Search Results (17,036)

Soy protein concentrate (SPC) is a cost-effective alternative to fish meal (FM) in aquaculture, but its deficiency in essential amino acids, particularly methionine, limits its application. This study evaluated the effects of methionine supplementation on growth, liver and intestinal health, and muscle quality in hybrid sturgeon (Acipenser baerii ♀ × A. schrenckii ♂) fed SPC-based diets. Four diets were formulated: an FM control diet, and SPC diets supplemented with 0% (M0), 0.25% (M2.5), and 0.50% (M5) methionine. Replacing FM with SPC without methionine (M0) significantly reduced weight gain and the protein efficiency ratio (PER) while increasing the feed conversion ratio (FCR) and hepatic lipid accumulation. Methionine supplementation (M5) restored growth performance, the PER, and muscle texture to levels comparable to the FM group. Intestinal enzyme activities (lipase and trypsin), villus height, and goblet cell counts significantly improved in the M5 group. Gene expression analysis showed that M5 upregulated tight junction genes (claudin1, occludin) and anti-inflammatory genes (tgfβ, lysozyme) while reducing pro-inflammatory cytokines (il1β, il8). In the liver, M5 reduced oxidative stress markers such as malondialdehyde (MDA) and improved antioxidant enzyme activities (SOD, CAT) while optimizing lipid metabolism, as evidenced by lower triglyceride (TG) and total cholesterol (TC) levels. Muscle quality analysis showed that M5 significantly increased muscle hardness, chewiness, and fiber density compared to M0. In conclusion, methionine supplementation at 0.50% effectively mitigates the negative effects of SPC, improving growth, liver and intestinal health, and muscle quality in hybrid sturgeon. Full article

Polysaccharides derived from Dendrobium officinale have been demonstrated to exhibit metabolic regulatory properties. However, the correlation between their structure and function, particularly their mechanism of action through gut microbiota, remains underexplored. This study systematically elucidates the structural characteristics of Dendrobium officinale polysaccharide (DOP) from the Guizhou (GZ) and Zhejiang (ZJ) provinces of China using nuclear magnetic resonance (NMR) and a series of chromatographic analyses, revealing their unique molecular features. Additionally, the metabolic regulatory activities were assessed through α-glucosidase inhibitory assay and in vitro intestinal flora activity assay. The findings include the following: (1) both DOP-GZ and DOP-ZJ predominantly consist of glycosidic linkages of β-1,4-Manp and β-1,4-Glcp; (2) zhe monosaccharide composition ratios of mannose to glucose are 2.51:1 for DOP-GZ and 2.66:1 for DOP-ZJ, with molecular weights of 356 kDa and 544 kDa, respectively, indicating significant structural differences between DOPs from different sources; (3) treatment with DOP-GZ and DOP-ZJ led to alterations in the α-diversity indices and Firmicutes-to-Bacteroidota ratios; (4) more importantly, DOP-GZ and DOP-ZJ significantly increase the abundance of beneficial bacteria (e.g., g_Proteobacteria_unclassified) while suppressing the growth of pathogenic bacteria (e.g., f_Enterobacteriaceae_unclassified), with statistically significant results. These findings not only uncover a novel mechanism by which DOPs regulate metabolism through gut microbiota but also provide a crucial theoretical basis for the application of DOPs in functional foods and pharmaceutical development. Full article

Background: Cystic Fibrosis is an inherited disorder caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene, encoding a chloride and bicarbonate channel widely expressed in epithelia. Loss of CFTR function leads to dehydration of the epithelium surface with thicker mucus secretions from tissues. The lungs, pancreas, liver, intestines, and sweat glands are the most common affected organs. However, pulmonary disease remains the main cause of morbidity and mortality. Fortunately, elexacaftor/tezacaftor/ivacaftor (ETI) therapy is showing unprecedented clinical benefits in patients with Cystic Fibrosis (CF) carrying at least one F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. However, almost 35% of the CF population living in the Mediterranean area still lacks effective CFTR modulator therapies because of the elevated incidence of patients with (pw)CF harboring CFTR rare mutations (RMs), different from F508del. Methods: Twenty-three pwCF harboring RM including the N1303K underwent off-label ETI treatment for 6-12 months. Respiratory function in terms of FEV1 and FVC was measured after 3, 6, and 12 months of treatment. In addition, we analyzed sweat chloride concentration, body mass index (BMI), and quality of life before and after treatment. Possible adverse effects were recorded. Results: All patients included in this off-label program displayed a substantial improvement in respiratory function. In particular, patients carrying the N1303K mutation showed an improvement in FEV1 and FVC similar to that observed in subjects harboring the F508del mutation, although sweat chloride concentration was not significantly decreased. No severe adverse effect was reported. Conclusions: This study strengthens the clinical efficacy of ETI in pwCF harboring the N1303K and other CFTR rare variants. Since these CFTR RMs have not been approved for ETI therapy in Europe, this study may promote the inclusion of these variants in the list of CFTR mutations responsive to ETI. Full article

Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal disease that affects millions of humans worldwide and imposes a huge social and economic burden. It is necessary to find safe and efficient drugs for preventing and treating UC. The aim of this study was to determine whether ganoderic acid (GA), the main bioactive components of Ganoderma lucidum, has preventive and therapeutic effect on UC in a dextran sulfate sodium (DSS)-induced UC mouse model. Our experimental results showed that GA significantly ameliorated the body weight loss and disease activity index (DAI) of UC mice. GA significantly restored 11% of the colon length and 69% of the spleen index compared to UC mice. GA significantly decreased the intestinal inflammatory response and improved the barrier function of the intestine by upregulating the tight junction proteins Zonula occludens-1 (ZO-1), occludin and claudin-1. A co-housing experiment showed that gut microbiota accounted for the therapeutic activity of GA on UC, which was confirmed by fecal microbiota transplantation from GA-treated mice to the UC mice. Furthermore, 16S rDNA high-throughput sequencing of fecal bacteria showed that GA significantly enriched the abundance of Lactobacillus, Oscillospira, Odoribacter and Ruminococcus, which were positively correlated with colon length. Furthermore, this study found the functional metabolites, including Indole-3-acetaldehyde (IAAld), Glutamine (Gln) and Glutathione (GSH), reduced barrier damage in the Caco-2 cell model. In conclusion, this study suggests that GA could ameliorate UC by improving intestinal barrier function via modulating gut microbiota and associated metabolites. Full article

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder marked by abdominal pain and irregular bowel habits. Recently, more and more evidence supports gut microbiota imbalance in IBS and highlights the potential of probiotics in restoring gut health and reducing symptoms. In this study, we explored the effects of Lactococcus cremoris PS133 (PS133) on an IBS-like condition in rats triggered by 5-hydroxytryptophan (5-HTP), a serotonin precursor. Eight-week-old Sprague Dawley rats received either PS133 or saline for 14 days, followed by 5-HTP to induce IBS-like symptoms. Colorectal distension tests showed that PS133 reduced visceral hypersensitivity. PS133 also protected intestinal mucin against 5-HTP-induced degradation, as seen in alcian blue staining, and increased the levels of tight junction proteins (occludin and zonula occludens-1) in the colon, indicating improved gut barrier integrity. Additionally, PS133 normalized the levels of substance P (a neuropeptide) in the spinal cord and altered 5-hydroxyindoleacetic acid (a serotonin metabolite) in the brain. Gut microbiota analysis revealed PS133 regulated specific bacterial groups, including [Eubacterium]_coprostanoligenes_group and Lactococcus. Overall, PS133 improved gut function, reduced IBS-like symptoms, and modulated gut microbiota, neurotransmitters, and intestinal barrier health in this IBS model. Full article

Ascites, a common complication of portal hypertension in cirrhosis, is characterized by the accumulation of fluid within the peritoneal cavity. While traditional theories focus on hemodynamic alterations and renin–angiotensin–aldosterone system (RAAS) activation, recent research highlights the intricate interplay of molecular and cellular mechanisms. Inflammation, mediated by cytokines (interleukin-1, interleukin-4, interleukin-6, tumor necrosis factor-α), chemokines (chemokine ligand 21, C-X-C motif chemokine ligand 12), and reactive oxygen species (ROS), plays a pivotal role. Besides pro-inflammatory cytokines, hepatic stellate cells (HSCs), sinusoidal endothelial cells (SECs), and smooth muscle cells (SMCs) contribute to the process through their activation and altered functions. Once activated, these cell types can worsen ascites accumulationthrough extracellular matrix (ECM) deposition and paracrine signals. Besides this, macrophages, both resident and infiltrating, through their plasticity, participate in this complex crosstalk by promoting inflammation and dysregulating lymphatic system reabsorption. Indeed, the lymphatic system and lymphangiogenesis, essential for fluid reabsorption, is dysregulated in cirrhosis, exacerbating ascites. The gut microbiota and intestinal barrier alterations which occur in cirrhosis and portal hypertension also play a role by inducing inflammation, creating a vicious circle which worsens portal hypertension and fluid accumulation. This review aims to gather these aspects of ascites pathophysiology which are usually less considered and to date have not been addressed using specific therapy. Nonetheless, it emphasizes the need for further research to understand the complex interactions among these mechanisms, ultimately leading to targeted interventions in specific molecular pathways, aiming towards the development of new therapeutic strategies. Full article

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM’s composition to restore its organization and function. Across diverse organ diseases, there are common denominators and distinguishing factors in this fibroinflammatory axis, which may be used to foster new insights into drug development across disease indications. The 2nd Extracellular Matrix Pharmacology Congress took place in Copenhagen, Denmark, from 17 to 19 June 2024 and was hosted by the International Society of Extracellular Matrix Pharmacology. The event was attended by 450 participants from 35 countries, among whom were prominent scientists who brought together state-of-the-art research on organ diseases and asked important questions to facilitate drug development. We highlight key aspects of the ECM in the liver, kidney, skin, intestine, musculoskeletal system, lungs, and solid tumors to advance our understanding of the ECM and its central targets in drug development. We also highlight key advances in the tools and technology that enable this drug development, thereby supporting the ECM. Full article

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel enteric coronavirus that causes severe clinical diarrhea and intestinal pathological injury in pigs. Selective autophagy is an important mechanism of host defense against virus invasion. However, the mechanism through which SADS-CoV-mediated selective autophagy mediates the innate immune response remains unknown. Here, we report that the host protein PABPC4 can inhibit SADS-CoV replication through targeting and degrading its N protein. Furthermore, we demonstrate that PABPC4 recruits MARCHF8 (an E3 ubiquitin ligase), which ubiquitinates the N protein and is degraded via NDP52/CALCOCO2 (a selective autophagy cargo receptor). Taken together, these findings reveal a new mechanism by which PABPC4 inhibits virus replication, and reveal a new target for antiviral drug development. Full article

Inflammatory bowel disease (IBD) induces immunological and autonomic imbalances. Exercise is a beneficial strategy for controlling IBD symptoms. We investigated the role of exercise on gastrointestinal (GI) motility changes and autonomic parameters in rats with ileitis. Rats were divided into control, ileitis, and exercise+ileitis groups. Ileitis was induced by TNBS (40 mM, intraileally). The exercise was swimming (1 h/day/4 weeks, 5%/bw). We assessed eating behaviour and oxidative stress. Body composition was assessed by bioimpedance. Autonomic balance and ECG parameters were measured by an electrocardiogram (ECG). Gastrointestinal motility was evaluated using the phenol red technique. In terms of body composition, total body water (TBW), body mass index (BMI), and fat-free mass (FFM) were higher in the ileitis group (216.80 ± 11.44 mL; 24.09 ± 2.15 g/cm²; 287.1 ± 14.66 g) (p < 0.05) vs. control rats (130.06 ± 28.23 mL; 16.38 ± 2.50 g/cm²; 193 ± 42.21 g) and exercise prevented (91.33 ± 12.33 mL; 11.73 ± 0.47 g/cm²; 133.8 ± 16.82 g) (p < 0.05) these changes. The exercise+ileitis group induces a reduction (p < 0.05) in gastric retention vs. ileitis and control (11.22 ± 1.91% vs. 35.17 ± 1.01% and 33.96 ± 1.77%). Ileitis increased intestinal retention in the duodenum (46.3 ± 2.56% vs. 24.98 ± 1.78%) and jejunum (34.22 ± 2.33% and 34.72 ± 2.83% vs. 47.32 ± 1.48%) (p < 0.05) and decreased intestinal retention in the ileum (p < 0.05) vs. the control group. Exercise+ileitis prevented (p < 0.05) changes in the duodenum (24.96 ± 1.66% vs. 46.3 ± 2.56%) and ileum (40.32 ± 3.75% vs. 14.08 ± 0.88%). Ileitis induces high MDA levels (p < 0.05) vs. control rats (4.43 ± 0.69 vs. 2.15 ± 0.12 nmol/mg of the tissue). This effect was prevented (p < 0.05) in the exercise+ileitis group (2.75 ± 0.21 vs. 4.43 ± 0.69 nmol/mg of the tissue). We observed a reduction in the LF component (p < 0.05) in the ileitis group vs. control group (31.32 ± 3.99 vs. 43.43 ± 3.86). The correlation indicated a stronger interrelationship between the autonomic parameter and intestinal retention in the ileum (r: 0.68; p: 0.04). The current study suggests intestinal ileitis alters GI motility and autonomic balance, and physical exercise can represent an essential non-pharmacological approach to IBD treatment. Full article

Microalgae, a marine-derived natural ingredient, has emerged as a rich source of bioactive compounds with the potential to modulate gut–brain axis activities. The objective of this study was to investigate whether supplementation with a microalgae extract from Tetradesmus obliquus strain Mi175.B1.a (TOME) influences gut health and reduces stress and anxiety in healthy adults experiencing mild to moderate gastrointestinal (GI) distress. Methods: Fifty-six healthy adults (age: 31.9 ± 7.7 years; body weight: 71.8 ± 12.6 kg; BMI: 24.6 ± 2.8 kg/m²) were enrolled in a randomized, double-blind, placebo-controlled, parallel-arm clinical trial. Participants were randomly allocated to receive capsules containing either 250 mg/day of TOME or a placebo for four weeks. Primary outcomes included the assessment of GI symptoms using the Gastrointestinal Symptom Rating Scale (GSRS) and Bristol Stool Scale (BSS). Secondary outcomes focused on subjective evaluation of mood, stress, and anxiety, as well as blood pressure responses to sympathetic nervous system activation induced by the cold pressor test (CPT). In addition, stool, plasma, and saliva samples were collected to assess biomarkers associated with stress, sympathetic activation, intestinal permeability, and GI health. 16S rRNA sequencing was performed to analyze changes in gut microbial populations. Results: Daily supplementation for four weeks with TOME was safe and well tolerated in the study population. In addition, TOME significantly reduced GSRS global scores (p = 0.02), as well as constipation (p = 0.05) and indigestion (p = 0.03) subcomponent scores compared to Placebo. There was also a significant increase in Shannon’s index before FDR correction (p = 0.05; FDR = 0.12) and stool butyrate level was significantly lower in the TOME group than in Placebo after 4 weeks of supplementation (p = 0.039). Both groups showed a significant reduction in perceived stress scores, but the TOME intervention group also had reduced Negative Affect scores (p < 0.001). In addition, plasma chromogranin A, a stress biomarker, was significantly reduced after TOME intervention (p = 0.03). There were no negative effects on blood lipids or other parameters related to sympathetic activation or cardiovascular health. Conclusions: Overall, these results suggest that 4-week supplementation with T. obliquus strain Mi175.B1.a improves GI symptoms, potentially through effects on the gut microbiota, and may promote positive effects on mental health. Additional research should follow up on mental health outcomes in populations with increased stress and anxiety and investigate mechanisms underlying improvements in GI health. This trial was registered at clinicaltrials.gov as NCT06425094. Full article

Background: Meckel’s diverticulum on the mesenteric side has been reported only as case reports in the literature and presents a diagnostic challenge, with ultimate recognition often taking place intraoperatively. We describe a case series of children with mesenteric Meckel’s diverticulum (MMD) treated at our institution, along with the results of a systematic review of the literature. Methods: Our experience on MMD was analyzed along with a systematic literature review performed according to PRISMA criteria. We identified studies published from 1941 to 2023 from PubMed, EMBASE, SCOPUS, and WOS. Search terms were variations of “Meckel”, “diverticulum”, and “mesenteric”. Inclusion criteria were patients < 18 years of age and articles written in English. Results: A total of three cases of MMD were observed and treated in our hospital. The mean age was 7.6 years. The most common symptoms were rectal bleeding and abdominal pain. Diagnostic workup included ultrasound and both upper and lower endoscopy. Surgery was performed by the laparoscopy-assisted technique. One case had to be reoperated due to postoperative intestinal occlusion. The mean length of hospital stay was 9.3 days. The literature search yielded 795 citations; out of the 590 papers remaining after the exclusion of 205 duplications, only 15 papers matched the inclusion criteria and were included and analyzed. Conclusions: MMD remains a rare and elusive pathology, sharing with its normal counterpart symptoms and signs. In our experience, and in the more recent literature, laparoscopy-assisted surgery appears safe and effective both for final diagnosis and definitive treatment. Full article

The blood–brain barrier (BBB) is essential for maintaining brain homeostasis by regulating molecular exchange between the systemic circulation and the central nervous system. However, its dysfunction, often driven by peripheral inflammatory processes, has been increasingly linked to the development and progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Emerging evidence suggests that the gut–brain axis plays a key role in BBB integrity, with intestinal dysbiosis and chronic inflammation contributing to barrier disruption through immune and metabolic pathways. Furthermore, the selective vulnerability of specific brain regions to BBB dysfunction appears to be influenced by regional differences in vascularization, metabolic activity, and permeability, making certain areas more susceptible to neurodegenerative processes. This review explored the molecular mechanisms linking peripheral inflammation, gut microbiota, and BBB dysfunction, emphasizing their role in neurodegeneration. A comprehensive literature review was conducted using Web of Science, PubMed, Scopus, Wiley, ScienceDirect, and Medline, covering publications from 2015 to 2025. The findings highlight a complex interplay between gut microbiota-derived metabolites, immune signaling, and BBB permeability, underscoring the need for targeted interventions such as microbiome modulation, anti-inflammatory therapies, and advanced drug delivery systems. The heterogeneity of the BBB across different brain regions necessitates the development of region-specific therapeutic strategies. Despite advancements, critical knowledge gaps persist regarding the precise mechanisms underlying BBB dysfunction. Future research should leverage cutting-edge methodologies such as single-cell transcriptomics and organ-on-chip models to translate preclinical findings into effective clinical applications. Addressing these challenges will be crucial for developing personalized therapeutic approaches to mitigate the impact of BBB dysfunction in neurodegenerative diseases. Full article

Sulfamethoxazole (SMX), a commonly used sulfonamide antibiotic, poses a threat to aquatic life due to its widespread presence in the environment. This study aims to investigate the specific effects of SMX on the development of marine medaka (Oryzias melastigma) embryos and larvae. Marine medaka embryos were exposed to SMX at concentrations of 0 (solvent control group, SC group), 1 μg/L (low concentration group, L group), 60 μg/L (middle concentration group, M group), and 1000 μg/L (high concentration group, H group). The results indicated that SMX exposure significantly accelerated the heart rate of embryos (p < 0.0001) and shortened the hatching time while also causing anomalies such as reduced pigmentation, smaller eye size, spinal curvature, and yolk sac edema. SMX also led to a decrease in the total length of the larvae. The M group and the H group exhibited a significant increase (p < 0.05) in lipid accumulation in the visceral mass of the larvae. In the L group and the M group, there was a significant increase (p < 0.0001) in the swimming distance of the larvae. At the molecular level, SMX exposure affected the transcript levels of the genes involved in the cardiovascular system (ahrra, arnt2, atp2a1, and cacan1da), antioxidant and inflammatory systems (cat, cox-1, gpx, pparα, pparβ, and pparγ), nervous system (gap43, gfap, α-tubulin), intestinal barrier function (claudin-1), detoxification enzymes (ugt2c1-like), and lipid metabolism (rxraa) in the embryos to larval stage. The microbiome analysis showed that at the phylum level, exposure to SMX resulted in an increase in the abundance of Proteobacteria. Additionally, the abundance of Actinobacteriota significantly increased in the L group (p < 0.05). At the genus level, the abundance of Bifidobacterium significantly increased in the L group (p < 0.05), while the abundance of Vibrio significantly increased in the H group (p < 0.05). The alpha diversity analysis revealed a significant decrease in the Chao1 index in the L and H groups, indicating a reduction in microbial richness. The beta diversity analysis showed differences in the microbial communities of marine medaka larvae among different SMX exposure groups. This study elucidates the negative impacts of SMX on the development of marine medaka embryos and larvae and their microbial composition, providing a scientific basis for assessing the risks of SMX in marine ecosystems. Full article

The transfer time of Atlantic salmon smolts from freshwater to seawater remains a challenge in aquaculture, with the “smolt window” referring to the optimal timeframe for seawater readiness. Our study monitored Atlantic salmon osmoregulatory adaptations during smoltification under continuous light (LL) and winter signal regime (6 weeks LD 12:12) followed by 6 or 8 weeks of constant light. Fish were subsequently reared in seawater for 8 weeks and subjected to a stress event of cyclic hypoxia at the conclusion of the trial. Significant differences in growth trajectories were observed between the LL and LD groups, with fish receiving the winter signal showing compensatory growth after seawater transfer. Gill Na⁺/K⁺-ATPase (NKA) activity, plasma ions, glucose, and cortisol levels confirmed the importance of the winter signal for seawater adaptation. Molecular markers, including nka isoforms, Na⁺-K⁺-2Cl⁻ cotransporter (nkcc), cystic fibrosis transmembrane conductance regulator (cftr), and Na⁺/HCO₃⁻ cotransporter (nbc), showed distinct temporal expression patterns, particularly in gills and midgut. Notably, the LD group with delayed seawater transfer exhibited enhanced growth and improved hypo-osmoregulatory capacity. These findings underscore the advantages of a winter signal in smoltification and suggest that delaying seawater transfer for up to 8 weeks could be beneficial. Full article

Bowel sounds, produced by intestinal peristalsis, are essential for diagnosing gastrointestinal disorders. However, acquiring and analyzing bowel sounds is challenging due to their unpredictable nature and individual variability. Biological tissues can affect bowel sounds during propagation, resulting in varying degrees of signal attenuation between the sound source and the transducer. This study aims to develop a numerical model of bowel sound propagation in the abdominal cavity, focusing on the impact of different biological layers on signal attenuation. Validation of the model demonstrated strong consistency between simulated and actual bowel sound signals, confirming the model’s accuracy and reliability. The model accounted for adipose tissue thickness, ranging from 5 to 20 mm across individuals, while muscle and skin thicknesses remained constant. Results indicated that signal attenuation increases with both the propagation distance and adipose tissue thickness. These findings provide insights into how tissue layers influence bowel sound propagation, offering a theoretical foundation for developing personalized and precise monitoring devices. Full article