MicroRNAs play a crucial role in regulating the immune responses induced by ischemia/reperfusion injury. Through their ability to modulate gene expression, microRNAs adjust immune responses by targeting specific genes and signaling pathways. This review focuses on the impact of microRNAs on the inflammatory pathways triggered during ischemia/reperfusion injury and highlights their ability to modulate inflammation, playing a critical role in the pathophysiology of ischemia/reperfusion injury. Dysregulated expression of microRNAs contributes to the pathogenesis of ischemia/reperfusion injury, therefore targeting specific microRNAs offers an opportunity to restore immune homeostasis and improve patient outcomes. Understanding the complex network of immunoregulatory microRNAs could provide novel therapeutic interventions aimed at attenuating excessive inflammation and preserving tissue integrity.

Successful pregnancy depends on precise molecular regulation of uterine physiology, especially during the menstrual cycle. Deregulated oxidative stress (OS), often influenced by inflammatory changes but also by environmental factors, represents a constant threat to this delicate balance. Oxidative stress induces a reciprocally regulated nuclear factor erythroid 2-related factor 2/peroxisome proliferator-activated receptor-gamma (Nrf2/PPARγ) pathway. However, increased PPARγ activity appears to be a double-edged sword in endometrial physiology. Activated PPARγ attenuates inflammation and attenuates OS to restore redox homeostasis. However, it also interferes with physiological processes during the menstrual cycle, such as hormonal signaling and angiogenesis. This review provides an elucidation of the molecular mechanisms that support the interplay between PPARγ and OS. Additionally, it offers fresh perspectives on the Nrf2/PPARγ pathway concerning endometrial receptivity and its potential implications for infertility.

A characteristic feature of uterine pathologies is a specific change in cell metabolism, which predominantly manifests as a shift in the need for nutrients, thereby directing cells to engage in different angiogenic marker activities. Angiogenesis is one of the main signals supporting the survival and development of cells and tissues not only under physiological conditions. Therefore, it is necessary that we understand pathological hyperactivation in all uterine diseases, from endometriosis through ovarian endometrioid adenocarcinoma to malignant transformed cells of the uterine epithelium and body. This work presents the gene expression results of selected angiogenesis targets (VEGF-A, TGF-β1, ANG1/2, and HIF-1α), cell migration, and cell–cell interaction determined in vitro. Our results suggest that angiogenesis varies in the tested pathological conditions (ectopic endometriosis—12Z; ovarian endometrioid adenocarcinoma—A2780; tumors—SK-UT-1 and RL-95-2) compared to physiological angiogenesis (HME1). The differential expression of angiogenic factors may contribute (or is a contributing factor) to the observed differences to acknowledge an inherent variability in angiogenesis among cell lines. Determining the genomic phenomena responsible for processes associated with inadequate angiogenesis in the pelvic region could help us to develop individual treatment strategies and explain resistance to treatment.

Infertility affects approximately one in six couples worldwide and can be caused by a variety of male and female factors, requiring a comprehensive diagnostic evaluation. In vitro fertilization (IVF) is a widely used assisted reproductive technology; however, despite advances in embryo culture systems, implantation and transfer success rates remain below 30%. Current IVF practice strongly relies on embryologists’ ability to select high-quality, euploid embryos for transfer. Nevertheless, embryo quality alone does not determine successful pregnancy outcomes. Implantation depends on complex biochemical and molecular interactions between the embryo and the receptive uterine endometrium. This review summarizes current knowledge on the molecular mechanisms underlying preimplantation embryo development and implantation. Particular attention is given to embryo metabolism, embryo–endometrium communication, and decidualization processes. Understanding these molecular pathways may facilitate the identification of novel biomarkers associated with embryo viability, implantation potential, and uterine receptivity, ultimately contributing to improved diagnostics and therapeutic strategies in female infertility research and assisted reproduction.

Epidemiologic studies suggest an association between psoriasis and adverse reproductive outcomes. Psoriasis is a chronic inflammatory disorder, and recurrent implantation failure (RIF) is increasingly linked to dysregulated immune states in the endometrium during the implantation window. To determine whether these conditions share a conserved immunoregulatory program, RNA sequencing datasets were integrated from psoriatic lesional and non-lesional skin and from mid-secretory endometrium of fertile women and women with RIF. Differential expression analysis identified 497 genes dysregulated across tissues, including 421 coding genes. Shared genes were mapped to a protein interaction network to detect densely connected modules, followed by functional and transcription factor motif enrichment. Supervised classification models were trained using module genes and evaluated across validation schemes. Immune cell enrichment inferred from bulk profiles supported tissue-specific remodeling, with broad immune infiltration in psoriatic lesions and selective lineage shifts in RIF endometrium. Network analysis revealed a dominant 29 gene module enriched for chemokine and cytokine signaling, extracellular matrix remodeling, and immunoregulatory signaling. Increased module activity was observed in psoriatic lesions, whereas attenuated activity was detected in endometrial samples, consistent with a dysregulated immune state in RIF. Motif enrichment highlighted 13 immune-related transcriptional regulators. Module-based models supported biologically meaningful separation in both comparisons, with area under the receiver operating characteristic curve up to 0.96 in endometrium and 0.97 in skin. Together, a shared immunoregulatory network module associated with chronic cutaneous inflammation and altered endometrial receptivity was identified, providing a foundation for network-based biomarker development in RIF.

Background: Parkinsons disease (PD) has a prolonged prodromal phase, but minimally invasive molecular biomarkers distinguishing manifest PD from prodromal synucleinopathy remain insufficiently characterized. Isolated REM sleep behavior disorder (iRBD) represents a high-risk prodromal condition and provides an opportunity to investigate early blood-based transcriptional alterations. Objective: To identify peripheral blood transcriptomic signatures distinguishing healthy controls (HC), individuals with iRBD, and patients with PD, and to explore whether longitudinal iRBD samples exhibit movement toward a PD-like transcriptional state. Methods: Peripheral blood RNA-seq data were analyzed using harmonized metadata, DESeq2 differential-expression analysis, internally validated machine-learning models, PD-like projection, and integrated biomarker-panel prioritization. Independent baseline samples were used for cross-sectional differential-expression and machine-learning analyses. iRBD follow-up and post-conversion observations were excluded from baseline model development and reserved for exploratory longitudinal analyses. Results: Baseline analyses included 71 independent samples: 20 HC, 31 iRBD, and 20 PD. An additional 19 iRBD follow-up observations, including three post-conversion observations, were available for exploratory analyses. Differential-expression analysis identified 170 FDR-significant genes in PD versus HC and 85 in PD versus iRBD, compared with one FDR-significant gene in iRBD versus HC. Internal machine-learning validation showed stronger discrimination of manifest PD, with a best ROC-AUC of 0.883 for HC versus PD and 0.889 for iRBD versus PD. Discrimination between HC and iRBD was weak, with a best ROC-AUC of 0.584. PD-like projection scores were lowest in HC, highest in PD, and heterogeneous among baseline iRBD samples. Follow-up iRBD samples showed an exploratory upward shift in the mean PD-like projection score. Integrated prioritization produced a 24-gene PD candidate panel and a 24-gene exploratory iRBD panel, with genes in each panel supported by machine-learning feature-stability evidence and differential expression analysis. Conclusions: Manifest PD was associated with a distinct peripheral blood transcriptional signature, whereas iRBD-associated alterations were substantially weaker and more heterogeneous. The prioritized panels represent candidates for independent technical and external validation and should not yet be interpreted as clinically validated diagnostic or prognostic tests.