Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the DNA-damaging chemotherapeutic agent cisplatin. Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC. In culture, elevation of intracellular taurine concentration to OC ascites-cell-associated levels suppressed proliferation of various OC cell lines and patient-derived organoids, reduced glycolysis, and induced cell protection from cisplatin. Taurine cell protection was associated with decreased DNA damage in response to cisplatin. A combination of RNA sequencing, reverse-phase protein arrays, live-cell microscopy, flow cytometry, and biochemical validation experiments provided evidence for taurine-mediated induction of mutant or wild-type p53 binding to DNA, activation of p53 effectors involved in negative regulation of the cell cycle (p21), and glycolysis (TIGAR). Paradoxically, taurine’s suppression of cell proliferation was associated with activation of pro-mitogenic signal transduction including ERK, mTOR, and increased mRNA expression of major DNA damage-sensing molecules such as DNAPK, ATM and ATR. While inhibition of ERK or p53 did not interfere with taurine’s ability to protect cells from cisplatin, suppression of mTOR with Torin2, a clinically relevant inhibitor that also targets DNAPK and ATM/ATR, broke taurine’s cell protection. Our studies implicate that elevation of intracellular taurine could suppress cell growth and metabolism, and activate cell protective mechanisms involving mTOR and DNA damage-sensing signal transduction.

The insulin‐like growth factor (IGF) axis, an evolutionarily conserved system, is critical in regulating cell growth, proliferation, and survival, affecting nearly all organ systems. This axis comprises two growth factors, IGF‐I and IGF‐II, and six insulin‐like growth factor–binding proteins (IGFBPs), modulating IGF activity. Due to their structural similarity to insulin, IGFs can interact with insulin receptors, facilitating glucose uptake in adipose and muscle tissues, suppressing hepatic glucose production, and modulating blood glucose levels. Pregnancy induces unique metabolic challenges, with the IGF axis adapting to support maternal metabolic changes and fetal growth. In pregnancies complicated by prediabetes or diabetes, disruptions in the IGF axis, including altered levels of IGFs and IGFBPs, have been linked to adverse outcomes such as macrosomia and intrauterine growth restriction. This review discusses the role of the IGF system in pregnancies with diabetes, focusing on how dysregulation of IGFs and IGFBPs contributes to pregnancy complications. We emphasize the dual role of the IGF axis in metabolism and growth and evaluate its potential as a therapeutic target in managing high‐risk pregnancies.

Preeclampsia disproportionately affects women with pregestational type 1 diabetes (T1D). This study aims to determine whether continuous glucose monitoring (CGM)-derived metrics during the first trimester predict the development of preeclampsia in pregnancies complicated by pregestational T1D, comparing their predictive capability against standard glycemic markers. This single-center, retrospective cohort study analyzed data from 2019 to 2023 at a tertiary center in Poland. Participants included women with T1D on sensor-augmented insulin pump (SAP) therapy, initiating monitoring by 13 weeks/6 days. Sensor mean glucose, TIR, CV%, GMI and time spent over 140, 180 and 250 mg/dL were analyzed and preeclampsia diagnosis adhered to ISSHP criteria, with data compared. Of 70 women, 13 (18.6 %) developed preeclampsia. Baseline HbA1c was similar. Sensor-derived glucose metrics revealed higher first-trimester mean glucose (121.6 mg/dL vs. 112.3 mg/dL, p = 0.0012), decreased TIR 63.3% (54.3-68.46) vs 70.16 % (67.31-76.57), p = 0.03, and coefficient of variation 38.42% vs 34.29, p = 0,055 for the PE group. Good glycemic control existed in both groups during later trimesters. Elevated first-trimester mean glucose and glucose variability could be linked with preeclampsia in T1D, in our study. Findings support CGM to refine risk models and strategies addressing early glycemic imbalances in T1D pregnancies.

The rise in type 2 diabetes (T2D) during pregnancy is mainly due to increasing obesity and metabolic disorders. Early gestational diabetes mellitus (eGDM),

Background Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is a standard treatment in selected ovarian cancer patients. However, hematological toxicity remains a clinical problem. The study aimed to identify predictors of early hematologic toxicity during PARP inhibitor maintenance therapy in high-grade serous ovarian cancer. Methods We retrospectively analyzed 130 patients receiving PARP inhibitors (niraparib, 49; olaparib, 81). Blood counts from first-line platinum chemotherapy and from the first 3 months of PARP inhibitor therapy were assessed. Adverse events were graded using the Common Terminology Criteria for Adverse Events v5.0. Weekly changes and minimal values for neutrophils, hemoglobin, and platelets were calculated (excluding post-intervention values). Results Thrombocytopenia was mainly related to niraparib treatment, and anemia was mainly related to olaparib treatment. During niraparib therapy, higher human epididymis protein 4 (He4) at diagnosis correlated with greater platelet decline and lower platelet nadir. In multivariable linear regression, higher body weight (β = 1.86, 95% CI 0.05 to 3.67, p = 0.044) and higher minimal hemoglobin during chemotherapy (β = 67.41, 95% CI 16.39 to 118.43, p = 0.011) were independently associated with higher minimal platelet count during niraparib treatment. In multivariable logistic regression, higher minimal neutrophil count during chemotherapy (OR = 4.51, 95% CI 1.47 to 17.96, p = 0.015) and lower minimal platelet count during chemotherapy (OR = 0.975, 95% CI 0.958 to 0.989, p = 0.001) were independently associated with grade 3 or 4 thrombocytopenia during niraparib treatment. In the olaparib cohort, lower minimal neutrophil count during chemotherapy (β = -0.414, 95% CI -0.755 to -0.074, p = 0.018) and higher hemoglobin concentration at qualification for PARP inhibitor therapy (β = 0.533, 95% CI 0.042 to 1.024, p = 0.034) were independently associated with higher minimal hemoglobin during treatment. Conclusions Early, severe cytopenias during PARP inhibitor therapy can be predicted using clinical data. Platinum-related side effects and parameters for disease diagnosis and eligibility for PARP inhibitor therapy identify high-risk patients, supporting risk-adapted monitoring and proactive dose optimization. These findings should be considered hypothesis-generating and require external validation before implementation in clinical decision-making. Clinical trial number Not applicable Graphical abstract