affinity-purification-of-a-fibrinolytic-enzyme-from-sipunculus-nudus

Affinity Purification of a Fibrinolytic Enzyme from Sipunculus nudus

The fibrinolytic enzyme from Sipunculus nudus (sFE) is a novel fibrinolytic agent that can both activate plasminogen into plasmin and degrade fibrin ...

a-comprehensive-approach-to-analyze-cell-components-cerebral-blood

A Comprehensive Approach to Analyze the Cell Components of Cerebral Blood Clots

Cerebral thrombosis, a blood clot in a cerebral artery or vein, is the most common type of cerebral infarction. The study of the cell components of ...

rapid-separation-display-active-fibrinogenolytic-agents-sipunculus

Rapid Separation and Display of Active Fibrinogenolytic Agents in Sipunculus nudus through Fibrinogen-Polyacrylamide Gel Electrophoresis

Fibrinogenolytic agents that can dissolve fibrinogen directly have been widely used in anti-coagulation treatment. Generally, identifying new ...

in-situ-detection-metabolically-active-cells-hepatocellular-carcinoma

In Situ Detection of Metabolically Active Cells in Hepatocellular Carcinoma Tissue Using MTT-Based Cryosection Imaging

Emerging evidence, including prior studies, highlights a subpopulation of cells within hepatocellular carcinoma (HCC) tissues that exhibit superior ...

Huaqiao University

Engineering Research Centre of Molecular Medicine of Ministry of Education

huaqiao university

Lung cancer, the leading cause of mortality in both men and women in the United States, is largely diagnosed at its advanced stages that there are no effective therapeutic alternatives. Although tobacco smoking is the well established cause of lung cancer, the underlying mechanism for lung tumorigenesis remains poorly understood. An important event in tumor development appears to be the epigenetic alterations, especially the change of DNA methylation patterns, which induce the most tumor suppressor gene silence. In one scenario, DNA methyltransferase (DNMT) that is responsible for DNA methylation accounts for the major epigenetic maintenance and alternation. In another scenario, DNMT itself is regulated by the environment carcinogens (smoke), epigenetic and genetic information. DNMT not only plays a pivotal role in lung tumorigenesis, but also is a promising molecular bio-marker for early lung cancer diagnosis and therapy. Therefore the elucidation of the DNMT and its related epigenetic regulation in lung cancer is of great importance, which may expedite the overcome of lung cancer.

Potential of DNMT and its Epigenetic Regulation for Lung Cancer Therapy.

Haemophilia A is an X-linked recessive monogenic hereditary bleeding disorder caused by a deficiency or functional defect in coagulation factor VIII (FVIII). Typically, only 30% haemophilia A patients are treated with FVIII-specific products successfully. Therefore, other promising clotting factors and FVIII-bypassing factors exhibiting sufficient FVIII-independent activity, low immunogenicity and prolonged half-life are needed to conquer this malady. Here, we will systematically review the current status of the diverse FVIII-bypassing factors for the treatment of FVIII-insensitive haemophilia A patients.

Promising coagulation factor VIII bypassing strategies for patients with haemophilia A.

Prostate cancer (PCa) is the second lethal disease for men in western countries. Although androgen receptor (AR) signaling has been widely investigated, noncoding RNAs (ncRNAs), deficient of open reading frame, have also received considerable attention. Growing studies showed that the aberrant ncRNAs expression contributed to cell proliferation, metastasis and drug resistance in PCa. Therefore, therapeutically targeting ncRNAs may synergize androgen deprivation therapy (ADT) to have a better effect to fight against PCa, especially castration-resistant prostate cancer (CRPC). This review would systematically summarize the multicellular events controlled by ncRNAs and give a snapshot of future scientific activities and clinical applications.

LncRNAs and miRNAs: potential biomarkers and therapeutic targets for prostate cancer.

Prostate cancer (PCa) is a major health problem in males. Metastasis-associated with lung adenocarcinoma transcript-1 (MALAT1), which is overexpressed in PCa tissue, is associated with physiological and pathological conditions of PCa. M2 macrophages are major immune cells abundant in the tumor microenvironment. However, it remains unknown whether M2 macrophages are involved in the effects or not, and molecular mechanisms of MALAT1 on PCa progression have not yet been comprehensively explored. Here we reported that, M2 macrophages (PMA/IL-4 treated THP1) induced MALAT1 expression in PCa cell lines. Knockdown MALAT1 expression level in PCa cell lines inhibited cellular proliferation, invasion, and tumor formation. Further mechanistic dissection revealed that M2 macrophages secreted IL-8 was sufficient to drive up MALAT1 expression level via activating STAT3 signaling pathway. Additional chromatin immunoprecipitation (ChIP) and luciferase reporter assays displayed that STAT3 could bind to the MALAT1 promoter region and transcriptionally stimulate the MALAT1 expression. In summary, our present study identified the IL-8/STAT3/MALAT1 axis as key regulators during prostate tumorigenesis and therefore demonstrated a new mechanism for the MALAT1 transcriptional regulation.

IL-8 Secreted from M2 Macrophages Promoted Prostate Tumorigenesis via STAT3/MALAT1 Pathway.

N6-methyladenosine (m6A) modification is the most prevalent internal modification of eukaryotic mRNA modulating gene expression. m6A modification is a dynamic reversible process regulated by three protein groups: methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). m6A modification is involved in all phases of RNA metabolism, including RNA folding, stability, splicing, nuclear exporting, translational modulation and degradation.

Association of N6-methyladenosine with viruses and related diseases.

N6-methyladenosine (m6A) modification, which alters gene expression, is the most prevalent internal modification of eukaryotic mRNA. m6A modification is dynamic and reversible that is regulated by three associated protein groups: methyltransferases or writers, demethylases or erasers, and m6A-binding proteins or readers. m6A modification is involved in all phases of RNA life, from RNA folding and structure, stability, splicing, nuclear export, translational modulation to RNA degradation. Recent findings show that the abnormal level of m6A modification causes aberrant expression of important viral genes. Here, we reviewe m6A role in gene expression and its contribution to the development  of human viral diseases. Particularly, we would focus on viruses associated with human diseases including HIV-1, IAV, HBV, HCV, EBV and so on to find a novel approach and provide a new sight for the innovative treatment of human viral diseases.

Association of N6-methyladenosine with viruses and virally induced diseases.

It is well-known that Epstein-Barr virus (EBV) is the promoter of cell tumourigenesis. We found that EBV is also a promoter of lymphoma cell dissemination, because we found the typical morphopathological phenomenon of cell adhesion, which confirmed that the adhesion of tumour cells was higher than that of normal cells. We also observed that tumour cells disrupted the dynamic pathological changes of vascular endothelial cells, and this made it clear that the rate of tumour cell metastasis was directly proportional to the degree of EBV infection. Furthermore, when we discovered exosomes, it was considered that this was associated with cancer stem cells, suggesting the formation of a microenvironment before tumour cell metastasis. In addition, competitive inhibition was found in cell adhesion, indicating the breakthrough point of preventing tumour cell metastasis, which has clinical reference value for tumour immunotherapy.

Epstein-Barr virus is a promoter of lymphoma cell metastasis.

In this study, detailed information on hepatocellular carcinoma (HCC) cells (HepG-2, SMMC-7721, and HuH-7) and normal human liver cell L02 treated by ferrocene derivatives (compounds ,  and ) is provided. The cell viability assay showed that compound  presented the most potent and selective anti-HCC activity. Further mechanism study indicated that the proliferation inhibition effect of compound  was associated with the cycle arrest at the G0/G1 phase and downregulation of cyclin D1/CDK4. Moreover, compound  could induce apoptosis in HCC cells by loss of mitochondrial membrane potential (ΔΨm), accumulation of reactive oxygen species (ROS), decrease in Bcl-2, increase in BAX and Bad, translocation of Cytochrome , activation of Caspase-9, -3, and cleavage of PARP. These results indicated that compound  would be a promising candidate against HCC through G0/G1 cell cycle arrest-related proliferation inhibition and mitochondrial pathway-dependent apoptosis.

Novel Ferrocene Derivatives Induce G0/G1 Cell Cycle Arrest and Apoptosis through the Mitochondrial Pathway in Human Hepatocellular Carcinoma.

T cell acute lymphoblastic leukemia (T-ALL) is one of the most common causes of death in pediatric malignancies. However, the clinical chemotherapy for T-ALL has been limited by numerous side effects, emphasizing that novel anti-T-ALL drugs are urgently needed. Herein, a series of 2-acyl-1-dimethylaminomethyl-ferrocenes for cancer therapy have been evaluated. Among them, F1 and F3 exhibited potent cytotoxicity against T-ALL cell lines, especially Jurkat cells, with low cytotoxicity for normal cells. Further mechanistic studies revealed that F1 and F3 could induce apoptosis in Jurkat cells by destructing mitochondrial membrane, enhancing reactive oxygen species (ROS) generation, decreasing the Bcl-2/Bax ratio, releasing Cytochrome c, and increasing the expression of Cleaved Caspase-9/-3 and Cleaved PARP. Additionally, F1 and F3 could suppress cell proliferation and arrest the cell cycle at G0/G1 phase through the PI3K/Akt/mTOR signaling pathway by down-regulating the expression of CDK6, Cyclin D1, p-Akt, p-GSK-3β, p-mTOR, p-p70 S6K, and up-regulating the expression of P21 and P27, which would also be a possible mechanism. Consequently, ferrocene derivatives F1 and F3 could induce apoptosis through a mitochondria-dependent pathway mediated by ROS, and cell cycle arrest at G0/G1 phase via the PI3K/Akt/mTOR signaling pathway in Jurkat cells. The present study provided fundamental insights into the clinical application of F1 and F3 for the treatment of T-ALL.

Novel Ferrocene Derivatives Induce Apoptosis through Mitochondria-Dependent and Cell Cycle Arrest via PI3K/Akt/mTOR Signaling Pathway in T Cell Acute Lymphoblastic Leukemia.

Thrombosis has been emerging as a major global life-threatening issue with high mortality and serious complications, especially in the post-COVID-19 era. Compared with the commonly used plasminogen activators thrombolytic drugs, fibrinolytic drugs are no longer heavily dependent on the patients' own plasminogen, which are poorly expressed in most patients. As a novel "direct acting" thrombolytic agent, fibrinolytic drugs are considered to have stronger thrombolytic efficacy and safety than the widely used plasminogen activators. However, the risk of their hemorrhage remains a major concern. Herein, the molecular mechanisms and solutions were summarized for the first time based on the systematic review of the latest developments, which could shed new light on the development of novel safety fibrinolytic drugs in the future.

Fibrinolytic drugs induced hemorrhage: mechanisms and solutions.

Current thrombolytic therapies primarily function by converting plasminogen into plasmin, a process dependent on the fibrin-activator complex. This dependence, coupled with the substantial molecular size of plasmin, constrains its effectiveness in degrading D-dimer and restricts its diffusion within thrombi. Here, we introduce a small facultative plasminogen-independent thrombolytic enzyme, snFPITE, isolated from Sipunculus nudus. Compared to traditional thrombolytic agents, snFPITE does not require plasminogen for thrombolysis, although its presence enhances lytic activity. This enzyme fully degrades cross-linked fibrin without leaving residual nondegradable D-dimer and generates a smaller fibrinolytic-active agent from plasminogen. A series of male rats and mice models further confirm that snFPITE is a safety injectable thrombolytic agent. Mechanistically, snFPITE activates plasminogen and degrades fibrin(ogen) in a multisite cleavage manner. snFPITE is inhibited by plasminogen activator inhibitor 1 and α2-antiplasmin via a competitive inhibition. We further identify 28 snFPITE candidate sequences, of which 10 are confirmed as functional genes.

ArticleTotal : 4	Year
Publication title Cited by 2	2023
Publication title Cited by 1	2023
Publication title Cited by 2	2024
Publication title	2025

Article	Year
Potential of DNMT and its Epigenetic Regulation for Lung Cancer Therapy. Current genomics\| PubMed ID: 20119531	2009
Promising coagulation factor VIII bypassing strategies for patients with haemophilia A. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis\| PubMed ID: 24614429	2014
LncRNAs and miRNAs: potential biomarkers and therapeutic targets for prostate cancer. American journal of translational research\| PubMed ID: 28077991	2016
IL-8 Secreted from M2 Macrophages Promoted Prostate Tumorigenesis via STAT3/MALAT1 Pathway. International journal of molecular sciences\| PubMed ID: 30591689	2018
Association of N6-methyladenosine with viruses and related diseases. Virology journal\| PubMed ID: 31711514	2019
Association of N6-methyladenosine with viruses and virally induced diseases. Frontiers in bioscience (Landmark edition)\| PubMed ID: 32114429	2020
Epstein-Barr virus is a promoter of lymphoma cell metastasis. Pathology\| PubMed ID: 32768248	2020
Novel Ferrocene Derivatives Induce G0/G1 Cell Cycle Arrest and Apoptosis through the Mitochondrial Pathway in Human Hepatocellular Carcinoma. International journal of molecular sciences\| PubMed ID: 33803555	2021
Novel Ferrocene Derivatives Induce Apoptosis through Mitochondria-Dependent and Cell Cycle Arrest via PI3K/Akt/mTOR Signaling Pathway in T Cell Acute Lymphoblastic Leukemia. Cancers\| PubMed ID: 34572904	2021
Fibrinolytic drugs induced hemorrhage: mechanisms and solutions. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis\| PubMed ID: 37395191	2023
A facultative plasminogen-independent thrombolytic enzyme from Sipunculus nudus. Nature communications\| PubMed ID: 40274794	2025

Mingqing Tang

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