Biomolecules

Electronic cigarettes (e-cigarettes) have emerged as a prevalent substitute for conventional cigarettes, garnering perceptions of being a safer option for health. Nicotine addicts use e-cigarettes to cease smoking. These products have also become common among young people because of their taste, smell, and attractive appearance. However, accumulating experimental and clinical evidence indicates that e-cigarette use is not risk-free. The inhalation of e-cigarette aerosols exposes users and their non-using peers to a complex mixture of chemical compounds, including aldehydes, heavy metals, and flavoring agents, many of which possess pro-oxidative and pro-inflammatory properties. This review summarizes and critically analyzes current evidence on the molecular and cellular mechanisms underlying the biological effects of e-cigarette aerosols. Particular attention is given to excessive production of reactive oxygen species, mitochondrial dysfunction, DNA damage, and the activation of redox-sensitive signaling pathways, including NF-κB and NRF2. These molecular alterations may trigger acute and, with prolonged exposure, chronic oxidative stress and inflammation, which in turn can affect gene expression, protein function, and metabolic pathways. While molecular and experimental studies often demonstrate adverse biological responses to e-cigarette aerosols, the translation of these findings into long-term clinical outcomes remains an area of ongoing investigation.

Human prostamide/prostaglandin F synthase (PGFS) catalyzes the NADPH-dependent conversion of prostaglandin H₂ (PGH2) to prostaglandin F₂α that plays a key role in regulating intraocular pressure and labor. Despite its physiological importance, structural and biochemical information of the human PGFS has been limited because of difficulties in obtaining sufficient quality of PGFS wild-type crystal and short half-life of PGH2. Here, we report the crystal structure of human PGFS with two active site mutations, C44S/C47S double mutant (DM), which mimics the reduced active form of the CXXC motif of human PGFS. Structural analysis revealed that PGFS DM adopts a typical thioredoxin (Trx)-like fold. Analysis of B-factors and MD simulations reveals that Tyr108–Asp124 is an intrinsically flexible region, devoid of any stabilizing crystal contacts. Unlike canonical Trx-like proteins, Pro167 in PGFS adopts a trans-conformation, inducing a specific Arg40 side chain localization that creates a positive charge near the CXXC motif. Activation of PGFS by reduction of disulfide bond in the CXXC motif enhanced the thermal stability via core stabilization, yet an unexpected increase in the structural disorder was detected with CD spectroscopy, especially upon ligand binding. These findings collectively establish PGFS as a structurally distinct and redox-regulated enzyme. Our results provide novel molecular insights into PGFS as an underexplored but promising therapeutic target.

Physically active individuals demonstrate enhanced immune competence. Efficient execution of effector function relies on chemokine receptor-regulated immune cell trafficking along chemokine gradients to sites of inflammation, infection, tumors, or tissue damage. This study investigates the impact of acute high-intensity interval training (HIIT) on chemokine receptor expression in leukocytes. Sixteen healthy participants completed a single HIIT session, and peripheral blood was collected before exercise (Bsl), immediately after (Ex02), and one hour later (Ex60). Surface expression of selected chemokine receptors was measured using flow cytometry on CD4⁺ T cells, γδ T cells, NK cells, and monocytes, followed by FlowSOM clustering. NK cells, CD4⁺ T cells, and γδ T cells were strongly mobilized at Ex02 and returned to or below baseline at Ex60. HIIT preferentially mobilized CX3CR1⁺ CXCR2⁺ CD56^dim NK cells, CD4⁺ T cells expressing CX3CR1^hi and CCR5⁺, and CX3CR1⁺ CD56⁺ γδ T cells, indicating mobilization of immune cells phenotypically associated with migratory and cytotoxic potential. Proportions of intermediate and non-classical monocytes increased at Ex02 and decreased at Ex60. In conclusion, HIIT induced a rapid redistribution of leukocyte subsets with chemokine receptor profiles suggesting enhanced endothelial interaction and migratory capacity toward effector tissues.