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International Journal of Molecular Sciences

International Journal of Molecular Sciences is an international, peer-reviewed, open access journal providing an advanced forum for biochemistry, molecular and cell biology, molecular biophysics, molecular medicine, and all aspects of molecular research in chemistry, and published semimonthly online by MDPI.
The Epigenetics Society, European Chitin Society (EUCHIS), Spanish Society for Cell Biology (SEBC) and others are affiliated with IJMS and their members receive a discount on the article processing charges.
Indexed in PubMed | Quartile Ranking JCR - Q1 (Biochemistry and Molecular Biology)

All Articles (107,514)

Integrative Analysis of Placental Methylomes Identifies Epigenetically Regulated Genes Implicated in Fetal Growth Restriction

  • Magdalena Bednarek-Jędrzejek,
  • Olga Taryma-Leśniak and
  • Sebastian Kwiatkowski
  • + 7 authors

Fetal growth restriction (FGR) is a major contributor to perinatal morbidity and mortality, most commonly arising from placental dysfunction, with increasing evidence implicating aberrant DNA methylation in its pathogenesis. To identify robust epigenetic alterations associated with FGR, we analyzed placental chorionic villi from an in-house early-onset FGR cohort and compared them with a publicly available dataset (GSE100197). DNA methylation profiling was performed using Illumina EPIC (in-house) and 450K (public) arrays, processed with identical normalization and quality-control pipelines, including adjustment for gestational age and estimation of placental cell-type composition. Differentially methylated positions (DMPs) were identified using linear regression models, revealing 10,427 DMPs in the in-house cohort and 7467 in the public dataset, with 108 shared DMPs showing consistent direction of change across both cohorts. Promoter-associated DMPs were mapped to genes involved in angiogenesis, morphogenesis, immune regulation, and transcriptional control, including EPHA1, ANGPTL6, ITGAX, BCL11B, and CYP19A1, while additional novel candidates such as SLC39A12, YEATS4, and MIR515 family members were also identified. Functional annotation suggests that these methylation changes may influence pathways essential for placental vascular development and structural organization. Overall, this cross-cohort comparison highlights reproducible epigenetic signatures of FGR and underscores the need for standardized approaches to clarify the molecular mechanisms underlying placental insufficiency.

31 January 2026

Analysis of tissue composition in placenta samples from fetal growth restriction (FGR) and controls in both the in-house and GSE100197 groups. (a,b) Predicted frequencies of six major placental cell types, including trophoblasts, stromal cells, Hofbauer cells, endothelial cells, nucleated red blood cells (nRBC), and syncytiotrophoblasts in (a) in-house and (b) GSE100197 samples. (c) Identification of outliers, according to abnormal cell-type composition. Each dot represents a sample, colored and shaped according to its origin (in-house or GSE100197) and outlier status. The dots highlighted in red indicate an outlier, suggesting potential bias of tissue composition on methylation analysis.

Adult growth hormone deficiency (GHD) is linked to increased cardiovascular and metabolic risk due to oxidative stress (OS), endothelial dysfunction, and unhealthy body composition. Long-term systemic effects of recombinant human growth hormone (rhGH) therapy remain insufficiently defined. This study assessed the impact of 24-month rhGH replacement on OS, vascular markers, body composition, and bone mineral density (BMD) in adults with severe GHD. Fifteen adults with confirmed GHD received rhGH for 24 months. Serum insulin-like growth factor 1 (IGF-1), oxidized LDL (Ox-LDL), thioredoxin (Trx), 8-oxoguanine DNA glycosylase 1 (OGG1), E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured at baseline and 12 and 24 months. Body composition and BMD were evaluated by DXA. IGF-1 increased significantly at 12 and 24 months (p < 0.001). Ox-LDL markedly decreased (p < 0.00001), while Trx and OGG1 increased (p < 0.05). Levels of E-selectin, ICAM-1, and VCAM-1 declined, indicating improved endothelial function. Lean body mass and BMD increased, while body fat parameters showed heterogeneous changes. Lipid profiles were unchanged. Significant correlations were observed between vascular markers and adiposity, and between BMD, triglycerides, and IGF-1. A 24-month course of rhGH therapy improves redox balance, vascular function, and body composition in adults with severe GHD, supporting the use of redox and vascular biomarkers to monitor treatment efficacy.

31 January 2026

Longitudinal changes in ox-LDL, Trx, E-selectin, P-selectin, ICAM-1, and VCAM-1 during 24-month rhGH therapy at baseline, 12 months, and 24 months. Statistical significance is indicated by asterisks: * p &lt; 0.05 vs. baseline; *** p &lt; 0.001 vs. baseline; **** p &lt; 0.00001 vs. baseline.

Chronic stress and sustained hypothalamic–pituitary–adrenal (HPA) axis activation are major contributors to metabolic bone diseases, including osteoporosis. However, the precise molecular mechanisms by which chronic stress-induced HPA axis dysregulation drives bone deterioration remain unclear. A Chronic Unpredictable Mild Stress (CUMS) model was established in male rats to simulate prolonged stress exposure. Animals were randomly allocated into three groups: control, 10-week CUMS, and 20-week CUMS (n = 10/group). Model validity was confirmed via behavioral assessments. Bone mineral density (BMD) and trabecular microarchitecture were quantified using micro-computed tomography (micro-CT). Serum corticosterone (CORT) levels, HPA axis negative feedback function, and the expression of pro-inflammatory cytokines (IL-1β, TNF-α) in HPA-regulatory brain regions (hippocampus, prefrontal cortex, hypothalamus) were assessed. Critically, glucocorticoid receptor (GR) expression and nuclear translocation in these brain regions and bone tissue were examined by immunofluorescence and Western blot analysis. CUMS exposure induced progressive, time-dependent bone loss, with the 20-week group exhibiting significantly greater reductions in BMD and trabecular quality compared to the 10-week and control groups. While the HPA axis showed initial hyperactivation, the 20-week group displayed adrenal exhaustion (reduced serum CORT) alongside elevated ACTH, indicating feedback failure. Mechanistically, stress significantly impaired GR nuclear translocation in both brain and bone tissues, coinciding with the upregulation of FKBP5 and pro-inflammatory cytokines. Notably, despite low systemic CORT at late stages, skeletal 11β-HSD1 expression was significantly upregulated, creating a local microenvironment of glucocorticoid toxicity that aggravated osteoblast apoptosis. Our findings demonstrate that chronic stress induces progressive, time-dependent bone loss through a cascade of HPA axis dysregulation and impaired GR signaling. The FKBP5-mediated impairment of GR nuclear translocation in both central and peripheral tissues fosters glucocorticoid resistance, perpetuating hypercortisolemia and a pro-inflammatory milieu that directly accelerates osteoblast apoptosis and bone deterioration. These findings identify the HPA-GR axis as a critical pathway linking chronic stress to osteoporosis and suggest that restoring GR signaling offers a potential therapeutic strategy.

31 January 2026

Depression Levels Intensify with the Duration of Chronic Stress. (A) Body weight increase curves for each group (n = 8, * p &lt; 0.05, ns &gt; 0.05); (B–G) Open Field Test (OFT): Total distance, center activity time, number of crossings, time spent in the periphery, time spent in the corners, and tracks of different groups (n = 8, ** p &lt; 0.01, * p &lt; 0.05, *** p &lt; 0.001, ns &gt; 0.05, ns: no significant difference); (H–L) Elevated Plus-Maze Test (EMP): Tracks, open arm movement time ratio, open arm/closed arm time ratio, number of entries into the open arms, and the ratio of open arm entries to total entries (n = 8, ** p &lt; 0.01, * p &lt; 0.05); (M) Forced Swim Test (FST): Immobility time during the 5 min test (n = 8, ** p &lt; 0.01, * p &lt; 0.05); (N) Sucrose Preference Test (SPT): Preference for sucrose solution (n = 8, ** p &lt; 0.01, * p &lt; 0.05).

Quantitative Measurement of Hexoses by Betaine Aldehyde Derivatisation

  • Paulina Kret-Bułat,
  • Przemysław Mielczarek and
  • Anna Bodzon-Kulakowska
  • + 3 authors

Hexoses, particularly glucose, are one of the most essential molecules for sustaining life; therefore, reliable methods for their analysis are very important. In our study, we present a qualitative and quantitative approach for analysing hexoses using MALDI IMS (Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging) with betaine aldehyde derivatisation and a CHCA (α-Cyano-4-hydroxycinnamic acid) matrix in positive ionisation mode. In this study, we demonstrated betaine aldehyde derivatisation of glucose from dried droplets and explored the analysis of hexoses in brain and liver tissue slices. We assessed whether our method could distinguish between mannose, galactose, glucose, and fructose and optimised the preparation of a biomimetic calibration curve using stable-isotope labelled glucose for hexose analysis. For this purpose, we investigated the number of betaine aldehyde layers required to obtain a proper calibration curve; examined whether changes in the spray nozzle position during CHCA matrix deposition could facilitate analysis and investigated how storage conditions influenced the calibration curve analysis. Finally, we optimised the technique for liver and brain analysis and assessed variations in hexose levels between brain, liver, kidney, and spinal cord tissues from control and morphine-addicted animals. We hope that our biomimetic approach to creating the calibration curve will be helpful for quantitative analysis and aid in developing various quantitative methods for assessing endogenous substances.

31 January 2026

MALDI MS/MS spectra of derivatised glucose (m/z 282); detected using the dried-droplet approach and in brain and liver tissue sections following on-tissue chemical derivatisation with betaine aldehyde and CHCA matrix deposition.

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Int. J. Mol. Sci. - ISSN 1422-0067