plasminogen activator (tisokinase / tisokinase, Kowa / Hapase)

✓ Approved

什么是 plasminogen activator？

plasminogen activator 是一种治疗药物，由Asahi Kasei研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intravenous (IV)。

药物档案

商品名	tisokinase, tisokinase, Kowa, Hapase
公司	Asahi Kasei
给药途径	Injectable (Others), Intravenous (IV)
状态	Approved

来源： ClinicalTrials.gov, Asahi Kasei

治疗适应症

plasminogen activator 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域	疾病/病症	分期
Cardiac disorders	Myocardial infarction	✓ Approved

相关研究文献

PubMedThe New phytologist2026-06-13

Time-delayed activator-repressor regulation of ginsenoside biosynthesis in Gynostemma pentaphyllum.

Huang Lijin L, Du Jinfa J, Chen Yuhong Y, Jin Dian D et al.

Jasmonic acid (JA) signaling is a key regulator of plant secondary metabolism, yet how it balances rapid activation with timely repression of ginsenoside biosynthesis remains unclear in Gynostemma pentaphyllum. Here, we investigated the transcriptional regulation mechanism of ginsenoside biosynthesis by JA-responsive basic helix-loop-helix (bHLH) transcription factors. By integrating transcriptome and phylogenetic analyses with yeast one-hybrid, electrophoretic mobility shift assays, dual-luciferase assays, transgenic hairy root overexpression, and RNA interference, together with metabolite profiling, we identified key regulators and defined their roles in the ginsenoside biosynthesis pathway of G. pentaphyllum. We characterized an antagonistic bHLH pair, GpGAB (g36559, Activator), and GpGIB (g21771, Inhibitor). GpGAB activated ginsenoside biosynthetic genes GpDS, GpPPDS, and GpUGT94AT1, whereas GpGIB repressed the expression of GpDS and GpPPDS. GpGAB also upregulated the expression of GpGIB, with GpGAB responding earlier than GpGIB to JA treatment. Taken together, our results support a model in which GpGAB and GpGIB form a time-delayed negative feedback loop that fine-tunes ginsenoside biosynthesis after JA induction, providing a mechanistic framework for dynamic transcriptional regulation of ginsenoside in G. pentaphyllum.

PMID 42286427

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PubMedFree radical biology & medicine2026-06-13

Nrf1 Regulates Lipid Metabolism through the PPAR⍺ Signaling Pathway and Influences the Fibrotic Process in Diabetic Nephropathy.

Qiu Ziying Z, Zhang Yanmin Y, Zhu Laiyu L, Zhao Xuanrui X et al.

In diabetic nephropathy (DN), oxidative stress disrupts normal metabolic processes, contributing to progressive kidney injury. Although Nfe2l1 (also known as Nrf1) is known to regulate oxidative stress and metabolism, its specific role in DN remains poorly understood. This study investigated how changes in Nrf1 expression influence DN-associated renal fibrosis. Nrf1 function was examined in multiple experimental settings, including: human DN kidney tissues; wild-type and proximal tubule-specific Nfe2l1 knockout mice subjected to high-fat diet plus STZ-induced DN; HK-2 cells exposed to high glucose and palmitic acid; and diabetic mice treated with the Nrf1 activator RUN-47. Nrf1 expression was markedly reduced in kidney tissues from patients with DN, as well as in the renal proximal tubules of DN mice and in high glucose and palmitic acid-treated HK-2 cells. Proximal tubule-specific Nfe2l1 knockout in mice and siRNA-mediated Nfe2l1 knockdown in HK-2 cells both aggravated tubular injury and fibrosis. Transcriptomic profiling indicated that Nrf1 modulates lipid metabolism through the PPARα signaling pathway and that its suppression exacerbates mitochondrial damage and lipid metabolism disorders. Mechanistically, Nrf1 directly binds to the PPARα promoter to transcriptionally activate its expression. Pharmacological inhibition and activation experiments confirmed that Nrf1 exerts its protective effects at least in part via PPARα signaling. Conversely, Nrf1 overexpression in HK-2 cells or pharmacological activation by RUN-47 significantly attenuated tubular damage, fibrotic changes, and lipid metabolism abnormalities. Notably, these protective effects were abrogated in the absence of Nrf1. Nrf1 downregulation in renal tubules promotes renal fibrosis in DN by impairing PPARα-mediated fatty acid oxidation, inducing mitochondrial dysfunction and lipid accumulation. Mechanistically, Nrf1 directly transcriptionally activates PPARα, and pharmacological activation of Nrf1 attenuates DN progression. These findings identify Nrf1 as a potential therapeutic target for slowing DN progression.

PMID 42285318

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PubMedbioRxiv : the preprint server for biology2026-06-12

Transcriptomic, Specific Marker, and Pathway Analysis of Smooth Muscle Cell Foam Cells Compared to Macrophage Foam Cells in Human Atherosclerosis.

Allahverdian Sima S, Mao Yuancheng Y, Xiang Pinhao P, Blanchard Valentin V et al.

Smooth muscle cells (SMCs) comprise the majority of cells in human atherosclerotic lesions and are thought to be a major source of cholesterol-overloaded foam cells in human and mouse atheromas. However, the transcriptomic profile, specific markers, and biologic itinerary of SMC foam cells relative to macrophage foam cells remain poorly defined. Single-cell RNA sequencing (scRNA-seq) was performed on fresh coronary artery segments from heart transplant recipients with early- to intermediate-stage atherosclerosis. Gene expression in a putative SMC foam cell cluster was compared with cultured SMCs loaded with aggregated low-density lipoprotein (agLDL) or cholesterol-methyl-β-cyclodextrin (Chol-MβCD). Candidate markers distinguishing SMC from macrophage foam cells were validated using additional publicly-available scRNA-seq datasets, Xenium spatial transcriptomics, and immunofluorescence microscopy of human coronary atheromas. Pathway analysis was performed using Gene Set Enrichment Analysis Hallmark gene sets. A distinct SMC foam cell cluster derived from fibromyocytes ("lipomyocytes") was identified using markers induced by in vitro cholesterol loading. agLDL loading reproduced the lipomyocyte transcriptional profile, whereas Chol-MβCD induced an inflammatory phenotype colocalizing with macrophages rather than lipomyocytes. Lipomyocytes highly expressed SERPINE1 , encoding plasminogen activator inhibitor-1 (PAI-1), and CFH , encoding complement factor H, which were validated in human coronary lesions by spatial transcriptomics and immunofluorescence microscopy. Compared with macrophage foam cells, lipomyocytes demonstrated distinct pathway activation, including enrichment of extracellular matrix, coagulation and angiogenesis pathways. SMC foam cells, or lipomyocytes, represent a distinct foam cell phenotype with unique markers and biologic programs that differ from macrophage foam cells during atherosclerotic plaque development. What Is New?: Smooth muscle cell (SMC) foam cells, or lipomyocytes, arise from fibromyocytes and exhibit a transcriptomic profile that is markedly distinct from that of macrophage foam cells.In vitro loading of SMCs with aggregated LDL recapitulates the gene expression profile of SMC foam cells in human coronary atheromas, whereas loading with cyclodextrin-bound cholesterol does not. Plasminogen activator inhibitor 1 (PAI-1, encoded by SERPINE1 ) and Complement Factor H are specific markers of SMC foam cells and are not expressed by macrophage foam cells. What Are the Clinical Implications?: SMCs contribute a substantial proportion, and potentially the majority, of foam cells in atherosclerotic lesions.Defining the biological trajectory of SMC foam cells within plaques is critical for understanding their roles in plaque progression, rupture and thrombosis, and for establishing their relevance as a distinct therapeutic target to reduce major cardiovascular events.

PMID 42282821

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PubMedJournal of agricultural and food chemistry2026-06-12

PeMYB6 Competes with PeMYB114 for Interaction with PebHLH42 to Regulate Anthocyanin Biosynthesis in Passion Fruit.

Chen Qiaowen Q, Zhu Zanlin Z, Liang Fan F, Zhou Shibin S et al.

Anthocyanin biosynthesis is tightly controlled by the MYB-bHLH-WD40 (MBW) complex in plants. Here, we investigated the regulatory mechanism underlying anthocyanin accumulation in passion fruit (Passiflora edulis Sims) peels. We identified PebHLH42, a nucleus-localized IIIf bHLH transcription factor that interacts with activator PeMYB114. The PeMYB114-PebHLH42 complex strongly activates PeCHS and PeANS transcription, promoting anthocyanin accumulation in tobacco leaves, whereas PebHLH42 alone shows no inductive effect. We also characterized PeMYB6, a nuclear R2R3-MYB repressor that harbors EAR and TLLLFR motifs. PeMYB6 overexpression reduces the anthocyanin and proanthocyanidin levels and represses flavonoid biosynthetic genes. Mechanistically, PeMYB6 competes with PeMYB114 for binding to PebHLH42, thus suppressing the activation of PeCHS and PeANS. Moreover, PeMYB114 activates PeMYB6 transcription, forming an activator-repressor feedback loop. These results reveal a refined regulatory module for passion fruit pigmentation and benefits molecular breeding for color modification.

PMID 42281433

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PubMedJournal of translational medicine2026-06-12

Dihydrotanshinone I as a novel signal transducer and activator of transcription 3 inhibitor for glioblastoma treatment.

Cheng Kai-Wen KW, Zhou Shao-Jun SJ, Zeng Jie J, Zhang Yang-Rui YR et al.

Among tumors affecting the central nervous system (CNS), glioblastoma multiforme (GBM) is the most aggressive and lethal form. Given the complex mechanisms of the CNS and the blood-brain barrier (BBB), effective therapies for GBM remain limited. To identify potential therapeutic candidates for glioma, we developed a small-molecule library to screen for compounds with potent anti-proliferative effects and BBB permeability. The mechanisms underlying their anti-glioma activity were further elucidated to provide insights into new treatment strategies. A library of small molecules was screened to identify agents that significantly inhibit glioma cells activity. The effects of the lead compound (Dihydrotanshinone I, DHT) on glioma progression were evaluated through a series of experimental approaches, including cell counting kit-8 assays, cell cycle analysis, apoptosis detection, wound healing, transwell migration, reactive oxygen measurement, subcutaneous xenograft mouse models, and intracranial orthotopic tumor models. To elucidate the underlying mechanisms, network pharmacology and transcriptomic analyses were employed. The mechanism of DHT in glioma pathogenesis was further validated using bioinformatics analyses and clinical glioma tissue samples. Based on pharmacokinetic evaluation, DHT was found to traverse the BBB, indicating its capacity to reach the cerebral parench. In vitro and in vivo experiments demonstrated that DHT significantly suppresses glioma growth and progression. Mechanistic analyses using network pharmacology and RNA sequencing revealed that DHT induces glioma cell apoptosis by inhibiting the Janus kinase-signal transducer and activator of transcription 3 (STAT3) signaling pathway, increasing intracellular reactive oxygen species levels and triggering intrinsic apoptotic cascades. Furthermore, bioinformatic analyses of clinical cohorts coupled with validation in patient-derived glioma specimens confirmed that elevated STAT3 expression was correlated with unfavorable prognosis and was significantly increased in patients with high-grade glioma. This study demonstrates that, in addition to its role as a key contributor to glioma malignancy and a prognostic marker, STAT3 is also a target of DHT, highlighting its potential as a promising therapeutic candidate for treating GBM.

PMID 42277880

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PubMedBioscience, biotechnology, and biochemistry2026-06-12

Hot-water extract of defatted Perilla frutescens seed residue suppresses osteoclast differentiation and improves bone-related parameters in ovariectomized mice.

Asano Hiroyuki H, Nishimoto Sogo S

The defatted residue of Perilla frutescens seeds, a by-product of edible oil production, remains largely underutilized in food applications. This study investigated the effects of a hot-water extract derived from this residue on osteoclast differentiation and bone-related changes. In bone marrow-derived macrophages, the extract inhibited receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation, as evidenced by the reduced formation of tartrate-resistant acid phosphatase-positive multinucleated cells and decreased tartrate-resistant acid phosphatase activity, without significantly affecting cell viability. In ovariectomized mice, the extract increased trabecular region length and cortical bone thickness. In a separate experiment, it enhanced femoral mechanical strength in a three-point bending test. High-performance liquid chromatography analysis identified rosmarinic acid and salviaflaside in the extract. These findings suggest that defatted Perilla frutescens seed residue may be a functional resource for improving bone health.

PMID 42284580

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plasminogen activator (tisokinase / tisokinase, Kowa / Hapase)

什么是 plasminogen activator？

药物档案

治疗适应症

相关研究文献

Time-delayed activator-repressor regulation of ginsenoside biosynthesis in Gynostemma pentaphyllum.

Nrf1 Regulates Lipid Metabolism through the PPAR⍺ Signaling Pathway and Influences the Fibrotic Process in Diabetic Nephropathy.

Transcriptomic, Specific Marker, and Pathway Analysis of Smooth Muscle Cell Foam Cells Compared to Macrophage Foam Cells in Human Atherosclerosis.

PeMYB6 Competes with PeMYB114 for Interaction with PebHLH42 to Regulate Anthocyanin Biosynthesis in Passion Fruit.

Dihydrotanshinone I as a novel signal transducer and activator of transcription 3 inhibitor for glioblastoma treatment.

Hot-water extract of defatted Perilla frutescens seed residue suppresses osteoclast differentiation and improves bone-related parameters in ovariectomized mice.

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