Background: ) is a plant with known medicinal properties, and its extracts have shown promise as potential anti-cancer agents. This study aimed to evaluate the nematocidal effects of L. patula extracts and investigate their impact on germline development, DNA damage responses, and apoptosis in ), a model organism for studying these processes.
Methods: was exposed to extracts to assess survival, development, and incidence of male phenotype. Germline abnormalities were examined using microscopy at different developmental stages. The DNA damage response was evaluated through the expression of the and . Apoptosis was quantified by monitoring cell death during the pachytene stage. LC-MS was used to identify bioactive compounds within the extracts.
Results: Exposure to extracts resulted in a dose-dependent reduction in worm survival and larval developmental progress, with no significant impact on the male incidence. Germline defects were observed, including increased nuclear spacing at premeiotic and pachytene stages, altered number of bivalents during diakinesis. These defects correlated with a significant decrease in brood size. Also, extracts activated the DNA damage response pathway, marked by increased expression of and . Moreover, the extracts induced apoptosis in the germline in a pCHK-1-independent manner. LC-MS analysis revealed 31 potential anti-tumor compounds, supporting the extract's cytotoxic properties.
Conclusions: extracts exhibit potent nematocidal and cytotoxic properties, suggesting their potential for cancer therapy. The observed DNA damage and apoptosis in emphasize the extract's promising role in anti-cancer drug development. Further studies are needed to explore the therapeutic potential of these compounds in clinical settings.
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http://dx.doi.org/10.3390/ph18010089 | DOI Listing |
Mol Plant
January 2025
State Key Laboratory of Wheat Improvement, School of Advanced Agricultural Sciences, Peking University, Beijing 100871, China; Beijing Life Science Academy, Beijing 102299, China. Electronic address:
It has been hypothesized that DNA damage has the potential to induce DNA hypermethylation, contributing to carcinogenesis in mammals. However, there is no sufficient evidence to support that DNA damage can cause genome-wide DNA hypermethylation. Here, we demonstrated that DNA single-strand breaks with 3'-blocked ends (DNA 3'-blocks) can not only reinforce DNA methylation at normally methylated loci but also can induce DNA methylation at normally nonmethylated loci in plants.
View Article and Find Full Text PDFReprod Biol Endocrinol
January 2025
Reproductive Medicine Center, Zhuhai Maternal and Child Health Care Hospital, 543 Ningxi Road, Zhuhai, 519000, China.
Purpose: Prior sperm DNA fragmentation index (DFI) thresholds for diagnosing male infertility and predicting assisted reproduction technology (ART) outcomes fluctuated between 15 and 30%, with no agreed standard. This study aimed to evaluate the impact of the sperm DFI on early embryonic development during ART treatments and establish appropriate DFI cut-off values.
Methods: Retrospectively analyzed 913 couple's ART cycles from 2021 to 2022, encompassing 1,476 IVF and 295 ICSI cycles, following strict criteria.
Cell Commun Signal
January 2025
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.
View Article and Find Full Text PDFSci Rep
January 2025
Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
An ideal chemotherapeutic agent damages DNA, specifically in cancer cells, without harming normal cells. Recently, we used Box A of HMGB1 plasmid as molecular scissors to produce DNA gaps in normal cells. The DNA gap relieves DNA tension and increases DNA strength, preventing DNA double-strand breaks (DSBs).
View Article and Find Full Text PDFNat Commun
January 2025
Robson DNA Science Centre, Charbonneau Cancer Institute, Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.
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