Thiostrepton

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by pulmonary vascular remodeling. It refers to the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs), and hypoxia is an important risk factor for this progression. The present study aims to investigate the role of YTHDF1 in the regulation of hypoxic PASMC proliferation and the underlying mechanism. Human PASMCs were transfected with si-YTHDF1/2/3 followed by treatment of hypoxia, and the PASMC proliferation and Foxm1 expression were detected...

δ-Tocotrienol plus AHA Step-1 diet in hypercholesterolemic subjects caused reductions in lipid parameters (14% to 18%) with 250 mg/d dose, and 500 mg/d resulted induction in these parameters. Although, α-tocopherol is the most bioavailable form of vitamin E. There are few reports on bioavailability of tocotrienols in humans. Pharmacokinetics and bioavailability of δ-tocotrienol was quantified on plasma levels of tocol isomers, cytokines, and microRNAs. Subjects were fed doses of 125 mg/d to 500 mg/d...

Background Intrauterine growth restriction (IUGR) is closely related to systemic or pulmonary hypertension (PH) in adulthood. Aberrant crosstalk between pulmonary vascular endothelial cells (PVECs) and pulmonary arterial smooth muscle cells (PASMCs) that is mediated by exosomes plays an essential role in the progression of PH. FoxM1 (Forkhead box M1) is a key transcription factor that governs many important biological processes. Methods and Results IUGR-induced PH rat models were established. Transwell plates were used to coculture PVECs and PASMCs...

BACKGROUND: Phospholipase D (PLD) is highly valuable in the food and medicine industries, where it is used to convert low-cost phosphatidylcholine into high-value phospholipids (PLs). Despite being overexpressed in Streptomyces, PLD production requires expensive thiostrepton feeding during fermentation, limiting its industrialization. To address this issue, we propose a new thiostrepton-free system. RESULTS: We developed a system using a combinatorial strategy containing the constitutive promoter kasOp* and PLD G215S mutation fused to a signal peptide sigcin of Streptoverticillium cinnamoneum pld...

Iron is essential for many biological functions in bacteria, but its poor solubility is a limiting factor for growth. Bacteria produce siderophores, soluble natural products that bind iron with high affinity, to overcome this challenge. Siderophore-iron complexes return to the cell through specific outer membrane transporters. The opportunistic pathogen Pseudomonas aeruginosa makes multiple transporters that recognize its own siderophores, pyoverdine and pyochelin, and xenosiderophores produced by other bacteria or fungi, which gives it a competitive advantage...

Gastric cancer is a leading cause of tumor-associated death worldwide. Metastasis and chemoresistance are crucial barriers for gastric cancer treatment. The Forkhead Box M1 (FOXM1) transcription factor has been reported as a promising treatment target for various types of tumors, but its effects on gastric cancer progression are not fully understood. In the present study, we found that FOXM1 expression levels were significantly up-regulated in human gastric cancer cell lines and tissues, and its expression was much higher in patients with metastasis...

No abstract text is available yet for this article.

OBJECTIVE: FoxM1 transcription factor contributes to tumor metastasis and poor prognosis in many cancers including triple-negative breast cancer (TNBC). In this study, we examined the effects of FoxM1 inhibitor Thiostrepton (THIO) alone or in combination with MEK inhibitor Selumetinib (SEL) on metastatic parameters in vitro and in vivo. METHODS: Cell viability was determined by MTT assay. Immunoblotting and immunohistochemistry was used to assess metastasis-related protein expressions in 4T1 cells and its allograft tumor model in BALB/c mice...

Programmed death-ligand 1 (PD-L1) is a major target to cancer immunotherapy, and anti-PD-L1 and anti-PD-1 antibody-mediated immunotherapy are being increasingly used. However, immune checkpoint inhibitors (ICIs) are ineffective in treating large tumors and cause various immune-related adverse events in nontarget organs, including life-threatening cardiotoxicity. Therefore, the development of new therapeutic strategies to overcome these limitations is crucial. The focus of this study is the forkhead box protein M1 (FOXM1), which is identified as a potential therapeutic target for cancer immunotherapy and is associated with the modulation of PD-L1 expression...

In recent years a large number of encapsulin nanocompartment-encoding operons have been identified in bacterial and archaeal genomes. Encapsulin-encoding genes and operons from GC-rich Gram-positive bacteria, particularly of the phylum Actinobacteria, are often difficult to overexpress and purify in a soluble form using standard Escherichia coli expression systems . Here, we present a protocol to heterologously overexpress encapsulin nanocompartments and encapsulin-containing operons in Streptomyces coelicolor...

Trypanosoma cruzi , the causal agent of Chagas disease, has peroxiredoxins (PRXs) expressed in all stages of the parasite and whose function is to detoxify oxidizing agents, such as reactive oxygen species (ROS). These proteins are central for the survival and replication of the parasite and have been proposed as virulence factors. Because of their importance, they have also been considered as possible therapeutic targets, although there is no specific drug against them. One of them, the mitochondrial PRX (TcMPX), is important in the detoxification of ROS in this organelle and has a role in the infectivity of  T...

Ferroptosis is a new form of regulated cell death that is mediated by intracellular iron and ester oxygenase, and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into nontoxic lipid alcohols. Although thiostrepton (TST) has been reported to exert antitumor effects, its role in pancreatic cancer and the underlying mechanisms remain unclear. In this study, we found that TST reduced the viability and clonogenesis of pancreatic cancer cell lines, along with intracellular iron overload, increasing reactive oxygen species (ROS) accumulation, malondialdehyde (MDA) overexpression, and glutathione peroxidase (GSH-PX) depletion...

Abnormal expression of Forkhead box protein M1 (FOXM1) and serine/threonine kinase Budding uninhibited by benzimidazoles 1 (BUB1B) contributes to the development and progression of several cancers, including chronic myelogenous leukemia (CML). However, the molecular mechanism of the FOXM1/BUB1B regulatory network and the role of Neosetophomone-B (NSP-B) in leukemia remains unclear. NSP-B, a meroterpenoid fungal secondary metabolite, possesses anticancer potential in human leukemic cells lines; however, the underlying mechanism has not been elucidated...

No abstract text is available yet for this article.

Noncanonical amino acids (NCAAs) are imperative to many facets of chemistry and biology. Herein, we report a method for the reductive hydrodifluoroalkylation of olefins that utilizes triethylamine base as the terminal reductant. The alkene acceptors include a range of electronically diverse alkenes, chief among them, dehydroalanine in variously protected forms, which provides access to synthetically relevant NCAA scaffolds under mild and general reaction conditions. We have demonstrated that a chiral auxiliary may be incorporated to provide diastereocontrol for pro-stereogenic substrates...

Cobalamin-dependent radical S-adenosylmethionine (SAM) methylases catalyze key steps in the biosynthesis of numerous biomolecules, including protein cofactors, antibiotics, herbicides, and other natural products, but have remained a relatively understudied subclass of radical SAM enzymes due to their inherent insolubility upon overproduction in Escherichia coli. These enzymes contain two cofactors: a [4Fe-4S] cluster that is ligated by three cysteine residues, and a cobalamin cofactor typically bound by residues in the N-terminal portion of the enzyme...

The forkhead box M1 (FoxM1) protein, a transcription factor, plays critical roles in regulating tumor growth and drug resistance, while cellular FLICE-inhibitory protein (c-FLIP), an anti-apoptotic regulator, is involved in the ubiquitin-proteasome pathway. In this study, we investigated the effects of c-FLIP on the expression and ubiquitination levels of FoxM1 along with drug susceptibility in non-small-cell lung cancer (NSCLC) cells. We first showed that the expression levels of FoxM1 and c-FLIP were increased and positively correlated (R2  = 0...

Understanding the biological and clinical impact of copy number aberrations (CNA) for the development of precision therapies in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring adverse prognosis in several types of cancer, including in the blood cancer multiple myeloma (MM). Although several genes across chr1q portend high-risk MM disease, the underpinning molecular aetiology remains elusive. Here, with reference to the 3D chromatin structure, we integrate MM patient multi-omics datasets with genetic variables to obtain an associated clinical risk map across chr1q and to identify 103 adverse prognosis genes in chr1q-amp MM...

BACKGROUND Forkhead box protein M1 (FoxM1) is an important transcription factor involved in the development and progression of various malignancies. However, its role in nasopharyngeal carcinoma (NPC) remains largely unknown. This study aimed to assess the effect of FoxM1 on NPC cell tumorigenesis as well as the underlying mechanism. MATERIAL AND METHODS NPC cell lines CNE-1 and CNE-2 were treated with vehicle and FoxM1 inhibitor thiostrepton or transfected with small interfering RNA. CCK-8 assay, flow cytometric assay, and Hoechst 33258 staining were performed to assess the viability, apoptosis and nuclear morphological impairment, and cell cycle, respectively...

The aberrant up-regulation of the oncogenic transcription factor Forkhead box M1 (FoxM1) is associated with tumor development, progression and metastasis in a myriad of carcinomas, thus establishing it as an attractive target for anticancer drug development. FoxM1 overexpression in hepatocellular carcinoma is reflective of tumor aggressiveness and recurrence, poor prognosis and low survival in patients. In our study, we have identified the antimalarial natural product, Artemisinin, to efficiently curb FoxM1 expression and activity in hepatic cancer cells, thereby exhibiting potential anticancer efficacy...