of cetuximab and siRNA in synergistic therapy of laryngeal squamous cell carcinoma
Liyin Wang, Milad Ashrafizadeh, Gautam Sethi, Xinjia Zhou
 doi: 10.1016/j.jpha.2025.101203
[Abstract](0) [PDF 29621KB](0)
Abstract:
Suboptimal treatment of laryngeal squamous cell carcinoma (LSCC) reduces survival rate. The poor bioavailability and resistance to cetuximab (Cet) and the instability of small interfering RNA (siRNA) limit their therapeutic efficacy in LSCC. This study aimed to develop a Cet and focal adhesion kinase (FAK) siRNA (siFAK) co-delivery nanosystem. Zeolitic imidazolate framework-8 (ZIF-8), with its large specific surface area and pH-responsive properties, is an ideal delivery carrier that allows controlled drug release in the acidic tumor microenvironment. Therefore, Cet was loaded onto ZIF-8 and encapsulated in a TU177 cell membrane (TCM) after the electrostatic adsorption of siFAK. Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), zeta potential, Xray diffraction, and particle size analyses were used to characterize Cet/siFAK@ZIF- 8@TCM. TU177 cells and subcutaneously transplanted tumor-bearing nude mice were used to evaluate the intracellular uptake, cytotoxicity, in vivo biocompatibility, biodistribution, biosafety, pH responsiveness, and anti-LSCC efficacy of Cet/siFAK@ZIF-8@TCM. After ZIF-8@TCM were loaded with Cet and siFAK, alterations in their physical and crystal structures, particle size, and zeta potential were observed. Meanwhile, the co-delivery system increased the loading of Cet through the electrostatic adsorption of siFAK to Cet-loaded ZIF-8. The intracellular uptake of Cet/siFAK@ZIF-8@TCM also protected siFAK from degradation, effectively reducing the messenger RNA (mRNA) and protein expression levels of FAK in LSCC cells. The ZIF-8@TCM nanosystem for co-delivery of Cet and siFAK exhibited pHresponsiveness and tumor-targeting capabilities, thereby exerting anti-LSCC effects. Co-delivery of Cet and siFAK via the pH-responsive ZIF-8@TCM system enabled the targeted release of the chemotherapeutic and gene, in turn maximizing their anti-LSCC effect while ensuring biosafety.
Mechanistic insights into honey-boiled detoxification of ChuanWu: a study on alkaloid transformation and supramolecular aggregation
Yu Zhenga, Nina Wei, Chang Lu, Weidong Li, Xiaobin Jia, Linwei Chen, Rui Chen, Zhipeng Chen
 doi: 10.1016/j.jpha.2025.101205
[Abstract](0) [PDF 0KB](0)
Abstract:
Background : ChuanWu (CW), the dried mother root of Aconitum carmichaelii Debx., is a well-known traditional Chinese medicine (TCM) recognized for its potent efficacy and inherent toxicity. The alkaloid components present in CW are significant contributors to its toxic properties. Both traditional knowledge and modern advancements have facilitated the development of detoxification strategies for CW, which include appropriate processing, rational compatibility, and specialized decoction methods. Among these approaches, honey-boiled CW emerges as a distinctive detoxification technique. However, research on the detoxification mechanism of honey- boiled CW remains limited.
Aim of the study : This study aimed to investigate the detoxification mechanism of honey-boiled CW by examining alkaloid transformation and supramolecular aggregation.
Materials and methods : Honey-boiled CW and water-boiled CW were prepared separately for comparative analysis. Ultra-high-performance liquid chromatography- tandem mass spectrometry ( UHPLC-MS/MS) was employed to analyze CW alkaloids, specifically diester alkaloids (DDAs), monoester alkaloids (MDAs), and non- 18 esterified diterpenoid alkaloids (NDAs). Transmission electron microscopy (TEM) was utilized to observe supramolecular aggregation in the honey-boiled CW decoction, which was subsequently isolated and chemically identified. Assemblies of natural deep eutectic solution (NADES) and monomers nanoparticles were prepared for pharmacokinetic studies after oral administration to rats. In addition, we compared the in vivo absorption differences between water-boiled CW, honey-boiled CW and NADES-boiled CW. The toxicity of various treatments for CW was assessed using the LD50 test, with evaluations of both hepatotoxicity and nephrotoxicity. The safety, as well as the anti-inflammatory and analgesic effects of different treatments of CW medicated serum on RAW264.7 cells, were examined through in vitro experiments. These anti-inflammatory and analgesic effects were then further validated through in vivo experiments conducted on mice. Journal Pre-proof4.
Results : Honey played a significant role in altering the alkaloids in boiled CW by promoting the conversion of highly toxic DDAs to less toxic MDAs and preventing the 3 hydrolysis of MDAs into NDAs. Additionally, the honey-boiled CW facilitated the formation of supramolecular aggregates with a diameter of approximately 250 nm. These aggregates effectively hindered the conversion of MDAs into NDAs by encapsulating them. The encapsulated MDAs within the supramolecular aggregates served as a stable drug delivery system under physiological conditions and demonstrated higher bioavailability compared to free benzoylmesaconine (BMA). Subsequent mouse experiments confirmed that honey-boiled CW significantly increased LD50 of CW while reducing hepatotoxicity and nephrotoxicity. Honey-boiled CW significantly improves cell safety and enhances anti-inflammatory and analgesic effects.
Conclusions : Honey-boiled CW exhibited a potent detoxification mechanism by influencing alkaloid transformation and facilitating the formation of supramolecular aggregates. This finding lays the groundwork for the development of detoxification or synergistic strategies within honey-boiled TCM.
Lipidome atlas of human myometrium reveals distinctive lipid signatures associated with adenomyosis: Combination of high-coverage lipidomics and mass spectrometry imaging
Shuo Liang, Jialin Liu, Maokun Liao, Dandan Liang, Yiyi Gong, Bo Zhang, Nan Zhao, Wei Song, Honghui Shi
 doi: 10.1016/j.jpha.2025.101197
[Abstract](4) [PDF 11920KB](0)
Abstract:
Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus, the pathological mechanism of which remains unclear yet. Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases. However, the lipidome signature of human myometrium, which could be crucial in the development of adenomyosis, remains unknown. In this study, we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultrahigh-performance liquid chromatography coupled with QqQ- mass spectrometry. A total of 317 lipid species were successfully quantified in the myometrial tissues from women with (n = 38) or without (n = 65) adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital. Up to 83 lipid species showed significant alternations in content between the two groups. These lipid aberrations involved multiple metabolic pathways, and emphasized inflammation, cell migration, and immune dysregulation upon adenomyosis. Moreover, receiver operating characteristic curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve of 0.906. Desorption electrospray ionization mass spectrometry imaging further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue. Collectively, these results extremely improved our understanding on the molecular basis of adenomyosis, and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.
Late-stage labeling of diverse peptides and proteins with iodine-125
Aleš Marek, Břetislav Brož, Michal Kriegelstein, Gabriela Nováková, Jana Hojcsková, Miroslava Blechová, Lenka Žáková, Jiří Jiráček, Lenka Maletínská
 doi: 10.1016/j.jpha.2025.101198
[Abstract](4) [PDF 5325KB](0)
Abstract:
The preparation of specifically 125I-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of iodine-125 late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically 125I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of IGF-BP-3 (the insulin-like growth factor binding protein, 29 kDa, 264 aa) and ALS (the acid-labile subunit, 93 kDa, 578 aa).
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Review papers
Recent trends and impact of localized surface plasmon resonance (LSPR) and surface-enhanced Raman spectroscopy (SERS) in modern analysis
Bibhu Prasad Nanda, Priyanka Rani, Priyanka Paul, Aman, Subrahmanya S. Ganti, Rohit Bhatia
2024, 14(11): 100959.   doi: 10.1016/j.jpha.2024.02.013
Abstract(219) HTML Full Text PDF(11)
Abstract:
An optical biosensor is a specialized analytical device that utilizes the principles of optics and light in bimolecular processes. Localized surface plasmon resonance (LSPR) is a phenomenon in the realm of nanophotonics that occurs when metallic nanoparticles (NPs) or nanostructures interact with incident light. Conversely, surface-enhanced Raman spectroscopy (SERS) is an influential analytical technique based on Raman scattering, wherein it amplifies the Raman signals of molecules when they are situated near specific and specially designed nanostructures. A detailed exploration of the recent ground-breaking developments in optical biosensors employing LSPR and SERS technologies has been thoroughly discussed along with their underlying principles and the working mechanisms. A biosensor chip has been created, featuring a high-density deposition of gold nanoparticles (AuNPs) under varying ligand concentration and reaction duration on the substrate. An ordinary description, along with a visual illustration, has been thoroughly provided for concepts such as a sensogram, refractive index shift, surface plasmon resonance (SPR), and the evanescent field, Rayleigh scattering, Raman scattering, as well as the electromagnetic enhancement and chemical enhancement. LSPR and SERS both have advantages and disadvantages, but widely used SERS has some advantages over LSPR, like chemical specificity, high sensitivity, multiplexing, and versatility in different fields. This review confirms and elucidates the significance of different disease biomarker identification. LSPR and SERS both play a vital role in the detection of various types of cancer, such as cervical cancer, ovarian cancer, endometrial cancer, prostate cancer, colorectal cancer, and brain tumors. This proposed optical biosensor offers potential applications for early diagnosis and monitoring of viral disease, bacterial infectious diseases, fungal diseases, diabetes, and cardiac disease biosensing. LSPR and SERS provide a new direction for environmental monitoring, food safety, refining impurities from water samples, and lead detection. The understanding of these biosensors is still limited and challenging.
Original articles
Dual-targeted halofuginone hydrobromide nanocomplexes for promotion of macrophage repolarization and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes in adjuvant-induced arthritis in rats
Junping Zhu, Ye Lin, Gejing Li, Yini He, Zhaoli Su, Yuanyuan Tang, Ye Zhang, Qian Xu, Zhongliu Yao, Hua Zhou, Bin Liu, Xiong Cai
2024, 14(11): 100981.   doi: 10.1016/j.jpha.2024.100981
Abstract(212) HTML Full Text PDF(16)
Abstract:
Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium. Currently, treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia. However, these modalities are unsatisfactory in achieving the desired therapeutic outcomes. Halofuginone hydrobromide (HF), an herbal active ingredient, has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation. However, HF's medical efficacy is limited due to its poor water solubility, short half-life (t1/2), and non-target toxicity. In the current study, by using the advantages of nanotechnology, we presented a novel dual-targeted nanocomplex, termed HA-M@P@HF NPs, which consisted of a hyaluronic acid (HA)-modified hybrid membrane (M)-camouflaged poly lactic-co-glycolic acid (PLGA) nanosystem for HF delivery. These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA (HFLS-RA). In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia, safeguarding against bone destruction in rats with adjuvant-induced arthritis (AIA). Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA, thereby offering a promising therapeutic strategy for RA.
Machine learning-driven optimization of mRNA-lipid nanoparticle vaccine quality with XGBoost/Bayesian method and ensemble model approaches
Ravi Maharjan, Ki Hyun Kim, Kyeong Lee, Hyo-Kyung Han, Seong Hoon Jeong
2024, 14(11): 100996.   doi: 10.1016/j.jpha.2024.100996
Abstract(92) HTML Full Text PDF(8)
Abstract:
To enhance the efficiency of vaccine manufacturing, this study focuses on optimizing the microfluidic conditions and lipid mix ratios of messenger RNA-lipid nanoparticles (mRNA-LNP). Different mRNA-LNP formulations (n = 24) were developed using an I-optimal design, where machine learning tools (XGBoost/Bayesian optimization and self-validated ensemble (SVEM)) were used to optimize the process and predict lipid mix ratio. The investigation included material attributes, their respective ratios, and process attributes. The critical responses like particle size (PS), polydispersity index (PDI), Zeta potential, pKa, heat trend cycle, encapsulation efficiency (EE), recovery ratio, and encapsulated mRNA were evaluated. Overall prediction of SVEM (>97%) was comparably better than that of XGBoost/Bayesian optimization (>94%). Moreover, in actual experimental outcomes, SVEM prediction is close to the actual data as confirmed by the experimental PS (94–96 nm) is close to the predicted one (95–97 nm). The other parameters including PDI and EE were also close to the actual experimental data.
Circulating memory T cells and TCF1+ T cells aid in diagnosis and monitor disease activity in vitiligo
Xinju Wang, Jianru Chen, Wei Wu, Jinrong Fan, Luling Huang, Weiwei Sun, Kaiqiao He, Shuli Li, Chunying Li
2024, 14(11): 100998.   doi: 10.1016/j.jpha.2024.100998
Abstract(91) HTML Full Text PDF(6)
Abstract:
Vitiligo is an immune memory skin disease. T-cell factor 1 (TCF1) is essential for maintaining the memory T-cell pool. There is an urgent need to investigate the characteristics of peripheral memory T-cell profile and TCF1+ T-cell frequencies in patients with vitiligo. In this study, 31 patients with active vitiligo (AV), 22 with stable vitiligo (SV), and 30 healthy controls (HCs) were included. We measured circulating memory and TCF1+ T-cell frequencies using flow cytometry. The Spearman's rank test was used to evaluate the correlation between cell frequencies and disease characteristics. Receiver operating characteristic curves (ROC) were constructed to investigate the discriminative power of the cell subpopulations. Circulating CD4+ and CD8+ terminally differentiated effector memory T-cell (TEMRA) frequencies were significantly higher in the AV group than in HCs (P < 0.05). TCF1+ T-cell subpopulations were widespread increased in patients with vitiligo (P < 0.05). After adjusting for potential confounders, CD8+ and CD4+ central memory (TCM) cells, and CD8+ TEMRA were correlated with disease activity (P < 0.05). The combined diagnostic value of the four (naïve, effector memory, TCM, and TEMRA) CD8+TCF1+ T-cell subsets was relatively high (area under the ROC curve (AUC) = 0.804, sensitivity = 71.70%, specificity = 83.34%), and the CD8+ T-cell subsets combination performed well in discriminating disease activity (AUC = 0.849, sensitivity = 70.97%, specificity = 90.91%). We demonstrated an altered circulating memory T-cell profile and increased TCF1+ T-cell percentage in patients with vitiligo. T-cell subpopulations had a strong value for vitiligo diagnosis and activity evaluation. This evidence presents a potential new pharmacological target for inhibiting autoimmunity that leads to vitiligo.
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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](1388) [PDF 2284KB](21)
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](3435) [PDF 5841KB](41)
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](1288) [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](380) [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](656) [PDF 6429KB](19)
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.
Carbon nanotubes:Evaluation of toxicity at biointerfaces
Debashish Mohanta, Soma Patnaik, Sanchit Sood, Nilanjan Das
2019, 9(5): 293-300.  
[Abstract](511) [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.
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](517) [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.
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](743) [PDF 3923KB](271)
摘要:
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.
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](743) [PDF 3923KB](369)
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](2351) [PDF 1336KB](1168)
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](187) [PDF 229KB](95)
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](169) [PDF 2055KB](82)
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](253) [PDF 64KB](123)
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](448) [PDF 4176KB](215)
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](706) [PDF 707KB](342)
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](573) [PDF 9014KB](283)
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.