Search Results (2,358)

Background/Objectives: Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) has no standard systemic therapy. VEGFR-targeting tyrosine kinase inhibitors (TKIs) are commonly used first-line, though no international standard exists; cisplatin-based chemotherapy is an alternative. We retrospectively reviewed the cyclophosphamide–epirubicin–cisplatin (CEP) regimen to determine whether prior TKI exposure compromises subsequent chemotherapy efficacy. Methods: We studied 31 patients given CEP for progressive R/M ACC (2018–2023). Tumor response was assessed by RECIST 1.1. Molecular subtype was determined by c-MYC/p63 immunohistochemistry (ACC-I, c-MYC-positive/p63-negative; ACC-II, p63-positive/c-MYC-low or negative). Multivariable models used Firth’s penalized likelihood Cox regression. Next-generation sequencing (NGS) was available in 21 of 31 patients. Results: Thirty-one patients were enrolled (median age 48; 17 [54.8%] with prior TKI). At median follow-up of 22.6 months, the objective response rate (ORR) was 19.4%, disease control rate 71.0%, median progression-free survival (PFS) 5.3 months, and median overall survival (OS) 10.3 months. Prior TKI did not lower efficacy: ORR 17.6% vs. 21.4%, PFS hazard ratio 0.76 (p = 0.519). All six partial responses occurred in ACC-I tumors (35.3% vs. 0% in ACC-II, p = 0.021). In the NGS subset (5 PIK3CA-mutant), PIK3CA mutation (OS HR 6.19, p = 0.024) and bone metastasis (OS HR 5.84, p = 0.027) remained associated with shorter OS after adjustment. No treatment-related deaths occurred. Conclusions: CEP is active in R/M ACC, and prior TKI exposure did not appear to reduce efficacy. Higher response rates in ACC-I tumors and the apparent PIK3CA-related survival deficit are exploratory observations that need prospective testing before they can guide treatment. Full article

Osteoarthritis (OA) is highly prevalent worldwide. Fibronectin (FN) has been associated with OA pathology; however, its role remains unexplored. In this study, we hypothesized that FNIII14 induces chondrocyte apoptosis by inactivating β1 integrin and aimed to clarify the role of FNIII14 in OA pathology. Immunohistochemistry, immunofluorescence, flow cytometry, a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, real-time quantitative polymerase chain reaction, and Western blotting were performed using cartilage obtained from patients who underwent total knee arthroplasty. In a mouse model, FNIII14 or phosphate-buffered saline was administered to the knees, and cartilage degeneration and synovitis were evaluated using the Mankin and Synovitis scores, respectively. Statistical significance was determined using the Mann–Whitney U or Kruskal–Wallis test (p < 0.05). FNIII14 was detected in highly degenerated OA cartilage, with decreased β1 integrin activity, suppressed cell proliferation, and induced apoptosis in chondrocytes. FNIII14 decreased the gene expression of cartilage-specific markers and anabolic factors and increased inflammatory cytokine gene expression and phosphorylation of extracellular signal-regulated protein kinase-1/2. FNIII14 induced cartilage degeneration in mouse knees with almost no synovitis. Regulation of FNIII14 production and action may play an important role in suppressing cartilage degeneration in human OA. Full article

Background and Clinical Significance: SWI/SNF chromatin remodeling complex-deficient malignancies constitute an aggressive group of undifferentiated tumors defined by inactivation of core subunits including SMARCA4 (BRG1) or SMARCB1 (INI1). In the head and neck, these tumors predominate in the sinonasal tract; oral cavity presentations are exceedingly rare, with reported cases predominantly representing metastatic disease. Peri-implant gingival masses in clinical practice are overwhelmingly reactive, but their occasional malignant nature mandates timely biopsy and thorough pathologic workup. We report the first comprehensively molecularly characterized case of a peri-implant gingival SWI/SNF complex-deficient tumor with confirmed biallelic SMARCA4 inactivation. Case Presentation: A 75-year-old man presented with a one-week history of a rapidly enlarging exophytic erythematous peri-implant gingival mass in the right posterior mandible (region 44–47). Incisional biopsy demonstrated an undifferentiated high-grade tumor with epithelioid, plasmablastoid, and focally rhabdoid morphology with necrosis. Immunohistochemistry showed complete loss of BRG1 (SMARCA4) with retained INI1 (SMARCB1), EMA positivity, Ki-67 of approximately 100%, and negativity across all lineage-specific markers (hematolymphoid, epithelial, melanocytic, endothelial, squamous). Comprehensive next-generation sequencing (Oncomine Comprehensive Assay Plus) confirmed biallelic SMARCA4 inactivation via a truncating nonsense mutation (p.Trp1346Ter; VAF 73.85%) combined with copy number loss, establishing the molecular mechanism underlying BRG1 protein loss. Co-occurring alterations included homozygous CDKN2A/CDKN2B deletion, MTAP loss (9p21.3), clonal TP53 and KEAP1 mutations, and intermediate–high tumor mutational burden (13.3 mutations/Mb) with microsatellite stability. The patient initiated carboplatin–paclitaxel and achieved a partial response at one month with further shrinkage by four months. This case illustrates a rare oral cavity manifestation of SWI/SNF complex deficiency arising in a peri-implant location, with a diagnostic workup that required integration of immunohistochemistry and molecular profiling for definitive characterization. The MTAP deletion co-occurring with homozygous CDKN2A/B loss identifies a potentially actionable synthetic lethal vulnerability to MAT2A and PRMT5 inhibitors currently under clinical investigation. An occult primary site could not be fully excluded due to absence of a dedicated staging workup. Conclusions: Rapidly enlarging peri-implant gingival masses should prompt timely biopsy and SWI/SNF marker testing when histology is high-grade and lineage-ambiguous. NGS-based molecular profiling confirms diagnosis, elucidates mechanism, and reveals actionable targets in this rare tumor class. Full article

Cutaneous Radiation Injuries (CRIs) and wounds within an area of radiation exposure (combined injury, CI) are a significant concern for nuclear accidents and radiation combat/terrorist events. CRIs and CI present unique clinical challenges, and effective countermeasures are urgently needed. Here we describe a murine model of CRI and CI in C57BL/6 mice using 16.9 Gy thoracic X-ray irradiation (5.3 Gy/min, 160 kV) ± experimental wound administered immediately. Wound repair and radiation-induced dermatitis were assessed after irradiation. Our previous studies showed that genistein (200 mg/kg, s.c.), administered 24 h prior to irradiation prevented radiation injuries in two murine models. We investigated the effects of genistein in the CI model. Macroscopic and histological analyses showed that radiation significantly delayed wound closure, although wounds did not significantly alter the progression of radiation dermatitis. Genistein improved the early rate of wound closure and significantly reduced dermatitis in mice. Histological analysis showed that genistein improved skin structure and reduced inflammation and fibrosis. Immunohistochemistry showed that genistein attenuated radiation-induced cyclin-dependent kinase inhibitor 1 (p21/waf1) and α-smooth muscle actin and preserved K15 positive skin adult stem cells. These findings suggest that genistein may be an effective prophylactic against CRIs and CI. Full article

Introduction: Immunotherapy with immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis has become an established treatment strategy across various malignancies. In this context, PD-L1 expression plays a key role in the clinical management of cancer patients. However, the prognostic significance of PD-L1 expression remains inconsistent across different cancer types. This study aimed to evaluate the prevalence of PD-L1 expression in three cancer types and to examine its association with key clinicopathological parameters, systemic inflammatory markers and patient outcomes. Methods: A retrospective cohort of 141 patients with lung, breast and head and neck cancers diagnosed between 2016 and 2021 was analysed. PD-L1 expression was analysed by immunohistochemistry using clone 22C3 and the scoring system for positivity was determined according to standard clinical scoring practices for each tumour type. Systemic inflammatory markers, including the platelet-to-lymphocyte ratio (PLR), were calculated from pre-treatment blood counts. Correlation and survival analyses were performed to evaluate the associations between PD-L1 expression levels, clinicopathological characteristics and prognosis. Bioinformatics analyses using GeneMania, STRING and TIMER (v.3) databases were conducted to explore functional enrichment, protein–protein interactions and immune-cell infiltration associated with PD-L1 expression. Results: PD-L1 positivity (≥1%) was observed in 56.75% of lung cancer cases, 44% of breast cancer cases and 92.85% of head and neck cancer cases. PD-L1 expression alone was not significantly associated with overall survival across the cancer cohorts. However, it was significantly associated with PLR in the lung cancer cohort (p = 0.036). Notably, low PLR was associated with improved survival in both lung cancer (p = 0.007) and breast cancer (p = 0.031). Bioinformatics analysis identified several PD-L1-interacting genes, including PD-1, CTLA4 and PTPN and demonstrated strong positive correlations between PD-L1 expression and the infiltration of CD8+ T cells, neutrophils and dendritic cells across the analysed malignancies. Conclusions: Despite its high expression in advanced solid tumours, PD-L1 showed limited prognostic value in our cancer cohort. In contrast, systemic inflammatory markers particularly PLR, emerged as a potential indicator of clinical outcome. Our data suggest that integrating PD-L1 status with systemic inflammatory markers may improve outcome prediction and help inform therapeutic decision-making in patients with advanced malignancies. Full article

The aim of this study was to investigate the association between the endometrial microbiome and local immune cell composition during the implantation window. We conducted a single-center prospective observational study including endometrial samples from 58 women without endometrial pathology. All samples were obtained during the mid-secretory phase (day 5 post-ovulation). Endometrial stromal CD3⁺ T cells, CD4⁺ T helpers, CD56⁺ NK cells and CD68⁺ macrophages were identified by immunohistochemistry and quantified as a percentage of stromal cells using HALO image analysis software. Microbiome composition was assessed by 16S rRNA gene sequencing (V4–V5 region). Lactobacillus dominance (LD) was defined as the genus with the highest centered log-ratio value within each sample. Endometrial immune cell composition showed a median 2.28% CD3⁺ T cells of stromal cells, 1.75% CD56⁺ NK cells, 1.44% CD68⁺ macrophages and 0.29% CD4⁺ T helpers. Lactobacillus-dominated microbiota was identified in 51.7% (30/58) of samples. Correlation analysis showed that Lactobacillus-related taxa were negatively associated with NK/T ratios and positively with T helper-related ratios. LD samples exhibited reduced NK cell abundance (1.17% vs. 2.12%, p = 0.006, q = 0.023) and a lower NK/T ratio (0.52 vs. 1.05, p = 0.004, q = 0.023) compared to non-LD samples. This study provides evidence for a link between microbial composition and local immune regulation in the endometrium. Full article

Background: p53 immunohistochemistry is widely used as a surrogate marker for molecular classification in endometrial cancer and is generally associated with aggressive tumor behavior. However, its independent prognostic value in real-world clinical settings remains uncertain. Methods: This retrospective cohort study included patients with histologically confirmed endometrial cancer treated at a tertiary center between 2015 and 2023. Patients with available p53 immunohistochemical results were classified as p53 wild-type or p53-abnormal status. Clinicopathologic characteristics were compared between groups. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were analyzed using the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazards models were used to identify independent prognostic factors. Sensitivity analyses were performed to assess the impact of treatment-related variables. Results: A total of 132 patients were included. p53-abnormal tumors were associated with older age, high-grade non-endometrioid histology, and more frequent use of adjuvant therapy. In Kaplan–Meier analysis, p53-abnormal status was associated with poorer OS (5-year OS: 54.8% vs. 77.1%, p = 0.029), with a similar trend observed for PFS. However, in multivariable analysis, p53 status was not independently associated with survival. Instead, advanced stage and residual disease remained significant prognostic factors. Sensitivity analyses incorporating treatment-related variables yielded consistent results, confirming the lack of independent prognostic impact of p53. Conclusions: Although p53-abnormal status was associated with adverse clinicopathologic features and worse unadjusted survival, it was not an independent prognostic factor after adjustment. These findings suggest that the prognostic impact of p53 is context-dependent and largely mediated by established clinical factors, particularly tumor burden. Integrated clinicopathologic and molecular assessment remains essential for accurate risk stratification in endometrial cancer. Full article

Background/Objectives: Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have transformed cancer treatment, yet therapeutic responses remain limited in many solid tumors due to poor and uneven drug distribution within the tumor microenvironment (TME). Here, we evaluated whether co-formulation of an anti-PD-1 antibody (RMP1-14, murine surrogate for pembrolizumab) with Imagent^® microbubble/liposome (MBLP) complexes and ultrasound activation could enhance tumor-specific delivery while reducing systemic exposure. Methods: Immunocompetent MC-38 colorectal tumor-bearing mice (B6(Cg)-Tyrc-2J/J, 7-week-old females) received isotype control, isotype/MBLP/US, RMP1-14 alone, RMP1-14/MBLP, or RMP1-14/MBLP/US. Survival was analyzed by Kaplan–Meier curves, tumor necrosis by H&E staining, antibody biodistribution by immunohistochemistry, and tumor perfusion by laser speckle imaging. Results: No significant differences in tumor size or body weight were observed between groups. Survival analysis showed significant improvements in the RMP1-14 (p = 0.013) and RMP1-14/MBLP/US (p = 0.047) groups versus isotype controls, with the RMP1-14/MBLP/US group achieving the longest mean survival (57.8 days vs. 26.5 days for RMP1-14 alone) and complete tumor regression in 2/8 mice. The RMP1-14/MBLP/US group demonstrated significantly greater tumor necrosis than all other groups. Immunohistochemical analysis confirmed a 6.1-fold increase in intratumoral antibody accumulation with MBLP/US versus RMP1-14 alone (p = 0.0003), alongside significantly reduced off-target exposure in spleen, liver, kidney, and heart. Laser speckle imaging revealed a transient ~30% increase in tumor perfusion during MBLP/US treatment, consistent with cavitation-mediated hemodynamic effects. Conclusions: These findings demonstrate that MBLP/US co-formulation enhances intratumoral delivery of checkpoint inhibitors, improves survival, and reduces systemic organ exposure, representing a promising platform to improve the efficacy and safety profile of antibody-based immunotherapy. Full article

Background/Objectives: Celiac disease (CD) is a T-cell-mediated autoimmune condition, triggered by gluten ingestion. Duodenal biopsy is the gold-standard diagnosis for CD, which is often limited by interobserver variability between pathologists. Immunohistochemistry (IHC) is a powerful technique for detecting biomarkers with potential diagnostic significance. This study aims to investigate five candidate biomarkers, BTNL8, NKp46, TdT, THEMIS, and TCRδ, that might improve the reproducibility of the diagnosis of CD. Methods: Formalin-fixed paraffin-embedded material, surplus to diagnostic requirements, was obtained from 46 subjects (untreated CD: n = 21, CD treated with gluten-free diet: n = 5; controls: n = 20) and immunostained for BTNL8, NKp46, TdT, THEMIS and TCRδ. BTNL8 staining was scored on a 0–3 semi-quantitative scale. NKp46, TdT, THEMIS, and TCR delta-positive intra-epithelial lymphocytes (IELs) were quantified as mean counts per 100 epithelial cells (ECs). Results: TCRδ-positive IELs were markedly elevated in CD biopsies (median 9.4 IELs/100 ECs) compared to healthy controls (median 0.5 IELs/100 ECs; p < 0.001), with a threshold of >2.1 TCRδ-positive IELs per 100 ECs yielding an AUC of 0.94 and interobserver agreement of 0.82. NKp46 expression was also increased in CD (median 13.8 IELs/100 ECs) versus controls (median 9.6; p < 0.001), with >12.8 NKp46-positive IELs per 100 ECs achieving an AUC of 0.86 and interobserver agreement of 0.82. Immunostaining for the other biomarkers demonstrated less clear differences between CD and healthy controls. Conclusions: Corroborating several recent publications, TCRδ immunostaining provides high diagnostic accuracy and good interobserver agreement in the diagnosis of CD on duodenal biopsy, even for patients on a gluten-free diet. Full article

Background: Estrogen deficiency negatively affects alveolar bone by disrupting key regulators of bone remodeling. Humic acids (HAs) are natural compounds with recognized antioxidant and anti-inflammatory properties that may attenuate bone resorption. This study investigated the effects of HAs on alveolar bone in an experimental model of estrogen depletion. Methods: Female C57BL/6 mice were randomly assigned to four groups: Sham, Sham + HA, ovariectomized (OVX), and OVX + HA. Estrogen deficiency was induced by bilateral ovariectomy. HAs derived from vermicomposted biomass were administered daily by oral gavage (80 mg/kg) for 28 days. At the end of the experimental period, mandibles were collected for structural, mineral, and histological analyses. Bone elemental composition was assessed using scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM/EDS). Alveolar bone loss was evaluated by histomorphometry, while RANKL and osteoprotegerin (OPG) expression were assessed by immunohistochemistry. Osteoclasts were quantified by tartrate-resistant acid phosphatase (TRAP) staining. Data were analyzed using two-way ANOVA followed by Bonferroni’s post hoc test. Results: Ovariectomy resulted in reduced calcium and phosphorus content, increased alveolar bone loss, elevated RANKL immunolabeling, increased osteoclast numbers, and a higher RANKL/OPG ratio (p < 0.05). HA treatment increased calcium and phosphorus content and attenuated alveolar bone loss in OVX animals (p < 0.05). Additionally, HA treatment partially increased OPG expression and reduced the RANKL/OPG ratio (p < 0.05), without significantly affecting RANKL immunolabeling or osteoclast numbers. Conclusions: HA therapy attenuated alveolar bone resorption in a model of estrogen depletion, possibly associated with modulation of the RANKL/OPG balance. Full article

Background/Objectives: Ciliated epithelial change in endometrial lesions is a recognized morphologic finding, but its immunophenotypic correlates and biological significance remain insufficiently defined. We investigated whether endometrial lesions with ciliated epithelial change show reproducible immunohistochemical alterations across benign, premalignant, and malignant diagnostic categories. Methods: We performed a retrospective immunohistochemical study of 315 formalin-fixed paraffin-embedded eutopic uterine endometrial specimens (no endometriotic/ectopic lesions included) collected between 2019 and 2024 and distributed equally across seven diagnostic categories (n = 45 each): normal endometrium, endometrial polyp, hyperplasia with cystic/disordered glands, hyperplasia with crowded glands, atypical hyperplasia/EIN, endometrioid carcinoma, and serous carcinoma. Marker expression was quantified by digital image analysis and compared between lesions with and without ciliated epithelial change, including lesions with ciliated epithelial change showing cytological atypia. Results: Ciliated epithelial change (CEC) was identified in 86/315 cases (27.3%), including 41 cases (13.0%) with atypical CEC. In benign categories, lesions with CEC showed lower E-cadherin expression and higher β-catenin expression, including more frequent nuclear β-catenin localization. In carcinomas, these patterns were not recapitulated and instead showed an opposite or attenuated profile, supporting a context-dependent rather than linear model. Vimentin was consistently reduced in lesions with CEC across diagnostic categories. p53 and CD44 showed heterogeneous findings and were less informative than the adhesion- and phenotype-related markers. Conclusions: Endometrial lesions with CEC show reproducible, context-dependent immunohistochemical alterations, most consistently involving E-cadherin, β-catenin, and vimentin. In particular, nuclear β-catenin reactivity in this setting should not be interpreted as evidence of canonical Wnt-pathway activation in the absence of CTNNB1 sequencing or validated downstream readouts, and the carcinoma findings cannot be assigned to a specific TCGA/ProMisE molecular subgroup using immunohistochemistry alone. The observations should therefore be regarded as exploratory and warrant validation in studies incorporating molecular classification, direct ciliogenesis markers (FOXJ1, acetylated α-tubulin, basal body markers), and outcome data. Full article

Pregnancy modulates the function of the thyroid gland to facilitate maternal immune tolerance, and nuclear factor kappa B (NF-κB) subunits, the IκB family, and toll-like receptors (TLRs) and complement signaling pathways may be implicated in maternal thyroid immunoregulation. However, it is unclear whether early pregnancy modulates the expression of NF-κB subunits, the IκB family, TLRs, and complement components in the maternal thyroid. The objective of this study was to analyze the effects of early pregnancy on the expression of genes and proteins of these signaling pathways in the maternal thyroid in ewes. In this study, ovine thyroids (n = 6 for each group) were sampled on day 16 of the estrous cycle (N16) and on days 13, 16, and 25 of pregnancy (P13, P16, and P25) with one conceptus. The ewes had an average weight of 41 kg and a body condition score of 3. The mRNA and protein expression of the NF-κB subunits and IκB family were analyzed by RT-qPCR, western blot, and immunohistochemistry. The results showed that the expression of all NF-κB subunits, the IκB family, and TLRs, as well as C1q, C1r, C2, C4a, C5b, and C9, peaked at P16 among these four stages (p < 0.05). In addition, C1s expression was greater at N16 and P16 than at P13 and P25 (p < 0.05), and C3 expression was stronger at P16 and P25 compared to N16 and P13 (p < 0.05). In conclusion, early pregnancy modulates the expression of NF-κB subunits, the IκB family, TLRs, and complement components in the ovine thyroid at both the mRNA and protein levels, which may be essential for maternal thyroid adaptation to pregnancy and beneficial for the prevention of pregnancy-related thyroid diseases in ewes. Full article

Although Dupuytren’s disease (DD) and relapsed Clubfoot (RC) are clinically distinct conditions, both exhibit fibrotic tissue remodeling and contracture. This exploratory study investigated whether DD and RC share molecular features associated with fibroproliferative contracture. Pathological tissues from DD nodules and contracted tissues from RC together with their respective control tissues (n = 6/group), were analyzed using label-free quantitative proteomics. The analysis identified 12 significantly upregulated proteins shared between both pathological conditions relative to their controls (|log₂FC| ≥ 1, p ≤ 0.05). These proteins included structural, signaling and tensile stress ECM proteins. Functional enrichment and network analyses revealed partially overlapping dysregulation of pathways associated with ECM organization and degradation, ECM–receptor interaction, matricellular signaling and mechanobiological processes. In DD samples (n = 10), immunohistochemistry confirmed increased expression of fibrosis-associated proteins (α-SMA, TGF-β1, TGFBI, COL III, COL VI, and COL XII) (at least p < 0.01). Despite these similarities, differences in individual protein abundance and collagen crosslinking were observed between tissues. The findings suggest that DD and RC may share aspects of fibrotic ECM-remodeling despite differences in age, localization, and disease origin. These findings provide initial insights into shared ECM-remodeling processes, although their interpretation should consider the relatively small sample size and biological heterogeneity of the analyzed tissues. Full article

Given higher compatible rates between oral lichen planus (OLP) and oral lichenoid lesions (OLLs) in histopathological and clinical features, this study aims to delineate a boundary between equivocal OLP and OLLs by biomarkers. The updated OLP diagnostic criteria in 2016 was our guideline in defining study cases of typical OLP and typical OLL with triggers, which include topical offending agents (OLL-agent), dental restorations (OLL-dental), and systemic offending drugs (OLL-drug). The expression intensity and distribution patterns of CD4, CD8, and CGRP in four groups were detected by immunohistochemistry assay (IHC). A total of 79 cases including OLP (24), OLL-agent (15), OLL-dental (21), and OLL-drug (19) were collected from an oral biopsy laboratory. Band-like distribution patterns of CD4 (100%, score 3), CD8 (54.17%, score 2), and CGRP (87.5%, score 3) in the subepithelial regions of the OLP group significantly differ from the OLL groups (each comparison pair, p = 0.0001). The sensitivity of CD4 (100%), specificity of CD4 (83.64%), negative predictive value of CD4 (100%), and accuracy of CD4 (83.80%) in the OLP group provide results for the diagnostic test evaluation. The band-like distribution pattern of CD4 in the subepithelial region may determine OLP when the biopsy specimen does not show typical microscopic features. Full article

NDRG1 protein engages with the orphan nuclear receptor NR4A1, effectively suppressing the transcriptional activity of NF-κB and influencing the inflammatory response. However, the specific roles of the NDRG family and NR4A transcription factors in inflammatory bowel disease (IBD) remain poorly defined, particularly regarding potential differential mechanisms between ulcerative colitis (UC) and Crohn’s disease (CD). We hypothesize that NDRG–NR4A interactions are differentially regulated in UC versus CD, contributing to disease-specific modulation of NF-κB signaling and inflammatory responses. Therefore, the aim was to analyze gene and protein expression of both protein families (NDRGs: NDRG1, NDRG2, NDRG3, and NDRG4; and NR4A: NR4A1, NR4A2, and NR4A3), their contributions to UC and CD, and their association with disease severity. In this cross-sectional and comparative study, we assess gene and protein expression of NR4A and NDRG1-4 in 38 UC patients, 10 CD patients, and 18 controls. Gene and protein expression levels were measured by RT-PCR (mucosa) and immunohistochemistry (colonic tissue), respectively. The colonic mucosa from remission UC patients showed upregulation of NDRG2 and the nuclear receptor genes NR4A1-3 compared with controls. NDRG4 was upregulated in active UC patients compared with controls. NDRG1 was downmodulated in active and remission UC patients compared with controls. All differences were statistically significant (p < 0.05). Decreased NR4A2 gene expression was associated with high-sensitivity C-reactive protein (p = 0.030) and erythrocyte sedimentation rate levels (p = 0.001). Our results provide the first evidence of differential alterations in the NDRG–NR4A axis in UC and CD, which could modulate NF κB signaling and the inflammatory profile differently in each disease, opening the possibility of new therapeutic options. Full article