Biology subjects

Jin, W.-L.

Publications and source records attributed to Jin, W.-L..

4 recordsLinked to original sources

bioRxiv2023

Network pharmacological analysis for the identification of the molecular mechanism of Lilium brownii (Baihe) against gastric cancer: 3-Demethylcolchicine targeting androgen receptor

Lilium brownii (Baihe) contains several bioactive compounds with anti-cancer properties. This study aimed to predict the anticancer targets and related pathways of Baihe for the treatment of gastric cancer (GC) by using network pharmacology and to further explore its potential mechanism in GC. The active compounds and their target proteins were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The OMIM, CTD, and GeneCards databases provided information on GC-related targets. After the overlap, the targets of Baihe against GC were collected. The STRING network platform and Cytoscape software were used for protein-protein interaction (PPI) network and core target investigations. Network pharmacology predicted that the principal targets were retrieved from the Starbase database in connection with the GC overall survival. Molecular docking was also used to validate Baihe and the targets high affinity. Finally, the DAVID online tool was used for the overlapping target Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The TCMSP database showed that Baihe has seven bioactive components. Apoptosis and p53 signaling pathways were primarily enriched in overlapping genes according to KEGG analysis. Androgen receptor (AR) was identified as a major target by combining the PPI network, KEEG enrichment, and target gene prognostic analysis. Molecular docking results verified that the Baihes 3-demethylcolchicine has a high affinity for the GC target AR. Based on the results of network pharmacology analysis based on data mining and molecular docking methods, the multi-target drug Baihe may be a promising therapeutic candidate for GC, but further in vivo/ex vivo research is required. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/536129v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@125dc69org.highwire.dtl.DTLVardef@a99703org.highwire.dtl.DTLVardef@1f97161org.highwire.dtl.DTLVardef@182bd38_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2020

Sodium valproate protects against neuronal ferroptosis in epilepsy via suppressing lysyl oxidase

Background and purposeEpilepsy is a chronic neurological disease that is characterized by repetitive seizures. Seizures-related complications such as cognitive deficits, anxiety and sleep disorders seriously impact the life quality of patients. Antiepileptic drugs are widely used for the treatment of epilepsy. Sodium valproate is served as the first-line antiepileptic drugs and possesses various pharmacological effects on the brain. Sodium valproate exerts neuroprotective effects in acute nervous system diseases such as ischemic brain damage by inhibiting oxidative stress. However, the mechanism of neuroprotection of sodium valproate in epilepsy is unclear. Lysyl oxidase (Lox) is a monoamine oxidase that acts on extracellular matrix collagen and elastin and it can promote accumulation of oxidative stress. Our previous studies have confirmed that Lox is involved in ferroptosis, a novel iron-dependent and lipid peroxidation-mediated cell death pathway, during epilepsy. In this study, we would like to investigate whether sodium valproate can exert neuroprotective effects on kainic acid-induced epileptic seizures by inhibiting Lox-mediated ferroptosis. MethodsEpileptic mouse models were established by intracranial injection of 250 ng/l kainic acid on right hippocampus. Sodium valproate and ferroptosis inhibitors were administrated by intraperitoneal injecting. The epileptic behavior of the mice within 4 hours was recorded after intracranial injection of kainic acid. Mouse hippocampus was acquired to analyze the mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and the production of 4-hydroxynonenal (4-HNE). In vitro, the protective effects of sodium valproate on glutamate-induced HT22 cell damage model was assessed by PI/Hoechst staining; The levels of PTGS2, 4-HNE and lipid ROS were analyzed by RT-qPCR, western blot and flow cytometry, respectively. RT-qPCR and Western blot analysis the mRNA and protein expression of Lox in the glutamate-induced HT22 cell damage model. The Lox overexpression model was established by intracranial injection of AAV on right hippocampus. ResultsPretreatment with sodium valproate and ferroptosis inhibitors could significantly alleviate the epileptic seizures in the kainic acid induced epilepsy mouse model. Western blot and RT-qPCR results showed that sodium valproate and ferroptosis inhibitors significantly inhibited the levels of 4-HNE and PTGS2. PI/Hoechst staining showed that 1 mM sodium valproate exerted protective effect on glutamate-induced HT22 cell injury model. There was no significant difference observed between sodium valproate and ferroptosis inhibitors co-intervention group and sodium valproate intervention group on glutamate-induced cell injury model. And sodium valproate could significantly inhibit the production of lipid reactive oxygen species and 4-HNE. The expression of Lox was significantly increased in the glutamate-induced HT22 cell injury model, which could be reversed by pretreatment of sodium valproate. And {beta}-aminopropionitrile (a specific inhibitor of Lox) could inhibit ferroptosis induced by glutamate, as well as ameliorate the epileptic seizures in the kainic acid induced epilepsy mouse model. Pretreatment with sodium valproate could not ameliorate the epileptic behavior in the Lox-overexpression mice. Western blot analysis showed that sodium valproate could not suppress the production of 4-HNE in kainic acid induced epileptic mice model. ConclusionsThe neuroprotective effect of sodium valproate in epileptic seizures is closely related to the inhibition of ferroptosis. The inhibition of ferroptosis is involved in the neuroprotective effect of sodium valproate on glutamate-induced HT22 cell damage model. Sodium valproate may exert neuroprotective effects in kainic acid-induced epileptic seizures by abrogating Lox-mediated ferroptosis.

neuroscience↗

bioRxiv2019

Single-Cell Map of Diverse Immune Phenotypes in the Metastatic Brain Tumor Microenvironment of Non Small Cell Lung Cancer

Cancer immunotherapies have shown sustained clinical success in treating primary non-small-cell lung cancer (NSCLC). However, patients with brain metastasis are excluded from the trials because the brain is viewed traditionally as an immune-privileged organ. The composition and properties of tumor-infiltrating myeloid cells in metastatic brain tumors are mostly unknown. To depict the baseline landscape of the composition, gene signature, and functional states of these immune cells, we performed - single-cell RNA sequencing (scRNAseq) for 12,196cellsafter data preprocessing, including 2,241 immunecells from three surgically removed brain lesions of treatment-naive NSCLC patients. We found a lack of T lymphocyte infiltration and activation, as well as the vast expansion of tumor-associated macrophage(TAM) in the brain lesions of NSCLC patients. By comparing our scRNAseq dataset with published data from early and late-stage primary NSCLC tumors, we showed that this compromised T cell response is unique to brain lesions. We identified a unique alternative activation (M2) gene expression pattern of the TAM in the brain metastasis and a lack of known T cell co-stimulator expression. Accumulation of M2 polarized TAM may, therefore, cause the comprised anti-tumor T cell response in metastatic brain lesions. These findings can contribute to the design of new immunotherapy strategies for NSCLC patients with brain metastasis.

cancer biology↗

bioRxiv2019

Lysyl oxidase promotes neuronal ferroptosis exacerbating seizure-induced hippocampal damage

Epilepsy is a serious neurological disorder and characterized by recurrent and unprovoked seizures. A critical pathological factor in the seizure genesis is neuronal loss. However, mechanisms which lead to neuronal death remain elusive. Our present investigation depicted that ferroptosis, a recently discovered iron- and lipid peroxidation-dependent cell death, probably served as a mechanism in murine models of kainic acid (KA)-induced seizures. And treatment with ferroptosis inhibitors ferrostatin-1 (Fer-1), liproxstatin-1 (Lipo-1) or deferoxamine (DFO) significantly suppressed seizure severity and frequency. Using gene expression profiling in HT22 cells after glutamate exposure (a validated ferroptotic cell death model), we identified lysyl oxidase (Lox) as a novel inducer of ferroptosis. Mechanistically, Lox promoted ferroptosis via activation of extracellular regulated protein kinase (ERK)-dependent 5-lipoxygenase (Alox5) phosphorylation at serine 663 residue signaling, subsequent leading to lipid reactive oxygen species (ROS) accumulation. In a murine model of KA-induced seizure, we illustrated that administration of {beta}-aminopropionitrile (BAPN), a specific Lox inhibitor, remarkably prevented seizure generation. Overall, these findings highlight Lox, a novel identified ferroptotic regulator in neurons, serves as a potential target for seizure-related disease including epilepsy.

neuroscience↗