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New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468). The results showed that most of the compounds displayed potent inhibition against BGC823, H4, and Bel7402, with IC50s of 1.84-0.39 μM. The best compound NST001A was tested in an in vivo antitumor assay on nude mice bearing Colo 205 xenografts, and showed significant inhibition of tumor growth at low concentrations. Therefore, celastrol C-6 derivatives are potential drug candidates for treating cancer.
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http://dx.doi.org/10.3390/molecules190710177 | DOI Listing |
BMC Biotechnol
September 2025
Faculty of Science, Department of Biotechnology and Food Technology, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, Gauteng, 2028, South Africa.
Patulin (PAT), a mycotoxin produced primarily by Penicillium expansum, poses significant health risks and frequently contaminates apples and apple-derived products, often exceeding permissible safety limits. This study investigated the potential of orotate phosphoribosyl transferase (URA5) to degrade PAT in apple juice under controlled conditions. PAT degradation was assessed at initial concentrations of 100 µg/L and 250 µg/L, with enzymatic treatment using 0.
View Article and Find Full Text PDFMol Syst Biol
September 2025
Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
The complex interplay between circulating metabolites and immune responses, which is pivotal to disease pathophysiology, remains poorly understood and understudied in systematic research. Here, we performed a comprehensive analysis of the immune response and circulating metabolome in two Western European cohorts (534 and 324 healthy individuals) and one from sub-Saharan Africa (323 healthy donors). At the metabolic level, our analysis revealed sex-specific differences in the correlation between phosphatidylcholine and cytokine responses following ex vivo stimulation.
View Article and Find Full Text PDFNature
September 2025
Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer, characterized by rapid proliferation, early metastatic spread, frequent early relapse and a high mortality rate. Recent evidence has suggested that innervation has an important role in the development and progression of several types of cancer. Cancer-to-neuron synapses have been reported in gliomas, but whether peripheral tumours can form such structures is unknown.
View Article and Find Full Text PDFNature
September 2025
Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Monocyte-derived macrophages (mo-macs) often drive immunosuppression in the tumour microenvironment (TME) and tumour-enhanced myelopoiesis in the bone marrow fuels these populations. Here we performed paired transcriptome and chromatin accessibility analysis over the continuum of myeloid progenitors, circulating monocytes and tumour-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. We show that lung tumours prime accessibility for Nfe2l2 (NRF2) in bone marrow myeloid progenitors as a cytoprotective response to oxidative stress, enhancing myelopoiesis while dampening interferon response and promoting immunosuppression.
View Article and Find Full Text PDFOncogene
September 2025
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Resistance to platinum-based drugs and PARP inhibitors (PARPi) is the leading cause of treatment failure in epithelial ovarian cancer (EOC). This study aimed to identify resistance mechanisms shared by both. Using bioinformatic analyses, EOC tissues, primary tumor cells and organoids, and chemoresistant cell lines, we identified lymphoid enhancer-binding factor 1 (LEF1) as a candidate, whose expression was increased in both platinum-resistant and PARPi-resistant tumors.
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