Harmine inhibits pulmonary fibrosis through regulating DNA damage repair-related genes and activation of TP53-Gadd45α pathway.

BACKGROUND: Harmine has many pharmacological activities and has been found to significantly inhibit the fibrosis of keloid fibroblasts. DNA damage repair (DDR) is essential to prevent fibrosis. This study aimed to investigate the effects of harmine on pulmonary fibrosis and its underlying mechanisms. METHODS: Bleomycin and TGF-ß1 were used to construct pulmonary fibrosis models in vivo and in vitro, then treated with harmine to explore harmine's effects in treating experimental pulmonary fibrosis and its related mechanisms. Then, RNA sequencing was applied to investigate further the crucial DDR-related genes and drug targets of harmine against pulmonary fibrosis. Finally, the expression levels of DDR-related genes were verified by real-time quantitative PCR (RT-qPCR) and western blot. RESULTS: Our in vivo experiments showed that harmine treatment could improve weight loss and lung function and reduce tissue fibrosis in mice with pulmonary fibrosis. The results confirmed that harmine could inhibit the viability and migration of TGF-ß1-induced MRC-5 cells, induce their apoptosis, and suppress the F-actin expression, suggesting that harmine could suppress the phenotypic transition from lung fibroblasts to lung myoblasts. In addition, RNA sequencing identified 1692 differential expressed genes (DEGs), and 10 DDR-related genes were screened as critical DDR-related genes. RT-qPCR and western blotting showed that harmine could down-regulate the expression of CHEK1, ERCC1, ERCC4, POLD1, RAD51, RPA1, TOP1, and TP53, while up-regulate FEN1, H2AX and GADD45α expression. CONCLUSIONS: Harmine may inhibit pulmonary fibrosis by regulating DDR-related genes and activating the TP53-Gadd45α pathway.

Exploring and clinical validation of prognostic significance and therapeutic implications of copper homeostasis-related gene dysregulation in acute myeloid leukemia.

The patterns and biological functions of copper homeostasis-related genes (CHRGs) in acute myeloid leukemia (AML) remain unclear. We explored the patterns and biological functions of CHRGs in AML. Using independent cohorts, including TCGA-GTEx, GSE114868, GSE37642, and clinical samples, we identified 826 common differentially expressed genes. Specifically, 12 cuproptosis-related genes (e.g., ATP7A, ATP7B) were upregulated, while 17 cuproplasia-associated genes (e.g., ATOX1, ATP7A) were downregulated in AML. We used LASSO-Cox, Kaplan-Meier, and Nomogram analyses to establish prognostic risk models, effectively stratifying patients with AML into high- and low-risk groups. Subgroup analysis revealed that high-risk patients exhibited poorer overall survival and involvement in fatty acid metabolism, apoptosis, and glycolysis. Immune infiltration analysis indicated differences in immune cell composition, with notable increases in B cells, cytotoxic T cells, and memory T cells in the low-risk group, and increased monocytes and neutrophils in the high-risk group. Single-cell sequencing analysis corroborated the expression characteristics of critical CHRGs, such as MAPK1 and ATOX1, associated with the function of T, B, and NK cells. Drug sensitivity analysis suggested potential therapeutic agents targeting copper homeostasis, including Bicalutamide and Sorafenib. PCR validation confirmed the differential expression of 4 cuproptosis-related genes (LIPT1, SLC31A1, GCSH, and PDHA1) and 9 cuproplasia-associated genes (ATOX1, CCS, CP, MAPK1, SOD1, COA6, PDK1, DBH, and PDE3B) in AML cell line. Importantly, these genes serve as potential biomarkers for patient stratification and treatment. In conclusion, we shed light on the expression patterns and biological functions of CHRGs in AML. The developed risk models provided prognostic implications for patient survival, offering valuable information on the regulatory characteristics of CHRGs and potential avenues for personalized treatment in AML.

Tirapazamine combined with photodynamic therapy improves the efficacy of ABZSO nanoparticles on Echinococcosis granulosus via further enhancing "breaking-then-curing".

BACKGROUND: Photodynamic therapy (PDT) has a promising application prospect in Echinococcus granulosus (Egs), however, the hypoxic environment of Egs and the hypoxia associated with PDT will greatly limit its effects. As a hypoxic-activated pre-chemotherapeutic drug, tirapazamine (TPZ) can be only activated and produce cytotoxicity under hypoxia environment. Albendazole sulfoxide (ABZSO) is the first choice for the treatment of Egs. This study aimed to explore the effects of ABZSO nanoparticles (ABZSO NPs), TPZ combined with PDT on the activity of Egs in vitro and in vivo. METHODS: The Egs were divided into control, ABZSO NPs, ABZSO NPs + PDT, and ABZSO NPs + TPZ + PDT groups, and the viability of Egs was determined using methylene blue staining. Then, the ROS, LDH and ATP levels were measured using their corresponding assay kit, and H2AX and TopoI protein expression was detected by western blot. The morphology of Egs with different treatments was observed using hematoxylin eosin (HE) staining and scanning electron microscopy (SEM). After that, the in vivo efficacy of ABZSO NPs, TPZ and PDT on Egs was determined in a Egs infected mouse model. RESULTS: In vitro experiments showed that the combined treatment of TPZ, ABZSO NPs and PDT significantly inhibited Egs viability; and significantly increased ROS levels and LDH contents, while decreased ATP contents in Egs; as well as up-regulated H2AX and down-regulated TopoI protein expression. HE staining and SEM results showed that breaking-then-curing treatment seriously damaged the Egs wall. Additionally, in vivo experiments found that the combination of ABZSO NPs, PDT and TPZ had more serious calcification and damage of the wall structure of cysts. CONCLUSIONS: ABZSO NPs combined with TPZ and PDT has a better inhibitory effect on the growth of Egs in vitro and in vivo based on the strategy of "breaking-then-curing".

In vitro and in vivo Efficacies of Novel Harmine Derivatives in the Treatment of Cystic Echinococcosis.

Introduction: Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease caused by the larvae of the Echinococcus granulosus sensu lato (s.l.) cluster. The current existing drugs have limited therapeutic efficacy against cystic echinococcosis, and thus, there is an urgent need to develop new drugs. Methods: In this study, 7 harmine (HM) derivatives were screened and the effects of HM derivatives on E. granulosus sensu stricto (s.s.) were evaluated by in vitro and mouse experiments. The safety of the HM derivatives was assessed by cytotoxicity assays, acute toxicity study in animals and subacute toxicity study. Results: These results show that the HM derivatives H-2-168 and DH-004 exhibited more significant antiparasitic effects at an initial concentration of 40 µM. The results of further studies showed that H-2-168 and DH-004 had dose-dependent effects against protoscoleces and had satisfactory therapeutic outcomes in vivo. Electron microscopy observations demonstrated that H-2-168 and DH-004 caused severe disruption of the parasite ultrastructure. Notably, the results of the acute toxicity and subchronic toxicity studies showed that H-2-168 and DH-004 had significantly improved safety. In addition, we found that H-2-168 and DH-004 induced DNA damage in E. granulosus s.s., which may be the mechanism by which these drugs produce their therapeutic effects. Discussion: Overall, the data from this work demonstrate that H-2-168 and DH-004 are highly effective candidate compounds with low toxicity for the treatment of CE and will provide a new therapeutic strategy for CE pharmacological treatment.

Effects of Dihydroartemisinin against Cystic Echinococcosis In Vitro and In Vivo.

Cystic echinococcosis (CE) is a disease caused by the infection of Echinococcus granulosus. We sought to investigate the effects of dihydroartemisinin (DHA) against CE under in vitro and in vivo conditions. Protoscoleces (PSCs) from E. granulosus were divided into control, DMSO, ABZ, DHA-L, DHA-M, and DHA-H groups. PSC viability after DHA treatment was determined based on the eosin dye exclusion test, alkaline phosphatase content detection, and ultrastructure observation. DNA oxidative damage inducer hydrogen peroxide (H2O2), reactive oxygen species (ROS) scavenger mannitol, and the DNA damage repair inhibitor velparib were used to explore the anti-CE mechanism of DHA. The anti-CE effects and CE-induced liver injury and oxidative stress of DHA at different doses (50, 100, and 200 mg/kg) were assessed in CE mice. DHA showed antiparasitic effects on CE in both in vivo and in vitro experiments. DHA could elevate the ROS level and induce oxidative DNA damage in PSCs, thereby destroying hydatid cysts. DHA could inhibit the growth of cysts in a dose-dependent manner and reduce the content of biochemical parameters associated with liver injury in CE mice. It also significantly reversed oxidative stress in CE mice, which was characterized as the decreased tumor necrosis factor alpha and H2O2 content, as well as the increase of the ratio of glutathione/oxidized glutathione and total superoxide dismutase content. DHA showed antiparasitic effects. DNA damages induced by oxidative stress played important roles in this process.

A mutation operator self-adaptive differential evolution particle swarm optimization algorithm for USV navigation.

To keep the global search capability and robustness for unmanned surface vessel (USV) path planning, an improved differential evolution particle swarm optimization algorithm (DePSO) is proposed in this paper. In the optimization process, approach to optimal value in particle swarm optimization algorithm (PSO) and mutation, hybridization, selection operation in differential evolution algorithm (DE) are combined, and the mutation factor is self-adjusted. First, the particle population is initialized and the optimization objective is determined, the individual and global optimal values are updated. Then differential variation is conducted to produces new variables and cross over with the current individual, the scaling factor is adjusted adaptively with the number of iterations in the mutation process, particle population is updated according to the hybridization results. Finally, the convergence of the algorithm is determined according to the decision standard. Numerical simulation results show that, compared with conventional PSO and DE, the proposed algorithm can effectively reduce the path intersection points, and thus greatly shorten the overall path length.

Comprehensive analysis and validation of novel immune and vascular remodeling related genes signature associated with drug interactions in pulmonary arterial hypertension.

Background: Previous studies revealed that the gene signatures are associated with the modulation and pathogenesis of pulmonary arterial hypertension (PAH). However, identifying critical transcriptional signatures in the blood of PAH patients remains lacking. Methods: The differentially expressed transcriptional signatures in the blood of PAH patients were identified by a meta-analysis from four microarray datasets. Then we investigated the enrichment of gene ontology and KEGG pathways and identified top hub genes. Besides, we investigated the correlation of crucial hub genes with immune infiltrations, hallmark gene sets, and blood vessel remodeling genes. Furthermore, we investigated the diagnostic efficacy of essential hub genes and their expression validation in an independent cohort of PAH, and we validate the expression level of hub genes in monocrotaline (MCT) induced PAH rats' model. Finally, we have identified the FDA-approved drugs that target the hub genes and their molecular docking. Results: We found 1,216 differentially expressed genes (DEGs), including 521 up-regulated and 695 down-regulated genes, in the blood of the PAH patients. The up-regulated DEGs are significantly associated with the enrichment of KEGG pathways mainly involved with immune regulation, cellular signaling, and metabolisms. We identified 13 master transcriptional regulators targeting the dysregulated genes in PAH. The STRING-based investigation identified the function of hub genes associated with multiple immune-related pathways in PAH. The expression levels of RPS27A, MAPK1, STAT1, RPS6, FBL, RPS3, RPS2, and GART are positively correlated with ssGSEA scores of various immune cells as positively correlated with the hallmark of oxidative stress. Besides, we found that these hub genes also regulate the vascular remodeling in PAH. Furthermore, the expression levels of identified hub genes showed good diagnostic efficacy in the blood of PAH, and we validated most of the hub genes are consistently dysregulated in an independent PAH cohort. Validation of hub genes expression level in the monocrotaline (MCT)-induced lung tissue of rats with PAH revealed that 5 screened hub genes (MAPK1, STAT1, TLR4, TLR2, GART) are significantly highly expressed in PAH rats, and 4 screened hub genes (RPS6, FBL, RPS3, and RPS2) are substantially lowly expressed in rats with PAH. Finally, we analyzed the interaction of hub proteins and FDA-approved drugs and revealed their molecular docking, and the results showed that MAPK1, TLR4, and GART interact with various drugs with appropriate binding affinity. Conclusion: The identified blood-derived key transcriptional signatures significantly correlate with immune infiltrations, hypoxia, glycolysis, and blood vessel remodeling genes. These findings may provide new insight into the diagnosis and treatment of PAH patients.

GraformerDIR: Graph convolution transformer for deformable image registration.

PURPOSE: Deformable image registration (DIR) plays an important role in assisting disease diagnosis. The emergence of the Transformer enables the DIR framework to extract long-range dependencies, which relieves the limitations of intrinsic locality caused by convolution operation. However, suffering from the interference of missing or spurious connections, it is a challenging task for Transformer-based methods to capture the high-quality long-range dependencies. METHODS: In this paper, by staking the graph convolution Transformer (Graformer) layer at the bottom of the feature extraction network, we propose a Graformer-based DIR framework, named GraformerDIR. The Graformer layer is consist of the Graformer module and the Cheby-shev graph convolution module. Among them, the Graformer module is designed to capture high-quality long-range dependencies. Cheby-shev graph convolution module is employed to further enlarge the receptive field. RESULTS: The performance and generalizability of GraformerDIR have been evaluated on publicly available brain datasets including the OASIS, LPBA40, and MGH10 datasets. Compared with VoxelMorph, the GraformerDIR has obtained performance improvements of 4.6% in Dice similarity coefficient (DSC) and 0.055 mm in the average symmetric surface distance (ASD) while reducing the non-positive rate of Jacobin determinant (Npr.Jac) index about 60 times on publicly available OASIS dataset. On unseen dataset MGH10, the GraformerDIR has obtained the performance improvements of 4.1% in DSC and 0.084 mm in ASD compared with VoxelMorph, which demonstrates the GraformerDIR with better generalizability. The promising performance on the clinical cardiac dataset ACDC indicates the GraformerDIR is practicable. CONCLUSION: With the advantage of Transformer and graph convolution, the GraformerDIR has obtained comparable performance with the state-of-the-art method VoxelMorph.

TransDIR: Deformable imaging registration network based on transformer to improve the feature extraction ability.

PURPOSE: Imaging registration has a significant contribution to guide and support physicians in the process of decision-making for diagnosis, prognosis, and treatment. However, existing registration methods based on the convolutional neural network cannot extract global features effectively, which significantly influences registration performance. Moreover, the smoothness of the displacement vector field (DVF) fails to be ensured due to the miss folding penalty. METHODS: In order to capture abundant global information as well as local information, we have proposed a novel 3D deformable image registration network based on Transformer (TransDIR). In the encoding phase, the transformer with the atrous reduction attention block is designed to capture the long-distance dependencies that are crucial for extracting global information. A zero-padding position encoder is embedded into the transformer to capture the local information. In the decoding phase, an up-sampling module based on an attention mechanism is designed to increase the significance of ROIs. Because of adding folding penalty term into loss function, the smoothness of DVF is improved. RESULTS: Finally, we carried out experiments on OASIS, LPBA40, MGH10, and MM-WHS open datasets to validate the effectiveness of TransDIR. Compared with LapIRN, the DSC score is improved by 1.1% and 0.9% on OASIS and LPBA40, separately. In addition, compared with VoxelMorph, the DSC score is improved by 2.8% on the basis of the folding index decreased by hundreds of times on MM-WHS. CONCLUSIONS: The results show that the TransDIR achieves robust registration and promising generalizability compared with LapIRN and VoxelMorph.

RA-SIFA: Unsupervised domain adaptation multi-modality cardiac segmentation network combining parallel attention module and residual attention unit.

BACKGROUND: Convolutional neural network has achieved a profound effect on cardiac image segmentation. The diversity of medical imaging equipment brings the challenge of domain shift for cardiac image segmentation. OBJECTIVE: In order to solve the domain shift existed in multi-modality cardiac image segmentation, this study aims to investigate and test an unsupervised domain adaptation network RA-SIFA, which combines a parallel attention module (PAM) and residual attention unit (RAU). METHODS: First, the PAM is introduced in the generator of RA-SIFA to fuse global information, which can reduce the domain shift from the respect of image alignment. Second, the shared encoder adopts the RAU, which has residual block based on the spatial attention module to alleviate the problem that the convolution layer is insensitive to spatial position. Therefore, RAU enables to further reduce the domain shift from the respect of feature alignment. RA-SIFA model can realize the unsupervised domain adaption (UDA) through combining the image and feature alignment, and then solve the domain shift of cardiac image segmentation in a complementary manner. RESULTS: The model is evaluated using MM-WHS2017 datasets. Compared with SIFA, the Dice of our new RA-SIFA network is improved by 8.4%and 3.2%in CT and MR images, respectively, while, the average symmetric surface distance (ASD) is reduced by 3.4 and 0.8mm in CT and MR images, respectively. CONCLUSION: The study results demonstrate that our new RA-SIFA network can effectively improve the accuracy of whole-heart segmentation from CT and MR images.

In vitro effects of harmine against Echinococcus granulosus protoscoleces by stimulating DNA damage.

Cystic echinococcosis (CE), a parasitic larval cystic stage of a small taeniid-type tapeworm (Echinococcus granulosus), causes illness in intermediate hosts and has become a threat to global public health. Currently, chemical compounds recommended by the WHO targeting CE are albendazole and mebendazole, however, none of them shows enhanced efficacy. Novel molecular compounds are urgently required to treat this disease. Our group uncover a drug, termed harmine (HM), that may be capable of treating CE. In this study, we aim to evaluate the anti-parasitic efficacy and the mechanism of DNA damage of HM against E. granulosus. In vitro, the results indicated that, within two and three days of treatment, ABZ killed 30.4% and 35.3% of protoscoleces, whereas HM killed 52.7% and 100% of protoscoleces, respectively. Furthermore, the presence of abnormalities in the internal structure of protoscoleces was examined by ultrastructural images of TEM, and the result showed that there were scattered nucleoli and heterochromatin margination phenomenon by HM treatment. DNA damage of protoscoleces was examined by using the comet assay, and results showed the DNA of protoscoleces was damaged. Moreover, EgATM, EgP53, EgTopo2a and EgRad54 genes were used to support the DNA damage by HM treatment, and results showed that all four genes were upregulated expression. In further, the result of HM treatment was tested by using designed siRNA to inhibit the expression of EgTopo2a and EgRad54. The results demonstrated that the viability was 88.75 ± 2.11% after suppressing the expression of EgTopo2a, which was significantly higher than that for HM alone group (P < 0.01). The viability was 10.11 ± 2.60% after transfected with EgRad54 siRNA, which was significantly lower compared with the HM alone group (P < 0.01). Based on our preliminary data, HM demonstrated significant parasiticidal activity against E. granulosus in vitro without obvious toxicity towards its host cells, suggesting that HM can be a potential anti-echinococcosis drug. HM was found to induce DNA damages of CE by activating the EgATM-EgP53-EgTopo2a signaling pathway. We therefore surmise that DNA damage response may be one of the mechanisms of HM against the parasite.

Harmine Combined with Rad54 Knockdown Inhibits the Viability of Echinococcus granulosus by Enhancing DNA Damage.

This study aimed at exploring the role of EgRad54 and the effect of harmine (HM) or HM derivatives (HMDs) on DNA damage in Echinococcus granulosus. DNA damage in E. granulosus protoscoleces (PSCs) was assessed by using a comet assay, after treatment with HM or HMDs. Efficiency of electroporation-based transfection of PSCs and subsequent EgRad54 knockdown was evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR) and fluorescence intensity. Viability of PSCs was determined via eosin exclusion test, and expression of related genes was analyzed via RT-qPCR. HM and HMDs significantly (p < 0.05) increased DNA damage in E. granulosus, and upregulated EgRad54 expression. Compared with HM and HMD-only treatment groups, EgRad54 knockdown combined with HM and HMD treatment further reduced E. granulosus viability. This combined approach resulted in significant (p < 0.05) downregulation of Rad54 and Topo2a expression, and upregulation of ATM expression, whereas H2A and P53 expression was significantly higher compared with control groups. These data show that EgRad54 knockdown, combined with HM or HMD treatment, enhances DNA damage in E. granulosus via upregulation of ATM and H2A, and downregulation of Rad54 and Topo2a, thereby inhibiting E. granulosus growth, and suggest that EgRad54 is a potential therapeutic target for cystic echinococcosis treatment.

Effect of Harmine and Its Derivatives Against Echinococcus granulosus and Comparison of DNA Damage Targets.

Cystic echinococcosis (CE) is a worldwide zoonotic disease. At present, the treatment options of CE are limited. The main drugs used in clinical chemotherapy of echinococcosis are albendazole and mebendazole, but they mainly exert longterm antiparasitic effects based on high doses. Therefore, there is an urgent need for effective and safe anti-CE drugs. Previous studies have identified harmine (HM) as a new anti-CE drug. In this study, the efficacy of harmine derivatives was evaluated in vitro and in vivo. The harmine derivatives were tested against E. granulosus protoscoleces (PSC) in vitro. The effect of harmine derivatives was time and concentration dependent at different concentrations, and the anti-CE effect was better than that of harmine. The mortality rate of PSC reached 100% on the 5th day after exposure to harmine derivatives at a concentration of 100 µmol · L -1. Compared with the untreated model control mice, the weight of the cyst was significantly reduced in infected mice treated with harmine derivatives. The effect of harmine derivatives was better than that of harmine, and there was significant difference between harmine derivatives and albendazole (P <0.001). Histopathological examination of experimental mice organs (liver, spleen, lung, brain and small intestine) showed that there was no change in the tissues except for mild inflammation in the liver. The neurotoxicity test in Caenorhabditis elegans showed that the derivative inhibited the movement, feeding, perceptual behavior and acetylcholinesterase activity of C. elegans , and its effect was lower than that of harmine. In addition, intervention with HM derivatives was preliminarily proved to cause DNA damage. This study reveals the potential of HM derivatives as a new class of anti-CE agents and indicates that Topo2a may be a promising target for the development of anti-CE drugs.

In vitro and in vivo Effects of Artesunate on Echinococcus granulosus Protoscoleces and Metacestodes.

BACKGROUND: In this study, we aim to investigate the efficiency of artesunate (AS) on Echinococcus granulosus protoscoleces and metacestodes. METHODS: For the in vitro assay, the eosin dye exclusion test and transmission electron microscope (TEM) were utilized to evaluate the effects of AS against protoscoleces (PSCs) from Echinococcus granulosus. In addition, mortality, ultrastructure change, reactive oxygen species (ROS) content and DNA damage were measured in order to explore the anti-echinococcosis mechanism of AS. For the in vivo assay, CE-infected mice were divided into model group, albendazole (ABZ) group (200 mg/kg), low AS (AS-L) group (50 mg/kg), moderate AS (AS-M) group (100 mg/kg), and high AS (AS-H) group (200 mg/kg). Upon 6 weeks oral administration, wet weight of cysts and the ultrastructural changes of cystic wall were utilized to evaluate the effects of AS on metacestodes. In addition, the liver biochemical parameters, tumor necrosis factor-α (TNF-α), glutathione/glutathione oxidized (GSH/GSSG) ratio in serum, and H2O2, total superoxide dismutase (T-SOD) in cyst fluid were detected. RESULTS: Both in vivo and in vitro experiments showed that AS showed anti-parasitic effects on CE. The AS could elevate the ROS level in the PSCs, which then resulted in obvious DNA damages. AS could significantly improve the liver biochemical parameters in infected mice compared with the model group (P < 0.05). Compared with the model group, AS-M and AS-H decrease the TNF-α content (P < 0.05); AS-H group significantly decrease in the serum GSH/GSSG ratio (P < 0.05). The content of H2O2 in hydatid fluid treated by AS showed significant decrease compared with the model group (P < 0.01), while the T-SOD level showed significant elevation compared with model group (P < 0.01). CONCLUSION: In this study, we confirmed that the effects of AS on Echinococcus granulosus protoscoleces and metacestodes may be related to the DNA damages induced by oxidative stress, which provided solid information for the research and development of drugs for cystic echinococcosis.

Pharmacokinetics and tissue distribution study of liposomal albendazole in naturally Echinococcus granulosus infected sheep by a validated UPLC-Q-TOF-MS method.

Albendazole (ABZ) is the first-line drug in treating echinococcosis, which is recommended by WHO. To address the poor bioavailability of albendazole, liposomal albendazole was formulated and is available in our hospital for many years. In this study, a sensitive, reliable and accurate UPLC-Q-TOF-MS method was developed and validated for the determination of albendazole and its metabolites, albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO2) and albendazole-2-aminosulfone (ABZSO2NH2) in naturally echinococcus granulosus (E. granulosus) infected sheep plasma and tissues with mebendazole (MBZ) as the internal standard (IS). Plasma and tissues samples were prepared by protein precipitation method. The separation was performed on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm) with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at 0.4 mL/min. The detection was performed on a quadrupole time-of-flight (Q-TOF) high-resolution mass spectrometer using positive electrospray ionization (ESI) source with a chromatographic run time of 6.0 min. The detection was operated using target ions of [M + H]+ at m/z 266.096 for ABZ, m/z 282.091 for ABZSO, m/z 298.086 for ABZSO2, m/z 240.081 for ABZSO2NH2 and m/z 296.104 for IS in selective ion mode, respectively. This method was validated in terms of selectivity, linearity, precision, accuracy, recovery, matrix effect, dilution effect, carryover effects, stability, calibration curve and LLOQ. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. This method has been successfully applied to the pharmacokinetic study following single and multiple oral dose of 10 mg/kg liposomal albendazole, and tissue distribution study following multiple oral dose of 10 mg/kg, with emulsion albendazole as the reference preparation. The results in the article will provide valuable information for use in clinical applications of liposomal albendazole and also be beneficial for further development of liposomal albendazole in future studies.