Search Results (253)

Necrosis is a characteristic feature of glioblastoma multiforme (GBM) and is closely associated with tumor-associated inflammation and poor clinical outcomes. However, the molecular consequences of necrotic cell death on endoplasmic reticulum (ER) stress signaling in GBM cells remain unclear. In this study, we examined the effects of necrotic cells on the ER stress signaling and unfolded protein response (UPR) in human glioblastoma cell lines. Exposure to necrotic cells reduced IRE1α phosphorylation and increased unspliced XBP1 (XBP1u) accumulation, without affecting PERK or ATF6 pathways. These changes were accompanied by enhanced IκBα phosphorylation and impaired autophagic degradation. Treatment with ER stress inducers failed to reverse XBP1u accumulation, and reduced phosphorylation of PKAc was observed together with decreased IRE1α activation. Transcriptomic analysis and quantitative reverse transcription PCR (qRT-PCR) revealed that necrotic cell-induced XBP1u was associated with altered expression of XBP1-related genes, while XBP1 knockdown produced similar transcriptional changes and enhanced the effects of necrotic cell treatment. These findings suggest that necrotic cells impair canonical IRE1α-XBP1 signaling and induce transcriptional reprogramming in glioblastoma cells, which may contribute to tumor progression. Full article

Alcoholic liver disease (ALD) is a spectrum of alcohol-induced disorders and represents a major global health challenge. B-cell receptor-associated protein 31 (BAP31) is an endoplasmic reticulum-resident chaperone involved in protein transport, apoptosis, cancer biology, and lipid metabolism. To explore its role in ALD, we used hepatocyte-specific BAP31 knockout mice (BAP31-LKO) and wild-type (WT) littermates exposed to ethanol to assess BAP31′s biochemical and metabolic impact. Following ethanol exposure, BAP31-LKO mice exhibited elevated serum alanine transaminase (23.2%, p < 0.05) and aspartate transaminase (31.4%, p < 0.05) levels compared to WT mice. Increased malondialdehyde (8.5%, p < 0.05) and reduced superoxide dismutase (22.8%, p < 0.05) in BAP31-LKO mice indicate exacerbated liver injury. Furthermore, BAP31 deficiency increased triglyceride (35.7%, p < 0.05) and free fatty acid (16.2%, p < 0.05) accumulation following ethanol treatment, while the expression of fatty acid oxidation-related genes, including Pparα, Cd36, Fatp2, Cpt2, and Acox1, was reduced in BAP31-LKO mice. The mRNA levels of Xbp1, Xbp1s, and Chop, as well as protein levels of p-eIF2α, IRE1α, GRP78, and CHOP, were increased in BAP31-LKO mice compared to WT controls, indicating aggravated ethanol-induced ER stress. Hepatic glycogen content was also reduced in BAP31-LKO mice, along with reduced Ppp1r3c expression, demonstrating impaired glycogen synthesis. Consistently, BAP31 knockdown amplified ethanol-induced lipid accumulation, inflammation, impaired glycogen storage, ER stress, and suppression of Pparα signaling in HepG2 cells. Together, these findings demonstrate that BAP31 deficiency exacerbates ethanol-induced liver steatosis, inflammation, and liver injury by impairing fatty acid oxidation and glycogen synthesis, and by amplifying ER stress responses. Full article

Background/Objectives: Increased fat intake and high content of saturated fatty acids in the diet are associated with higher body weight and an increased risk of obesity. This study aimed to determine the impact of a high-fat diet (HFD) on white adipose tissue (WAT) metabolism and to verify whether this effect depends on the sources of lipids in HFD. Methods: Male C57BL/6J mice, 7 weeks old, received a control (Ctrl.) or high-fat diet (HFD) with 10% and 45% energy from fat, respectively, for 15 weeks. Lard was used as the main dietary fat in the HFD group. Next, the HFD group was subdivided into HFD-L, HFD-CO, HFD-OO and HFD-FO groups differing in the lipid sources (lard, coconut oil, olive oil, fish oil, respectively). The experiment was continued for 12 consecutive weeks. The study analyzed the concentration of different fatty acids in visceral (VAT) and subcutaneous (ScAT) adipose tissue; the levels of autophagy markers: beclin1, Atg5, LC3, p62, AMPK; ER stress markers: phos-PERK, CHOP, XBP-1 and oxidative stress parameters: TAS and TBARS in VAT and ScAT. Results: Mice in all HFD groups showed increased body mass and adipose tissue hypertrophy. Blood glucose concentration remained elevated in the HFD-L group but normalized in other HFD groups by the end of the dietary intervention. Fatty acid content in VAT and ScAT reflected the dietary sources in HFD. The HFD-L, HFD-CO, HFD-OO groups showed increased beclin1, ATG5, and p62 levels in VAT but the LC3-II/LC3-I ratio was similar to the control, suggesting impaired autophagic flux. In the HFD-FO group, the LC-II/LC-I ratio was elevated, along with decreased p62 levels, indicating active autophagic degradation. Changes in autophagy activity were insignificant in ScAT. ER stress markers were also mostly unaffected by HFD in both adipose tissue depots. TAS and TBARS values in VAT and ScAT were similar in the HFD-L and HFD-CO groups, and the HFD-OO group showed increased TAS and decreased TBARS, while the HFD-FO reduced TBARS. Conclusions: Antioxidant capacity and autophagy activity in WAT depended on fat content and lipid source, especially in the visceral depot. Fish oil induced changes in cellular metabolism, especially in VAT, diminishing the detrimental effects of HFD. Full article

Background and Objective: Prostate cancer remains one of the most prevalent and potentially lethal malignancies among men worldwide, and timely and accurate diagnosis, along with the stratification of patients by disease severity, is critical for personalized treatment and improved outcomes for this cancer. One of the tools used for diagnosis is bioinformatics. However, traditional biomarker discovery methods often lack transparency and interpretability, which means that clinicians find it difficult to trust biomarkers for their application in a clinical setting. Methods: This paper introduces a novel approach that leverages Explainable Machine Learning (XML) techniques to identify and prioritize biomarkers associated with different levels of severity of prostate cancer. The proposed XML approach presented in this study incorporates some traditional machine learning (ML) algorithms with transparent models to facilitate understanding of the importance of the characteristics for bioinformatics analysis, allowing for more informed clinical decisions. The proposed method contains the implementation of several ML classifiers, such as Naive Bayes (NB), Random Forest (RF), Decision Tree (DT), Support Vector Machine (SVM), Logistic Regression (LR), and Bagging (Bg); followed by SHAPly values for the XML pipeline. In this study, for pre-processing of missing values, imputation was applied; SMOTE (Synthetic Minority Oversampling Technique) and the Tomek link method were applied to handle the class imbalance problem. The k-fold stratified validation of machine learning (ML) models and SHAP values (SHapley Additive explanations) were used for explainability. Results: This study utilized a novel tissue microarray data set that has 102 patient data comprising prostate cancer and healthy patients. The proposed model satisfactorily identifies genes as biomarkers, with highest accuracy obtained being 81.01% using RF. The top 10 potential biomarkers identified in this study are DEGS1, HPN, ERG, CFD, TMPRSS2, PDLIM5, XBP1, AJAP1, NPM1 and C7. Conclusions: As XML continues to unravel the complexities within prostate cancer datasets, the identification of severity-specific biomarkers is poised at the forefront of precision oncology. This integration paves the way for targeted interventions, improving patient outcomes, and heralding a new era of individualized care in the fight against prostate cancer. Full article

Based on comprehensive experimental datasets—proximate/ultimate analyses, XPS, solid-state ¹³C NMR, and Raman spectroscopy—we constructed and optimized a compositionally faithful macromolecular model of SG coking coal. Using density-functional theory (DFT) calculations, we simulated electrostatic-potential (ESP) fields and frontier molecular orbitals (FMO) to probe elementary oxidation steps relevant to combustion, and focused on how heteroatom speciation and carbon ordering govern site-selective reactivity. Employing multi-peak deconvolution and parameter synthesis, we obtained an aromatic fraction f_a = 76.56%, a bridgehead-to-periphery ratio X_BP = 0.215, and Raman indices I_D1/I_G ≈ 1.45 (area) with FWHM(G) ≈ 86.7 cm⁻¹; the model composition C₁₉₀H₁₄₄N₂O₂₁S and its predicted ¹³C NMR envelope validated the structural assignment against experiment. ESP–FMO synergy revealed electron-rich hotspots at phenolic/ether/carboxyl and thiophenic domains and electron-poor belts at H-terminated edges/aliphatic bridges, rationalizing carbon-end oxidation of CO, weak electrostatic steering by O₂/CO₂, and a benzylic H-abstraction → edge addition → O-insertion/charge-transfer sequence toward CO₂/H₂O, with thiophenic sulfur comparatively robust. We quantified surface functionalities (C–O 65.46%, O–C=O 24.51%, C=O 10.03%; pyrrolic/pyridinic N dominant; thiophenic-S with minor oxidized S) and determined a naphthalene-dominant, stacked-polyaromatic architecture with sparse alkyl side chains after Materials Studio optimization. The findings are significant for mechanistic understanding and control of coking-coal oxidation, providing actionable hotspots and a reproducible workflow (multi-probe constraints → model building/optimization → DFT reactivity mapping → spectral back-validation) for blend design and targeted oxidation-inhibition strategies. Full article

Background: Colorectal cancer (CRC), particularly the microsatellite-stable (MSS) subtype, remains largely unresponsive to immune checkpoint inhibitors (ICIs) due to immune escape, tumor-associated macrophage (TAM) enrichment, and cytokine-driven suppression that sustain a TAM-dominant tumor microenvironment (TME). To overcome these barriers, a pH-responsive solid lipid nanoparticle (SLN) system was engineered to co-deliver CB-5083 (a VCP/p97 inhibitor), miR-142 (a PD-L1-targeting microRNA), and imiquimod (R, a TLR7 agonist) for spatially confined induction of endoplasmic reticulum stress (ERS) and immune reprogramming in MSS CRC. Methods: The SLNs were coated with PEG–PGA for pH-triggered de-shielding and functionalized with PD-L1- and EGFR-binding peptides plus an ER-homing peptide, enabling tumor-selective and subcellular targeting. Results: The nanoplatform displayed acid-triggered PEG–PGA detachment, selective CRC/TAM uptake, and ER localization. CB-mediated VCP inhibition activated IRE1α/XBP1s/LC3II, PERK/eIF2α/ATF4/CHOP, and JNK/Beclin signaling, driving apoptosis and autophagy, while miR-142 suppressed PD-L1 expression and epithelial–mesenchymal transition markers. R facilitated dendritic cell maturation and M1 polarization. Combined CB + miR + R/SLN-CSW suppressed IL-17, G-CSF, and CXCL1, increased infiltration of CD4⁺ and CD8⁺ T cells, reduced Tregs and M2-TAMs, and inhibited tumor growth in CT-26 bearing mice. The treatment induced immunogenic cell death, reprogramming the TME into a T cell-permissive state and conferring resistance to tumor rechallenge. Biodistribution analysis confirmed tumor-preferential accumulation with minimal off-target exposure, and biosafety profiling demonstrated low systemic toxicity. Conclusions: This TME-responsive nanoplatform therefore integrates ERS induction, checkpoint modulation, and cytokine suppression to overcome immune exclusion in MSS CRC, representing a clinically translatable strategy for chemo-immunotherapy in immune-refractory tumors. Full article

Retinal degeneration (RD) is an intractable ophthalmic disorder with no effective treatments, and its pathogenesis is complex, involving multiple genes. Endoplasmic reticulum (ER) stress and neuronal apoptosis are key factors that drive neurodegeneration in retinal degeneration. B cell receptor-associated protein 31 (BAP31) is a transmembrane protein predominantly found in the ER, which plays an important role in regulating ER stress and apoptosis. To date, no studies have directly confirmed the association between BAP31 and retinal degenerative diseases. However, considering that ER dysfunction is a key trigger for retinal photoreceptor cell damage and that BAP31 acts as a core regulator of ER function, we hypothesize that BAP31 may be involved in the development of retinal degeneration by regulating ER homeostasis. Our study aimed to investigate the pathogenic mechanisms of BAP31 in retinal disorders. A rod-specific conditional knockdown of BAP31 mouse model (Rho-iCre-BAP31^fl/fl(−/−)) was employed to explore the role of BAP31 in retinal pathogenesis. The Rho-iCre-BAP31^fl/fl(−/−) mice exhibited phenotypes similar to retinitis pigmentosa (RP), including decreased ERG responses, photoreceptor degeneration, and reduced visual function. Optical coherence tomography (OCT) results showed that the outer nuclear layer (ONL) of the retina in conditional knockdown mice exhibited progressive thinning after 9 months of age; histopathological examination results were consistent with those of OCT. These findings indicated that the rod photoreceptor cells in the conditional knockdown mice showed damage and irregular arrangement starting at 9 months of age, with more prominent changes by 12 months. RNA sequence analysis of 12-month-old mice indicated enrichment of the phototransduction pathway, with significant downregulation of key genes (rhodopsin, recoverin, Gnat1, Pde6a, and Pde6b) involved in retinal development and phototransduction, along with a marked increase in Gfap expression (indicating glial activation and retinal damage). Quantitative real-time PCR and Western blot analyses showed significant upregulation of unfolded protein response (UPR) marker proteins (BIP, CHOP, XBP1, ATF4, ATF6), demonstrating robust ER stress activation. The findings suggest that BAP31 deficiency induces retinal degeneration, and the activation of the ER stress may contribute to the pathogenic mechanisms underlying this process. Full article

This review synthesizes current knowledge on the roles of X-box binding protein 1 (XBP1) in development and regenerative medicine. XBP1 is defined as a key transcription factor that regulates biological processes from embryogenesis to adult tissue homeostasis via both endoplasmic reticulum(ER) stress-dependent and independent mechanisms. Evidence for its regulatory role in cell fate determination and tissue maintenance across multiple systems is presented. The therapeutic potential of targeting XBP1 is explored, particularly for the regeneration of skeletal muscle, skin, and bone. Critical future research priorities are outlined, such as deciphering the precise functions of the Inositol requiring enzyme 1 (IRE1α)/XBP1 signaling axis and evaluating the long-term safety of its modulation. XBP1 is thus confirmed as a prime target for advancing developmental biology and pioneering new regenerative therapies. Full article

Background/Objective: Proteotoxic stress induced by inhibitors of the ubiquitin–proteasome system has been successful in multiple myeloma but not in solid cancers such as prostate cancer. Our objective is to find a combination with proteasome inhibitors that increases apoptotic cell death in all types of prostate cancer without harming non-cancer cells. Methods: The effectiveness of rencofilstat, a pan-cyclophilin inhibitor, combined with the ixazomib proteasome inhibitor, was investigated in multiple prostate cancer and non-cancer cells. Inducible knockdown of stress response XBP1s and cyclophilins A/B and inducible expression of XBP1s and cyclophilin B were developed in prostate cancer to determine functional roles. Results: Rencofilstat + ixazomib increased apoptotic cell death in prostate cancer but not in non-cancer cells. We investigated the effects on XBP1s and PERK, important unfolded protein response factors required for cells to survive proteotoxic stress. The results revealed that XBP1s had a pro-survival role early, but maintenance at later times of rencofilstat + ixazomib treatment resulted in cell death. In addition, decreased PERK and phospho-eIF2α likely maintained protein synthesis to further enhance proteotoxic stress. In contrast, rencofilstat + ixazomib did not alter XBP1s or PERK in non-cancer cells. Additional genetic experiments showed that the RCF targets cyclophilins A, B, and D had protective effects. Rencofilstat increased extracellular secretion of cyclophilin B, but rencofilstat + ixazomib reduced glycosylation and, likely, the biological function of CD147 (CypB receptor) and decreased downstream ERK signaling. Conclusions: Rencofilstat + ixazomib may be a new strategy for increasing proteotoxic stress and apoptotic cell death in advanced prostate cancer cells with less toxic side effects. Full article

Neutrophils are among the first cells to be recruited to the lungs during Chlamydia pneumoniae infection in mouse models; however, their regulatory functions are not yet fully understood. This study examined the mechanisms and significance of IL-10-producing neutrophils throughout C. pneumoniae pulmonary infection in C57BL/6 mice. Our findings revealed that infection with C. pneumoniae induces IL-10 secretion in bone marrow-derived neutrophils, depending on Toll-like receptor 2 (TLR2) activation. This process involves TLR2-dependent mitochondrial reactive oxygen species (ROS) production, which triggers the endoplasmic reticulum (ER) stress pathway, including IRE1α and subsequent Xbp1 splicing. Inhibition of this pathway or depletion of neutrophils (using the 1A8 monoclonal antibody) significantly reduces IL-10 levels in bronchoalveolar lavage fluid (BALF) in vivo. Conversely, the absence of IL-10-producing neutrophils, whether through depletion or TLR2 deficiency, leads to increased IL-12p70 and IFN-γ-positive NK cells, along with decreased regulatory T cells and M2-like macrophages. This results in a lower bacterial burden in the lungs but causes more severe pulmonary damage and decreased survival rates. These findings highlight that IL-10 produced by neutrophils via the TLR2-mitochondrial ROS–ER stress pathway is essential for modulating pulmonary immune responses and maintaining immune homeostasis during C. pneumoniae infection, thereby preventing excessive inflammation and tissue damage. Full article

Zika virus (ZIKV) can infect and replicate in the endoplasmic reticulum (ER) of different human cell types, including neural progenitor cells, radial glial cells, astrocytes, and microglia in the brain. ZIKV infection of microglia is expected to trigger both ER stress and the induction of an antiviral response through production of type-I interferons and pro-inflammatory cytokines, contributing to neuroinflammation during infection. Despite their critical role in ZIKV pathogenesis, the interplay between ER stress and the antiviral response during infection has not been fully characterized in human microglia. In this work, we show that infection of a human microglia cell line with ZIKV triggers the induction of an antiviral response and the activation of the endonuclease activity of the unfolded protein response sensor IRE1. Interestingly, we observed that both IRE1 and XBP1 were sequestered to the viral replication sites during infection. Moreover, pharmacological inhibition or hyperactivation of the endonuclease activity of IRE1 resulted in reduced viral titers. As such, while inhibition of IRE1 resulted in an increased type-I interferon response, hyperactivation led to a decrease in ZIKV RNA levels and the appearance of ER-derived cytoplasmic structures containing NS3, IRE1, and XBP1. Together, our data indicate that regulation of the endonuclease activity of IRE1 is critical for both ZIKV replication and immune activation, highlighting the potential of the ER stress sensor as a target for the development of antivirals to treat ZIKV infections. Full article

Background/Objectives: This study aimed to investigate the effects of long-term aerobic exercise on high-fat diet (HFD)-induced hepatic steatosis and its underlying enterohepatic communication mechanisms. Methods: C57BL/6J mice were divided into four groups: normal-diet with sedentary (ND-SED), normal-diet with exercise (ND-EXE), HFD with sedentary (HFD-SED), and HFD with exercise (HFD-EXE). After 16 weeks of HFD feeding, ND-EXE and HFD-EXE groups underwent an 8-week aerobic exercise intervention. Hepatic lipid accumulation was assessed via histology and triglyceride (TG) quantification. Liver function and glucose tolerance were evaluated. Gut microbiota composition (16S rRNA sequencing), hepatic bile acid profiles (LC-MS metabolomics), and gene expression were analyzed. Results: HFD induced hepatic steatosis, glucose intolerance, and liver injury in mice, all of which were ameliorated by exercise. Compared to HFD-SED mice, which exhibited impaired gut microbiota diversity, exercise restored key genera such as Faecalibaculum, and Turicibacter. Functional analysis revealed that exercise modulated microbiota shifts in lipid metabolism and secondary bile acid biosynthesis. HFD-EXE mice displayed altered hepatic bile acid composition, characterized by increased tauroursodeoxycholic acid (TUDCA) and reduced taurohyodeoxycholic acid (THDCA). Notably, TUDCA levels correlated with Turicibacter abundance, while deoxycholic acid (DCA) was associated with Faecalibaculum, independent of precursor availability. Exercise also suppressed hepatic endoplasmic reticulum (ER) stress and downregulated lipogenic genes via the inositol-requiring enzyme 1 alpha (IRE1α)- spliced X-box binding protein 1 (Xbp1s) pathway, while concurrently activating farnesoid X receptor (FXR) signaling to enhance fatty acid oxidation through the FXR-short heterodimer partner (SHP) related to hepatic secondary bile acid abundance change. Conclusions: The beneficial effect of long-term aerobic exercise on high-fat diet-induced hepatic steatosis in mice is potentially mediated through structural changes in the gut microbiota, which influence the abundance of hepatic secondary bile acids (TUDCA, DCA) and subsequently regulate the expression of genes involved in lipid metabolism. Full article

iPSCs and their derivatives are used to investigate the molecular genetic mechanisms of human diseases, to identify therapeutic targets, and to screen for small molecules. Combining technologies for generating patient-specific iPSC lines and genome editing allows us to create cell models with unique characteristics. We obtained and characterized three iPSC lines by reprogramming peripheral blood mononuclear cells of a patient with Huntington’s disease (HD) using episomal vectors encoding Yamanaka factors. iPSC lines expressed pluripotency marker genes, had normal karyotypes and were capable of differentiating into all three germ layers. The obtained iPSC lines are useful for modeling disease progression in vitro and studying pathological mechanisms of HD, such as ER stress. A transgene of genetically encoded biosensor XBP1-TagRFP was introduced into the iPSCs to visualize ER stress state of cells. The study demonstrated that iPSC-derived medium spiny neurons develop ER stress, though the IRE1-mediated pathway does not seem to be involved in the process. Full article

The progression of inflammation during sepsis represents a multifaceted biological cascade that requires effective therapeutic interventions to improve survival. In septic neonatal foals, oxidative stress (OS) arises due to a compromised antioxidant defense system. Oxidative stress may disrupt the functionality of redox-sensitive organelles, such as the endoplasmic reticulum (ER). Endoplasmic reticulum stress disorder affects multiple cellular signaling pathways, including redox balance, inflammation, and apoptosis, and contributes to the pathogenesis of sepsis. The study aimed to elucidate whether OS conditions in sepsis influenced gene expression associated with ER stress. Blood samples were collected from 7 healthy and 21 hospitalized neonatal foals and processed for RNA extraction. RNA sequencing was employed to identify ER stress-responsive genes. Novel findings reported here indicate activation of the ER stress pathway in foals with sepsis. Several genes associated with ER stress, such as clusterin (CLU), BCL2-like 1 (BCL2L1), ubiquitin specific peptidase 14 (USP14), bifunctional apoptosis regulator (BFAR), and optic atrophy 1 (OPA1), were upregulated and positively correlated with sepsis scores and negatively correlated with the combined activities of antioxidant enzymes. In contrast, X-box binding protein 1 (XBP1), homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1), leucine-rich repeat kinase 2 (LRRK2), and selenoprotein S (SELENOS) were negatively correlated with sepsis scores and were downregulated in sepsis and positively correlated with the combined activities of antioxidant enzymes. Furthermore, a positive correlation was observed between cAMP responsive element binding protein 3 like 2 (CREB3L2) and BCL2L1, as well as between the expressions of USP14 and YOD1 deubiquitinase (YOD1) in sepsis. Similarly, the expression levels of XBP1 and Herpud1 demonstrated a positive correlation with each other in sepsis. Additionally, the downregulation of genes with protective function against OS, such as XBP1, HERPUD1, and SELENOS, in septic foals also highlights their significance in mitigating OS in sepsis treatment. The study reported here highlights the potential of ER stress as a promising therapeutic target and prognostic marker in septic foals. Full article

Mycotoxins represent a group of highly toxic secondary metabolites produced by diverse fungal pathogens. Mycotoxin contaminations frequently occur in foods and feed and pose significant risks to human and animal health due to their carcinogenic, mutagenic, and immunosuppressive properties. Notably, deoxynivalenol, zearalenone, fumonisins (mainly including fumonisins B1, B2, and FB3), aflatoxin B1 (AFB1), and T-2/HT-2 toxins are the major mycotoxin contaminants in foods and feed. Undoubtedly, exposure to these mycotoxins can disrupt gut health, particularly damaging the intestinal epithelium in humans and animals. In this review, we summarized the detrimental effects caused by these mycotoxins on the intestinal health of humans and animals. The fundamental molecular mechanisms, which cover the induction of inflammatory reaction and immune dysfunction, the breakdown of the intestinal barrier, the triggering of oxidative stress, and the intestinal microbiota imbalance, were explored. These signaling pathways, such as MAPK, Akt/mTOR, TNF, TGF-β, Wnt/β-catenin, PKA, NF-kB, NLRP3, AHR, TLR2, TLR4, IRE1/XBP1, Nrf2, and MLCK pathways, are implicated. The abnormal expression of micro-RNA also plays a critical role. Finally, we anticipate that this review can offer new perspectives and theoretical foundations for controlling intestinal health issues caused by mycotoxin contamination and promote the development of prevention and control products. Full article