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Search Results (617)

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Keywords = digestive system diseases

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16 pages, 13113 KiB  
Article
Ambient Particulate Matter Exposure Impairs Gut Barrier Integrity and Disrupts Goblet Cell Function
by Wanhao Gao, Wang Lin, Miao Tian, Shilang Fan, Sabrina Edwards, Joanne Tran, Yuanjing Li and Xiaoquan Rao
Biomedicines 2025, 13(8), 1825; https://doi.org/10.3390/biomedicines13081825 - 25 Jul 2025
Viewed by 341
Abstract
Background: As a well-known environmental hazard, ambient fine particulate matter (PM2.5, aerodynamic diameter ≤ 2.5 µm) has been positively correlated with an increased risk of digestive system diseases, including appendicitis, inflammatory bowel disease, and gastrointestinal cancer. Additionally, PM2.5 exposure [...] Read more.
Background: As a well-known environmental hazard, ambient fine particulate matter (PM2.5, aerodynamic diameter ≤ 2.5 µm) has been positively correlated with an increased risk of digestive system diseases, including appendicitis, inflammatory bowel disease, and gastrointestinal cancer. Additionally, PM2.5 exposure has been shown to alter microbiota composition and diversity in human and animal models. However, its impact on goblet cells and gut mucus barrier integrity remains unclear. Methods: To address this, 8-week-old male and female interleukin-10 knockout (IL10−/−) mice, serving as a spontaneous colitis model, were exposed to concentrated ambient PM2.5 or filtered air (FA) in a whole-body exposure system for 17 weeks. Colon tissues from the PM2.5-exposed mice and LS174T goblet cells were analyzed using H&E staining, transmission electron microscopy (TEM), and transcriptomic profiling. Results: The average PM2.5 concentration in the exposure chamber was 100.20 ± 13.79 µg/m3. PM2.5 exposure in the IL10−/− mice led to pronounced colon shortening, increased inflammatory infiltration, ragged villi brush borders, dense goblet cells with sparse enterocytes, and lipid droplet accumulation in mitochondria. Similar ultrastructure changes were exhibited in the LS174T goblet cells after PM2.5 exposure. Transcriptomic analysis revealed a predominantly upregulated gene expression spectrum, indicating an overall enhancement rather than suppression of metabolic activity after PM2.5 exposure. Integrated enrichment analyses, including GO, KEGG, and GSEA, showed enrichment in pathways related to oxidative stress, xenobiotic (exogenous compound) metabolism, and energy metabolism. METAFlux, a metabolic activity analysis, further substantiated that PM2.5 exposure induces a shift in cellular energy metabolism preference and disrupts redox homeostasis. Conclusions: The findings of exacerbated gut barrier impairment and goblet cell dysfunction following PM2.5 exposure provide new evidence of environmental factors contributing to colitis, highlighting new perspectives on its role in the pathogenesis of colitis. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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35 pages, 2034 KiB  
Review
The Role of Gut Microbiota in Gastrointestinal Immune Homeostasis and Inflammation: Implications for Inflammatory Bowel Disease
by Elisabetta Bretto, Miquel Urpì-Ferreruela, Gherzon Rimer Casanova and Begoña González-Suárez
Biomedicines 2025, 13(8), 1807; https://doi.org/10.3390/biomedicines13081807 - 24 Jul 2025
Viewed by 644
Abstract
Inflammatory bowel disease (IBD), a heterogeneous group of recurring inflammatory conditions of the digestive system that encompass both ulcerative colitis (UC) and Crohn’s disease (CD), pose a significant public health challenge, currently lacking a definitive cure. The specific etiopathogenesis of IBD is not [...] Read more.
Inflammatory bowel disease (IBD), a heterogeneous group of recurring inflammatory conditions of the digestive system that encompass both ulcerative colitis (UC) and Crohn’s disease (CD), pose a significant public health challenge, currently lacking a definitive cure. The specific etiopathogenesis of IBD is not yet fully understood, but a multifactorial interplay of genetic and environmental factors is suspected. A growing body of evidence supports the involvement of intestinal dysbiosis in the development of IBD, including the effects of dysbiosis on the integrity of the intestinal epithelial barrier, modulation of the host immune system, alterations in the enteric nervous system, and the perpetuation of chronic inflammation. A comprehensive understanding of these mechanisms is important to define preventive measures, to develop new effective and lasting treatments, and to improve disease outcome. This review examines the complex tri-directional relationship between gut microbiota, mucosal immune system, and intestinal epithelium in IBD. In addition, nonpharmacological and behavioral strategies aimed at restoring a proper microbial–immune relationship will be suggested. Full article
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18 pages, 4848 KiB  
Article
Determining Frequency of Multiple Organ System Involvement and Concurrent Lesions Identified in Feedyard Mortalities and Potential Associations with Cattle Demographics
by Madeline R. Mancke, Brad J. White, Eduarda M. Bortoluzzi, Brandon E. Depenbusch, Paige H. Schmidt, Rachel E. Champagne, Makenna Jensen, Phillip A. Lancaster and Robert L. Larson
Vet. Sci. 2025, 12(7), 666; https://doi.org/10.3390/vetsci12070666 - 15 Jul 2025
Viewed by 335
Abstract
Necropsies are commonly used to diagnose the causes of death in feedyard cattle, but the documentation of multiple organ system involvement and concurrent lesions is limited. This observational study aimed to determine the frequency of such findings and their associations with animal demographics. [...] Read more.
Necropsies are commonly used to diagnose the causes of death in feedyard cattle, but the documentation of multiple organ system involvement and concurrent lesions is limited. This observational study aimed to determine the frequency of such findings and their associations with animal demographics. Systemic necropsies were conducted for 889 cattle mortalities with minimal autolysis across six feedyards in the Central High Plains during the summers of 2022 and 2023. Lesions and abnormalities were recorded along with arrival weight, sex, days on feed (DOFs), and number of treatments. The results showed that 72% of mortalities had more than one gross lesion, averaging 2.3 lesions per animal. The most common organ systems affected together were digestive and pulmonary (19%), followed by cardiovascular, digestive, and pulmonary (6%), and cardiovascular and pulmonary (5%). Common concurrent lesions included bronchopneumonia with an interstitial pattern (BIP) and gastrointestinal lesions (GI) (8%), bronchopneumonia and GI (7%), and acute interstitial pneumonia (AIP) and GI (3%). A generalized linear mixed effects model revealed that the likelihood of multiple lesions increased with DOFs (p = 0.02). These findings highlight the value of thorough necropsy documentation to enhance our understanding of disease and guide improved feedyard management and treatment practices. Full article
(This article belongs to the Section Anatomy, Histology and Pathology)
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17 pages, 5753 KiB  
Protocol
Protoplast-Based Regeneration Enables CRISPR/Cas9 Application in Two Temperate Japonica Rice Cultivars
by Marion Barrera, Blanca Olmedo, Matías Narváez, Felipe Moenne-Locoz, Anett Rubio, Catalina Pérez, Karla Cordero-Lara and Humberto Prieto
Plants 2025, 14(13), 2059; https://doi.org/10.3390/plants14132059 - 5 Jul 2025
Viewed by 627
Abstract
Rice (Oryza sativa L.), a staple food for over half of the global population, plays a pivotal role in food security. Among its two primary groups, japonica and indica, temperate japonica varieties are particularly valued for their high-quality grain and culinary [...] Read more.
Rice (Oryza sativa L.), a staple food for over half of the global population, plays a pivotal role in food security. Among its two primary groups, japonica and indica, temperate japonica varieties are particularly valued for their high-quality grain and culinary uses. Although some of these varieties are adapted to cooler climates, they often suffer from reduced productivity or increased disease susceptibility when cultivated in warmer productive environments. These limitations underscore the need for breeding programs to incorporate biotechnological tools that can enhance the adaptability and resilience of the plants. However, New Genomic Techniques (NGTs), including CRISPR-Cas9, require robust in vitro systems, which are still underdeveloped for temperate japonica genotypes. In this study, we developed a reproducible and adaptable protocol for protoplast isolation and regeneration from the temperate japonica cultivars ‘Ónix’ and ‘Platino’ using somatic embryos as the starting tissue. Protoplasts were isolated via enzymatic digestion (1.5% Cellulase Onozuka R-10 and 0.75% Macerozyme R-10) in 0.6 M AA medium over 18–20 h at 28 °C. Regeneration was achieved through encapsulation in alginate beads and coculture with feeder extracts in 2N6 medium, leading to embryogenic callus formation within 35 days. Seedlings were regenerated in N6R and N6F media and acclimatized under greenhouse conditions within three months. The isolated protoplast quality displayed viability rates of 70–99% within 48 h and supported transient PEG-mediated transfection with GFP. Additionally, the transient expression of a gene editing CRISPR-Cas9 construct targeting the DROUGHT AND SALT TOLERANCE (OsDST) gene confirmed genome editing capability. This protocol offers a scalable and genotype-adaptable system for protoplast-based regeneration and gene editing in temperate japonica rice, supporting the application of NGTs in the breeding of cold-adapted cultivars. Full article
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31 pages, 2999 KiB  
Review
Nanomedicine Strategies in the Management of Inflammatory Bowel Disease and Colorectal Cancer
by Asia Xiao Xuan Tan, Brandon Yen Chow Ong, Tarini Dinesh and Dinesh Kumar Srinivasan
Int. J. Mol. Sci. 2025, 26(13), 6465; https://doi.org/10.3390/ijms26136465 - 4 Jul 2025
Viewed by 526
Abstract
The gut microbiota has emerged as a key area of biomedical research due to its integral role in maintaining host health and its involvement in the pathogenesis of many systemic diseases. Growing evidence supports the notion that gut dysbiosis contributes significantly to diseases [...] Read more.
The gut microbiota has emerged as a key area of biomedical research due to its integral role in maintaining host health and its involvement in the pathogenesis of many systemic diseases. Growing evidence supports the notion that gut dysbiosis contributes significantly to diseases and their progression. An example would be inflammatory bowel disease (IBD), a group of conditions that cause inflammation and swelling of the digestive tract, with the principal types being ulcerative colitis (UC) and Crohn’s disease (CD). Another notable disease with significant association to gut dysbiosis would be colorectal cancer (CRC), a malignancy which typically begins as polyps in the colon or rectum, but has the potential to metastasise to other parts of the body, including the liver and lungs, among others. Concurrently, advances in nanomedicine, an evolving field that applies nanotechnology for disease prevention, diagnosis, and treatment, have opened new avenues for targeted and efficient therapeutic strategies. In this paper, we provide an overview of the gut microbiota and the implications of its dysregulation in human disease. We then review the emerging nanotechnology-based approaches for both therapeutic and diagnostic purposes, with a particular focus on their applications in IBD and CRC. Full article
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18 pages, 4409 KiB  
Article
Immunogenicity of Matrix Protein 2 Ectodomain (M2e) Displayed on Nodavirus-like Particles as Avian Influenza Vaccine for Poultry
by Anis Suraya Mohamad Abir, Wen Siang Tan, Abdul Rahman Omar, Kok Lian Ho, Munir Iqbal and Abdul Razak Mariatulqabtiah
Vaccines 2025, 13(7), 701; https://doi.org/10.3390/vaccines13070701 - 27 Jun 2025
Viewed by 523
Abstract
Avian influenza is an economically significant disease affecting poultry worldwide and is caused by influenza A viruses that can range from low to highly pathogenic strains. These viruses primarily target the respiratory, digestive, and nervous systems of birds, leading to severe outbreaks that [...] Read more.
Avian influenza is an economically significant disease affecting poultry worldwide and is caused by influenza A viruses that can range from low to highly pathogenic strains. These viruses primarily target the respiratory, digestive, and nervous systems of birds, leading to severe outbreaks that threaten poultry production and pose zoonotic risks. The ectodomain of the avian influenza virus (AIV) matrix protein 2 (M2e), known for its high conservation across influenza strains, has emerged as a promising candidate for developing a universal influenza vaccine in a mouse model. However, the efficacy of such expression against poultry AIVs remains limited. The objective of this study was to evaluate the immunogenicity of nodavirus-like particles displaying the M2e proteins. In this study, three synthetic heterologous M2e genes originated from AIV strains H5N1, H9N2 and H5N2 were fused with the nodavirus capsid protein (NVC) of the giant freshwater prawn Macrobrachium rosenbergii (NVC-3xAvM2e) prior to immunogenicity characterisations in chickens. The expression vector pTRcHis-TARNA2 carrying the NVC-3xAvM2e gene cassette was introduced into E. coli TOP-10 cells. The recombinant proteins were purified, inoculated into one-week-old specific pathogen-free chickens subcutaneously and analysed. The recombinant protein NVC-3xAvM2e formed virus-like particles (VLPs) of approximately 25 nm in diameter when observed under a transmission electron microscope. Dynamic light scattering (DLS) analysis revealed that the VLPs have a polydispersity index (PDI) of 0.198. A direct ELISA upon animal experiments showed that M2e-specific antibodies were significantly increased in vaccinated chickens after the booster, with H5N1 M2e peptides having the highest mean absorbance value when compared with those of H9N2 and H5N2. A challenge study using low pathogenic AIV (LPAI) strain A/chicken/Malaysia/UPM994/2018 (H9N2) at 106.5 EID50 showed significant viral load in the lung and cloaca, but not in the oropharyngeal of vaccinated animals when compared with the unvaccinated control group. Collectively, this study suggests that nodavirus-like particles displaying three heterologous M2e have the potential to provide protection against LPAI H9N2 in chickens, though the vaccine’s efficacy and cross-protection across different haemagglutinin (HA) subtypes should be further evaluated. Full article
(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)
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21 pages, 1877 KiB  
Review
Puerarin as a Phytochemical Modulator of Gastrointestinal Homeostasis in Livestock: Molecular Mechanisms and Translational Applications
by Jiehong Zhou, Jianyu Lv, Xin Chen, Tian Li, Jianzhong Shen, Zhanhui Wang, Chongshan Dai and Zhihui Hao
Antioxidants 2025, 14(6), 756; https://doi.org/10.3390/antiox14060756 - 19 Jun 2025
Viewed by 820
Abstract
The gut serves as the main site for nutrient digestion and absorption. Simultaneously, it functions as the body’s largest immune organ, playing a dual role in sustaining physiological equilibrium and offering immunological defense against intestinal ailments. Maintaining the structural and functional integrity of [...] Read more.
The gut serves as the main site for nutrient digestion and absorption. Simultaneously, it functions as the body’s largest immune organ, playing a dual role in sustaining physiological equilibrium and offering immunological defense against intestinal ailments. Maintaining the structural and functional integrity of the intestine is paramount for ensuring animal health and productivity. Puerarin, a naturally derived isoflavonoid from the Pueraria species, exhibits multifaceted bioactivities, such as antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Emerging evidence highlights puerarin’s capacity to enhance gut health in farm animals through four pivotal mechanisms: (1) optimization of intestinal morphology via crypt-villus architecture remodeling, (2) augmentation of systemic and mucosal antioxidant defenses through Nrf2/ARE pathway activation, and (3) reinforcement of intestinal barrier function by regulating tight junction proteins (e.g., ZO-1, occludin), mucin secretion, intestinal mucosal immune barrier, the composition of microbiota, and the derived beneficial metabolites; (4) regulating the function of the intestinal nervous system via reshaping the distribution of intestinal neurons and neurotransmitter secretion function. This review synthesizes current knowledge on puerarin’s protective effects on intestinal physiology in farm animals, systematically elucidates its underlying molecular targets (including TLR4/NF-κB, MAPK, and PI3K/Akt signaling pathways), and critically evaluates its translational potential in mitigating enteric disorders such as post-weaning diarrhea and inflammatory bowel disease in agricultural practices. Full article
(This article belongs to the Topic Recent Advances in Veterinary Pharmacology and Toxicology)
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27 pages, 1715 KiB  
Review
Osteopontin: Its Properties, Recent Studies, and Potential Applications
by Büşra Karasalih, Hatice Duman, Mikhael Bechelany and Sercan Karav
Int. J. Mol. Sci. 2025, 26(12), 5868; https://doi.org/10.3390/ijms26125868 - 19 Jun 2025
Cited by 1 | Viewed by 735
Abstract
OPN is a phosphorylated glycoprotein found in all vertebrate organisms and expressed in many tissues and secretions. It is a pleiotropic protein that plays diverse roles in various pathological and physiological processes. OPN is involved in many tissue transformation events such as intestinal [...] Read more.
OPN is a phosphorylated glycoprotein found in all vertebrate organisms and expressed in many tissues and secretions. It is a pleiotropic protein that plays diverse roles in various pathological and physiological processes. OPN is involved in many tissue transformation events such as intestinal and brain development, the regulation of immune system activity, immune cell activation, and inflammatory responses. This protein increases the functionality of the digestive system by regulating the intestinal microbiome and may help strengthen the intestinal barrier. OPN can also influence cognitive development and behavior. In addition, its recent association with cancer has gained critical importance. The increased expression of OPN has been observed in many cancer types, which may promote tumor cell metastasis. OPN is also effective in bacterial interaction and infections; it can prevent bacterial adhesion, supporting the development of new therapeutic approaches for oral care. Furthermore, the supplementation of OPN in infant formula has positively influenced the immune and intestinal health of infants. Many recent studies have focused on these aspects. This article provides a review and comparison of the existing knowledge on the structure and functions of OPN. It emphasizes how milk-derived OPN impacts human and infant health and disease. Full article
(This article belongs to the Special Issue Latest Review Papers in Macromolecules 2025)
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15 pages, 1190 KiB  
Article
Physicochemical Characteristics of Phospholipid Vesicles for Spirulina-Based Dietary Supplement Delivery
by Massimo Milia, Ines Castangia, Francesco Corrias, Matteo Aroffu, Mattia Casula, Maria Letizia Manca, Maria Manconi, Hamza Bouakline and Alberto Angioni
Molecules 2025, 30(12), 2581; https://doi.org/10.3390/molecules30122581 - 13 Jun 2025
Cited by 1 | Viewed by 441
Abstract
Spirulina (Arthrospira platensis) is a microalga widely used as a dietary supplement in sports nutrition and in treating metabolic diseases such as diabetes, obesity and metabolic syndrome. Spirulina’s cell structure limits digestibility and reduces the availability of bioactive compounds. The extraction [...] Read more.
Spirulina (Arthrospira platensis) is a microalga widely used as a dietary supplement in sports nutrition and in treating metabolic diseases such as diabetes, obesity and metabolic syndrome. Spirulina’s cell structure limits digestibility and reduces the availability of bioactive compounds. The extraction processes, coupled with encapsulation, can enhance the bioavailability of nutritional and antioxidant compounds, protecting them from degradation, preserving their functional activity, and supporting controlled release. The physicochemical properties of liposomes (Lps), bilosomes (Bls), and gelatin-enriched bilosomes (G-Bls) with incorporated Spirulina extracts were investigated. The delivery systems exhibited small particle size (101.8 ± 0.5 to 129.7 ± 1.2 nm), homogeneous distribution (polydispersity index (PDI) 0.17 ± 6.67 to 0.33 ± 9.06), negative surface charges (−31.9 ± 5.2 to 31.1 ± 6.4 mV), and high entrapment efficiency (>80%). G-Bls demonstrated effective retention of the extract, with a low release rate at pH 1.2 (41.8% ± 6.1) and controlled release at pH 7.0 (52.5% ± 3.0). Biocompatibility studies on Caco-2 cells showed that G-Bls maintained high cell viability at 200 μg·mL−1 (87.89% ± 10.35) and significantly mitigated H2O2-induced oxidative stress at 20 and 200 μg·mL−1, increasing cell viability by 23.47% and 19.28%. G-Bls are a promising delivery system for enhancing the stability, bioavailability, and protective effects of Spirulina extracts, supporting their potential application in dietary supplements aimed at promoting sports performance and recovery, mitigating exercise-induced oxidative stress, and managing metabolic disorders. Full article
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24 pages, 1150 KiB  
Article
Seaweed Consumption Practices in Coastal Communities of Tawi-Tawi, Philippines
by Albaris B. Tahiluddin, Fauzia R. Esmola, Suhana A. Abduraup, Aisa Mae B. Camsain, Wahaymin M. Jamil, Angelica B. Bermil, Romar A. Ujing, Adzlan D. Gunong, Samiya U. Damsik, Sitti Darmiya S. Baid, Fatima Qhurdee N. Hapid, Telmigi M. Mohammad, Aljenda A. Ujing, Abdel-Azeem M. Alsim, Marhamin H. Jumsali, Mur-hamida S. Eldani-Tahiluddin, Jonald C. Bornales, Al-Rastum II A. Sappayani and Rizal Jhunn F. Robles
Phycology 2025, 5(2), 25; https://doi.org/10.3390/phycology5020025 - 11 Jun 2025
Viewed by 1926
Abstract
Seaweeds represent a vital yet often understudied component of the diet and cultural heritage of many coastal communities globally. This study investigated seaweed consumption practices in coastal communities of Tawi-Tawi, Philippines, through one-to-one interviews (n = 280) and focus group discussions ( [...] Read more.
Seaweeds represent a vital yet often understudied component of the diet and cultural heritage of many coastal communities globally. This study investigated seaweed consumption practices in coastal communities of Tawi-Tawi, Philippines, through one-to-one interviews (n = 280) and focus group discussions (n = 7). The study revealed that nearly all (99%) of the population consumes seaweeds, with women comprising the majority of consumers who have done so since childhood (68% female vs. 32% male). These consumers were predominantly married (79%), within the 21–40 age group (53%), with families of 5–7 members (43%), practicing Islam (97%), and belonging to the Sama tribe (71%). A significant portion (48%) had resided in the area for 21–30 years, attained elementary to high school education (66%), and had a monthly income ranging from 1000 to 10,000 Philippine pesos (72%). Seaweed consumption was a family-wide practice (88%), including children, who typically started around 4–8 years old (61%), driven by perceived nutritional benefits (43%), preferred flavor (80%), affordability (19%), ease of preparation (33%), and cultural integration (23%). The primary edible seaweeds identified were Kappaphycus alvarezii (63%), K. striatus (58%), Kappaphycus spp. (47%), Eucheuma denticulatum (57%), Caulerpa lentillifera (64%), Caulerpa spp. (51%), C. cf. macrodisca ecad corynephora (45%), C. racemosa (30%), and Solieria robusta (49%), with less frequent consumption of K. malesianus (8%), Chaetomorpha crassa (3%), Gracilaria spp. (0.72%), and Hydroclathrus clathratus (0.36%). Specific plant parts were preferred for certain species, and preparation predominantly involved raw (75%) or cooked (77%) salads with spices, primarily prepared by mothers (72%). Consumers generally avoided seaweeds showing signs of ice-ice disease (95%), pale coloration (91%), or epiphyte infestation (84%). Consumption frequency was typically 1–3 times per week (45%), with knowledge largely passed down through generations (95%). Seaweed salads were primarily consumed as a viand (92%) at home (97%), with locals perceiving seaweed consumption as contributing to a healthy diet (40%) and overall well-being [e.g., aiding hunger (76%), improving digestion (20%), preventing obesity (14%), and aiding brain development (3%)]. The study’s findings emphasize the significant yet often overlooked role of seaweeds in the food systems and cultural heritage of Tawi-Tawi’s coastal communities. Future efforts should prioritize the sustainable management of wild resources, explore the cultivation of diverse edible species, and enhance nutritional awareness. Further research into traditional seaweed knowledge holds broader value. Full article
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13 pages, 1529 KiB  
Article
Preliminary Study of CCR9 and MAdCAM-1 Upregulation and Immune Imbalance in Canine Chronic Enteropathy: Findings Based on Histopathological Analysis
by Macarena Pino, Galia Ramirez, Caroll Beltrán, Eduard Martinez, Ismael Pereira, Jaime Villegas, Federico Cifuentes and Daniela Siel
Animals 2025, 15(12), 1710; https://doi.org/10.3390/ani15121710 - 10 Jun 2025
Viewed by 548
Abstract
Canine chronic enteropathy (CE) is a gastrointestinal disorder characterized by persistent or recurrent digestive symptoms lasting more than three weeks. It shares similarities with human inflammatory bowel disease but its immunopathogenesis remains poorly characterized in dogs. The aim of this study was to [...] Read more.
Canine chronic enteropathy (CE) is a gastrointestinal disorder characterized by persistent or recurrent digestive symptoms lasting more than three weeks. It shares similarities with human inflammatory bowel disease but its immunopathogenesis remains poorly characterized in dogs. The aim of this study was to characterize the local and systemic immune profile of dogs with CE by assessing cytokine and chemokine expression in serum and intestinal tissue, as well as the mRNA expression of immune-related receptors such as integrins, chemokine receptors, and cytokines. Duodenal biopsies and blood samples were collected from five dogs diagnosed with a CE and five healthy controls. Serum concentrations of cytokines and chemokines were determined by multiplex ELISA, and mRNA expression in the intestinal mucosa was analyzed by quantitative PCR. Dogs with a CE showed increased expression of pro-inflammatory cytokines, including TNF-α and IFN-γ, and increased concentrations of chemokines such as CXCL10 and CCL2 in both serum and tissue samples. Increased mRNA expression of the chemokine receptor CCR9 and the adhesion molecule MAdCAM-1 were also observed in intestinal samples. These findings provide new insights into the immune response involved in CE and may aid the development of future diagnostic biomarkers and targeted therapies for canine chronic enteropathies. Full article
(This article belongs to the Section Animal Physiology)
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15 pages, 4938 KiB  
Article
Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway
by Zhibin Liu, Ke Huang, Hai Huang, Eungyung Kim, Hyeonjin Kim, Chae Yeon Kim, Dong Joon Kim, Sang In Lee, Sangsik Kim, Do Yoon Kim, Kangdong Liu, Zae Young Ryoo, Mee-Hyun Lee, Lei Ma and Myoung Ok Kim
Antioxidants 2025, 14(6), 694; https://doi.org/10.3390/antiox14060694 - 8 Jun 2025
Viewed by 713
Abstract
Esophageal squamous cell carcinoma (ESCC), one of the most frequent malignant tumors of the digestive system, is marked by a poor prognosis and high mortality rate. There is a critical need for effective therapeutic strategies with minimal side effects. Isoquercitrin (IQ) is a [...] Read more.
Esophageal squamous cell carcinoma (ESCC), one of the most frequent malignant tumors of the digestive system, is marked by a poor prognosis and high mortality rate. There is a critical need for effective therapeutic strategies with minimal side effects. Isoquercitrin (IQ) is a natural compound with potent antioxidant properties in cancer and cardiovascular diseases. However, its specific effects and mechanisms in ESCC remain largely unexplored. This study aims to investigate the effects of IQ in ESCC cells and elucidate the mechanisms underlying its therapeutic effects. Specifically, its impact on cell proliferation, colony formation, migration, and invasion was assessed using cell viability assay, morphology, transwell, and colony formation assays. The effects on apoptosis were evaluated by flow cytometry, while immunofluorescence (IF) staining and Western blotting were performed to confirm the underlying mechanisms. The in vivo anti-cancer effects of IQ were then evaluated using a xenograft tumor model. Our results demonstrate that IQ inhibits ESCC cell growth and colony formation while promoting its apoptosis by enhancing caspase activation and downregulating Bcl-2 expression. Furthermore, IQ suppresses cell migration by modulating the epithelial–mesenchymal transition-related proteins. Additionally, IQ induces excessive autophagy by promoting reactive oxygen species accumulation and inhibiting the AKT/mTOR signaling pathway. Importantly, IQ effectively reduces tumor growth in vivo, highlighting its potential as a therapeutic agent for ESCC. Full article
(This article belongs to the Special Issue Redox Signaling in Cancer: Mechanisms and Therapeutic Opportunities)
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15 pages, 1068 KiB  
Article
Microvascular Complications and Cancer Risk in Type 2 Diabetes: A Population-Based Study
by Yu-Hsin Yen, James Cheng-Chung Wei, Fu-Shun Yen, Yung-Shuo Kao, Heng-Jun Lin, Der-Yang Cho, Chii-Min Hwu and Chih-Cheng Hsu
Cancers 2025, 17(11), 1760; https://doi.org/10.3390/cancers17111760 - 23 May 2025
Viewed by 722
Abstract
Background: Microvascular complications in type 2 diabetes (T2D) and cancer share biological pathways, including chronic inflammation, dysregulated angiogenesis, and endothelial dysfunction, yet their impact on cancer risk and mortality remains unclear. This study evaluated whether T2D patients with microvascular complications face increased [...] Read more.
Background: Microvascular complications in type 2 diabetes (T2D) and cancer share biological pathways, including chronic inflammation, dysregulated angiogenesis, and endothelial dysfunction, yet their impact on cancer risk and mortality remains unclear. This study evaluated whether T2D patients with microvascular complications face increased cancer incidence or cancer-related mortality. Methods: Using the Taiwan National Health Insurance Research Database, we identified individuals newly diagnosed with T2D (2008–2021) and assessed the outcomes with multivariable Cox proportional hazards models. Results: Our findings indicate that T2D patients with diabetic neuropathy, retinopathy, or chronic kidney disease do not have a significantly increased risk of major cancers, including those of the oral cavity, thyroid, breast, respiratory tract, digestive system, or lymphoid tissues. Similarly, microvascular complications were not associated with higher cancer-related mortality. However, microvascular complications significantly increased all-cause mortality in a dose-dependent manner: adjusted hazard ratio (aHR) 1.16 [95% CI: 1.15–1.17] for one complication, aHR 1.42 [1.38–1.45] for two, and aHR 1.71 [1.60–1.83] for three. Conclusions: In this nationwide cohort study, we demonstrate that while microvascular complications are associated with increased all-cause mortality in T2D, they do not appear to elevate cancer risk or cancer-specific mortality. These findings provide crucial epidemiological insights into the relationship between diabetes complications and cancer. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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24 pages, 1312 KiB  
Review
Targeting Phosphodiesterase 4 in Gastrointestinal and Liver Diseases: From Isoform-Specific Mechanisms to Precision Therapeutics
by Can Chen, Mei Liu and Xiang Tao
Biomedicines 2025, 13(6), 1285; https://doi.org/10.3390/biomedicines13061285 - 23 May 2025
Viewed by 846
Abstract
Phosphodiesterase 4 (PDE4) serves as a crucial regulator of cyclic adenosine monophosphate (cAMP) signaling and has been identified as a significant therapeutic target for inflammatory and metabolic disorders impacting the gastrointestinal (GI) tract and liver. Although pan-PDE4 inhibitors hold therapeutic promise, their clinical [...] Read more.
Phosphodiesterase 4 (PDE4) serves as a crucial regulator of cyclic adenosine monophosphate (cAMP) signaling and has been identified as a significant therapeutic target for inflammatory and metabolic disorders impacting the gastrointestinal (GI) tract and liver. Although pan-PDE4 inhibitors hold therapeutic promise, their clinical use has been constrained by dose-dependent adverse effects. Recent progress in the development of isoform-specific PDE4 inhibitors, such as those selective for PDE4B/D, alongside targeted delivery systems like liver-targeting nanoparticles and probiotic-derived vesicles, is reshaping the therapeutic landscape. This review consolidates the latest insights into PDE4 biology, highlighting how the structural characterization of isoforms informs drug design. We conduct a critical evaluation of preclinical and clinical data across various diseases, including inflammatory bowel diseases (IBDs), alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, and digestive tract tumors, with an emphasis on mechanisms extending beyond cAMP modulation, such as microbiota remodeling and immune reprogramming. Additionally, we address challenges in clinical translation, including biomarker discovery and the heterogeneity of trial outcomes, and propose a roadmap for future research directions. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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20 pages, 5008 KiB  
Article
Integration of Transcriptomics and Metabolomics Reveals Mechanisms of High-Temperature Stress Tolerance in the Hepatopancreas of Penaeus monodon
by Li Liu, Peng Zhao, Lishi Yang, Yundong Li, Zhong Huang, Qibin Yang, Yukai Yang, Jianzhi Shi, Yibiao Chen and Jianhua Huang
Biology 2025, 14(6), 591; https://doi.org/10.3390/biology14060591 - 23 May 2025
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Abstract
High temperatures in summer often trigger disease outbreaks in shrimp, resulting in significant economic losses. To investigate the heat tolerance mechanisms of Penaeus monodon, juvenile tiger shrimp were subjected to a high-temperature stress of 38 °C for 144 h. The cumulative survival [...] Read more.
High temperatures in summer often trigger disease outbreaks in shrimp, resulting in significant economic losses. To investigate the heat tolerance mechanisms of Penaeus monodon, juvenile tiger shrimp were subjected to a high-temperature stress of 38 °C for 144 h. The cumulative survival rate of shrimp sharply decreased to 5.29% in the later 144 h. The heat-sensitive shrimps (S group) were collected in the first 24 h, while those that survived beyond 120 h were collected as the heat-tolerant group (T group). The hepatopancreas of two groups was subjected to transcriptomic and metabolomic analysis. The results revealed that, compared to the S group, the T group exhibited a total of 3527 DEGs, including 2199 upregulated and 1328 downregulated genes. Additionally, 353 DAMs were identified in the T group, with 75 metabolites showing increased levels and 278 metabolites displaying decreased levels. The results revealed that the mechanisms of heat tolerance involve energy supply strategies, immune system regulation, amino acid metabolism, and glutathione metabolism. Energy supply strategies include the digestion and absorption of carbohydrates and proteins, glycolysis/gluconeogenesis, fructose and mannose metabolism, and pyruvate metabolism, all of which collectively meet energy demands in high-temperature environments. The immune system is regulated by C-type lectin receptor pathways and IL-17 signaling pathways, which together coordinate innate immunity to prevent pathogen invasion. In amino acid metabolism, various glycogenic amino acids, such as histidine, phenylalanine, valine, and serine, are metabolized for energy, while excess ammonia is converted to γ-glutamyl-glutamate and L-glutamate to mitigate ammonia accumulation. Combined transcriptomic and metabolomic analyses further indicate that glutathione metabolism plays a crucial role in the adaptation of P. monodon to high-temperature environments. This study explains the high-temperature tolerance mechanism of P. monodon from the aspects of gene expression regulation and material metabolism regulation and also provides a scientific basis and basic data for the selection and breeding of new varieties of P. monodon with a high-temperature tolerance. Full article
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