Gene Expression Changes as Biomarkers of Immunosenescence in Bulgarian Individuals of Active AgeNikolova, Todorova, Hammoudeh
et alBiomedicines (2025) 13 (3)
Abstract: Background/Objectives: Immunosenescence implies innate and adaptive immunity dysfunction, which naturally occurs with aging. It is a complex multifactorial process which can be triggered by either genetic changes, immune changes or both. Numerous research studies have shown that the process of senescence goes alongside chronic immune activation. The purpose of this study is to analyze the changes in the expression of genes associated with adaptive and innate immune responses in order to identify reliable biomarkers for immune aging. Methods: For that aim, 55 clinically healthy individuals of active age (21-65 years) were distributed based on immunophenotyping in two groups, with and without signs of premature senescence. A gene expression analysis was subsequently made on those two groups, and the differentially expressed genes were presented and interpreted. Results: Altogether, forty-eight (48) genes exhibited differential expression between the two groups, most of which showed up-regulation (45) (fold change more than 2), and only three were down-regulated (fold change less than -2). The highest positive fold change showed IL-1β (10.76), BCL6 (13.25) and CCL4 (15.91), while the highest negative fold changes were documented for IL23R (-3.10), IL5 (-2.66) and PTGS2 (COX-2) (-2.15). Conclusions: Our results reveal that immunosenescence is positively associated with chronic inflammation, which is typical for the aging process. On the other hand, we identified markers of possible protective effects against oxidative stress and tumorigenesis. These findings can aid the early diagnosis of chronic degenerative diseases in subclinical phase, as well as the development of strategies to prevent the processes of premature immune aging.
Inhibition of DJ-1 induces TFAM secretion from cancer cells to suppress tumor growth via promoting M1 macrophage polarizationXu, Wu, Yang
et alCell Signal (2025)
Abstract: DJ-1, also known as PARK7 (Parkinson's disease protein 7), which is involved in cell viability, apoptosis, transcriptional regulation, and oxidative stress adaptation, is also involved in the pathogenesis of various human diseases including carcinogenesis. Here, we aimed to determine the novel mechanism by which DJ-1 inhibition suppresses tumor growth. Our results showed that DJ-1 knockdown in cancer cells promoted the secretion of a significantly larger amount of mitochondrial transcription factor A (TFAM) into the cell culture medium. DJ-1 knockdown promotes p53 translocation to the mitochondria and stimulates the intrinsic mitochondrial apoptosis pathway, resulting in TFAM release. Moreover, DJ-1 knockdown induced the downregulation of sirtuin 3 (SIRT3), which increased the acetylation of TFAM and triggered its release. Furthermore, we found that extracellular TFAM played a critical role in antitumor activity by upregulating the expression of chemokine (CC motif) ligand 4 (CCL4) and chemokine (C-X-C motif) ligand 5 (CXCL5) in cancer cells, contributing to the promotion of M1 macrophage polarization in the tumor microenvironment (TME). Finally, we confirmed that the DJ-1 inhibitor suppressed tumor growth by increasing TFAM release from cancer cells and M1 macrophage polarization in vivo. These findings indicate that the depletion of DJ-1 stimulates apoptosis-dependent TFAM secretion that triggers M1 macrophage polarization, indicating a new therapeutic strategy by interfering with the DJ-1 function in cancer therapy.Copyright © 2025. Published by Elsevier Inc.
Reduced Serum PD-L1 and Markers of Inflammation in Response to Alternate Day Fasting With a Low-Carbohydrate Intervention: A Secondary Analysis of a Single-Arm TrialAkasheh, Fantuzzi, Varady
et alCurr Dev Nutr (2025) 9 (3), 104566
Abstract: This secondary analysis aimed to examine the effect of a single-arm alternate day fasting intervention with a 30% low-carbohydrate diet on biomarkers of inflammation and immune activation in adults with obesity. A 12-week weight-loss period was followed by a 12-week weight maintenance period. Anthropometrics and blood samples were collected at baseline and weeks 12 and 24. Multiplex assay was used to measure serum biomarkers including programmed death ligand 1 (PD-L1), interleukin 8 (IL-8), IL-1 receptor antagonist (IL-1ra), chemokine ligand (CCL)2, CCL4, interferon gamma (IFnγ), IFNγ-induced protein 10 (IP-10), and cluster of differentiation 40 ligand (CD40-L). In 28 participants, body weight and fat mass decreased during the weight-loss period but stabilized during the weight maintenance period. Serum PD-L1 decreased from baseline to week 12 (P = 0.005) but not at week 24. Moreover, IL-1ra and CCL4 concentrations decreased from baseline to week 24 (P < 0.001 and P < 0.008, respectively). Changes were not significant for in CCL2, IL-8, CD40-L, IFNγ, or IP-10. In conclusion, alternate day fasting-low carbohydrate modulates circulating immune biomarkers, which may be relevant to diabetes, cancer, and autoimmunity. This trial was registered at clinicaltrials.gov as NCT03528317 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934424/).© 2025 Published by Elsevier Inc. on behalf of American Society for Nutrition.
Quantum physical analysis of caffeine and nicotine in CCL4 and DMSO solvent using density functional theorySah, Chaudhary, Sahani
et alSci Rep (2025) 15 (1), 10372
Abstract: This work used the 6-311++G(d, p) basis set in the DFT/B3LYP and DFT/CAM-B3LYP technique to build the molecular structures of the nicotine and caffeine molecules. The minimum energy gives stability to these molecules with their corresponding dipole moment. The optimized structure to compute Raman spectroscopy and UV-Vis in CCl4 and DMSO solvent, employing the basis set 6-311++G(d, p), the DFT/B3LYP and CAM-B3LYP hybrid function, with the C-PCM model. The re-optimized molecule is used to study NLOs property which also give the dipole moment, polarizability and hyperpolarizability of titled molecules. We used AIM to investigate these molecules' intramolecular interactions, bond critical points, and interbasin paths. Multiwfn software 3.8 produces the NCI-RGD diagram, which we use to determine weak interaction, electron density, Van der Waals interaction, steric effect, and hydrogen bond. Similarly, we analyze the covalent bond with the molecular surface using ELF and LOL techniques.© 2025. The Author(s).
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