Search Results (33)

The Golgi of goblet cells represents a specialized machine for mucin glycosylation. This process occurs in a specialized form of the secretory pathway, which remains poorly examined. Here, using high-resolution three-dimensional electron microscopy (EM), EM tomography, serial block face scanning EM (SBF-SEM) and immune EM we analyzed the secretory pathway in goblet cells and revealed that COPII-coated buds on the endoplasmic reticulum (ER) are extremely rare. The ERES vesicles with dimensions typical for the COPII-dependent vesicles were not found. The Golgi is formed by a single cisterna organized in a spiral with characteristics of the cycloid surface. This ribbon has a shape of a cup with irregular perforations. The Golgi cup is filled with secretory granules (SGs) containing glycosylated mucins. Their diameter is close to 1 µm. The cup is connected with ER exit sites (ERESs) with temporal bead-like connections, which are observed mostly near the craters observed at the externally located cis surface of the cup. The craters represent conus-like cavities formed by aligned holes of gradually decreasing diameters through the first three Golgi cisternae. These craters are localized directly opposite the ERES. Clusters of the 52 nm vesicles are visible between Golgi cisternae and between SGs. The accumulation of mucin, started in the fourth cisternal layer, induces distensions of the cisternal lumen. The thickness of these distensions gradually increases in size through the next cisternal layers. The spherical distensions are observed at the edges of the Golgi cup, where they fuse with SGs and detach from the cisternae. After the fusion of SGs located just below the apical plasma membrane (APM) with APM, mucus is secreted. The content of this SG becomes less osmiophilic and the excessive surface area of the APM is formed. This membrane is eliminated through the detachment of bubbles filled with another SG and surrounded with a double membrane or by collapse of the empty SG and transformation of the double membrane lacking a visible lumen into multilayered organelles, which move to the cell basis and are secreted into the intercellular space where the processes of dendritic cells are localized. These data are evaluated from the point of view of existing models of intracellular transport. Full article

The greater amberjack (Seriola dumerili), a key species in marine aquaculture, relies heavily on its intestine for nutrient absorption and immune function. However, the structural and functional specialization of its intestinal segments remains poorly understood. In this study, we divided the intestine of S. dumerili into foregut, midgut, and hindgut, and conducted a multi-omics analysis integrating histological staining (H&E/AB-PAS), digestive enzyme assays, transcriptome sequencing, and 16S rRNA microbiota profiling to characterize structural, functional, molecular, and microbial differences across intestinal segments. Histological examinations revealed that brush border microvillus length, muscle layer thickness, and folding height were significantly greater in the foregut and hindgut compared to the midgut, while mucus and goblet cell density was higher in the foregut and midgut. Digestive enzyme assays showed that lipase activity peaked in the foregut, α-amylase in the midgut, and protease in the midgut and hindgut. Alkaline phosphatase (AKP) and acid phosphatase (ACP) activities were highest in the foregut and midgut. Immune-related enzyme activities (SOD (Superoxide dismutase), GSH-Px (Glutathione peroxidase), T-AOC (Total Antioxidant Capacity)) were elevated and MDA levels were lower in the midgut, indicating its role as the primary immune site. Transcriptome analysis identified segment-specific expression of nutrient transporters, such as slc6a19b (hindgut, protein), apoa1b (foregut, lipid), and slc37a4 (midgut, carbohydrate). Microbiome analysis revealed Ruminococcus dominance in the foregut (lipid digestion) and Prevotella, Bifidobacterium, and Lactobacillus enrichment in the midgut (carbohydrate metabolism and immunity). These findings highlight functional zonation in S. dumerili: the foregut specializes in lipid digestion, the midgut in carbohydrate metabolism and immunity, and the hindgut in protein digestion. This study provides foundational insights for optimizing aquaculture practices and advancing research in nutrition, immunology, and disease modeling in S. dumerili. Full article

Probiotics have gained increasing recognition for their potential to mitigate antibiotic-associated diarrhea (AAD). However, the precise mechanisms underlying their effects remain unclear. This study developed a mouse model of AAD using ceftriaxone to investigate the alleviating effects and mechanisms of Bifidobacterium animalis A6 (A6). The findings indicated that A6 supplementation effectively attenuated ceftriaxone-associated diarrhea in mice. The morphological damage to the villi and crypts was partially restored and more neatly reorganized following the A6 intervention. Additionally, intestinal morphology observations revealed a significant increase in the thickness of the mucus layer in the A6-treated group. Further examination of key regulatory genes associated with mucus secretion demonstrated that the A6 intervention effectively upregulated the expression of mucin1, thereby reinforcing the mucus layer. Concurrently, the A6 intervention upregulated the expression of the AQP4 and SLC26A3 genes in the intestine, which is responsible for restoring water absorption capacity in AAD mice. Additionally, the A6 treatment reduced ceftriaxone-induced harm to the intestinal microbiota of the mice, boosting beneficial bacteria like Bacteroidales, Akkermansia, Bifidobacterium, and Lactobacillus. Overall, this study offers valuable insights into the potential therapeutic role of A6 in restoring intestinal homeostasis and alleviating symptoms associated with AAD. Full article

Underwater vehicles typically rely on batteries or other energy sources for operation, where drag reduction can significantly lower energy consumption and extend operational endurance. Inspired by the skin structure of loaches, a flexible structure with scales and mucus pores was designed. First, numerical simulations were conducted. To accurately demonstrate the interaction between the flexible flow field and the fluid flow field and to capture the movement boundaries of the plates, a bidirectional fluid–structure interaction simulation method was used. The numerical results indicate that the flexible structure has a positive effect on drag reduction. In channel experiments, the drag reduction effects of flexible and non-flexible structures were compared. Both showed optimal drag reduction at a water flow speed of 2 m/s and mucus flow speed of 0.1 m/s. The maximum drag reduction rate for the flexible structure was 28.5%, compared to 22.8% for the non-flexible structure. This difference is attributed to the flexible structure altering the flow pattern of the near-wall boundary layer, reducing the velocity gradient of the boundary layer, and increasing its thickness. The findings of this study can provide guidance for future research on flexible surface drag reduction technologies. Full article

Cystic fibrosis (CF), also known as mucoviscidosis, is the most common autosomal recessive genetic disease in the Caucasian population, with an estimated frequency of 1:2000–3000 live births. CF results from the mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene localized in the long arm of chromosome 7. The product of CFTR gene expression is CFTR protein, an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that regulates the transport of chloride ions (Cl⁻) across the apical cell membrane. Primary manifestations of CF include chronic lung and pancreas function impairment secondary to the production of thick, sticky mucus resulting from dehydrated secretions. It is well known that CF can cause both anterior and posterior ocular abnormalities. Conjunctival and corneal xerosis and dry eye disease symptoms are the most characteristic manifestations in the anterior segment. In contrast, the most typical anatomical and functional changes relating to the posterior segment of the eye include defects in the retinal nerve fiber layer (RNFL), vascular abnormalities, and visual disturbances, such as reduced contrast sensitivity and abnormal dark adaptation. However, the complete background of ophthalmic manifestations in the course of CF has yet to be discovered. This review summarizes the current knowledge regarding ocular changes in cystic fibrosis. Full article

Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). Ureaplasma parvum (UP) is clinically the most isolated microorganism in chorioamnionitis, but its pathogenicity remains debated. Chorioamnionitis is associated with ileal barrier changes, but colonic barrier alterations, including those of the mucus barrier, remain under-investigated, despite their importance in NEC pathophysiology. Therefore, in this study, the hypothesis that antenatal UP exposure disturbs colonic mucus barrier integrity, thereby potentially contributing to NEC pathogenesis, was investigated. In an established ovine chorioamnionitis model, lambs were intra-amniotically exposed to UP or saline for 7 d from 122 to 129 d gestational age. Thereafter, colonic mucus layer thickness and functional integrity, underlying mechanisms, including endoplasmic reticulum (ER) stress and redox status, and cellular morphology by transmission electron microscopy were studied. The clinical significance of the experimental findings was verified by examining colon samples from NEC patients and controls. UP-exposed lambs have a thicker but dysfunctional colonic mucus layer in which bacteria-sized beads reach the intestinal epithelium, indicating undesired bacterial contact with the epithelium. This is paralleled by disturbed goblet cell MUC2 folding, pro-apoptotic ER stress and signs of mitochondrial dysfunction in the colonic epithelium. Importantly, the colonic epithelium from human NEC patients showed comparable mitochondrial aberrations, indicating that NEC-associated intestinal barrier injury already occurs during chorioamnionitis. This study underlines the pathogenic potential of UP during pregnancy; it demonstrates that antenatal UP infection leads to severe colonic mucus barrier deficits, providing a mechanistic link between antenatal infections and postnatal NEC development. Full article

This study aimed to determine the effects of Zn sources, used with potato fiber (PF) or lignocellulose (LC), on electrolyte concentration and the mucus layer in the large intestine of pigs. The experiment involved 24 barrows with an initial body weight of 10.8 ± 0.82 kg, divided into four groups fed the following diets: LC and ZnSO₄, LC and Zn glycinate (ZnGly), PF and ZnSO₄, or PF and ZnGly. Fiber supplements provided 10 g crude fiber/kg diet, while Zn additives introduced 120 mg Zn/kg diet. After four weeks of feeding, the pigs were sacrificed and digesta and tissue samples were taken from the cecum and colon. PF increased the water content and decreased the phosphorus concentration in the large intestine in comparison with LC. PF also increased calcium, iron, and chloride concentrations in the descending colon. Mucus layer thickness and histological parameters of the large intestine were not affected. ZnGly diets increased MUC12 expression in the cecum as compared to the LC-ZnSO₄ group. In the ascending colon, the PF-ZnGly diet increased MUC5AC expression, while both PF groups had greater MUC20 expression in comparison with the LC-ZnSO₄ group. In the transverse colon, the LC-ZnGly group and both PF groups had higher MUC5AC expression in comparison with the LC-ZnSO₄ group, and both ZnGly groups had higher MUC20 expression than ZnSO₄ groups. PF and ZnGly increased MUC4 and MUC5AC expression in the descending colon. PF and ZnGly may exert a beneficial effect on colon health in pigs by upregulating the expression of the MUC5AC and MUC20 genes and are more effective than LC and ZnSO₄. Full article

Alcoholic liver disease (ALD) represents a significant global health concern, yet the available treatment options remain limited. Numerous studies have shown that gut microbiota is a critical target for the treatment of ALD. Additionally, there is increasing evidence that host metabolism also plays a crucial role in the development of ALD. Akkermansia muciniphila has been demonstrated to ameliorate experimental ALD through its modulatory effects on the intestinal vascular barrier, enhancement of mucus layer thickness, and promotion of intestinal tight junction proteins. Nevertheless, there is a dearth of studies investigating the impact of A. muciniphila on host metabolism and gut microbiota. Here, C57BL/6 mice were utilized to establish a modified NIAAA model in order to investigate the impact of the oral administration of A. muciniphila during the development of ALD. Furthermore, we employed targeted metabolomics to analyze the serum metabolomic profiles of the mice and 2bRAD-M sequencing to comprehensively examine the underlying mechanisms of the efficacy of A. muciniphila on ALD. Our results illustrated that the oral administration of A. muciniphila alleviated alcohol-induced liver injury in conjunction with encouraged serum levels of ornithine and diminished the elevation of oxalic acid levels induced by alcohol intake. In addition, A. muciniphila also inhibited the proliferation of harmful bacteria, such as Escherichia coli and Helicobacter hepaticus, induced by alcohol consumption while promoting the growth of butyrate-producing and commensal bacteria, including Paramuribaculum intestinale and Bacteroides ovatus. In conclusion, this study suggests that A. muciniphila restores ALD by regulating the gut microbiota, and this corrective effect is associated with alterations in the serum metabolism. Our research supplies a theoretical basis for developing A. muciniphila as an innovative generation of probiotic for preventing and managing ALD. Full article

Glasswort (Salicornia herbacea L.) is a halophyte plant known to contain high contents of minerals and phytochemicals. The purpose of this study was to investigate the effect of fermented glasswort on gut health in D-galactose (D-gal)-induced aging rats. Forty rats were randomly divided into five groups: control (CON), D-gal alone (CD), D-gal plus fructooligosaccharide as a positive control (FOS, 400 mg/kg), D-gal plus low dose fermented glasswort (LGW, 10 mg/kg), and D-gal plus high-dose fermented glasswort (HGW, 20 mg/kg). Each treatment was orally administered to rats of each group for eight weeks. All groups except for the CON group (treated with saline) were intraperitoneally injected with D-gal (150 mg/kg). Our results showed that butyric acid among short-chain fatty acids (SCFAs), goblet cells of colon, and thickness of mucus layer in colon were increased in fermented glasswort groups. In addition, fermented glasswort reduced levels of thiobarbituric acid-reactive substances (TBARS, a related oxidative stress marker) and expression levels of inflammation-related proteins such as IL-1β. These results suggest that fermented glasswort can improve age-related gut health. Full article

Consumed food travels through the gastrointestinal tract to reach the small intestine, where it interacts with the microbiota, forming a complex relationship with the dietary components. Here we present a complex in vitro cell culture model of the small intestine that includes human cells, digestion, a simulated meal, and a microbiota represented by a bacterial community consisting of E. coli, L. rhamnosus, S. salivarius, B. bifidum, and E. faecalis. This model was used to determine the effects of food-grade titanium dioxide nanoparticles (TiO₂ NPs), a common food additive, on epithelial permeability, intestinal alkaline phosphatase activity, and nutrient transport across the epithelium. Physiologically relevant concentrations of TiO₂ had no effect on intestinal permeability but caused an increase in triglyceride transport as part of the food model, which was reversed in the presence of bacteria. Individual bacterial species had no effect on glucose transport, but the bacterial community increased glucose transport, suggesting a change in bacterial behavior when in a community. Bacterial entrapment within the mucus layer was reduced with TiO₂ exposure, which may be due to decreased mucus layer thickness. The combination of human cells, a synthetic meal, and a bacterial mock community provides an opportunity to understand the implications of nutritional changes on small intestinal function, including the microbiota. Full article

During aging, the protective function of mucus barrier is significantly reduced among which changes in colonic mucus barrier function received the most attention. Additionally, the incidence of colon-related diseases increases significantly in adulthood, posing a threat to the health of the elderly. However, the specific changes in colonic mucus barrier with aging and the underlying mechanisms have not been fully elucidated. To understand the effects of aging on the colonic mucus barrier, changes in the colonic mucus layer were evaluated in mice aged 2, 12, 18, and 24 months. Microbial invasion, thickness, and structure of colonic mucus in mice at different months of age were analyzed by in situ hybridization fluorescence staining, AB/PAS staining, and cryo-scanning electron microscopy. Results showed that the aged colon exhibited intestinal mucus barrier dys-function and altered mucus properties. During aging, microorganisms invaded the mucus layer to reach epithelial cells. Compared with young mice, the thickness of mucus layer in aged mice in-creased by 11.66 μm. And the contents of the main components and glycosylation structure of colon changed. Among them, the proportion of goblet cells decreased significantly in older mice, and the expression of spdef genes that regulate goblet cell differentiation decreased. Further, the expression of key enzymes involved in mucin core structure formation and glycan modification also changed with aging. The expression of core 1 β1,3-galactosyltransferase (C1GalT1) which is the key enzyme forming the main core structure increased by one time, while core 2 β1,6 N-acetylglucosaminyltransferase (C2GnT) and core 3 β1,3 N-acetylglucosaminyltransferase (C3GnT) decreased 2 to 6- and 2-fold, respectively. Also, the expression of sialyltransferase, one of the mucin-glycan modifying enzymes, was decreased by 1-fold. Overall, our results indicate that the goblet cells/glycosyltransferase/O-glycan axis plays an important role in maintaining the physicochemical properties of colonic mucus and the stability of intestinal environment. Full article

Defatted rice bran (DRB) is a by-product of rice bran derived after the oil extraction. DRB contains several bioactive compounds, including dietary fiber and phytochemicals. The supplementation with DRB manifests chemopreventive effects in terms of anti-chronic inflammation, anti-cell proliferation, and anti-tumorigenesis in the azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colitis-associated colorectal cancer (CRC) model in rats. However, little is known about its effect on gut microbiota. Herein, we investigated the effect of DRB on gut microbiota and short chain fatty acid (SCFA) production, colonic goblet cell loss, and mucus layer thickness in the AOM/DSS-induced colitis-associated CRC rat model. The results suggested that DRB enhanced the production of beneficial bacteria (Alloprevotella, Prevotellaceae UCG-001, Ruminococcus, Roseburia, Butyricicoccus) and lessened the production of harmful bacteria (Turicibacter, Clostridium sensu stricto 1, Escherichia–Shigella, Citrobacter) present in colonic feces, mucosa, and tumors. In addition, DRB also assisted the cecal SCFAs (acetate, propionate, butyrate) production. Furthermore, DRB restored goblet cell loss and improved the thickness of the mucus layer in colonic tissue. These findings suggested that DRB could be used as a prebiotic supplement to modulate gut microbiota dysbiosis, which decreases the risks of CRC, therefore encouraging further research on the utilization of DRB in various nutritional health products to promote the health-beneficial bacteria in the colon. Full article

The European beaver is a herbivorous rodent whose diet changes seasonally, and in winter consists of large quantities of woody plants. It is distinguished among other mammals by a unique organization of the stomach that comprises the cardiogastric gland and by the unusual process of mucus formation in the gastric mucosa. The aim of study was to (i) characterize the structure of the beaver esophagus with particular attention to the mucosal epithelium; (ii) compare the histological structure of the esophagi collected in spring, summer, and winter; (iii) provide preliminary data on the structure of the esophagus in beaver fetuses. The study was conducted on esophagi of 18 adult beavers captured in Poland in April, August, and December, and on 3 fetal organs. The results obtained in adults show that the mucosa is lined with thick stratified squamous keratinized epithelium with a structure similar to that of the skin epidermis. Ultrastructural studies reveal the presence of multiple lamellar and non-lamellar bodies in granular cells, whose morphology and location gradually change while reaching the upper epithelial layers. The muscularis mucosa comprises a layer of longitudinally oriented bundles of smooth muscle cells. Both mucosa and submucosa do not comprise any glands. The thick muscularis externa consists mainly of internal circular and external longitudinal layers of striated muscle fibers. The keratinized layer of mucosa epithelium was 2-3-fold thicker in esophagi collected in winter than in those collected in spring and summer, while the epithelial cell layer thickness remained unchanged regardless of the season. Immunolabeling for proliferating cell nuclear antigen shows a higher index of epithelium proliferation in esophagi collected in winter than in spring and summer. No seasonal differences were noted in other layers of the esophagus. Fetal organs have epithelium covered with a keratinized layer, thinner than in adults, and the muscularis externa comprises both striated and smooth muscle cells. Full article

Skin is a natural barrier between the body and the external environment, and this important multifunctional organ plays roles in body temperature regulation, sensory stimulation, mucus secretion, metabolite excretion and immune defense. Lampreys, as ancient vertebrates, rarely experience infection of damaged skin during farming and efficiently promote skin wound healing. However, the mechanism underlying these wound healing and regenerative effects is unclear. Our histology and transcriptomics results demonstrate that lampreys regenerate a nearly complete skin structure in damaged epidermis, including the secretory glands, and will almost not be infected, even if experiencing full-thickness damage. In addition, ATGL, DGL and MGL participate in the lipolysis process to provide space for infiltrating cells. A large number of red blood cells migrate to the site of injury and exert proinflammatory effects, upregulating the expression of proinflammatory factors such as IL-8 and IL-17. Based on a lamprey skin damage healing model, adipocytes and red blood cells in the subcutaneous fat layer can promote wound healing, which provides a new approach for the study of skin healing mechanisms. Transcriptome data reveal that mechanical signal transduction pathways are mainly regulated by focal adhesion kinase and that the actin cytoskeleton plays an important role in the healing of lamprey skin injuries. We identified RAC1 as a key regulatory gene that is necessary and partially sufficient for wound regeneration. Insights into the mechanisms of lamprey skin injury and healing will provide a theoretical basis for overcoming the challenges associated with chronic healing and scar healing in the clinic. Full article

Type 2 diabetes (T2D) is usually accompanied by obesity and nonalcoholic fatty-liver-related insulin resistance. The link between T2D and dysbiosis has been receiving increasing attention. Probiotics can improve insulin sensitivity by regulating imbalances in microbiota, but efficacy varies based on the probiotic used. This study screened the main strain in the feces of healthy adult mice and found it to be a new Lactobacillus (abbreviated as Lb., named as CGMCC No. 21661) after genetic testing. We designed the most common Bifidobacterium longum subsp. longum (CGMCC1.2186, abbreviated as B. longum. subsp.), fecal microbiota transplantation (FMT), and Lb. CGMCC No. 21661 protocols to explore the best way for modulating dysbiosis to improve T2D. After 6 weeks of gavage in T2D mice, it was found that all three protocols had a therapeutic alleviating effect. Among them, compared with the B. longum. subsp. and FMT, the Lb. CGMCC No. 21661 showed a 1- to 2-fold decrease in blood glucose (11.84 ± 1.29 mmol/L, p < 0.05), the lowest HOMA-IR (p < 0.05), a 1 fold increase in serum glucagon-like peptide-1 (5.84 ± 1.1 pmol/L, p < 0.05), and lowest blood lipids (total cholesterol, 2.21 ± 0.68 mmol/L, p < 0.01; triglycerides, 0.4 ± 0.15 mmol/L, p < 0.01; Low-density lipoprotein cholesterol, 0.53 ± 0.16 mmol/L, p < 0.01). In addition, tissue staining in the Lb. CGMCC No. 21661 showed a 2- to 3-fold reduction in T2D-induced fatty liver (p < 0.0001), a 1- to 2-fold decrease in pancreatic apoptotic cells (p < 0.05), and a significant increase in colonic mucus layer thickness (p < 0.05) compared with the B. longum. subsp. and FMT. The glucose and lipid lowering effects of this Lb. CGMCC No. 21661 indicate that it may provide new ideas for the treatment of diabetes. Full article