Search Results (11,537)

Mixed hepatocellular carcinoma (HCC)–neuroendocrine carcinoma (NEC) is a major type of liver mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN). Primary liver NEC, which is very rare, is mostly associated with HCC rather than pure NEC. To characterize the cancer cell heterogeneity of the HCC and NEC components, we comprehensively analyzed the protein expression of three cancer cell biological markers (TERT, Ki-67, and p53) and five differentiation markers (one hepatocyte marker and four neuroendocrine markers) via immunohistochemistry and immunofluorescence using curative resection tissues from three patients with liver MiNEN. TERT/Ki-67/p53 proteins, which are related to cell proliferation and malignancy, were independently expressed in the HCC and NEC components; Ki-67 was highly expressed among the three proteins in both cancer components, and the expression of all three markers was higher in the NEC component than in the HCC component. Despite the intracomponent and intercomponent heterogeneity, the expression signatures of the three markers were similar between the two components, potentially suggesting a common origin of mixed HCC-NEC. An in-depth exploration of intracomponent heterogeneity using differentiation markers revealed multiple intermediate phenotypes of cancer cells, i.e., HCC-like and NEC-like cells, mainly in the HCC component. Histologically NEC-like cells rather than HCC-like cells tended to have an intermediate percentage of Ki-67-positive cells, compared with NEC cells. The spatial distribution of various intermediate cancer cell phenotypes suggests that mixed HCC-NEC may involve the transdifferentiation from HCC cells to NEC cells through the dedifferentiation of HCC. Full article

Pyropia haitanensis, an economically significant cultivated seaweed in China, exhibits substantial geographical variations in nutritional and sensory qualities that influence its market value. The nutritional quality of the samples, including total sugar, total protein, and amino acid content, as well as color quality, assessed through phycobiliprotein and chlorophyll content, and sensory quality evaluated using an electronic nose and electronic tongue, were determined. To elucidate these quality variations, this study employed an integrated metabolomics and chemometrics approach to analyze samples from five major cultivation regions. Principal component analysis (PCA) effectively differentiated the samples; orthogonal partial least squares discriminant analysis (OPLS-DA) validated this classification with robust model parameters (R²X = 0.791, R²Y = 0.995, Q² = 0.984) and identified key discriminatory metabolites. Weighted gene co-expression network analysis (WGCNA) identified origin-specific metabolic modules correlated with quality traits, revealing that pathways such as cysteine and methionine metabolism underpin the observed differences in flavor profiles across cultivation regions. Furthermore, mediation analysis quantitatively confirmed that inorganic nitrogen primarily influences key flavor attributes by regulating sulfur-containing amino acid and nucleotide metabolism. This study systematically elucidates the metabolic mechanisms governing quality formation in P. haitanensis, providing a scientific foundation for quality control and geographical origin traceability. Full article

Ultraviolet (UV) irradiation induces complex skin damage, including hyperpigmentation, oxidative stress, and alterations in proteins related to keratinocyte differentiation and epidermal barrier-associated status. This study investigated the multifunctional protective effects of Padina arborescens ethanolic extract (PAEE) against skin damage in melanocytes, keratinocytes, and zebrafish. In alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells, PAEE effectively suppressed the protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling pathway, which was associated with reduced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, leading to decreased melanin synthesis. PAEE also exhibited photoprotective properties by reducing reactive oxygen species (ROS), inhibiting interleukin-1 beta (IL-1β), and attenuating matrix metalloproteinase-1 (MMP-1) upregulation associated with UVB (ultraviolet B)-induced photodamage in HaCaT keratinocytes. Notably, PAEE restored the UVB-reduced expression of filaggrin and involucrin, representative markers of keratinocyte differentiation and epidermal barrier-associated status, in HaCaT keratinocytes. In zebrafish embryos, PAEE suppressed α-MSH-induced melanin accumulation and UVB-induced ROS generation at non-toxic concentrations. Taken together, these results suggest that PAEE exerts anti-melanogenic and photoprotective effects in cellular and zebrasfish models and may serve as a promising marine-derived ingredient for cosmeceutical applications targeting UVB-related skin damage. Full article

Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) as a crucial cytokine can mediate the inflammatory and immune regulatory responses of an organism. It plays a significant mediatory role in the innate immune system of insects. Firstly, the LITAF family of cotton bollworm (Helicoverpa armigera, Lepidoptera: Noctuidae) was analyzed, and the differentially expressed genes of HaLITAFs were screened from the 2-tridecanone-treated transcriptome. Subsequently, these two differentially expressed HaLITAF genes were cloned and analyzed, and the effect of different larval stages, tissues, and plant secondary metabolites on their gene expression were detected in H. armigera. The cotton bollworm contains 13 LITAF genes, and there are no repetitive sequences among them. Upon 2-tridecanone treatment, only HaLITAF5 and HaLITAF7 were significantly upregulated in the LITAF family of cotton bollworm larvae after 6 h. The HaLITAF5 and HaLITAF7 proteins, respectively, comprised 78 and 113 amino acids, and both contained a CXXC motif, hydrophobic amino acid region and HXCPXCXXXXG motif. Both of them belong to the LITAF analogues (zf-LITAF-like) superfamily. The expressions of HaLITAF5 and HaLITAF7 were both the lowest in fourth-instar larvae and the highest in sixth-instar larvae, and both were abundantly expressed in the midgut of sixth-instar larvae. Following a 28 h treatment with 2-tridecanone, the expression levels of HaLITAF5 and HaLITAF7 peaked. HaLITAF7 exhibited the highest expression level after a 4 h exposure to tannic acid, whereas HaLITAF5 reached its peak after 28 h of tannic acid treatment. The maximum expression levels of HaLITAF5 and HaLITAF7 were observed after 28 h and 4 h of quercetin treatment, respectively. Subsequent to ZQ-8 treatment, HaLITAF5 expression peaked at 28 h, while HaLITAF7 expression peaked at 8 h. Both HaLITAF5 and HaLITAF7 were overexpressed after different kinds of plant secondary metabolite stresses, and thereby, they may be regulated in the expression of genes related to downstream detoxification metabolic processes. This provides a theoretical foundation for further studies on the functional mechanism of the LITAF gene in H. armigera. Full article

Primary Sjögren’s disease (SjD) is characterized by lymphocyte infiltration into exocrine glands. Mitochondrial dysfunction is a critical pathological mechanism underlying SjD, and mitophagy plays a vital role in clearing damaged mitochondria. This study used bioinformatic analysis to explore the potential roles of mitophagy-related genes in SjD pathogenesis and immune infiltration. Bioinformatic analysis was performed on the SjD microarray datasets to identify differentially expressed genes (DEGs). Mitophagy-related DEGs were selected and analyzed using functional enrichment, protein–protein interaction (PPI) networks, and machine learning (Least Absolute Shrinkage and Selection Operator [LASSO] and Random Forest) to identify hub genes. Their diagnostic value was assessed by receiver operating characteristic (ROC) curves. Immune infiltration and its correlation with hub genes were also evaluated. Hub gene expression in the salivary glands of patients was validated using qRT-PCR. Regulatory networks were also predicted. Three hub genes (GABARAPL1, PINK1, and SQSTM1) were identified. They showed high diagnostic specificity and were downregulated in SjD salivary glands. Immune infiltration analysis revealed increased levels of activated natural killer (NK) cells, memory B cells, plasma cells, CD8+ T cells, Tfh cells, and M1 macrophages, but decreased levels of Tregs and M2 macrophages. Hub gene expression was correlated with specific immune cell subsets. Regulatory network predictions highlighted potential upstream regulators and therapeutic compounds. This study identified three mitophagy-related hub genes linked to immune dysregulation in SjD, providing novel insights into disease mechanisms and potential therapeutic targets. Full article

Cunninghamia lanceolata (C. lanceolata), a pivotal economic timber species in southern China, faces increasing threats from global warming and heat stress. Due to limited knowledge regarding its stress response mechanisms, uncovering the molecular basis of heat tolerance is crucial for breeding resilient varieties. Therefore, the objective of this study was to elucidate the physiological and molecular mechanisms of C. lanceolata in response to heat stress. In this study, we performed a time-series transcriptomic analysis on leaves of C. lanceolata ‘6421’ seedlings exposed to heat stress (39 °C) for 0, 1, 4, 8, 12, and 16 h. A total of 1130 differentially expressed genes (DEGs) were identified, with functions primarily enriched in signal transduction, protein folding, and the MAPK and NF-kappa B signaling pathways. Weighted gene co-expression network analysis (WGCNA) revealed a complex regulatory network, identifying ClHsf8 as a central hub transcription factor. To validate its function, ClHsf8 was cloned and overexpressed in tobacco (Nicotiana benthamiana). Under heat stress conditions, transgenic plants exhibited enhanced thermotolerance compared to wild-type controls, characterized by significantly higher activities of antioxidant enzymes (SOD, POD, and CAT) and reduced accumulation of MDA and H₂O₂. Our findings elucidate the molecular regulatory mechanisms of C. lanceolata in response to high temperatures and demonstrate the functional role of ClHsf8 in conferring heat tolerance, providing a theoretical foundation for the genetic improvement of heat-resilient cultivars. Full article

Milk fat synthesis in dairy cows is a complex process affected by ruminal fermentation, systemic metabolism, and mammary gland activity. To explore the metabolic interplay across these systems, a multi-tissue metabolomics approach (rumen fluid, plasma, and milk) using ultra-high-performance liquid chromatography–mass spectrometry was used to identify metabolic differences between Chinese Holstein cows with high (H-MF, 5.82 ± 0.41%) and low (L-MF, 3.60 ± 0.12%) milk fat content under the same diet. The bovine mammary epithelial cells (BMECs) were also cultured to evaluate the impact of a key metabolite, malic acid (MA), on lipid metabolism. Our findings reveal distinct metabolic profiles across rumen fluid, plasma, and milk, with 96, 109, and 79 differential metabolites, respectively, between the L-MF and H-MF groups. In rumen fluid, H-MF cows showed higher levels of lauric acid and succinic acid, linked to fatty acid biosynthesis, while the L-MF cows had elevated citraconic and orotic acids, associated with amino acid metabolism and liver stress. Plasma from the H-MF cows contained higher β-hydroxybutyric acid, methionine sulfoxide, and phosphatidylcholine, supporting lipogenesis, whereas L-MF plasma showed increased 3-hydroxy-L-proline, indicating tissue catabolism. In milk, the L-MF cows had higher MA, while the H-MF cows exhibited elevated L-carnitine, linked to fatty acid β-oxidation. Metabolite trend analysis during rumen fluid–plasma–milk showed that 211 metabolites were classified into 8 profiles. Profile 1 had the largest number of metabolites whose levels were down-regulated from rumen to plasma and enriched in lipid metabolism. Profile 3 (mainly related to amino acid metabolism) and profile 4 (mainly related to energy metabolism) exhibited opposite trends from plasma to milk. In vitro, 200 μM of MA reduced the triglyceride content in BMECs and down-regulated lipogenic genes and their protein expression levels (fatty acid synthase, stearoyl-CoA desaturase and sterol regulatory element binding protein 1). These results highlight how rumen fluid, plasma, and milk metabolites collectively influence milk fat synthesis, with MA acting as a key regulator of lipid metabolism in mammary epithelial cells. Full article

Fowl adenovirus serotype 4 (FAdV-4) has been identified as the primary pathogen responsible for hydropericardium-hepatitis syndrome (HHS), resulting in significant economic losses in major poultry-producing countries since 2015. Timely and accurate diagnosis of FAdV-4 infection is essential for the effective prevention and control of HHS. In this study, the two nonstructural genes of FAdV-4, 100K and 22K, were inserted into the expression vector pET-32a (+) respectively. The expressed recombinant proteins were used as coating antigens to develop two indirect ELISA methods, designated as 100K-ELISA and 22K-ELISA. Both ELISAs demonstrated high specificity, showing no cross-reactivity with serum samples positive for other avian diseases. Both ELISAs yielded positive results when applied to 50 serum samples from SPF chickens experimentally infected with FAdV-4 and negative results when applied to 50 serum samples from SPF chickens immunized with an inactivated FAdV-4 vaccine. Similarly, the field sample testing results demonstrated a significant ability to distinguish between vaccinated and infected samples. The 100K-ELISA and 22K-ELISA, which are based on nonstructural proteins, may be effective tools for differentiating between FAdV-4 infection and vaccination, offering a promising approach for differentiating infected from vaccinated animals (DIVA) strategies in poultry. Full article

Weaning stress is frequently associated with intestinal oxidative stress, inflammatory activation, and epithelial apoptosis in piglets. This study investigated whether dietary supplementation with Chinese yam (Dioscorea oppositifolia L., YAM) alleviates weaning-induced intestinal injury by modulating the oxidative stress-inflammation-apoptosis axis. 48 weaned piglets were assigned to a control diet or diets supplemented with low (1%)/high (2%) doses of YAM. Intestinal morphology, antioxidant capacity, inflammatory signaling, and apoptosis-related markers were assessed, and jejunal transcriptomic profiling was also performed. Supplementing with YAM improved villus architecture and enhanced intestinal antioxidant properties, manifested as increased total antioxidant capacity and reduced malondialdehyde levels. At the molecular level, YAM activated the Keap-1/Nrf2/HO-1 pathway and upregulated the expression of antioxidant-related genes, including superoxide dismutase 2 (SOD2), catalase (CAT), and NAD(P)H quinone dehydrogenase 1 (NQO1), and suppressed NF-κB signaling by reducing Myd88 and p-p65 protein levels. In addition, YAM modulated mitochondrial apoptosis by upregulating Bcl-2 and reducing the expression of Bax and Cleaved caspase-3. Transcriptomic analysis identified 1227 differentially expressed genes between the control and high-dose groups (784 upregulated and 443 downregulated). Mechanism-oriented module analysis further confirmed coordinated enhancement of antioxidant pathways alongside suppression of inflammatory and apoptotic gene signatures. These findings demonstrate that dietary YAM supplementation attenuates weaning-associated intestinal injury by rebalancing oxidative stress, inflammatory signaling, and apoptosis-related pathways, thereby supporting its potential application as a functional feed additive in swine production. Full article

The tomato hind (Cephalopholis sonnerati) is a marine aquaculture fish species with high economic value. Elucidating the mechanisms underlying its growth regulation is crucial for the development of the aquaculture industry. To analyze the biological mechanisms underlying growth differences, individuals with extreme body sizes at 8 months of age from the same batch were selected in this study. A combined experiment of “body size × feeding status” was constructed, and transcriptome sequencing and weighted gene co-expression network analysis (WGCNA) were performed on brain and muscle tissues. The results showed that 2553 differentially expressed genes (DEGs) were identified between individuals with distinct body sizes, which were significantly enriched in growth regulation pathways such as PI3K–Akt, MAPK, and FoxO. Feeding differences affected 4480 genes, which were significantly enriched in signaling pathways including the insulin signaling pathway. WGCNA further identified co-expression modules (brown4, blue, coral1) significantly correlated with growth, as well as hub genes including pik3r1 and eif4ebp2. Comprehensive analysis demonstrated that the growth regulation of C. sonnerati operates as a cascade network. Brain tissues perceive signals through neuroactive ligand–receptor interactions and integrate and transduce these signals via core pathways including Ras–MAPK and PI3K–Akt. Finally, growth processes are executed in muscle tissues by regulating glycogen metabolism, protein synthesis, and other processes, which are precisely regulated by terminal processes such as cellular senescence. Among them, pik3r1 and eif4ebp2, as key molecular switches, play a central role in integrating upstream signals and precisely regulating downstream growth programs. This study preliminarily clarifies the molecular mechanism network of growth differences in C. sonnerati, providing a theoretical basis and candidate genes for the genetic improvement of its growth traits. Full article

Background/Objectives: The significant negative correlation between protein and oil content in soybean seeds is a long-standing bottleneck for conventional breeding. Its root cause lies in insufficient understanding of related molecular regulatory processes. Methods: We selected the CSSL_R19, a chromosome segment substitution line, to thoroughly investigate the intrinsic effects of the substituted segment on the high seed storage protein (SSP) and low fatty acid (FA) phenotype. Transcriptomic, proteomic, and metabolomic analyses were performed on the recurrent parent and R19. Results: A total of 1821 differentially expressed genes (DEGs), 12 differentially expressed proteins (DEPs), and 10 differentially accumulated metabolites (DEMs) were detected. Subsequently, an integrative examination of the data demonstrated that 28 DEGs, 5 DEPs, and 4 DEMs participated in biological processes such as carbohydrate metabolism, lipid degradation, as well as protein synthesis and transport. Mechanistically, down-regulation of PGM reduces the carbon source supply for FA synthesis; up-regulation of LOX, LACS, ACX, and KAT promotes FA degradation. SRP, SAR1, and HSP70 are involved in the synthesis and transport of SSP. Crucially, qRT-PCR validation performed on all 28 core DEGs showed that their expression trends were highly consistent with the transcriptome data, confirming the reliability of the findings. Conclusions: In conclusion, we propose a potential regulatory network that enhances SSP accumulation and reduces FA content. Altogether, these findings advance our understanding of storage compound accumulation in soybeans and guide future breeding strategies. Full article

Gonadotropin-releasing hormone 1 (GnRH1) and its receptor (GnRHR1) are central neuropeptides on the hypothalamic–hypophysis–gonadal (HHG) axis and play key roles in vertebrate reproduction. Although GnRH1/GnRHR1 signaling has been extensively studied in models such as mouse, rat, zebrafish, and human, knowledge from other species is limited. This work used cloning, Sanger sequencing, and qPCR to highlight the molecular structure, evolutionary history, and sex-differentiated transcription of GnRH1/GnRHR1 signaling from hamster. These findings showed that GnRH1/GnRHR1 hamster proteins exhibit a molecular evolutionary history highly similar for peptides reported in other species and with which they share a high degree of structural homology. Expression profiles indicated a GnRH1 transcript in several tissues with higher expression levels in testes, adrenals, uterus, epididymis, female hypothalamus, and Harderian glands. GnRHR1 expression levels were seen exclusively in male and female hypophysis with higher levels in female hypophysis. Expression levels showed significant differences for GnRH1 in several tissues during estrous; GnRHR1 expression during estrous was detected only in hypophysis with increased expression levels seen during metestrus and diestrus. These results suggest a highly conserved homology of GnRHR1/GnRHR1 signaling, thus highlighting its evolutionary importance. These expression levels underscore the importance of GnRHR1 as a master regulator of reproductive endocrinology and could implicate hamster peptides as potential therapeutic biological models for human endocrine diseases. Full article

Background/Objectives: Ulcerative colitis (UC) involves inflammatory response, oxidative stress, changes in metabolites, and the gut microbiota. Jingangteng capsule (JGTC) has been utilized clinically for the treatment of inflammatory diseases for many years. However, the efficacy of JGTC in ameliorating UC remains unclear, and the underlying mechanisms have not yet been elucidated. This study aims to investigate the effect and mechanism of JGTC on UC. Methods: The chemical compositions of JGTC were examined using ultra-high-performance liquid chromatography with quadrupole time-of-fight mass spectrometry. The anti-UC effect of JGTC was evaluated by assessing the disease activity index (DAI), colon length, intestinal barrier recovery, and inflammatory factors in a dextran sulfate sodium (DSS)-induced colitis model. Mechanisms were investigated through fecal 16S rDNA sequencing, metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), Western blotting, and network pharmacology analysis. Results: JGTC significantly reduced the DAI scores in UC mice, increased their body weight and colon length (p < 0.001), repairing damaged intestinal tissue. It decreased the levels of inflammatory cytokines TNF-α, IL-6, IL-1β, and LPS (p < 0.01, p < 0.001), alleviating intestinal inflammation. It also raised the expression of tight junction proteins ZO-1, Claudin-1, and Occludin (p < 0.05, p < 0.001), thereby enhancing intestinal barrier function. Fecal metabolomic analysis revealed that the favorable alterations in amino acid and lipid metabolites were more pronounced. Heat maps showed strong correlations between pharmacological indicators and gut microbiota, as well as between the main differential metabolites and gut microbial communities. UPLC-QTOF-MS detection yielded 33 components of JGTC, and network pharmacology analysis based on these components predicted pathways of action of JGTC in UC. Functional pathways closely associated with significantly differential metabolites and metabolic pathways were also investigated. The PI3K-AKT-mTOR pathway was one of them, which is consistent with the conclusions drawn from network pharmacology. JGTC significantly modulated key factors in this pathway, inhibiting the expression of PI3K, Akt, PDK1, and mTOR, while augmenting the expression of PTEN (p < 0.05, p < 0.01, p < 0.001). It also mitigated the levels of related oxidative stress factors MDA, MPO, and D-LA, and raised SOD levels (p < 0.01, p < 0.001). Conclusions: JGTC improved the excessive inflammatory response in UC by regulating intestinal flora and metabolic disorders, affecting the PI3K-AKT-mTOR signaling pathway, restoring intestinal tissue damage and intestinal barrier, and inhibiting inflammatory and oxidative stress factors. Full article

Stanford type A aortic dissection (TAAD) is a life-threatening cardiovascular condition associated with high mortality. Ferroptosis has been implicated in TAAD pathogenesis, but comprehensive analyses and experimental validation of ferroptosis-related driver genes (FRDGs) remain limited. This study systematically investigated FRDGs in TAAD using bioinformatics and experimental approaches. Differentially expressed ferroptosis-related driver genes (DEFRDGs) were identified by integrating the GSE153434 dataset with the FerrDb database. Functional enrichment analysis was subsequently performed, followed by the construction of a protein–protein interaction (PPI) network, assessment of immune cell infiltration, and prediction of potential miRNA interactions. Candidate hub genes were then validated using an independent cohort (GSE52093) and clinical tissue samples, with their diagnostic value evaluated via receiver operating characteristic (ROC) curve analysis and their protein expression confirmed by immunohistochemistry. We identified 25 DEFRDGs (17 upregulated, 8 downregulated) enriched in oxidative stress, iron binding, and ferroptosis/HIF-1 signaling pathways. Six hub genes (HIF1A, IL6, TIMP1, SAT1, HMOX1, LPCAT3) were significantly upregulated in validation cohorts, five genes (HIF1A, TIMP1, SAT1, HMOX1, LPCAT3) achieved an area under the curve (AUC) of 1.000, while IL6 also exhibited high diagnostic accuracy (AUC = 0.914). Fibroblast infiltration was elevated in TAAD tissues. Further miRNA interaction prediction revealed the potential involvement of miRNAs, such as miR-138-5p, miR-18b-5p, miR-199a-5p, miR-185-5p, miR-506-3p and miR-4644. Immunohistochemistry confirmed increased protein expression of HIF1A, SAT1, and LPCAT3. These three genes emerge as key ferroptosis-related drivers in TAAD. Their consistent upregulation and strong diagnostic performance support ferroptosis as a potential therapeutic target and provide a basis for mechanism-focused interventions. Full article

Background: Indoleamine 2,3-dioxygenase (IDO) is an immune checkpoint that has been shown to play a key immunomodulatory role in various solid tumors, including breast cancer (BC). Although increased IDO expression has been previously observed in some BC subtypes, mainly triple-negative BC (TNBC), the clinical relevance of this protein across the entire range of BC and its exact correlations with other immune checkpoints remain to be elucidated. We herein aimed to further investigate the differential expression patterns of IDO and programmed death-ligand 1 (PD-L1) in variable BC subtypes and in distinct compartments of breast cancer tissue, and to explore their potential associations with standard patient- and tumor-related clinicopathological parameters as well as prognosis. Methods: This was a retrospective multi-center cohort study of 150 female patients with BC. The clinicopathological parameters analyzed were retrieved from the medical records of patients while sections from archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were also obtained for the performance of immunohistochemistry. The expression of IDO and PD-L1 was evaluated separately on tumor cells (IDO/CA, PD-L1/CA), lymphocytes (IDO/L, PD-L1/L) and stromal cells (IDO/S, PD-L1/S) and the results were correlated with the remaining clinical and pathological features of patients, as well as with local recurrence, metastasis and survival. Results: The mean age of patients was 59.5 years (SD = 13.4 years). Positive expression of IDO/CA, IDO/L and IDO/S was found in 6%, 93.3% and 90.7% of tissue samples, respectively, while 4%, 11.2% and 6.7% of tumors were positive for PD-L1/CA, PD-L1/L and PD-L1/S, respectively. A significantly higher rate of positive IDO/CA expression was observed in triple-negative BC (TNBC) patients (p = 0.037). Positive expression of IDO-CA was also significantly associated with positivity for PD-L1/L and PD-L1/S (p = 0.001 and p = 0.015, respectively). Multivariable logistic regression analysis showed independent correlations between IDO/CA and IDO/L and the presence of invasive ductal carcinoma (IDC) (OR = 1.10; p = 0.026) and N1 status (OR = 10.93; p = 0.039), respectively, IDO/S and both N1 (OR = 14.64; p = 0.018) and positive HER2 status (OR = 6.11; p = 0.019), PD-L1/L and high Ki67 (OR = 7.96; p = 0.001) as well as negative ER (OR = 0.08; 0.003) and PR status (OR = 0.09; p = 0.002), PD-L1/S and both NST (no special type) histology (OR = 4.68; p = 0.032) and negative ER status (OR = 0.21; p = 0.044). No statistically significant associations were observed between the expression patterns of the examined biomarkers and recurrence, metastasis or survival. Conclusions: In our study, IDO expression on tumor cells was predominantly observed in TNBC and was found to correlate with PD-L1 expression in the lymphocytic and stromal compartments. Furthermore, expression of PD-L1 among lymphocytes was found to independently correlate with unfavorable clinicopathological parameters, including high proliferation rate and negative hormone receptor status. Full article