The National Academy of Sciences of Belarus

There is little information on non‐thyroid cancer risks, including haematological malignancies (HM), among the residents of most contaminated regions after the Chernobyl (Chornobyl) nuclear power plant accident. We studied the incidence of lymphoma, multiple myeloma and leukaemia in relation to the raion‐average age‐specific cumulative absorbed red bone marrow (RBM) dose among the residents of Gomel and Mogilev oblasts in Belarus, which were highly contaminated. The follow‐up period was 40 years (1978–2018). HM cases and population size data were received from the Belarusian national cancer registry and the state department of statistics. Our ecological study included 7328 lymphoma, 9476 leukaemia and 2003 multiple myeloma incident cases and 90.8 million person‐years in people who were born before the accident and have attained age <80 years old. The mean (median) RBM dose accumulated by December 31, 2018 was 14.2 (6.4) mGy. We found no evidence of increased risks of Hodgkin and non‐Hodgkin lymphoma, multiple myeloma or total leukaemia associated with two‐year lagged raion‐average cumulative RBM dose after adjustment for sex, attained age, urban/rural status and calendar period effects. There was a suggestion of an elevated relative risk of myeloid leukaemia per 100 mGy after exclusion of Gomel and Mogilev cities. Little evidence was found on interaction between selected factors, except sex, and RBM dose for each study outcome. Studies with individually reconstructed cumulative absorbed RBM doses are warranted to provide more insight on dose‐effect relationships between HM risk, specifically leukaemia, and protracted environmental exposure at a low dose range.

The enzyme aromatase (CYP19A1) is an important target for the discovery of new therapeutic drugs against breast cancer. A series of novel heteroaryl steroidal derivatives, C-2- and C-16-thiadiazole-substituted estranes, were synthesized and biologically evaluated as potential aromatase inhibitors. These compounds exhibited cytotoxicity against breast cancer cells with IC₅₀ values of 5.5 µM and higher. The lead compound, 2-(2'-P(O)(NH^tBu)₂-1',3',4'-thiadiazole)-Δ^1,3,5(10)-estratrien-17-one, was shown to be selective against MCF7 cells with IC₅₀ (MCF7) = 5.5 µM vs IC₅₀ (MDA-MB-231) = 26.1 µM. It acts as both a potent selective agent blocking CYP19A1 and an effective apoptosis inducer, with no effects on the hormone receptors ERα and AR. The toxicity of the lead compound against normal epithelial cells has not been revealed. Molecular docking was used to more accurately define the binding mode of the lead compound to CYP19A1. In a word, here we describe a novel heteroaryl steroidal derivative promising as a CYP19A1 inhibitor for the treatment of hormone-dependent breast cancer.

Andrographolide (AG), a natural diterpenoid compound derived from Andrographis paniculata, exhibits potential against non-alcoholic steatohepatitis (NASH). However, its therapeutic utility is limited by poor solubility, short half-life, and low bioavailability. This study aimed to enhance AG's efficacy by encapsulating it into exosome-like nanoparticles (ELNs) isolated from Nauclea officinalis (N. officinalis, Rubiaceae family) and evaluating its anti-NASH activity in WRL68 cells. This study isolated Nauclea officinalis-derived ELNs (N-ELNs) via ultracentrifugation. Loganin, andrographolide, and asiatic acid were detected in N-ELNs using the HPLC method. RNA sequencing and target gene analysis identified miRNAs in N-ELNs and their cross-kingdom targets in the human genome. AG-loaded N-ELNs (AG-N-ELNs) were prepared using a passive loading method and characterized by transmission electron microscopy, nanoparticle tracking analyzer, and high-performance liquid chromatography. Their effects were tested in free fatty acid (FFA)-exposed WRL68 cells. As for the results, AG suppressed Nuclear Factor kappa-B p50 (NF-κB p50) activation, downregulated NLRP3 expression, and reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in WRL68 cells. It also restored mitochondrial membrane potential and decreased reactive oxygen species (ROS). N-ELNs targeted the ACC/ CPT1 axis to alleviate lipid deposition, reducing total cholesterol and triglyceride levels. AG-N-ELNs outperformed both AG and N-ELNs individually, demonstrating superior anti-NASH activity through synergistic effects of AG's anti-inflammatory/antioxidant properties and N-ELNs' miRNA-mediated metabolic regulation. In conclusion, AG-N-ELNs effectively alleviate NASH-like pathological features in vitro through multi-target regulation, offering a promising strategy for NASH treatment. Further in vivo validation and formulation optimization are warranted.