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20 pages, 1831 KiB  
Article
Saccharomyces boulardii CNCM I-745 Supernatant Improves Markers of Gut Barrier Function and Inflammatory Response in Small Intestinal Organoids
by Louisa Filipe Rosa, Steffen Gonda, Nadine Roese and Stephan C. Bischoff
Pharmaceuticals 2025, 18(8), 1167; https://doi.org/10.3390/ph18081167 - 6 Aug 2025
Abstract
Objectives: Saccharomyces boulardii CNCM I-745, a probiotic yeast, is effectively used for the treatment of acute diarrhea as well as for the prevention and treatment of traveller‘s diarrhea and diarrhea under tube feeding. The underlying mechanisms are not fully elucidated. Both antitoxic [...] Read more.
Objectives: Saccharomyces boulardii CNCM I-745, a probiotic yeast, is effectively used for the treatment of acute diarrhea as well as for the prevention and treatment of traveller‘s diarrhea and diarrhea under tube feeding. The underlying mechanisms are not fully elucidated. Both antitoxic and regulatory effects on the intestinal barrier, mediated either by the yeast or yeast-derived substrates, have been discussed. Methods: To examine the effects of Saccharomyces boulardii released substrates (S.b.S) on gastrointestinal (GI) barrier function, a murine small intestinal organoid cell model under stress was used. Stress was induced by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GFRed). Stressed organoids were treated with S.b.S (200 µg/mL), and markers of GI barrier and inflammatory response were assessed. Results: GFRed-induced stress was characterized by disturbances in selected tight junction (TJ) (p < 0.05), adherent junction (AJ) (p < 0.001), and mucin (Muc) formation (p < 0.01), measured by gene expressions, whereby additional S.b.S treatment was found to reverse these effects by increasing Muc2 (from 0.22 to 0.97-fold change, p < 0.05), Occludin (Ocln) (from 0.37 to 3.5-fold change, p < 0.0001), and Claudin (Cldn)7 expression (from 0.13 ± 0.066-fold change, p < 0.05) and by decreasing Muc1, Cldn2, Cldn5, and junctional adhesion molecule A (JAM-A) expression (all p < 0.01). Further, S.b.S normalized expression of nucleotide binding oligomerization domain (Nod)2- (from 44.5 to 0.51, p < 0.0001) and matrix metalloproteinase (Mmp)7-dependent activation (from 28.3 to 0.02875 ± 0.0044 ** p < 0.01) of antimicrobial peptide defense and reduced the expression of several inflammatory markers, such as myeloid differentiation primary response 88 (Myd88) (p < 0.01), tumor necrosis factor α (Tnfα) (p < 0.01), interleukin (IL)-6 (p < 0.01), and IL-1β (p < 0.001). Conclusions: Our data provide new insights into the molecular mechanisms by which Saccharomyces boulardii CNCM I-745-derived secretome attenuates inflammatory responses and restores GI barrier function in small intestinal organoids. Full article
(This article belongs to the Topic Probiotics: New Avenues)
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21 pages, 5034 KiB  
Article
The Activation of the Microglial NLRP3 Inflammasome Is Involved in Tuberous Sclerosis Complex-Related Neuroinflammation
by Ran Ding, Shengxuan Zhang, Linxue Meng, Lingman Wang, Ziyao Han, Jianxiong Gui, Jiaxin Yang, Li Cheng, Lingling Xie and Li Jiang
Int. J. Mol. Sci. 2025, 26(15), 7244; https://doi.org/10.3390/ijms26157244 - 26 Jul 2025
Viewed by 375
Abstract
Tuberous sclerosis complex (TSC) is a systemic disease caused by mutations in either the TSC1 (encoding hamartin) or TSC2 (encoding tuberin) gene, with mutations in the TSC2 gene potentially leading to more severe clinical symptoms. Neurological symptoms are a common clinical manifestation of [...] Read more.
Tuberous sclerosis complex (TSC) is a systemic disease caused by mutations in either the TSC1 (encoding hamartin) or TSC2 (encoding tuberin) gene, with mutations in the TSC2 gene potentially leading to more severe clinical symptoms. Neurological symptoms are a common clinical manifestation of TSC, and neuroinflammation is thought to play an important role. Glial cells are a major source of neuroinflammation, but whether microglia are involved in the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the expression of interleukin-1β (IL-1β) in TSC patients remains unclear. We used a transcriptome sequencing dataset for bioinformatics analysis to explore the differences in the expression of microglial inflammasome-associated hub genes. TSC2 knockdown (TSC2 KD) microglia (HMC3 cell line) were generated by lentivirus, and the expression of inflammasome-associated hub genes, microglial activation, and NLRP3 inflammasome activation were verified. In addition, experiments were performed to explore the regulatory effects of rapamycin. Bioinformatics analysis identified a total of eight inflammasome-associated hub genes. By detecting GFP fluorescence, TSC2 mRNA, TSC2 protein expression, and the phosphorylation of the mammalian target of rapamycin (p-mTOR)/mTOR, we confirmed that the TSC2 KD microglia model was successfully established. Compared with the control group, the TSC2 KD group presented higher mRNA levels and fluorescence intensities of microglia AIF1 and CD68, as well as greater reactive oxygen species (ROS) production. Eight inflammasome-associated hub gene mRNA assays revealed that the expression of the NLRP3 and IL1B genes was increased. Compared with the control group, the TSC2 KD group presented increased levels of NLRP3 and Pro-IL-1β proteins in cells and Cleaved-Caspase 1 and Cleaved-IL-1β proteins in the supernatant, suggesting NLRP3 inflammasome activation. Rapamycin intervention alleviated these changes, demonstrating that the TSC2 gene regulation of microglial activation and NLRP3 inflammasome activation are correlated with mTOR phosphorylation. In conclusion, microglia are activated in TSC patients and participate in the NLRP3 inflammasome-associated neuroinflammatory response, and rapamycin treatment can alleviate these changes. Full article
(This article belongs to the Section Molecular Neurobiology)
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25 pages, 3057 KiB  
Article
Phylogenetic Diversity and Symbiotic Effectiveness of Bradyrhizobium Strains Nodulating Glycine max in Côte d’Ivoire
by Marie Ange Akaffou, Romain Kouakou Fossou, Anicet Ediman Théodore Ebou, Zaka Ghislaine Claude Kouadjo-Zézé, Chiguié Estelle Raïssa-Emma Amon, Clémence Chaintreuil, Saliou Fall and Adolphe Zézé
Agronomy 2025, 15(7), 1720; https://doi.org/10.3390/agronomy15071720 - 17 Jul 2025
Viewed by 576
Abstract
Soybean (Glycine max) is a protein-rich legume crop that plays an important role in achieving food security. The aim of this study was to isolate soybean-nodulating rhizobia from Côte d’Ivoire soils and evaluate their potential as efficient strains in order to [...] Read more.
Soybean (Glycine max) is a protein-rich legume crop that plays an important role in achieving food security. The aim of this study was to isolate soybean-nodulating rhizobia from Côte d’Ivoire soils and evaluate their potential as efficient strains in order to develop local bioinoculants. For this objective, 38 composite soil samples were collected from Côte d’Ivoire’s five major climatic zones. These soils were used as substrate to trap the nodulating rhizobia using the promiscuous soybean variety R2-231. A total of 110 bacterial strains were isolated and subsequently identified. The analysis of ITS (rDNA16S-23S), glnII and recA sequences revealed a relatively low genetic diversity of these native rhizobia. Moreover, the ITS phylogeny showed that these were scattered into two Bradyrhizobium clades dominated by the B. elkanii supergroup, with ca. 75% of all isolates. Concatenated glnII-recA sequence phylogeny confirmed that the isolates belong in the majority to ‘B. brasilense’, together with B. vignae and some putative genospecies of Bradyrhizobium that needs further elucidation. The core gene phylogeny was found to be incongruent with nodC and nifH phylogenies, probably due to lateral gene transfer influence on the symbiotic genes. The diversity and composition of the Bradyrhizobium species varied significantly among different sampling sites, and the key explanatory variables identified were carbon (C), magnesium (Mg), nitrogen (N), pH, and annual precipitation. Based on both shoot biomass and leaf relative chlorophyll content, three isolates consistently showed a higher symbiotic effectiveness than the exotic inoculant strain Bradyrhizobium IRAT-FA3, demonstrating their potential to serve as indigenous elite strains as bioinoculants. Full article
(This article belongs to the Section Agricultural Biosystem and Biological Engineering)
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14 pages, 474 KiB  
Article
Calcium Metabolism, Immunity and Reproduction in Early Postpartum Dairy Cows
by Szilvia Kusza, Zoltán Bagi, Putri Kusuma Astuti, George Wanjala, Ottó Szenci and Árpád Csaba Bajcsy
Animals 2025, 15(14), 2103; https://doi.org/10.3390/ani15142103 - 16 Jul 2025
Viewed by 331
Abstract
Vitamin D is essential for calcium homeostasis, bone mineralization, immunity, and disease prevention. In a field study with Holstein-Friesian dairy cows, the impact of prepartum vitamin D3 treatment on early postpartum placental gene expression, focusing on calcium metabolism, feto-placental growth, and immune [...] Read more.
Vitamin D is essential for calcium homeostasis, bone mineralization, immunity, and disease prevention. In a field study with Holstein-Friesian dairy cows, the impact of prepartum vitamin D3 treatment on early postpartum placental gene expression, focusing on calcium metabolism, feto-placental growth, and immune response, had been investigated. Eight multiparous cows were treated with 10 mL vitamin D3 (1 million IU cholecalciferol/mL) intramuscularly on day 273 of pregnancy, while eight others remained untreated and served as controls. Placental tissues were collected post-calving, and gene expression was analyzed using quantitative real-time PCR. Among 23 genes, 5 showed significant downregulation in the treated group: CaBP-9k (reduced by 88.1% from 32.80 ± 91.50 to 3.90 ± 8.54), ESR1 (reduced by 95.7% from 7.89 ± 17.87 to 0.34 ± 0.34), LHR (reduced by 96.5% from 3.75 ± 5.45 to 0.13 ± 0.17), NOD1 (reduced by 94.1% from 4.21 ± 7.00 to 0.25 ± 0.30), and TLR1 (reduced by 99.7% from 24.80 ± 61.45 to 0.07 ± 0.08). These results suggest that vitamin D3 supplementation affects key pathways related to calcium transport, reproductive function, and immune response in the bovine placenta. These molecular changes may help to explain improved calcium homeostasis and reduced postpartum complications, offering insights into how targeted nutritional interventions can enhance reproductive efficiency in high-producing dairy cows. Full article
(This article belongs to the Special Issue Advances in Cattle Genetics and Breeding)
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15 pages, 1833 KiB  
Article
Comparative Analysis of Gut Microbiota Responses to New SN-38 Derivatives, Irinotecan, and FOLFOX in Mice Bearing Colorectal Cancer Patient-Derived Xenografts
by Katarzyna Unrug-Bielawska, Zuzanna Sandowska-Markiewicz, Magdalena Piątkowska, Paweł Czarnowski, Krzysztof Goryca, Natalia Zeber-Lubecka, Michalina Dąbrowska, Ewelina Kaniuga, Magdalena Cybulska-Lubak, Aneta Bałabas, Małgorzata Statkiewicz, Izabela Rumieńczyk, Kazimiera Pyśniak, Michał Mikula and Jerzy Ostrowski
Cancers 2025, 17(13), 2263; https://doi.org/10.3390/cancers17132263 - 7 Jul 2025
Viewed by 477
Abstract
Background: Symbiotic gut microbiota can enhance cancer therapy efficacy, while treatment-induced dysbiosis may reduce effectiveness or increase toxicity. Our preclinical study compared the anticancer effects and impact on fecal microbiota and metabolites of two water-soluble SN-38 derivatives (BN-MePPR and BN-MOA), with those observed [...] Read more.
Background: Symbiotic gut microbiota can enhance cancer therapy efficacy, while treatment-induced dysbiosis may reduce effectiveness or increase toxicity. Our preclinical study compared the anticancer effects and impact on fecal microbiota and metabolites of two water-soluble SN-38 derivatives (BN-MePPR and BN-MOA), with those observed after treatment with Irinotecan, and the FOLFOX regimen in NOD scid gamma mice bearing patient-derived colon adenocarcinoma xenografts (CRC PDX). Methods: Five individual experiments with Irinotecan and its derivatives and eight individual experiments with FOLFOX were conducted using eight CRC PDX models. Chemotherapeutics were administered intraperitoneally 4–5 times at 5-day intervals. Fecal samples were collected before and after treatment. Microbiota composition was analyzed by 16S rRNA gene (V3–V4 regions) sequencing. Mass spectrometry was used to quantify short-chain fatty acids (SCFAs) and amino acids (AAs). Results: All treatments significantly inhibited tumor growth versus controls. However, no significant changes were observed in gut microbiota α- and β-diversity between treated and untreated groups. Tumor progression in controls was associated with increased abundance of Marvinbryantia, Lactobacillus, Ruminococcus, and [Eubacterium] nodatum group. FOLFOX-treated mice showed increased Marvinbryantia, Bacteroides, and Candidatus Arthromitus, and decreased Akkermansia. No distinct taxa changes were found in the Irinotecan or derivative groups. SCFA levels remained unchanged across groups, while BN-MePPR, BN-MOA, and Irinotecan all increased AA concentrations. Conclusions: Contrary to earlier toxicological data, these findings indicate a relatively limited impact of the tested chemotherapeutics on the gut microbiome and metabolome, emphasizing the importance of research method selection in preclinical studies. Full article
(This article belongs to the Section Cancer Therapy)
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13 pages, 1208 KiB  
Article
Acaricidal Activity of Biosurfactants Produced by Serratia ureilytica on Tetranychus urticae and Their Compatibility with the Predatory Mite Amblyseius swirskii
by Arnoldo Wong-Villareal, Esaú Ruiz-Sánchez, Marcos Cua-Basulto, Saúl Espinosa-Zaragoza, Avel A. González-Sánchez, Ernesto Ramos-Carbajal, Cristian Góngora-Gamboa, René Garruña-Hernández, Rodrigo Romero-Tirado, Guillermo Moreno-Basurto and Erika P. Pinson-Rincón
Microbiol. Res. 2025, 16(7), 150; https://doi.org/10.3390/microbiolres16070150 - 4 Jul 2025
Viewed by 346
Abstract
This study evaluated the acaricidal effects of biosurfactants produced by Serratia ureilytica against the two-spotted spider mite Tetranychus urticae and their compatibility with the predatory mite Ambliseus swirski. The biosurfactants were obtained via liquid cultures of the bacterial strains. In the laboratory, [...] Read more.
This study evaluated the acaricidal effects of biosurfactants produced by Serratia ureilytica against the two-spotted spider mite Tetranychus urticae and their compatibility with the predatory mite Ambliseus swirski. The biosurfactants were obtained via liquid cultures of the bacterial strains. In the laboratory, T. urticae was exposed via acaricide-immersed leaves and A. swirskii via acaricide-coated glass vials. In the greenhouse, mite-infested plants were sprayed with the biosurfactants. In the laboratory, biosurfactants produced by S. ureilytica NOD-3 and UTS exhibited strong acaricidal activity, causing 95% mortality in adults and reducing egg viability by more than 60%. In the greenhouse trial, all biosurfactants significantly suppressed T. urticae populations at all evaluated periods (7, 14, and 21 days post-application). Gas chromatography–mass spectrometry (GC-MS) analysis of the biosurfactants identified several fatty acids, including hexadecanoic acid, pentanoic acid, octadecanoic acid, decanoic acid, and tetradecanoic acid, as well as the amino acids L-proline, L-lysine, L-valine, and glutamic acid. These fatty acids and amino acids are known structural components of lipopeptides. Furthermore, the bioinformatic analysis of the genomes of the three S. ureilytica strains revealed nonribosomal peptide synthetase (NRPS) gene clusters homologous to those involved in the biosynthesis of lipopeptides. These findings demonstrate that S. ureilytica biosurfactants are promising eco-friendly acaricides, reducing T. urticae populations by >95% while partially sparing A. swirskii. Full article
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20 pages, 550 KiB  
Review
Molecular Mechanisms Underlying Root Nodule Formation and Activity
by Katarzyna Nuc and Przemysław Olejnik
Agronomy 2025, 15(7), 1552; https://doi.org/10.3390/agronomy15071552 - 26 Jun 2025
Viewed by 624
Abstract
Symbiotic interactions between legumes and a group of soil bacteria, known as rhizobia, lead to the formation of a specialized organs called root nodules. Inside them, atmospheric nitrogen (N2) is fixed by bacteria and reduced to forms available to plants, catalyzed [...] Read more.
Symbiotic interactions between legumes and a group of soil bacteria, known as rhizobia, lead to the formation of a specialized organs called root nodules. Inside them, atmospheric nitrogen (N2) is fixed by bacteria and reduced to forms available to plants, catalyzed by the nitrogenase enzyme complex. The development of a symbiotic relationship between legumes and nodule bacteria is a multi-stage, precisely regulated process, characterized by a high specificity of partner selection. Nodulation involves the enhanced expression of certain plant genes, referred to as early- and late-nodulin genes. Many nodulin genes encode hydroxyproline-rich glycoproteins (HRGPs) and proline-rich proteins (PRPs) which are involved in various processes, including infection thread formation, cell signaling, and defense responses, thereby affecting nodule formation and function. Cyclophilins (CyPs) belong to a family of proteins with peptidyl-prolyl cistrans isomerase activity. Proteins with cyclophilin domain can be found in the cytoplasm, endoplasmic reticulum, nucleus, chloroplast, and mitochondrion. They are involved in various processes, such as protein folding, cellular signaling, mRNA maturation, and response to biotic and abiotic stress. In this review, we aim to summarize the molecular processes involved in the development of symbiosis and highlight the potential role of cyclophilins (peptidyl-prolyl cis-trans isomerases) in this process. Full article
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14 pages, 2425 KiB  
Article
Unique Function in Cancer Stemness and Prognostic Significance of EMX2 in Esophageal Squamous Cell Carcinoma
by Shoichi Fumoto, Keiji Tanimoto, Takuya Noguchi, Jun Hihara, Eiso Hiyama, Keiko Otani, Megu Ohtaki, Yutaka Shimada, Masahiko Nishiyama and Keiko Hiyama
Biomedicines 2025, 13(6), 1373; https://doi.org/10.3390/biomedicines13061373 - 4 Jun 2025
Viewed by 612
Abstract
Background/Objective: The Empty Spiracles Homeobox 2 (EMX2) gene is a homeobox transcription factor that is critical for the development of the central nervous system and genitourinary system during embryogenesis. EMX2 has been shown to regulate cellular differentiation, migration, and proliferation through its involvement [...] Read more.
Background/Objective: The Empty Spiracles Homeobox 2 (EMX2) gene is a homeobox transcription factor that is critical for the development of the central nervous system and genitourinary system during embryogenesis. EMX2 has been shown to regulate cellular differentiation, migration, and proliferation through its involvement in transcriptional control. Dysregulation of EMX2 expression has been implicated in various pathological conditions, including cancer, but the precise molecular mechanisms underlying EMX2 functions in cancer remain incompletely understood. In this study, we focus on the expression profile and the prognostic significance of EMX2 in esophageal squamous cell carcinoma (ESCC). Methods/Results: The expression levels of EMX2 in clinical ESCC samples varied and appeared to be lower than those in adjacent normal tissues. In addition, EMX2 expression was detected in some of the 20 ESCC cell lines but not in others and was correlated with 5-FU sensitivity. EMX2 expression in ESCC cell lines was strongly associated with colony formation capacity in soft agar, and EMX2 knockdown decreased colony formation. Enforced expression of EMX2 decreased the side population (SP) ratio in FACS analysis but increased colony formation in SP fractions. Although it is a preliminary experiment, xenograft in immunodeficient (NOD) scid mice suggested that the forced expression of EMX2 increased tumorigenic capacity in vivo. A Kaplan–Meyer analysis of patients from whom 20 ESCC cell lines or 18 ESCC tissue samples were obtained indicated that EMX2 expression was a poor prognostic marker. Conclusion: EMX2 has a unique function in ESCC stemness and its expression is the stamped marker of poor prognosis in ESCC patients. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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15 pages, 293 KiB  
Article
Clinical and Genetic Characteristics of Pediatric Patients with Inflammatory Bowel Disease Transitioning to Adult Medicine: A Single-Center Ten-Year Experience
by Giammarco Mocci, Giorgia Orrù, Francesca Maria Onidi, Mara Corpino, Antonella Marongiu, Giovanni Maria Argiolas, Matteo Runfola, Romina Manunza, Giorgia Locci, Elisabetta Tamponi, Teresa Zolfino, Paolo Usai Satta, Alessandro Muscas, Rossano Rossino, Salvatore Savasta and Mauro Congia
J. Clin. Med. 2025, 14(11), 3741; https://doi.org/10.3390/jcm14113741 - 27 May 2025
Viewed by 628
Abstract
Background/Objectives: Inflammatory bowel diseases (IBDs) comprise a group of chronic idiopathic disorders, including ulcerative colitis (UC), Crohn’s disease (CD), and indeterminate colitis (IC). Complex genetic factors, in addition to environmental triggers, have been shown to play a fundamental role in the pathogenesis [...] Read more.
Background/Objectives: Inflammatory bowel diseases (IBDs) comprise a group of chronic idiopathic disorders, including ulcerative colitis (UC), Crohn’s disease (CD), and indeterminate colitis (IC). Complex genetic factors, in addition to environmental triggers, have been shown to play a fundamental role in the pathogenesis of IBD, contributing to disease susceptibility. The transition of adolescents with inflammatory bowel disease (IBD) to adult care represents a significant challenge for patients, their families, and healthcare providers. Approximately 25% of individuals with IBD receive a diagnosis before the age of 16, and this population is at increased risk for adverse clinical outcomes. As a result, the transition of care has garnered substantial attention in the scientific and clinical communities over the past decade. This study aims to analyze a cohort of pediatric Sardinian patients with IBD to assess clinical characteristics at diagnosis and at the time of transition and determine potential correlations between NOD2/CARD15 gene variants and HLA class II with the disease phenotype. Methods: From January 2014 to August 2024, we performed an observational, cross-sectional study that included pediatric patients with IBD enrolled in the only pediatric IBD reference center in Sardinia. Data were obtained from the patients’ medical records and from a questionnaire administered at the inclusion visit. In addition, we genotyped a portion of our cohort for the Leu1007fsinsC (SNP13), Gly908Arg (SNP12), and Arg702Trp (SNP8) variants of the NOD2/CARD15 gene, as well as for HLA-DRB1, -DQA1, and -DQB1 class II genes. The obtained results were compared with pediatric data from the national epidemiological IBD registry and existing literature. Results: Seventy-one IBD patients were enrolled (UC 43, CD 28, M 34, F 37). Median age at diagnosis was 12.2 years (IQR 2–17). After a median disease duration of 5 years (IQR: 1–16), only three UC patients experienced proximal extension of proctitis or left-sided colitis, and no CD patients experienced new localizations of disease. Fifteen patients developed extraintestinal manifestations. No significant difference was found in median diagnostic delay (DD) between UC [4 months (IQR: 1–84)] and CD patients [4.5 months (IQR: 1–48)]. At the transition visit, overall, twenty-nine patients (42%) were exposed to one biologic agent (vs. 3% at baseline; p < 0.02); 3 patients (4%) were exposed to two or more biologic agents. 7% of patients (5/71) underwent surgery. By comparing the distribution of NOD2/CARD15 SNPs between pediatric patients and an adult CD population, we found a significant association between gene allelic variants and pediatric onset (p = 0.00048). Our study also revealed a statistically significant association between Sardinian pediatric patients carrying NOD2/CARD15 mutations and early-onset CD (p < 0.009492), along with a stenosing phenotype (p < 0.024) and increased surgical risk (p < 0.026). No significant associations were observed between HLA class II alleles and IBD in our population. Conclusions: Our results provide important insights into the clinical and epidemiological features of the pediatric IBD population. In addition, our study highlights the significant role of NOD2/CARD15 gene polymorphisms in pediatric onset CD. These variants influence the age of onset and disease phenotype, characterized by greater severity and a higher risk of surgical intervention in pediatric patients. Full article
16 pages, 1455 KiB  
Article
Multimorbidity Through the Lens of the Eye: Pathogenic Variants for Multiple Systemic Disorders Found in an Autosomal Dominant Congenital Cataract Cohort
by Vanita Berry, Manav B. Ponnekanti, Nancy Aychoua, Alex Ionides, Chrysanthi Tsika, Roy A. Quinlan and Michel Michaelides
Genes 2025, 16(5), 604; https://doi.org/10.3390/genes16050604 - 20 May 2025
Viewed by 621
Abstract
Background: This paper will identify the potential genetic causes of multimorbidity associated with autosomal dominant congenital cataract (ADCC). Methods: Whole exome sequencing (WES) was performed on 13 individuals affected with ADCC. Subsequent bioinformatic analyses identified variants with deleterious pathogenicity scores. Results: Disease-causing variants [...] Read more.
Background: This paper will identify the potential genetic causes of multimorbidity associated with autosomal dominant congenital cataract (ADCC). Methods: Whole exome sequencing (WES) was performed on 13 individuals affected with ADCC. Subsequent bioinformatic analyses identified variants with deleterious pathogenicity scores. Results: Disease-causing variants were identified in 8 genes already linked to cataract (CHMP4B, CRYAA, CRYBA1, CRYGD, CYP21A2, GJA8, OPA1, and POMGNT1), but variants previously associated with systemic disorders were also found in a further 11 genes (ACTL9, ALDH18A1, CBS, COL4A3, GALT, LRP5, NOD2, PCK2, POMT2, RSPH4A, and SMO). All variants were identified via pipeline data analysis, prioritising rare coding variants using Kaviar and the Genome Aggregation Database. The following ADCC-associated non-ocular phenotypes were identified in four patients in the cohort: (i) Horner’s pupils, vaso-vagal syncope, and paroxysmal orthostatic tachycardia syndrome; (ii) reduced kidney function and high cholesterol; (iii) hypertension, high cholesterol, and kidney stones; and (iv) grade 1 spondylolysis. Conclusions: We report 11 novel genes identified in an ADCC patient cohort associated with systemic disorders found, along with 8 known cataract-causing genes. Our findings broaden the spectrum of potentially cataract-associated genes and their related lens phenotypes, as well as evidence multimorbidities in four patients, highlighting the importance of careful multisystem phenotyping following genetic analysis. Full article
(This article belongs to the Special Issue Advances in Medical Genetics)
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20 pages, 12812 KiB  
Article
Quantitative Proteomics Revealed the Molecular Regulatory Network of Lysine and the Effects of Lysine Supplementation on Sunit Skeletal Muscle Satellite Cells
by Mingxu Wang, Fan Bai, Qinan Zhao, Jianan Shi, Yutian Hao and Jindi Wu
Animals 2025, 15(10), 1425; https://doi.org/10.3390/ani15101425 - 14 May 2025
Viewed by 489
Abstract
Stimulating skeletal muscle satellite cells (SMSCs) with amino acids improves their proliferation and differentiation, enhancing skeletal muscle mass, thereby increasing lean meat rate. This study explored lysine (Lys)’s effects on SMSCs and their protein profiles in Sunit sheep. SMSCs were successfully isolated, assessing [...] Read more.
Stimulating skeletal muscle satellite cells (SMSCs) with amino acids improves their proliferation and differentiation, enhancing skeletal muscle mass, thereby increasing lean meat rate. This study explored lysine (Lys)’s effects on SMSCs and their protein profiles in Sunit sheep. SMSCs were successfully isolated, assessing their survival and proliferation after Lys stimulation at varying concentrations using the CCK-8 assay. Western blotting revealed Lys-induced changes in myogenic differentiation protein expression, while immunocytochemistry detected α-Actinin and Myostatin within the SMSCs. TMT proteomics identified differentially expressed proteins, which underwent functional and interaction analyses, with RT-qPCR validating the corresponding gene expression. This study revealed that 4 mmol/L of Lys significantly boosted SMSC proliferation. A 24 h stimulation with this concentration reduced Myostatin expression, and increased MYOD1 and α-Actinin levels in the SMSCs. A proteomic analysis identified 577 differentially expressed proteins, primarily associated with lipoblast differentiation and muscle development, as highlighted by the GO enrichment analysis. A pathway analysis further demonstrated these proteins’ involvement in the autophagy–lysosome and NOD-like receptor signaling pathways. Lys enhances SMSC proliferation, differentiation, and adipogenesis in Sunit sheep, exhibiting antioxidant properties and supporting muscle stability and amino acid metabolism. It may also have anti-inflammatory, anti-pyroptotic, and proteolysis-inhibitory effects, offering insights into muscle growth mechanisms through amino acid supplementation in ruminants. Full article
(This article belongs to the Section Animal Physiology)
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23 pages, 7907 KiB  
Article
Exploring the Mechanism of Luteolin in Protecting Chickens from Ammonia Poisoning Based on Proteomic Technology
by Yu Jin, Azi Shama, Haojinming Tang, Ting Zhao, Xinyu Zhang, Falong Yang and Dechun Chen
Metabolites 2025, 15(5), 326; https://doi.org/10.3390/metabo15050326 - 14 May 2025
Viewed by 539
Abstract
Background: Ammonia (NH3), a harmful gas, reduces livestock productivity, threatens their health, and causes economic losses. Luteolin (Lut), an anti-inflammatory flavonoid, may counteract these effects. Methods: Our study explored luteolin’s protective mechanisms on chicken splenic lymphocytes under ammonia stress using a [...] Read more.
Background: Ammonia (NH3), a harmful gas, reduces livestock productivity, threatens their health, and causes economic losses. Luteolin (Lut), an anti-inflammatory flavonoid, may counteract these effects. Methods: Our study explored luteolin’s protective mechanisms on chicken splenic lymphocytes under ammonia stress using a simulation model and four-dimensional fast data-independent acquisition (4D-FastDIA) proteomics. We identified 316 proteins, with 69 related to ammonia’s negative effects and 247 to Lut’s protection. Thirty differentially expressed proteins (DEPs) were common to both groups, with 27 showing counter-regulation with Lut. Results: Gene Ontology (GO) analysis showed DEPs enriched in molecular responses to interferons and the negative regulation of immune responses, mainly located extracellularly. Molecular function analysis revealed DEPs in antigen binding and synthase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis linked DEPs to pathways like estrogen signaling, NOD-like receptor signaling, cytokine–cytokine receptor interaction, and JAK-STAT signaling. The quantitative real-time polymerase chain reaction (qRT-PCR) results indicated that the mRNA levels of Interferon Alpha and Beta Receptor subunit 2 (IFNAR2) and Signal Transducer and Activator of Transcription 1 (STAT1) were trending downward. This observation was in strong agreement with the downregulation noted in the proteomics analysis. Conclusions: Lut’s protective role against ammonia’s adverse effects on chicken splenic lymphocytes is linked to the modulation of key signaling pathways, offering insights for further research on treating ammonia exposure with Lut. Full article
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13 pages, 3254 KiB  
Article
Association Analysis of SLC11A1 Polymorphisms with Somatic Cell Score in Chinese Holstein Cows
by Kai Liu, Yufang Liu, Tuo Li, Qiuling Li, Jinyu Wang, Yongfu An, Yuze Yang, Kaiyang Li and Mingxing Chu
Animals 2025, 15(10), 1370; https://doi.org/10.3390/ani15101370 - 9 May 2025
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Abstract
Mastitis is an important disease limiting milk production in dairy cows. Somatic cell score is commonly used as one of the main ways to gauge the level of mastitis in dairy cows, with higher somatic cell scores usually indicating possible mastitis. However, the [...] Read more.
Mastitis is an important disease limiting milk production in dairy cows. Somatic cell score is commonly used as one of the main ways to gauge the level of mastitis in dairy cows, with higher somatic cell scores usually indicating possible mastitis. However, the main molecular markers affecting somatic cell scores remain unknown. The aim of this study was to investigate the association between single nucleotide polymorphisms in the SLC11A1 gene and somatic cell score in Chinese Holstein cows. In this study, 210 Chinese Holstein cows were genotyped and potential SNPs were detected by DNA sequencing, PCR-SSCP and PCR-RFLP analysis. Our results revealed two SNPs were identified in the CDS region of SLC11A1: c.723C>T and c.1144C>G. For the c.723C>T polymorphic site, two genotypes (AA, AB) were found and the genotype frequencies were 0.790 and 0.210, respectively. The results of the association analysis showed that the mean somatic cell score of the AA genotypes were significantly lower than those of the AB genotypes, suggesting that the A allele is a potential marker for improving mastitis resistance in Chinese Holstein cows. For the c.1144C>G polymorphic site, three genotypes (CC, CD, and DD) were found and the genotype frequencies were 0.629, 0.352 and 0.019, respectively. The association analysis revealed that the mean somatic cell score of CC genotypes was lower than that of CD and DD genotypes, however, no significant differences were observed among the various genotype groups when subjected to pair-wise comparisons. The bioinformatic analysis showed that these mutations affected the secondary and tertiary structure of SLC11A1 mRNA, suggesting that they may affect gene expression or protein translation and function. Finally, we predicted the SLC11A1 protein interaction network and found that SPI1, NOD2, TLR2 and S100A12 interacted with SLC11A1 and were reported as candidate genes associated with mastitis resistance. The results indicated that the SNP (c.723C>T) could be potential molecular marker for improving mastitis resistance traits in Chinese Holstein cows. We recommend further validation of this SNP in larger populations and its potential integration into breeding programs to enhance mastitis resistance in dairy cows. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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17 pages, 9850 KiB  
Article
m6A Methylation Mediated Autophagy and Nucleotide-Binding Oligomerization Domain-like Receptors Signaling Pathway Provides New Insight into the Mitigation of Oxidative Damage by Mulberry Leaf Polysaccharides
by Wenqiang Jiang, Yan Lin, Linjie Qian, Siyue Lu, Zhengyan Gu, Xianping Ge and Linghong Miao
Int. J. Mol. Sci. 2025, 26(9), 4345; https://doi.org/10.3390/ijms26094345 - 2 May 2025
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Abstract
m6A methylation modification is an important genetic modification involved in biological processes such as sexual maturation, antibacterial, and antiviral in aquatic animals. However, few studies have been conducted in aquatic animals on the relationship between m6A methylation modification and [...] Read more.
m6A methylation modification is an important genetic modification involved in biological processes such as sexual maturation, antibacterial, and antiviral in aquatic animals. However, few studies have been conducted in aquatic animals on the relationship between m6A methylation modification and autophagy-inflammation induced by lipid metabolism disorders. In the present study, a high-fat (HF) group and HF-MLP group (1 g mulberry leaf polysaccharides (MLPs)/1 kg HF diet) were set up. The mid-hind intestines of Megalobrama amblycephala juveniles from the two groups were collected for MeRIP-seq and RNA-seq after an 8-week feeding trial. The m6A peaks in the HF and HF-MLP groups were mainly enriched in the 3′ Untranslated Region (3′UTR), Stop codon, and coding sequence (CDS) region. Compared with the HF group, the m6A peaks in the HF-MLP group were shifted toward the 5′UTR region. ‘RRACH’ was the common m6A methylation motif in the HF and HF-MLP groups. Methyltransferase mettl14 and wtap expression in the intestines of the HF-MLP group were significantly higher compared with the HF group (p < 0.05). A total of 21 differentially expressed genes(DEGs) with different peaks were screened by the combined MeRIP-seq and RNA-seq analysis. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis enriched BCL2 interacting protein 3 (bnip3) to autophagy–animal and mitophagy–animal signaling pathways, etc., and nucleotide-binding domain leucine-rich repeat protein 1 (nlrp1) was enriched to the Nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway. Combined MeRIP-seq and RNA-seq analysis indicated that the expression pattern of bnip3 was hyper-up and that of nlrp1 was hyper-down. Gene Set Enrichment Analysis (GSEA) analysis confirmed that the intestinal genes of HF-MLP group positively regulate lysosomal and autophagy–animal signaling pathways. In the present study, we demonstrated that m6A methylation modification plays a role in regulating autophagy-inflammatory responses induced by HF diets by MLPs, and further explored the molecular mechanisms by which MLPs work from the epigenetic perspective. Full article
(This article belongs to the Special Issue Fish Nutrition Program and Epigenetic Regulation)
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19 pages, 3466 KiB  
Article
Tannic Acid and Ethacridine Lactate Attenuate Markers of Stress-Induced Intestinal Barrier Dysfunctions in Murine Small Intestinal Organoids
by Louisa Filipe Rosa, Steffen Gonda, Nadine Roese and Stephan C. Bischoff
Biomolecules 2025, 15(5), 650; https://doi.org/10.3390/biom15050650 - 30 Apr 2025
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Abstract
(1) Background: Tannacomp® is a drug consisting of tannin albuminate, a complex of tannic acid (TA) and ethacridine lactate (Eta) used for treating acute and traveler’s diarrhea. TA is thought to modulate gastrointestinal barrier function, but the underlying mechanisms and whether Eta [...] Read more.
(1) Background: Tannacomp® is a drug consisting of tannin albuminate, a complex of tannic acid (TA) and ethacridine lactate (Eta) used for treating acute and traveler’s diarrhea. TA is thought to modulate gastrointestinal barrier function, but the underlying mechanisms and whether Eta has similar effects remains unclear. (2) Methods: to investigate the effects of TA and Eta on the intestinal barrier, stress responses were induced in murine intestinal organoids by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GFRed). Further, organoids were exposed to either TA (0.01 mg/mL) or Eta (0.002 mg/mL) and markers of inflammatory response and gut barrier function were assessed. (3) Results: TA and Eta reduced several inflammatory markers such as interleukin 6, interleukin 1β, tumor necrosis factor α, and myeloid differentiation primary response 88 in stressed organoids. In addition, TA and Eta attenuated LPS- and GFRed-mediated gut barrier dysfunctions, with normalization of tight junction, adherent junction and mucin gene expression and reduction of Nod2- and matrix metalloproteinase 7-dependent activation of antimicrobial peptides. (4) Conclusions: our data show that TA and Eta modulate markers of inflammation and the intestinal barrier and suggest novel mechanisms of action of this drug that could broaden its treatment indications. Full article
(This article belongs to the Section Molecular Medicine)
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