Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (305)

Search Parameters:
Keywords = indoleamines

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
16 pages, 4135 KB  
Article
IDO-Mediated Immune and Metabolic Dysregulation in Schwann Cells Exposed to Mycobacterium leprae
by Atta Ur Rahman, Raíssa Couto Santana, Mylena Masseno de Pinho Pereira, Claudia Luciana dos Santos Moura, Débora Santos da Silva, Otto Castro Araujo, Thyago Leal-Calvo, Isabela Espasandin, Tatiana Pereira da Silva, Euzenir Nunes Sarno, Bruno Jorge de Andrade Silva, Rubem Sadok Figueiredo Menna-Barreto, Márcia Maria Jardim, Cristiana Santos de Macedo, Flávio Alves Lara and Roberta Olmo Pinheiro
Cells 2025, 14(19), 1550; https://doi.org/10.3390/cells14191550 - 3 Oct 2025
Abstract
Leprosy is a chronic infectious disease that targets the peripheral nervous system, leading to peripheral neuropathy. Mycobacterium leprae primarily infects Schwann cells, adipocytes, and macrophages, altering their metabolism and gene expression. This study investigates the metabolic interaction between M. leprae and Schwann cells, [...] Read more.
Leprosy is a chronic infectious disease that targets the peripheral nervous system, leading to peripheral neuropathy. Mycobacterium leprae primarily infects Schwann cells, adipocytes, and macrophages, altering their metabolism and gene expression. This study investigates the metabolic interaction between M. leprae and Schwann cells, with a focus on indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan catabolism via the kynurenine pathway. We found that M. leprae induces IDO expression in Schwann cells, suggesting a role in immune modulation and neuropathy. Inhibition of IDO with 1-methyl-L-tryptophan (1-MT) reduced Schwann cell viability and metabolic activity in response to M. leprae. After 24 h of infection, M. leprae impaired mitochondrial membrane potential, although no significant changes in autophagy or mitochondrial ultrastructure were observed by electron microscopy. Interestingly, IDO1 inhibition upregulated the expression of antioxidant genes, including GPX4, NFE2L2, and HMOX1. In conclusion, these findings highlight a central role for IDO in shaping the metabolic and immunological response of Schwann cells to M. leprae infection. IDO induction contributes to immune regulation and cellular stress, while its inhibition disrupts cell viability and promotes antioxidant gene expression. These results position IDO as a potential therapeutic target for modulating host–pathogen interactions and mitigating nerve damage in leprosy. Full article
(This article belongs to the Section Cells of the Nervous System)
Show Figures

Figure 1

26 pages, 5170 KB  
Article
Minocycline Treatment Improves Memory and Reduces Anxiety by Lowering Levels of Brain Amyloid Precursor Protein and Indoleamine 2,3-Dioxygenase in a Rat Model of Streptozotocin-Induced Alzheimer’s Disease
by Grzegorz Świątek, Jowita Nowakowska-Gołacka, Monika Słomińska-Wojewódzka, Wojciech Glac, Oliwia Harackiewicz, Ewelina Kurowska-Rucińska and Danuta Wrona
Int. J. Mol. Sci. 2025, 26(19), 9397; https://doi.org/10.3390/ijms26199397 - 26 Sep 2025
Abstract
Minocycline (MINO), a classic antibiotic, may have psychotropic activity related to the modulation of the tryptophan-kynurenine pathway. In this study, we investigated the effects of MINO on (1) memory and anxiety behaviors, (2) the modulation of brain levels of amyloid precursor protein (APP) [...] Read more.
Minocycline (MINO), a classic antibiotic, may have psychotropic activity related to the modulation of the tryptophan-kynurenine pathway. In this study, we investigated the effects of MINO on (1) memory and anxiety behaviors, (2) the modulation of brain levels of amyloid precursor protein (APP) and 2,3-indoleamine dioxygenase (IDO1) levels, and (3) peripheral inflammatory markers in a streptozotocin (STZ)-induced rat model of sporadic Alzheimer’s disease (sAD). After repeated treatment with a dose of 35 mg/kg MINO for seven consecutive days, male Wistar rats with sAD showed (1) improvements in early (29 days after injection, probe test) reference memory (decreased latency to reach the platform, increased time in the critical quadrant of the Morris water maze) and anxiety disorders (increased time in the open arms of the elevated plus maze; increased exploration and entrances in the center of the white–light illuminated open field) 45–46 and 90–91 days after STZ injection; (2) reduced APP and IDO1 levels in the hippocampus and prefrontal cortex; and (3) induction of anti-inflammatory response in blood (increased TCD4+ lymphocyte number and interleukin-10 production). This suggests that MINO, due to its anti-inflammatory action, improves memory and anxiety behavior related to sAD, indicating its neuroprotective and psychotropic properties. Full article
(This article belongs to the Special Issue Drug Repurposing: Emerging Approaches to Drug Discovery (2nd Edition))
Show Figures

Figure 1

27 pages, 834 KB  
Hypothesis
Hepatic Metabolic Dysregulation as a Potential Amplifier of Leukemogenesis Following mRNA Vaccination: A Novel Mechanistic Hypothesis
by Batuhan Erdoğdu, Ozan Kaplan, Mustafa Çelebier, Ümit Yavuz Malkan and İbrahim Celalettin Haznedaroğlu
Medicina 2025, 61(9), 1687; https://doi.org/10.3390/medicina61091687 - 17 Sep 2025
Viewed by 450
Abstract
Background: The liver’s role as a metabolic gatekeeper positions it uniquely to influence systemic metabolic homeostasis and potentially modulate leukemogenesis through hepato-hematopoietic crosstalk. Recent observations of rare hematological malignancies following mRNA vaccination warrant mechanistic investigation. Hypothesis: We propose that mRNA vaccines, through their [...] Read more.
Background: The liver’s role as a metabolic gatekeeper positions it uniquely to influence systemic metabolic homeostasis and potentially modulate leukemogenesis through hepato-hematopoietic crosstalk. Recent observations of rare hematological malignancies following mRNA vaccination warrant mechanistic investigation. Hypothesis: We propose that mRNA vaccines, through their preferential hepatic tropism via lipid nanoparticles (LNPs), may transiently dysregulate hepatic metabolism in susceptible individuals, creating metabolic perturbations that amplify pre-existing leukemogenic vulnerabilities through five interconnected mechanisms: (1) competitive folate sequestration for vaccine-induced lymphoproliferation, potentially starving bone marrow precursors of essential one-carbon units; (2) hepatic lipid processing overload from LNP accumulation, exacerbating phospholipid dysregulation in pre-leukemic clones; (3) cytokine-mediated upregulation of hepatic indoleamine 2,3-dioxygenase (IDO), accelerating tryptophan catabolism and creating an immunosuppressive milieu favoring leukemic escape; (4) inflammatory induction of hepcidin, sequestering hepatic iron while triggering compensatory intestinal iron hyperabsorption and potential bone marrow iron overload; and (5) increased hepatic NADPH demand for antioxidant defense and lipid metabolism, diverting reducing equivalents from bone marrow stromal support. Implications: This hypothesis suggests that transient hepatic metabolic perturbations may create a permissive milieu for leukemogenesis in metabolically vulnerable individuals. The proposed mechanisms generate testable predictions and identify potential therapeutic targets, including folate supplementation, IDO inhibition, and iron chelation in high-risk cohorts. Full article
(This article belongs to the Special Issue Advances in Cancer Cell Metastasis and Its Inhibition)
Show Figures

Figure 1

20 pages, 4318 KB  
Article
IDO Activation Affects BDNF/TrkB Signaling Pathway, Oxidative Stress, and Mitochondrial Enzymatic Activities in Temporal Lobe Epilepsy
by Jingwen Xu, Liping Wei, Junling Fu, Ziting Kong and Lun Cai
Curr. Issues Mol. Biol. 2025, 47(9), 764; https://doi.org/10.3390/cimb47090764 - 16 Sep 2025
Viewed by 250
Abstract
Indoleamine 2,3-dioxygenase (IDO) activation by seizures elevates toxic tryptophan metabolites linked to seizure exacerbation. Brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling, oxidative stress, and mitochondrial respiratory chain complex dysfunction contribute to temporal lobe epilepsy (TLE), but their regulatory links remain unclear. Male [...] Read more.
Indoleamine 2,3-dioxygenase (IDO) activation by seizures elevates toxic tryptophan metabolites linked to seizure exacerbation. Brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling, oxidative stress, and mitochondrial respiratory chain complex dysfunction contribute to temporal lobe epilepsy (TLE), but their regulatory links remain unclear. Male Kunming mice were grouped into Control, Control + 1-Methyl-DL-tryptophan (1-MT), TLE, and TLE + 1-MT. TLE was induced with 300 mg/kg pilocarpine. Two weeks after modeling, 1-MT (50 mg/kg) was administered twice daily for two weeks in 1-MT groups. Assessments included video monitoring to record seizure frequency and duration; Nissl and Fluoro-Jade B (FJB) staining to evaluate neuronal damage; real-time quantitative PCR (qRT-PCR) and Western blot to detect IDO, BDNF, and TrkB expression; assays for the following oxidative stress markers: malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT); and detection of mitochondrial complex I/IV activities. Results showed TLE mice had significantly increased IDO expression, BDNF/TrkB over-activation, elevated oxidative stress, impaired mitochondrial complex I/IV activities, severe neuronal damage, and increased seizure frequency/duration. 1-MT intervention reversed all these pathological changes, restoring levels to near-control status. This indicates IDO activation promotes TLE progression, which is associated with modulation of the BDNF/TrkB signaling pathway, exacerbation of oxidative stress, and impairment of mitochondrial complex I/IV activities—supporting IDO as a potential therapeutic target for TLE. Full article
(This article belongs to the Section Molecular Medicine)
Show Figures

Figure 1

14 pages, 1088 KB  
Article
Combined Serum IL-6 and CYFRA 21-1 as Potential Biomarkers for Radon-Associated Lung Cancer Risk: A Pilot Study
by Narongchai Autsavapromporn, Aphidet Duangya, Pitchayaponne Klunklin, Imjai Chitapanarux, Chutima Kranrod, Churdsak Jaikang, Tawachai Monum and Shinji Tokonami
Biomedicines 2025, 13(9), 2145; https://doi.org/10.3390/biomedicines13092145 - 3 Sep 2025
Viewed by 498
Abstract
Background: Radon, a naturally occurring radioactive gas, is increasingly recognized as a major risk factor for lung cancer (LC), especially among non-smokers. The objective of this study was to identify serum biomarkers for the early detection of LC in individuals at high [...] Read more.
Background: Radon, a naturally occurring radioactive gas, is increasingly recognized as a major risk factor for lung cancer (LC), especially among non-smokers. The objective of this study was to identify serum biomarkers for the early detection of LC in individuals at high risk due to prolonged residential radon exposure in Chiang Mai, Thailand, and to assess whether the use of single or combined biomarkers improves the sensitivity and specificity of detection. Methods: A total of 15 LC patients and 30 healthy controls (HC) were enrolled. The HC group was further stratified into two subgroups: low radon (LR, n = 15) and high radon (HR, n = 15) exposure. All participants were non-smokers or former smokers. Serum levels of cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor-alpha (TGF-alpha), and indoleamine 2,3-dioxygenase-1 (IDO-1) were measured using the Milliplex® Kit on a Luminex® Multiplexing Instrument (MAGPIX® System). Results: Serum CEA, IL-6 and IL-8 levels were significantly higher in LC patients compared to the HC group (p < 0.05). Among analyzed biomarkers, only IL-8 was significantly elevated in LC patients compared to the HR group (p = 0.04). Notably, CYFRA 21-1 was the only biomarker that significantly differed between LR and HR groups (p = 0.004). The diagnostic potential of these biomarkers was evaluated using receiver operating characteristic (ROC) analysis. Individually, IL-6 showed the highest discriminative ability for differentiating LC patients from both HC and HR groups, with high specificity but moderate sensitivity. Combining IL-6 and IL-8 improved specificity and increased the area under the ROC curve (AUC), though it did not enhance sensitivity for distinguishing LC from HC. For distinguishing LC from HR individuals, IL-6 and CYFRA 21-1 exhibited strong diagnostic performance. Their combination significantly improved diagnostic accuracy, yielding the highest AUC, sensitivity, and specificity. In contrast, CEA, IL-8, TGF-alpha, and IDO-1 demonstrated limited diagnostic utility. Conclusions: Based on the available literature, this is the first study to evaluate the combined use of IL-6 and CYFRA 21-1 as potential biomarkers for LC screening in individuals with high residential radon exposure. Our findings highlight their utility, particularly in combination, for improving diagnostic accuracy in this high-risk population. Full article
Show Figures

Figure 1

38 pages, 2700 KB  
Review
From Microbial Switches to Metabolic Sensors: Rewiring the Gut–Brain Kynurenine Circuit
by Masaru Tanaka and László Vécsei
Biomedicines 2025, 13(8), 2020; https://doi.org/10.3390/biomedicines13082020 - 19 Aug 2025
Viewed by 1310
Abstract
The kynurenine (KYN) metabolic pathway sits at the crossroads of immunity, metabolism, and neurobiology, yet its clinical translation remains fragmented. Emerging spatial omics, wearable chronobiology, and synthetic microbiota studies reveal that tryptophan (Trp) metabolism is regulated by distinct cellular “checkpoints” along the gut–brain [...] Read more.
The kynurenine (KYN) metabolic pathway sits at the crossroads of immunity, metabolism, and neurobiology, yet its clinical translation remains fragmented. Emerging spatial omics, wearable chronobiology, and synthetic microbiota studies reveal that tryptophan (Trp) metabolism is regulated by distinct cellular “checkpoints” along the gut–brain axis, finely modulated by sex differences, circadian rhythms, and microbiome composition. However, current interventions tackle single levers in isolation, leaving a key gap in the precision control of Trp’s fate. To address this, we drew upon an extensive body of the primary literature and databases, mapping enzyme expression across tissues at single-cell resolution and linking these profiles to clinical trials investigating dual indoleamine 2,3-dioxygenase 1 (IDO1)/tryptophan 2,3-dioxygenase (TDO) inhibitors, engineered probiotics, and chrono-modulated dosing strategies. We then developed decision-tree algorithms that rank therapeutic combinations against biomarker feedback loops derived from real-time saliva, plasma, and stool metabolomics. This synthesis pinpoints microglial and endothelial KYN hotspots, quantifies sex-specific chronotherapeutic windows, and identifies engineered Bifidobacterium consortia and dual inhibitors as synergistic nodes capable of reducing immunosuppressive KYN while preserving neuroprotective kynurenic acid. Here, we highlight a framework that couples lifestyle levers, bio-engineered microbes, and adaptive pharmaco-regimens into closed-loop “smart protocols.” By charting these intersections, this study offers a roadmap for biomarker-guided, multidisciplinary interventions that could recalibrate KYN metabolic activity across cancer, mood, neurodegeneration, and metabolic disorders, appealing to clinicians, bioengineers, and systems biologists alike. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
Show Figures

Graphical abstract

27 pages, 11958 KB  
Article
In Silico and In Vivo Studies Reveal the Potential Preventive Impact of Cuminum cyminum and Foeniculum vulgare Essential Oil Nanocapsules Against Depression-like States in Mice Fed a High-Fat Diet and Exposed to Chronic Unpredictable Mild Stress
by Karem Fouda and Rasha S. Mohamed
Sci. Pharm. 2025, 93(3), 37; https://doi.org/10.3390/scipharm93030037 - 14 Aug 2025
Viewed by 766
Abstract
Hyperlipidemia, oxidative stress, and excessive inflammatory cytokine production are risk factors for depression. The potential preventive effects of essential oils (EOs) such as cumin and fennel EOs on depression may stem from their hypolipidemic, antioxidant, and anti-inflammatory activities. This work aimed to investigate [...] Read more.
Hyperlipidemia, oxidative stress, and excessive inflammatory cytokine production are risk factors for depression. The potential preventive effects of essential oils (EOs) such as cumin and fennel EOs on depression may stem from their hypolipidemic, antioxidant, and anti-inflammatory activities. This work aimed to investigate the effects of cumin and fennel EO nanocapsules in a mouse model of depression caused by a high-fat diet (HFD) and chronic mild stress (CMS) using both in silico and in vivo studies. The cumin and fennel EOs were extracted, analyzed by GC-MS, and encapsulated in nano-form using gum Arabic and maltodextrin as wall materials. The freeze-dried nanocapsules were evaluated in HFD/CMS-treated mice. Molecular docking was used to examine the significance of the oils’ compounds in blocking the active sites of hydroxymethylglutaryl-CoA (HMG-CoA) and indoleamine 2,3-dioxygenase (IDO). According to the molecular docking results, the interactions between EO components and HMG-CoA or IDO indicate that these EOs may have hypercholesterolemic and antidepressive effects. Cumin and fennel EO nanocapsules showed hypolipidemic, antioxidant, and anti-inflammatory effects in vivo. This was demonstrated by the down-regulation of oxidants (ROS, MDA, and NO) and inflammatory markers (TLR4, TNF-α, and IL-6) in the brain, changes in lipid profile parameters, and the up-regulation of antioxidant enzymes (SOD, CAT, and GSH). The in silico and in vivo outputs revealed the potential preventive impact of cumin and fennel EO nanocapsules against depression-like states in the mouse model through the prevention of dyslipidemia, neuroxidation, and neuroinflammation. More human studies are needed to fully understand the antidepressive effects of cumin and fennel EO nanocapsules. Full article
Show Figures

Figure 1

31 pages, 4843 KB  
Review
Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets
by Uttapol Permpoon, Jiyeong Moon, Chul Young Kim and Tae-gyu Nam
Int. J. Mol. Sci. 2025, 26(15), 7616; https://doi.org/10.3390/ijms26157616 - 6 Aug 2025
Cited by 1 | Viewed by 2075
Abstract
Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose [...] Read more.
Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article
(This article belongs to the Special Issue Understanding Aging in Health and Disease)
Show Figures

Figure 1

21 pages, 3587 KB  
Article
Carboxymethyl Dextran-Based Biosensor for Simultaneous Determination of IDO-1 and IFN-Gamma in Biological Material
by Zuzanna Zielinska, Anna Sankiewicz, Natalia Kalinowska, Beata Zelazowska-Rutkowska, Tomasz Guszcz, Leszek Ambroziak, Miroslaw Kondratiuk and Ewa Gorodkiewicz
Biosensors 2025, 15(7), 444; https://doi.org/10.3390/bios15070444 - 10 Jul 2025
Viewed by 521
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO-1) and interferon-gamma (IFN-γ) are proteins that play a significant role in inflammatory conditions and tumor development. The detection of IDO1 and IFN-γ is crucial for understanding their interplay in immune responses. This study introduced a novel method for the [...] Read more.
Indoleamine 2,3-dioxygenase 1 (IDO-1) and interferon-gamma (IFN-γ) are proteins that play a significant role in inflammatory conditions and tumor development. The detection of IDO1 and IFN-γ is crucial for understanding their interplay in immune responses. This study introduced a novel method for the simultaneous quantitative determination of IDO-1 and IFN-γ in different biological samples/materials. The method is based on an optical biosensor, with surface plasmon resonance detection carried out by the imaging version of the sensor (SPRi). Biotinylated antibodies immobilized on the surfaces of the linker and carboxymethylated dextran served as the recognition elements for the developed biosensor. Relevant studies were conducted to optimize the activities of the biosensor by employing appropriate reagent concentrations. Validation was performed for each protein separately; low detection and quantification limits were obtained (for IDO-1 LOD = 0.27 ng/mL, LOQ = 0.81 ng/mL; for IFN-γ LOD = 1.76 pg/mL and LOQ = 5.29 pg/mL). The sensor operating ranges were 0.001–10 ng/mL for IDO-1 and 0.1–1000 pg/mL for IFN-γ. The constructed biosensor demonstrated its sensitivity and precision when the appropriate analytical parameters were determined, based on the proposed method. It can also selectively capture IDO-1 and IFN-γ from a large sample matrix. The biosensor efficiency was confirmed by the determination of IDO-1 and IFN-γ in simultaneous measurements of the plasma and urine samples of patients diagnosed with bladder cancer and the control group. The outcomes were compared to those obtained using a certified ELISA test, demonstrating convergence between the two methodologies. The preliminary findings demonstrate the biosensor’s efficacy and suitability for comprehensive analyses of the examined biological samples. Full article
(This article belongs to the Special Issue Micro/Nanofluidic System-Based Biosensors)
Show Figures

Figure 1

20 pages, 3541 KB  
Review
Immunoregulation in Fungal Infections: A Review and Update on the Critical Role of Myeloid-Derived Suppressor Cells
by Valéria de Lima Kaminski, Ana Luiza Oliveira Menezes, Kauan Gonçalves de Lima, Stephani Leonelo de Almeida, Diego Vinícius Alves da Silva, Filipe Nogueira Franco, Nycolas Willian Preite and Flávio Vieira Loures
J. Fungi 2025, 11(7), 496; https://doi.org/10.3390/jof11070496 - 30 Jun 2025
Viewed by 892
Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune cells that play a central role in regulating host immune responses during fungal infections. Their recruitment is mediated by pathogen recognition receptors, particularly Dectin-1 and CARD9 signaling, which promote the production of reactive [...] Read more.
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune cells that play a central role in regulating host immune responses during fungal infections. Their recruitment is mediated by pathogen recognition receptors, particularly Dectin-1 and CARD9 signaling, which promote the production of reactive oxygen species (ROS) and IL-1β. Once activated, MDSCs suppress T-cell and natural killer cell functions through immunosuppressive cytokines like IL-10 and TGF-β, as well as enzymes such as arginase-1 and indoleamine 2,3-dioxygenase 1 (IDO-1). This review explores the role of MDSCs in fungal infections caused by Candida spp., Paracoccidioides brasiliensis, Aspergillus spp., and Cryptococcus neoformans, emphasizing their impact on immune modulation and disease progression. The emerging evidence suggests that fungal bioactive compounds, such as polysaccharides, can influence MDSC activity and restore immune balance. Notably, therapies targeting MDSCs have demonstrated promise in both fungal infections. In particular, infections with P. brasiliensis and C. neoformans show improved T-cell responses following MDSC-targeted interventions. Additionally, polysaccharides from Grifola frondosa and exposure to Aspergillus sydowii affect MDSC behavior, supporting the potential of modulating these cells therapeutically. Together, these findings highlight the relevance of MDSCs in fungal pathogenesis and underscore their potential as targets for immunotherapeutic strategies in infectious diseases. Full article
(This article belongs to the Special Issue Fungal Cell Biology)
Show Figures

Figure 1

22 pages, 1245 KB  
Review
Predicting Immunotherapy Efficacy with Machine Learning in Gastrointestinal Cancers: A Systematic Review and Meta-Analysis
by Sara Szincsak, Péter Király, Gabor Szegvari, Mátyás Horváth, David Dora and Zoltan Lohinai
Int. J. Mol. Sci. 2025, 26(13), 5937; https://doi.org/10.3390/ijms26135937 - 20 Jun 2025
Cited by 1 | Viewed by 1139
Abstract
Machine learning (ML) algorithms hold the potential to outperform the selection of patients for immunotherapy (ICIs) compared to previous biomarker studies. We analyzed the predictive performance of ML models and compared them to traditional clinical biomarkers (TCBs) in the field of gastrointestinal (GI) [...] Read more.
Machine learning (ML) algorithms hold the potential to outperform the selection of patients for immunotherapy (ICIs) compared to previous biomarker studies. We analyzed the predictive performance of ML models and compared them to traditional clinical biomarkers (TCBs) in the field of gastrointestinal (GI) cancers. The study has been registered in PROSPERO (number: CRD42023465917). A systematic search of PubMed was conducted to identify studies applying different ML algorithms to GI cancer patients treated with ICIs using tumor RNA gene expression profiles. The outcomes included were response to immunotherapy (ITR) or survival. Additionally, we compared the ML methodology details and predictive power inherent in the published gene sets using 5-fold cross-validation and logistic regression (LR), on an available well-defined ICI-treated metastatic gastric cancer (GC) cohort (n = 45). A set of standard clinical ICI biomarkers (MLH, MSH, and CD8 genes, plus PMS2 and PD-L1)) and de-novo calculated principal components (PCs) of the original datasets were also included as additional points of comparison. Nine articles were identified as eligible to meet the inclusion criteria. Three were pan-cancer studies, five assessed GC, and one studied colorectal cancer (CRC). Classification and regression models were used to predict ICI efficacy. Next, using LR, we validated the predictive power of applied ML algorithms on RNA signatures, using their reported receiver operating characteristics (ROC) analysis area under the curve (AUC) values on a well-defined ICI-treated gastric cancer (GC) dataset (n = 45). In two cases our method has outperformed the published results (reported/LR comparison: 0.74/0.831, 0.67/0.735). Besides the published studies, we have included two benchmarks: a set of TCBs and using principal components based on the whole dataset (PCA, 99% explained variance, 40 components). Interestingly, a study using a selected gene set (immuno-oncology panel) with AUC = 0.83 was the only one that outperformed the TCB (AUC = 0.8) and the PCA (AUC =0.81) results. Cross-validation of the predictive performance of these genes on the same GC dataset and an investigation of their prognostic role on a collated multi-cohort GC dataset of n = 375 resected, or chemotherapy-treated patients revealed that genes mannose-6-phosphate receptor (M6PR), Indoleamine 2,3-Dioxygenase 1 (IDO1), Neuropilin-1 (NRP1), and MAGEA3 performed similarly, or better than established biomarkers like PD-L1 and MSI. We found an immuno-oncology panel with an AUC = 0.83 that outperformed the clinical benchmark or the PC results. We recommend further investigation and experimental validation in the case of M6PR, IDO1, NRP1, and MAGEA3 expressions based on their strong predictive power in GC ITR. Well-designed studies with larger sample sizes and nonlinear ML models might help improve biomarker selections. Full article
(This article belongs to the Special Issue Recent Advances in Gastrointestinal Cancer, 2nd Edition)
Show Figures

Figure 1

22 pages, 1884 KB  
Review
Melatonin/Chitosan Biomaterials for Wound Healing and Beyond: A Multifunctional Therapeutic Approach
by Karolina Kulka-Kamińska, Patrycja Brudzyńska, Mayuko Okura, Tatsuyuki Ishii, Marco Skala, Russel J. Reiter, Andrzej T. Slominski, Kazuo Kishi, Kerstin Steinbrink, Alina Sionkowska and Konrad Kleszczyński
Int. J. Mol. Sci. 2025, 26(13), 5918; https://doi.org/10.3390/ijms26135918 - 20 Jun 2025
Viewed by 1410
Abstract
Chitosan is increasingly utilized in combination with melatonin in novel formulations for a wide range of therapeutic applications. As a biocompatible and biodegradable polymer, chitosan exhibits notable properties, including antioxidant, antimicrobial, moisturizing, and absorption capabilities, in addition to a high potential for chemical [...] Read more.
Chitosan is increasingly utilized in combination with melatonin in novel formulations for a wide range of therapeutic applications. As a biocompatible and biodegradable polymer, chitosan exhibits notable properties, including antioxidant, antimicrobial, moisturizing, and absorption capabilities, in addition to a high potential for chemical modification due to its functional groups. These characteristics make it a valuable material in biomedical, pharmaceutical, cosmetic, food packaging, and environmental applications. Melatonin, an indoleamine primarily synthesized in the pineal gland but also found in various peripheral organs and in diverse organisms—including plants, bacteria, and fungi—has been extensively investigated for its antioxidant, anti-apoptotic, and anti-inflammatory activities, as well as its roles in immunomodulation, mitochondrial function, and melanin biosynthesis. This review summarizes recent advances in the combined use of chitosan and melatonin, with emphasis on their synergistic effects in wound healing, anti-cancer therapies, tissue engineering (i.e., skin and bone regeneration), and drug delivery systems. Additional potential applications are discussed in the context of cosmetology, aesthetic medicine, and veterinary practice. Full article
(This article belongs to the Special Issue The Chitosan Biomaterials: Advances and Challenges—2nd Edition)
Show Figures

Graphical abstract

10 pages, 1123 KB  
Article
Indoleamine 2,3-Dioxygenase Regulates Placental Trophoblast Cell Invasion
by Yoshiki Kudo and Jun Sugimoto
Int. J. Mol. Sci. 2025, 26(12), 5889; https://doi.org/10.3390/ijms26125889 - 19 Jun 2025
Viewed by 443
Abstract
To clarify the physiological importance of the tryptophan catabolizing enzyme, indoleamine 2,3-dioxygenase, in human pregnancy, we have studied how the expression of this enzyme controls extravillous cytotrophoblast invasion into the decidua. We have generated an Ishikawa cell line stably transfected with a plasmid [...] Read more.
To clarify the physiological importance of the tryptophan catabolizing enzyme, indoleamine 2,3-dioxygenase, in human pregnancy, we have studied how the expression of this enzyme controls extravillous cytotrophoblast invasion into the decidua. We have generated an Ishikawa cell line stably transfected with a plasmid encoding indoleamine 2,3-dioxygenase under the control of a tetracycline inducible promoter. Using this Ishikawa cell line and extravillous cytotrophoblast cell line, HTR-8/SVneo, we developed a quantitative in vitro trophoblast invasion assay. When trophoblast cells were cultured on a layer of Ishikawa cells expressing indoleamine 2,3-dioxygenase, tryptophan degradation was enhanced and trophoblast cell invasion was suppressed. These findings suggest that indoleamine 2,3-dioxygenase expressed in the decidua may play a role in regulating trophoblast invasion. Full article
(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)
Show Figures

Figure 1

17 pages, 5282 KB  
Article
Discovery of Novel Imidazothiazole-Based Hydroxamic Acid Derivatives as Potent Indoleamine 2,3-Dioxygenase 1 and Histone Deacetylase 6 Dual Inhibitors
by Shi Zhang, Yan-Fei Wang, Hai-Rui Lu, Xue-Qin Yang, Ye Zhang, Xian-Li Ma and Ri-Zhen Huang
Molecules 2025, 30(12), 2508; https://doi.org/10.3390/molecules30122508 - 7 Jun 2025
Viewed by 876
Abstract
In order to take advantage of both immunotherapeutic and epigenetic antitumor agents, a series of imidazothiazole-based hydroxamic acid derivatives were designed based on the pharmacophore fusion strategy and evaluated as potent IDO1 and HDAC6 dual inhibitors. Among these inhibitors, the most potent compound [...] Read more.
In order to take advantage of both immunotherapeutic and epigenetic antitumor agents, a series of imidazothiazole-based hydroxamic acid derivatives were designed based on the pharmacophore fusion strategy and evaluated as potent IDO1 and HDAC6 dual inhibitors. Among these inhibitors, the most potent compound 3-(4-Bromophenyl)-N-{4-[(7-(hydroxyamino)-7-oxoheptyl)amino]phenyl}imidazo[2,1-b]thiazole-5-carboxamide (10e) showed considerable IDO1 inhibitory activity and a good selectivity profile for HDAC6 over the other HDAC isoforms. The intracellular inhibition of HDAC6 by 10e was validated by Western blot analysis. Docking studies illustrated that the possible binding modes of compound 10e interacted with IDO1 and HDAC6. Moreover, compound 10e was found to arrest the cell cycle at the G2/M phase in HCT-116 cells. In particular, compound 10e also exhibited potent in vivo antitumor efficacy in CT26 tumor-bearing BALB/c mice models, with no significant toxicity. Collectively, this work provides a promising lead compound that serves as IDO1/HDAC6 dual inhibitor for the development of novel antitumor agents. Full article
Show Figures

Graphical abstract

14 pages, 1274 KB  
Article
Indoximod Attenuates Inflammatory Responses in Acetic Acid-Induced Acute Colitis by Modulating Toll-like Receptor 4 (TLR4) Signaling and Proinflammatory Cytokines in Rats
by Gulcin Ercan, Hatice Aygun, Ahmet Akbaş, Osman Sezer Çınaroğlu and Oytun Erbas
Medicina 2025, 61(6), 1033; https://doi.org/10.3390/medicina61061033 - 3 Jun 2025
Viewed by 913
Abstract
Background and Objectives: Acute ulcerative colitis is characterized by excessive mucosal inflammation and epithelial disruption, often driven by dysregulated cytokine and immune signaling. Indoximod (1-methyl-DL-tryptophan), although not a direct enzymatic inhibitor, modulates the indoleamine 2,3-dioxygenase (IDO) pathway and has been reported to exert [...] Read more.
Background and Objectives: Acute ulcerative colitis is characterized by excessive mucosal inflammation and epithelial disruption, often driven by dysregulated cytokine and immune signaling. Indoximod (1-methyl-DL-tryptophan), although not a direct enzymatic inhibitor, modulates the indoleamine 2,3-dioxygenase (IDO) pathway and has been reported to exert immunoregulatory effects in various models of inflammation. This study aimed to evaluate the protective effects of Indoximod in an acetic acid-induced colitis model in rats, focusing on histopathological changes and inflammatory mediators. Materials and Methods: Thirty male Wistar albino rats were randomly assigned to three groups (n = 10 per group): Group 1 (Control) received 0.9% saline oral gavage; Group 2 (Colitis) received intrarectal 4% acetic acid to induce colitis and were then treated with saline; Group 3 (Colitis + Indoximod) received 4% acetic acid followed by oral gavage administration of Indoximod (30 mg/kg) for 15 consecutive days. Histopathological evaluation of colonic tissues was performed using hematoxylin and eosin (H&E) staining. Colonic expression of Toll-like receptor 4 (TLR4) and plasma levels of tumor necrosis factor-alpha (TNF-α), pentraxin-3 (PTX-3), and platelet-activating factor (PAF) were quantified using enzyme-linked immunosorbent assay (ELISA). Results: Acetic acid-induced colitis significantly increased mucosal damage, TLR4 expression, and circulating levels of TNF-α, PTX-3, and PAF compared with controls (p < 0.001). Indoximod treatment markedly reduced histological injury and significantly suppressed TLR4 and TNF-α levels (p < 0.01), along with partial reductions in PTX-3 (p < 0.05). However, PAF levels remained elevated despite treatment, indicating limited efficacy in PAF-associated pathways. Conclusions: Indoximod exhibited anti-inflammatory effects in this acute colitis model, likely by downregulating key proinflammatory mediators. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
Show Figures

Figure 1

Back to TopTop