Semaglutide, a glucagon-like peptide 1 receptor agonist, is an antidiabetic that has recently shown promising immunomodulatory and antitumor effects. Breast cancer is the most common type of cancer affecting women worldwide. The aim of this study was to analyze the effects of semaglutide on the antitumor immunity in a 4T1 mouse breast cancer model. After induction of breast cancer, BALB/C mice were treated intraperitoneally with semaglutide. Semaglutide administration decelerated tumor appearance, growth and progression. The antidiabetic drug showed neither a direct cytotoxic effect in vitro, nor an angiogenic effect. Furthermore, depletion of NK cells had no affect on tumor growth in semaglutide treated mice suggesting a non-NK cell-dependent mechanism. However, semaglutide increased the accumulation and maturation of CD11c⁺ dendritic cell, while decreasing the percentage of FoxP3⁺ regulatory T cells in the spleen and primary tumor. In addition, semaglutide increased tumor infiltration and promoted the antitumor phenotype of T cells, in vivo. Furthermore, semaglutide enhanced the cytotoxic capacity of CD8⁺ T cells, in vitro. These results suggest that semaglutide enhances the acquired antitumor immune response and has potential for the future treatment of malignancies.

The emergence of anti-TNF agents has revolutionized the management of inflammatory bowel disease, yet a significant proportion of patients experience primary non-response or secondary loss of response due to immunogenicity. As the field of precision medicine advances, genetic predictors such as human leukocyte antigen (HLA) variants are gaining increasing attention. This review provides a comprehensive synthesis of current evidence on the role of HLA genotypes in inflammatory bowel disease susceptibility and disease behavior, with a focus on their mechanistic and clinical relevance in anti-TNF therapy. Special emphasis is placed on HLA-DQA1*05, a validated predictor of anti-drug antibody formation and reduced therapeutic durability. We explore the immunological basis of HLA-mediated immunogenicity, summarize pharmacogenetic and biomarker findings, and discuss how HLA typing may be integrated into treatment algorithms to improve patient stratification and long-term outcomes. As immunogenetics continues to inform clinical decision-making, understanding the interplay between HLA polymorphisms and therapeutic response offers new opportunities for biomarker-guided, personalized care in inflammatory bowel disease.

A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine ligand were synthesized and characterized. The DNA and protein binding properties of [ZnCl₂(terpy^tBu)] (C1), [{cis-PtCl(NH₃)₂(μ-pyrazine)ZnCl(terpy^tBu)}](ClO₄)₂ (C2), [{trans-PtCl(NH₃)₂(μ-pyrazine)ZnCl(terpy^tBu)}](ClO₄)₂ (C3), [{cis-PtCl(NH₃)₂(μ-4,4′-bipyridyl)ZnCl(terpy^tBu)}](CIO₄)₂ (C4) and [{trans-PtCl(NH₃)₂(μ-4,4′-bipyridyl)ZnCl(terpy^tBu)}](CIO₄)₂ (C5) (where terpy^tBu = 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine), were investigated by electronic absorption, fluorescence spectroscopic, and molecular docking methods. Complexes featuring transplatin exhibited lower K_b and K_sv constant values compared to cisplatin analogs. The lowest K_sv value belonged to complex C1, while C4 exhibited the highest. Molecular docking studies reveal that the binding of complex C1 to DNA is due to van der Waals forces, while that of C2–C5 is due to conventional hydrogen bonds and van der Waals forces. The tested complexes exhibited variable cytotoxicity toward mouse colorectal carcinoma (CT26), human colorectal carcinoma (HCT116 and SW480), and non-cancerous mouse mesenchymal stem cells (mMSC). Particularly, the mononuclear C1 complex showed pronounced selectivity toward cancer cells over non-cancerous mMSC. The C1 complex notably induced apoptosis in CT26 cells, effectively arrested the cell cycle in the G0/G1 phase, and selectively down-regulated Cyclin D.

Heyde syndrome, marked by aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome, is often underreported. Shear stress from a narrowed aortic valve degrades von Willebrand factor multimers, leading to angiodysplasia formation and von Willebrand factor deficiency. This case report aims to raise clinician awareness of Heyde syndrome, its complexity, and the need for a multidisciplinary approach. We present a 75-year-old man with aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome type 2A. The patient was successfully treated with argon plasma coagulation and blood transfusions. He declined further treatment for aortic stenosis but was in good overall health with improved laboratory results during follow-up. Additionally, we provide a comprehensive review of the molecular mechanisms involved in the development of this syndrome, discuss current diagnostic and treatment approaches, and offer future perspectives for further research on this topic.

The newly developed mononuclear 5,6-epoxy-5,6-dihydro-1,10phenanthroline platinum(II) complex revealed notable antitumor effects in vitro and in vivo. In this study, the effects of this platinum(II) complex on the immune response were assessed. Peritoneal macrophages and splenocytes obtained from mice were treated with lipopolysaccharide (LPS)/Concanavalin A (ConA) along with platinum(II) complex and measurement of cytokine concentrations and immunophenotyping was performed. Our findings indicate that the platinum(II) complex exhibits significant immunomodulatory effects on peritoneal macrophages and splenocytes.

Triple-negative breast cancer (TNBC), a highly invasive type of cancer, is difficult to treat due to insufficient specific targets and low survival rates. Current therapy often encounters drug resistance or relapse; thus, repurposing existing drugs could revolutionize cancer treatment. This study examined the anticancer effects of the antipsychotics Cariprazine (CAR), Olanzapine (OLZ), and Clozapine (CLZ), and the immunomodulatory potential of CAR, in vitro and in vivo in TNBC models. In vitro, CAR, OLZ, and CLZ significantly inhibited the proliferation of TNBC cells. This inhibition occurred via the induction of mitochondrial apoptosis, G0/G1 cell cycle arrest, and the suppression of autophagy, as evidenced by the down-regulation of Bcl-2, p62, and pAKT; the upregulation of Bax and active caspase 3; the decrease of ΔΨM; and the promotion of cytochrome c release. In addition, CAR inhibited MDA-MB-231 cells migration. In vivo, CAR inhibited tumor growth in the 4T1 xenograft model without causing adverse effects and resulted in the mRNA upregulation caspase 9, p53, p21, and Beclin-1. In addition, CAR influenced the immune response by promoting the production of proinflammatory cytokines TNF-α, IFN-γ, IL-17, and IL-1β and increasing the percentage of TNF-α⁺, IL-17⁺, IL-1β⁺, and IFN-γ⁺ CD3⁺ splenocytes. In conclusion, compared with other antipsychotics, 5-FU, and cisplatin, CAR exerted the most potent anticancer activity in TNBC in vitro and in vivo. This efficacy may be attributed to its ability to regulate apoptosis and autophagy, promote G0/G1 cell cycle arrest, and modulate antitumor immune response, suggesting its therapeutic potential in breast cancer.