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Introduction: is a flagellated protozoan parasite causing giardiasis, a common intestinal infection characterized by diarrhea, abdominal cramps, and nausea. Treatments employed to combat this parasitic infection have remained unchanged for the past 40 years, leading to the emergence of resistant strains and prompting the search for new therapeutic agents.
Methods: This study investigated the cytotoxic effects of ivermectin (IVM) on trophozoites. We conducted dose-response experiments to assess IVM-induced cytotoxicity. We utilized various biochemical and ultrastructural analyses to explore the underlying mechanisms of cell death, including reactive oxygen species (ROS) production, DNA fragmentation, cell cycle arrest, and apoptosis markers.
Results: Our findings demonstrate that IVM induces dose-dependent cytotoxicity and triggers cell death pathways. We found that IVM treatment generates elevated levels of reactive oxygen species (ROS), DNA fragmentation, and arrests of trophozoites in the cell cycle's S phase. Additionally, ultrastructural analysis reveals morphological alterations consistent with apoptosis, such as cytoplasmic vacuolization, chromatin condensation, and tubulin distribution.
Discussion: The insights gained from this study may contribute to developing new therapeutic strategies against giardiasis, addressing the challenge posed by drug-resistant strains.
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http://dx.doi.org/10.3389/fmicb.2024.1484805 | DOI Listing |
Sci Transl Med
September 2025
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China.
Triple-negative breast cancers (TNBCs) lack predictive biomarkers to guide immunotherapy, especially during early-stage disease. To address this issue, we used single-cell RNA sequencing, bulk transcriptomics, and pathology assays on samples from 171 patients with early-stage TNBC receiving chemotherapy with or without immunotherapy. Our investigation identified an enriched subset of interferon (IFN)-induced CD8 T cells in early TNBC samples, which predict immunotherapy nonresponsiveness.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
The mutagenic translesion synthesis (TLS) pathway, which is critically dependent on REV1's ability to recruit inserter TLS polymerases and the POLζ extender polymerase, enables cancer cells to bypass DNA lesions while introducing mutations that likely contribute to the development of chemotherapy resistance and secondary malignancies. Targeting this pathway represents a promising therapeutic strategy. Here, we demonstrate that the expression of the C-terminal domain (CTD) of human REV1, a ca.
View Article and Find Full Text PDFCancer Res Commun
September 2025
Spanish National Cancer Research Centre, Madrid, Madrid, Spain.
Purpose: Advanced, pre-treated TNBC has a dismal prognosis and lacks effective options beyond standard cytotoxics. We previously showed, via phosphoproteomic screening, that CDK6 and ERK hyperactivation are linked to adverse outcomes and represent actionable targets. This prompted us to evaluate palbociclib and binimetinib in advanced TNBC after one or two prior therapies.
View Article and Find Full Text PDFJ Virol
September 2025
Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, China.
Unlabelled: Cholesterol 25-hydroxylase (CH25H), an interferon-stimulated gene (ISG), has been implicated in broad-spectrum antiviral immunity. Here, we identify CH25H as a potent suppressor of hepatitis B virus (HBV) replication that significantly outperforms IFN-α in reducing HBV DNA, pregenomic RNA (pgRNA), HBsAg, and HBeAg, without inducing cytotoxicity. However, CH25H is weakly expressed in hepatocytes and only modestly induced by type I interferon.
View Article and Find Full Text PDFJ Burn Care Res
September 2025
Shanghai Starriver Bilingual School, Shanghai, China.
Background: Despite the advancements of pharmacological treatments and gauze dressings in the field of skin wound healing, these methods present numerous limitations. Therefore, developing a multifunctional material capable of efficiently promoting skin wound healing is particularly crucial.
Methods: Citric acid (CA)-modified chitosan (CS) loaded with Shikonin (SK) (CA-CS-SK) hydrogel was prepared via the freeze-thaw method.