Objectives: To measure plasma pro-apoptotic and pro-necrotic activity in severe acute kidney injury (AKI) patients within a randomized controlled trial of continuous veno-venous hemofiltration with high cut-off filters (CVVH-HCO) versus standard filters (CVVH-Std).
Methods: We measured pro-apoptotic and pro-necrotic plasma activity by trypan blue exclusion cell viability assay, detection of DNA fragmentation, and by determination of caspase-3 activity and annexin V-based apoptosis and necrosis detection assay.
Results: Compared to no apoptosis or necrosis after incubation with healthy plasma, 14-18% of cells showed apoptosis and 4-8% showed necrosis after incubation with plasma from AKI patients. When comparing different measures of pro-apoptotic or pro-necrotic activity, CVVH-HCO and CVVH-Std showed no differential effects on such activity, which remained high over the first 3 days of treatment. However, using annexin V-FITC, there was a significant drop in pro-apoptotic activity across the filter for the CVVH-HCO group (p = 0.043) but not for the CVVH-Std group (p = 0.327) and a significant difference between the two groups (CVVH-HCO vs. CVVH-Std p = 0.006).
Conclusions: Patients with severe AKI have increased pro-apoptotic and pro-necrotic activity. Although on single-pass effect assessment, CVVH-HCO was superior to CVVH-Std in decreasing annexin V-FITC-assessed pro-apoptotic activity, there was no overall attenuation of such activity during the first 3 days of treatment.
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http://dx.doi.org/10.1159/000363220 | DOI Listing |
Sci Rep
August 2024
Pharmacology Department, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks an actionable target with limited treatment options beyond conventional chemotherapy. Therapeutic failure is often encountered due to inherent or acquired resistance to chemotherapy. Previous studies implicated PI3K/Akt/mTOR signaling pathway in cancer stem cells (CSCs) enrichment and hence chemoresistance.
View Article and Find Full Text PDFDalton Trans
August 2023
Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Michel 11, 15121 Alessandria, Italy.
The complex [PtCl(cyclohexane-1,2-diamine)] has been combined in a Pt(IV) molecule with two different bioactive molecules (, the histone deacetylase inhibitor 2-propylpentanoic acid or valproic acid, VPA, and the potential antimetastatic molecule 4-isopropenylcyclohexene-1-carboxylic acid or perillic acid, PA) in order to obtain a set of multiaction or multitarget antiproliferative agents. In addition to traditional thermal synthetic procedures, microwave-assisted heating was used to speed up their preparation. All Pt(IV) complexes showed antiproliferative activity on four human colon cancer cell lines (namely HCT116, HCT8, RKO and HT29) in the nanomolar range, considerably better than those of [PtCl(cyclohexane-1,2-diamine)], VPA, PA, and the reference drug oxaliplatin.
View Article and Find Full Text PDFFront Immunol
March 2023
Department of Oncology, University of Oxford, Oxford, United Kingdom.
The human immunodeficiency virus (HIV) is still a global pandemic and despite the successful use of anti-retroviral therapy, a well-established cure remains to be identified. Viral modulation of cell death has a significant role in HIV pathogenesis. Here we sought to understand the major mechanisms of HIV-induced death of lymphocytes and the effects on viral transmission.
View Article and Find Full Text PDFCells
February 2023
Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Measure of drug-mediated immune reactions that are dependent on the patient's genotype determine individual medication protocols. Despite extensive clinical trials prior to the license of a specific drug, certain patient-specific immune reactions cannot be reliably predicted. The need for acknowledgement of the actual proteomic state for selected individuals under drug administration becomes obvious.
View Article and Find Full Text PDFMolecules
August 2022
Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland.
The phenothiazine derivatives, tricyclic 10-3,6-diazaphenothiazine () and pentacyclic 7-(3'-dimethylaminopropyl)diquinothiazine (), have recently been shown to exhibit promising anticancer activities in vitro. In this report, we demonstrated that and could be pro-apoptotic agents in lung carcinoma, the human lung carcinoma A549 and non-small lung carcinoma H1299, in the range of IC = 1.52-12.
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