Background: Immunological imbalances characteristic of endometriosis may develop as early as the primary manifestations of the disease in adolescence. Objective: To evaluate subpopulation dynamics of monocytes and lymphocytes in peripheral blood and peritoneal fluid of adolescents with peritoneal endometriosis at diagnosis and after 1-year progestogen therapy. Methods: This study included 70 girls, 13–17 years old, diagnosed laparoscopically with peritoneal endometriosis (n = 50, main group) or paramesonephric cysts (n = 20, comparison group). Phenotypes of monocytes and lymphocytes of the blood and macrophages of the peritoneal fluid were analyzed by flow cytometry at diagnosis and during progestogen therapy. Results: Differential blood counts of CD16⁺ (p < 0.001) and CD86⁺ (p = 0.017) monocytes were identified as independent risk factors for peritoneal endometriosis in adolescents. During the treatment, cytotoxic lymphocytes CD56dimCD16bright (p = 0.049) and CD206+ monocytes (p < 0.001) significantly increased while CD163+ monocytes decreased in number (p = 0.017). The CD56dimCD16bright blood counts before (p < 0.001) and during progestogen therapy (p = 0.006), as well as CD206⁺ blood counts during the treatment (p = 0.038), were associated with the efficacy of pain relief after 1-year progestogen therapy. Conclusions: Adolescents with peritoneal endometriosis have altered counts of pro- and anti-inflammatory monocytes and lymphocytes both before and after 1-year progestogen therapy, correlating with treatment efficacy and justifying long-term hormonal therapy.

Bisphenol A (BPA) is a widespread plasticizer widely used in the food industry worldwide. However, a consensus on the safe level of its daily intake does not currently exist, while there are numerous data pointing to a link between prenatal exposure to BPA and early neuropsychiatric disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The global average human-equivalent dose of BPA is estimated at 30 ng/kg body weight/day. Thus, the research herein was conducted on newborn and juvenile rat offspring of both sexes delivered from rats treated with 30 ng/kg body weight/day orally from day 6 to 21 of pregnancy and for a further 21 days during lactation. Our data indicate that prenatal exposure to 30 ng/kg/day from gestation day 6 to delivery induced sexually dimorphic, region-specific alterations in the neonatal (PD1) rat brains, impacting inflammatory reactions, estrogen receptor signaling, and neural progenitor dynamics. Prenatally BPA-treated males exhibited a pro-inflammatory state characterized by an increased total number of ramified Iba1+ microglia cells in the hippocampus alongside upregulation of Aif1, Nfkb, Tnf, Il1b, and Hif1a. Conversely, prenatally BPA-treated females showed only an increased total number of hippocampal Iba1+ cells and displayed inflammatory resilience, lacking upregulation of these markers. Both sexes exhibited a pro-inflammatory state in the prefrontal cortex via upregulation of Nfkb, Tnf, Il1b, and Hif1a. While both sexes showed decreased Tgfb in the prefrontal cortex, they deployed distinct compensatory responses: males upregulated the neuroprotector Igf1 only in the hippocampus, whereas in females, it was upregulated in both the hippocampus and the prefrontal cortex. Estrogen receptor expression was also highly dimorphic. In the hippocampus, males displayed an imbalance via Esr1 upregulation and Esr2 downregulation, while females showed Esr2 downregulation alone. In the prefrontal cortex, these transcriptional profiles were the opposite. Finally, neural progenitor markers were altered. In the prefrontal cortex, BPA drove the upregulation of Sox2 and Pax6 in males but Sox9 in females; in the hippocampus, only Pax6 was upregulated, and only in males. The PAX6 protein level in the hippocampus was significantly increased in males but decreased in females. In juvenile offspring (PD21), behavioral patterns characterized by hyper-exploration, increased environmental investigation, and heightened emotional reactivity during social exposure were more pronounced in female offspring. These baseline neonatal disparities followed by behavioral changes underscore the necessity of sex-specific approaches when evaluating early-life neurodevelopment and subsequent adult behavioral and biological vulnerabilities.

Lung cancer is the most common type of cancer worldwide. Tumors carrying a mutation in the STK11 gene are associated with severe prognosis and resistance to therapy. New treatments for pulmonary adenocarcinoma highlight the efficacy of High-LET neutron therapy, often combined with drug therapy. PCSK9, whose inhibitors are used to treat dyslipidemia, may also be a new target in lung cancer therapy. CRISPR-Cas9-mediated STK11 mutation was performed in murine LLC1 lung adenocarcinoma cells. Human A549 cells that naturally carry a homozygous loss-of-function mutation in the STK11 gene were also used. Cells were irradiated with protons, neutrons, and photons (2 Gy) and analyzed for survival, apoptosis, clonogenic survival assay, and evolocumab (PCSK9 inhibitor) sensitivity. In vivo xenograft (Nude) and syngeneic (C57BL/6) subcutaneous tumor models were neutron-irradiated (5 Gy). Tumor cell proliferation, microenvironment, and protein expression were assessed. High-LET irradiation confirmed the STK11-deficient lines radio resistance, which did not reduce under PCSK9 inhibitor treatment conditions in vitro. In animal models, the PCSK9 inhibitor decreased Ki67 index of tumor cells and infiltration of cancer-associated fibroblasts and macrophages in the combination therapy group. Particle therapy resistance serves as a crucial prognostic marker in the management of lung adenocarcinoma. Using cell lines and animal models, we successfully described this resistance phenotype and demonstrated the promising use of a PCSK9 inhibitor to enhance the efficacy of hadron radiotherapy against lung cancer.