Intestinal Uptake Research Articles

The effect of butylscopolamine on [18F]FDG uptake in the gastrointestinal tract is negligible and regionally variable

BackgroundButylscopolamine (or hyoscine butylbromide, trade name Buscopan®) is occasionally administered as a premedication to reduce non-specific FDG uptake in the gastrointestinal tract based on its antiperistaltic effect. To date, there are no consistent recommendations for its use. The aim of this study was to quantify the reduction in intestinal and non-intestinal uptake by butylscopolamine administration and to derive relevance for clinical evaluation.Results458 patients (PET/CT for lung cancer) were retrospectively reviewed. 218 patients with butylscopolamine and 240 patients without butylscopolamine had comparable characteristics. While the SUVmean in the gullet/stomach and small intestine was significantly reduced with butylscopolamine, the colon and rectum/anus showed no difference. The liver and salivary glands showed a reduced SUVmean, while skeletal muscle and blood pool were unaffected. An effect of butylscopolamine was particularly evident in men and patients under 65 years of age. There was no difference in the perceived confidence in the assessment of intestinal findings in the subjective evaluation, although in the butylscopolamine group further diagnostics appeared advisable more frequently.ConclusionsButylscopolamine reduces gastrointestinal FDG accumulation only in selected segments and, despite a significant effect, only to a small extent. A general recommendation for the use of butylscopolamine cannot be derived from these results, its use for specific issues could be considered individually.

Antidiabetic Activity of <i>Vasant Kusumakar Ras</i> in Streptozotocin and High Fat Diet Induced Type 2 Diabetes Mellitus in Sprague Dawley Rats

Background: VasantKusumakar Ras (VK Ras) is a traditional Ayurvedic preparation used in the treatment of Type-2 diabetes mellitus. Despite its clinical anti-diabetic claims, no pre-clinical attempts were made to rule out its efficacy as an antidiabetic agent. Objectives: The present study was carried out to find the anti-diabetic effect of VK Ras against a High-Fat Diet (HFD), and low-dose streptozotocin (STZ) induced type 2 diabetes and to explore the mode of action of VK Ras. Materials and Methods: Different doses of VK Ras were administered to diabetic rats for 35 days. The biochemical markers analysis, intestinal glucose uptake, and liver glycogen content were estimated at the end of the study and also vital organs were weighed and subjected to histopathological evaluation. Results: VK Ras treatment reduced blood glucose in a dose-dependent manner. The insulin, HbA1C, HOMA-IR, and lipid profiles were improved in VK Ras-treated animals as compared to diabetic control animals. The relative organ weights were changed in diabetic rats, and treatment with VK Ras corrected the organ weights. Intestinal glucose uptake and liver glycogen content were decreased with treatment. Further, the histopathological analysis of the pancreas and other vital organs had shown that dose-dependent restoration of organ function with VK Ras treatment. Conclusions: VK Ras treatment reduces insulin resistance as well as corrects the lipid, hepatic and renal abnormalities that arise from diabetes, these effects may be mediated by interfering with glucose transport from the gut and insulin release from the β pancreatic cells.

Fibroblast Growth Factor 23 Bone Regulation and Downstream Hormonal Activity.

Mineral homeostasis of calcium and phosphate levels is one critical component to the maintenance of bone mineral density (BMD) and strength. Diseases that disrupt calcium and phosphate balanced have highlighted not only the role these minerals play in overall bone homeostasis, but also the factors, hormones and downstream transporters, responsible for mineral metabolism. The key phosphaturic hormone elucidated from studying rare heritable disorders of hypophosphatemia is Fibroblast Growth Factor 23 (FGF23). FGF23 is predominantly secreted from bone cells in an effort to maintain phosphate balance by directly controlling renal reabsorption and indirectly affecting intestinal uptake of this mineral. Multiple factors have been shown to enhance bone mRNA expression; however, FGF23 can also undergo proteolytic cleavage to control secretion of the biologically active form of the hormone. The review focuses specifically on the regulation of FGF23 and its secretion from bone as well as its hormonal actions under physiological and disease conditions.

Oral drug delivery: Influence of mucus on cellular interactions and uptake of lipid-based nanocarriers in Caco-2 cells

This study aimed to investigate the impact of the mucus gel barrier on intestinal mucosal uptake of lipid-based nanocarriers (NCs). Zwitterionic- (ZW), polyglycerol- (PG) and polyethylene glycol- (PEG) surfactant-based o/w nanoemulsions were developed. NCs were assessed regarding their size and zeta potential, stability in biorelevant media and mucus, mucus permeation behavior, cellular interactions and uptake by Caco-2 cells with and without mucus and by a Caco-2/HT29-MTX co-culture. All NCs were in the size range of 178 – 204 nm and exhibited a zeta potential between -4.2 and +1.2 mV. ZW- and PG-NCs demonstrated mucus permeating properties comparable to PEG-NCs. In contrast, ZW- and PG-NCs showed high cellular uptake, whereas limited cellular uptake was observed in case of PEG-NCs. Furthermore, mucus on Caco-2 cells as well as the mucus secreting co-culture had a significant impact on the cellular uptake of all tested NCs. According to these results, ZW- and PG-NCs are advantageous to overcome the mucus and epithelial barrier of the intestinal mucosa. Statement of significanceWithin this study the impact of mucus on cellular uptake of lipid-based nanocarriers (NCs) with different surface decorations was investigated. The potential of NCs with zwitterionic-, polyglycerol- and polyethylene glycol-surfactants on their surface to overcome the mucus and epithelial barrier was evaluated. Zwitterionic- and polyglycerol-NCs showed mucus permeating properties similar to PEG-NCs. In contrast, zwitterionic- and polyglycerol-NCs substantially outperformed PEG-NCs in their cellular uptake properties. According to these findings, zwitterionic- and polyglycerol-NCs have the potential to overcome both the mucus and epithelial barrier of the mucosa.

FRI-333 - Combination of intestinal bile salt uptake inhibition with pharmacological repression of bile salt synthesis improves liver health in cholestatic mice

FRI-333 - Combination of intestinal bile salt uptake inhibition with pharmacological repression of bile salt synthesis improves liver health in cholestatic mice

Development of active jejunal glucose absorption in broiler chickens

Growth in chickens, especially meat-type chickens (broilers), is extremely rapid, but studies on the regulatory mechanism of intestinal glucose absorption with growth are few, contradictory, and unclear. Here, we investigated the regulation of intestinal glucose absorption with growth in broiler chickens using oral glucose gavage, intestinal Evans blue transit, intestinal glucose absorption, scanning electron microscopy, and glucose absorption- and cell junction-related gene expression analyses. Peak blood glucose levels after oral glucose gavage occurred at 10 and 50 min in chickens at 1 wk (C1W) and 5 wk (C5W) of age, respectively. The area under the curve for glucose levels was greater for the C5W than the C1W (P=0.035). The stain ratio in the small intestine in the C5W was lower than that in the C1W (P=0.01), but there were no differences in the tissue regions stained with Evans blue and the migration distance of Evans blue from Meckel's diverticulum. In everted sac and Ussing chamber experiments, we observed reduced intestinal glucose uptake and electrogenic glucose absorption in the jejunum of the C5W. Phloridzin, an inhibitor of sodium/glucose cotransporter 1 (SGLT1), suppressed the glucose-induced short-circuit current in the C1W (P=0.016) but not the C5W. Although the addition of NaCl solution stimulated the glucose-induced short-circuit current in the C1W, no differences between the treatments were observed (P=0.056), which was also the case in the C5W. Additionally, tissue conductance was diminished in the C5W compared with that in the C1W. Moreover, in the C5W, the intestinal tract was more developed and the jejunal villi were enlarged. In conclusion, glucose absorption throughout the intestine could be greater in C5W than in C1W; however, reduced SGLT1 sensitivity, decreased ion permeability, and intestinal overdevelopment lead to decreased local glucose absorption in the jejunum with growth in broiler chickens. These data provide a detailed analysis of intestinal glucose absorption in growing broiler chickens, and can contribute to the development of novel feeds.

Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine

Chemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance and its underlying mechanisms in mice. We compared energy balance-associated parameters among the three groups of mice: CON, CYT, and PF (pair-fed mice with the CYT group) that were intravenously administered vehicle or CYT. Weight gain, fat mass, skeletal muscle mass, grip strength, and nocturnal energy expenditure were significantly lowered in the CYT group than in the CON and PF groups. The CYT group demonstrated less energy intake than the CON group and higher respiratory quotient than the PF group, indicating that CYT induced cachexia independently from the anorexia-induced weight loss. Serum triglyceride was significantly lower in the CYT group than in the CON group, whereas the intestinal mucosal triglyceride levels and the lipid content within the small intestine enterocyte were higher after lipid loading in the CYT group than in the CON and PF groups, suggesting that CYT inhibited lipid uptake in the intestine. This was not associated with obvious intestinal damage. The CYT group showed increased zipper-like junctions of lymphatic endothelial vessel in duodenal villi compared to that in the CON and CYT groups, suggesting their imperative role in the CYT-induced inhibition of lipid uptake. CYT worsens cachexia independently of anorexia by inhibiting the intestinal lipid uptake, via the increased zipper-like junctions of lymphatic endothelial vessel.

Lactobacillus fermentum MCC2760 abrogate high-fat induced perturbations in the enterohepatic circulation of bile acids in rats

This study in hyperlipidemic rats elucidated the effect of Lactobacillus fermentum MCC2760 on intestinal bile acid (BA) uptake, hepatic BA synthesis, and enterohepatic BA transporters. Diets rich in saturated fatty acids [coconut oil (CO)] and omega-6 fatty acids [sunflower oil (SFO)] at 25g fat/100g diet were fed to rats with or without MCC2760 (109 cells/kg body weight). After 60days of feeding, intestinal BA uptake and expression of Asbt, Osta/b mRNA and protein, and hepatic expression of Ntcp, Bsep, Cyp7a1, Fxr, Shp, Lrh-1, and Hnf4a mRNA were measured. Hepatic expression of HMG-CoA reductase protein and its activity and total BAs in serum, liver, and feces were assessed. Hyperlipidaemic groups (HF-CO and HF-SFO) had: 1) increased intestinal BA uptake, Asbt and Osta/b mRNA expression, and ASBT staining 2) increased BA in serum, 3) decreased hepatic expression of Ntcp, Bsep, and Cyp7a1 mRNA, and NTCP staining 4) increased activity of HMG-CoA reductase, 5) increased hepatic expression of Fxr and Shp mRNA, 6) decreased hepatic expression of Lrh-1 and Hnf4a mRNA, and 7) decreased BA in Feces when compared to their respective controls (N-CO and N-SFO) and experimental groups (HF-CO+LF and HF-SFO+LF). Immunostaining revealed increased intestinal Asbt and hepatic Ntcp protein expression in the HF-CO and HF-SFO groups compared to control and experimental groups. Incorporating probiotics like MCC2760 abrogated hyperlipidemia-induced changes in the intestinal uptake, hepatic synthesis, and enterohepatic transporters of BA in rats. Probiotic MCC2760 can be used to modulate lipid metabolism in high-fat-induced hyperlipidemic conditions.

Constitutive Loss of Ptpn2 in Mice Causes Features of Anemia Including Iron Deficiency

Background: Anemia is the most frequent extraintestinal manifestation of inflammatory bowel disease (IBD) and is associated with the risk of Crohn’s disease. Anemia significantly impairs quality of life, increases hospitalization rates, and increases medical care costs of IBD patients. Iron deficiency is the most frequent cause of anemia in IBD; however, the mechanisms involved are still poorly understood. Here, we investigated the role of the IBD risk gene, protein tyrosine phosphatase non-receptor type 2 ( PTPN2), in regulating iron homeostasis. Methods: Constitutive Ptpn2 wild type (WT), heterozygous (Het), and knockout (KO) 3-week-old mice were analyzed for serum iron content, complete blood count parameters, and intestinal and extraintestinal non-heme iron. Protein and RNA from duodenal epithelial cells (DECs) were assayed by western blotting and qPCR. Localization of the brush border ferrous iron transporter, DMT1, and the ferrous iron absorption driver, NHE3, in duodenal tissue was determined by immunohistochemistry (IHC). Results: Ptpn2-KO mice had reduced i) serum iron ( p=0.0007; n=10); ii) serum iron carrier transferrin saturation ( p=0.0077; n=8); iii) hemoglobin ( p=0.0002; n=5); iv) hematocrit ( p=0.0023; n=5); v) intestinal non-heme iron: duodenum ( p=0.0128; n=10) and jejunum ( p=0.0006; n=8); and vi) extraintestinal tissue non-heme iron: liver ( p=0.0014; n=10), spleen ( p=0.04; n=10), kidney ( p=0.0004; n=7), and gastrocnemius muscle ( p=0.0436; n=9) vs. Ptpn2-WT and Het mice. This indicated that loss of Ptpn2 causes characteristics of anemia including decreased serum iron and tissue iron storage and impaired intestinal iron homeostasis. DEC gene expression of the intracellular iron storage molecule ferritin ( Fth1) was reduced ( p=0.048; n=4) while the basolateral cellular iron importer transferrin receptor 1 ( Tfrc1) was significantly increased ( p=0.0048; n=5) in Ptpn2-KO mice. Reduced FTH1 protein expression ( p=0.007; n=12) and increased TFRC1 protein expression ( p=0.0021; n=8) in DECs of Ptpn2-KO mice was confirmed by western blot, indicating cellular iron deficiency. DMT1 (n=6) and NHE3 (n=8) protein expression in DECs was unaltered, whereas IHC showed reduced apical membrane DMT1 and NHE3 in the duodenal epithelium of Ptpn2-KO mice (n=6), suggesting a possible mechanism of impaired intestinal non-heme iron uptake. Conclusions: Loss of Ptpn2 in mice causes features of anemia including iron deficiency associated with mislocalization of DMT1 and reduced apical membrane expression of NHE3. These findings identify a critical role for PTPN2 in regulating systemic iron homeostasis. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lipid-Based Nanocarriers Enabled Oral Delivery of Oleanolic Acid Derivative DKS26 for Diabetes Management.

Oleanolic acid derivative DKS26 has hypolipidemic, islet, and hepatoprotective effects. However, high lipophilicity and low water solubility led to DKS26 extremely low oral bioavailability. Herein, lipid-based nanocarriers, including lipid nanodiscs (sND/DKS26) and liposomes (sLip/DKS26), are prepared to improve DKS26 oral absorption. In comparison to free DKS26 (5.81%), the absolute oral bioavailabilities are significantly increased to 29.47% (sND/DKS26) and 37.25% (sLip/DKS26) without detectable toxicity or immunogenicity even after repeated administrations. Both sND/DKS26 and sLip/DKS26 significantly reduce the feeding glucose level and the AUC of OGTT in db/db diabetic mice. Aiding by the newly developed scFv-based nanocarrier separation methods, no intact nanocarriers are detected in blood circulation after oral administration, suggesting that both formulations are unable to penetrate the intestinal epithelium. They enhance DKS26 absorption mainly by improving intestinal cell uptake and rapid intracellular release of the payload. Since pre-existing anti-PEG is widely detected in humans, the present oral absorption pathway of both nanocarriers successfully avoids unfavorable immunological responses after interaction with anti-PEG antibodies. The application of lipid-based nanocarriers paves an efficient and safe avenue for the clinical translation and application of poorly soluble therapeutics derived from traditional Chinese medicine.

The zeaxanthin present in a tomato line rich in this carotenoid is as bioavailable as that present in the food sources richest in this xanthophyll

It is strongly suspected that, like lutein, zeaxanthin (ZEA) plays a biological role in the human eye. Many studies also suggest that it could reduce the risk of age-related macular degeneration and improve cognition. Unfortunately, it is only present in a very limited number of foods. This is why a new tomato line, named “Xantomato”, whose fruits can synthesize this compound, was generated. However, whether ZEA in Xantomato is bioavailable enough for Xantomato to qualify as a nutritionally relevant ZEA source is not known. The objective was to compare the bioaccessibility and intestinal cell uptake efficiency of ZEA from Xantomato to that present in the richest sources of this compound. Bioaccessibility was assessed using in vitro digestions and uptake efficiency using Caco-2 cells. Xantomato ZEA bioaccessibility was not statistically different from that of common fruits and vegetables rich in this compound. Xantomato ZEA uptake efficiency (7.8%) was lower (P < 0.05) than that of orange pepper (10.6%) but not different from that of corn (6.9%). Therefore, the results of the in vitro digestion/Caco-2 cell model suggest that Xantomato ZEA could be as bioavailable as that found in common food sources of this compound.

Uncovering the gastrointestinal passage, intestinal epithelial cellular uptake, and AGO2 loading of milk miRNAs in neonates using xenomiRs as tracers

BackgroundHuman breast milk has a high microRNA (miRNA) content. It remains unknown whether and how milk miRNAs might affect intestinal gene regulation and homeostasis of the developing microbiome after initiating enteral nutrition. However, this requires that relevant milk miRNA amounts survive the gastrointestinal (GI) passage, are taken up by cells, and become available to the RNA interference machinery. It seems important to dissect the fate of these miRNAs after oral ingestion and GI passage. ObjectivesOur goal was to analyze the potential transmissibility of milk miRNAs via the gastrointestinal system in neonate humans and a porcine model in vivo to contribute to the discussion of whether milk miRNAs could influence gene regulation in neonates and thus might vertically transmit developmental relevant signals. MethodsWe performed cross-species profiling of miRNAs via deep sequencing and utilized dietary xenobiotic taxon-specific milk miRNA (xenomiRs) as tracers in human and porcine neonates, followed by functional studies in primary human fetal intestinal epithelial cells using adenovirus-type 5-mediated miRNA gene transfer. ResultsMammals share many milk miRNAs yet exhibit taxon-specific miRNA fingerprints. We traced bovine-specific miRNAs from formula nutrition in human preterm stool and 9 d after the onset of enteral feeding in intestinal cells (ICs) of preterm piglets. Thereafter, several xenomiRs accumulated in the ICs. Moreover, a few hours after introducing enteral feeding in preterm piglets with supplemented reporter miRNAs (cel-miR-39-5p/-3p), we observed their enrichment in blood serum and in argonaute RISC catalytic component 2 (AGO2)-immunocomplexes from intestinal biopsies. ConclusionsMilk-derived miRNAs survived GI passage in human and porcine neonates. Bovine-specific miRNAs accumulated in ICs of preterm piglets after enteral feeding with bovine colostrum/formula. In piglets, colostrum supplementation with cel-miR-39-5p/-3p resulted in increased blood concentrations of cel-miR-39-3p and argonaute RISC catalytic component 2 (AGO2) loading in ICs. This suggests the possibility of vertical transmission of miRNA signaling from milk through the neonatal digestive tract.

Engineered Nano-carrier systems for the oral targeted delivery of follicle stimulating Hormone: Development, characterization, and, assessment of in vitro and in vivo performance and targetability

Follicle stimulating hormone (FSH) is widely used for the treatment of female infertility, where the level of FSH is suboptimal due to which arrest in follicular development and anovulation takes place. Currently, only parenteral formulations are available for FSH in the market. Due to the drawbacks of parenteral administration and the high market shares of FSH, there is a need for easily accessible oral formulation. Therefore, enteric coated capsules filled with FSH loaded nanostructured lipid carriers (NLCs) or liposomes were prepared. Preliminary studies such as circular dichroism, SDS-PAGE, FTIR and ELISA were conducted to analyze FSH. Prepared formulations were optimized with respect to the size, polydispersity index, zeta potential, and entrapment efficiency using the design of experiments. Optimized formulations were subjected to particle counts and distribution analysis, TEM analysis, in vitro drug release, dissolution of enteric coated capsules, cell line studies, everted sac rat's intestinal uptake study, pharmacokinetics, pharmacodynamics, and stability studies. In the case of liposomes, RGD conjugation was done by carbodiimide chemistry and conjugation was confirmed by FTIR, 1HNMR and Raman spectroscopy. The prepared formulations were discrete and spherical. The release of FSH from enteric coated capsules was slow and sustained. The increased permeability of nano-formulations was observed in Caco-2 monoculture as well as in Caco-2 and Raji-B co-culture models. NLCs and liposomes showed an improvement in oral bioavailability and efficacy of FSH in rats. This may be due to mainly chylomicron-assisted lymphatic uptake of NLCs; whereas, in the case of liposomes, RGD-based targeting of β1 integrins of M cells on Peyer's patches may be the main reason for the better effect by FSH. FSH was found to be stable chemically and conformationally. Overall, the study reveals the successful development and evaluation of FSH loaded NLCs and liposomes.

Angiotensin-converting enzyme 2-at the heart of the COVID-19 pandemic.

ACE2 is the indispensable entry receptor for SARS-CoV and SARS-CoV-2. Because of the COVID-19 pandemic, it has become one of the most therapeutically targeted human molecules in biomedicine. ACE2 serves two fundamental physiological roles: as an enzyme, it alters peptide cascade balance; as a chaperone, it controls intestinal amino acid uptake. ACE2's tissue distribution, affected by co-morbidities and sex, explains the broad tropism of coronaviruses and the clinical manifestations of SARS and COVID-19. ACE2-based therapeutics provide a universal strategy to prevent and treat SARS-CoV-2 infections, applicable to all SARS-CoV-2 variants and other emerging zoonotic coronaviruses exploiting ACE2 as their cellular receptor.

TPGS and Doca dual-modified mesoporous silica nanoparticle-supported lipid bilayers enhance the efficient delivery and in vivo absorption of Coenzyme Q10

Coenzyme Q10 (CoQ10) has a wide range of nutraceutical functions and therapeutic values, nevertheless, its biomedical application as a health product or drug is hampered by the low absorption efficiency and bioavailability. In the present study, the hybrid mesoporous silica nanoparticle-supported lipid bilayers (LMSNs) as nanocarriers for CoQ10 are prepared by fusing the phospholipid membrane onto MSNs cores. Further, LMSNs are functionalized with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), deoxycholic acid (Doca) and chitosan (CS) sequentially, to obtain the TPGS-LMSNs and DCs-TPGS-LMSNs samples, respectively. MSNs, liposomes, and unmodified LMSNs are also prepared as controls. The results reveal that various nanocarriers have a high loading capacity for CoQ10, low cytotoxicity towards Caco-2 cells, and sustained release property in different pH mediums. In contrast to other nano-formulations, [email protected] show the higher cellular uptake efficiency and the resulting ROS inhibition effect, which can be taken up by cells via caveolae-mediated route, macropinocytosis, and unique bile acid uptake pathway mediated by ASBT. Efficient delivery of DC-TPGS-LMSNs is further illustrated by in vivo intestinal uptake and pharmacokinetics study, in which [email protected] exhibit higher absorption efficiency, longer circulation time, and more enhanced bioavailability than other formulations after oral administration. The results suggest that multifunctional LMSNs might be the potent candidate for CoQ10 delivery, and the findings will contribute to the rational design of novel drug delivery vehicles.

Quercetin Inhibits Hephaestin Expression and Iron Transport in Intestinal Cells: Possible Role of PI3K Pathway

Previous studies demonstrated that quercetin, a polyphenolic compound, inhibits the transport of iron by down-regulation of ferroportin (FPN1), an iron export protein. We have previously demonstrated that activation of the PI3K signaling pathway by zinc stimulates the intestinal iron uptake and transport by stimulating the expression of iron regulatory protein 2 (IRP2) dependent divalent metal iron transporter 1 (DMT1, apical iron transporter) expression and caudal-related homeobox transcription factor 2 (CDX2) dependent hephaestin (HEPH, basolateral ferroxidase required for iron oxidation) expression, respectively. Since polyphenols are antagonists of the PI3K pathway, we hypothesized that quercetin might inhibit basolateral iron transport via the down-regulation of hephaestin (HEPH). Here in we investigated the effect of quercetin on iron uptake, transport, and expression of iron transporters in intestinal cells. In differentiated Caco-2 cells grown on permeable supports, quercetin inhibited the basolateral iron transport while increasing the iron uptake, possibly due to higher cellular retention. Further, quercetin down-regulated the protein and mRNA expression of HEPH and FPN1 but not that of IRP2 or DMT1. In addition, quercetin also abrogated the zinc-induced Akt, CDX2 phosphorylation, and HEPH expression. Together these results suggest that inhibition of iron transport by quercetin is mediated via the down-regulation of CDX2-dependent HEPH expression via inhibition of the PI3K pathway.

Brush Border Membrane Vesicles from Rats and Gerbils Can Be Utilized to Evaluate the Intestinal Uptake of All-trans and 9-cis β-Carotene

Intestinal brush border membrane vesicles (BBMV) have previously been used to investigate the absorptive processes of a wide variety of nutrients. The first objective of this work was to develop a BBMV system to study carotenoid uptake using rat small intestine. The uptake of all-trans β-carotene by rat BBMV was linear up to 5.9 µmol/L, suggesting passive uptake at the concentrations used in this study. Both all-trans β-carotene and 9-cis β-carotene were taken up at a similar rate by the rat BBMV. The vesicle system was then utilized to investigate the uptake of retinol and β-carotene by BBMV isolated from Mongolian gerbils which had been subjected to three different vitamin A depletion and refeeding protocols. Three groups of gerbils (n = 10/group) were fed vitamin A-deficient diets for 8 wk. One group was killed at that point (marginally depleted), a second group was refed vitamin A for 5 d and a third group was further depleted of vitamin A for 5 d. Pooled BBMV from the marginally depleted group demonstrated greater uptake of all-trans β-carotene than pooled BBMV from the other two groups of gerbils while those from the group refed vitamin A for 5 d had greater uptake than the group that was depleted for 5 additional days (P < 0.01). In contrast, the uptake of retinol by BBMV was not significantly different among the three groups of gerbils. The results of the gerbil study suggest that as they become increasingly vitamin A deficient, impairment of all-trans β-carotene uptake by intestinal mucosal cells may be taking place. The BBMV system should prove valuable for the evaluation of the intestinal mucosal cell membrane uptake of carotenoids and retinoids under various nutritional conditions.

Early flora colonization affects intestinal immunoglobulin G uptake in piglets, which may be mediated by NF-κB-FcRn pathway.

The passive immunity of newborn piglets is mainly derived from immunoglobulin G (IgG) in breast milk, and the incomplete transfer of passive immune is considered to be an important cause of piglet death. This study was conducted to investigate the effect of early intestinal flora colonization on IgG uptake and its possible mechanism. The newborn piglets and IPEC-J2 cells were used to investigate the possible factors and regulatory mechanisms affecting intestinal IgG uptake. In vivo, all 40 piglets were euthanized on postnatal d 0, 1, 3, and 7, with 10 piglets per time. The blood sample, gastric contents, jejunal contents and mucosa were collected for analysis. In vitro, IPEC-J2 cells transwell culture system was used to establish the IgG transporter model to explore the specific regulatory mechanism of IgG transport. Our results demonstrated that the intestinal IgG uptake was positively correlated with the expression of Neonatal Fc receptor (FcRn). With the increase of age, the intestinal flora of newborn piglets was gradually enriched. The function of intestinal genes also changes with the colonization of intestinal flora. We found that the expression trend of TLR2, TLR4 and NF-κB (P65) in intestine was consistent with that of FcRn. Furthermore, the in vitro results demonstrate that the NF-κB signaling pathway is involved in regulating FcRn-mediated IgG transmembrane transport. Early flora colonization affects intestinal IgG uptake in piglets, which may be mediated by NF-κB-FcRn pathway.

Neutrophil Membrane-Coated Mesoporous Silica Nanoparticles Loaded with Hydrocortisone Alleviate DSS-Induced Colitis in Mice

The incidence and prevalence of ulcerative colitis (UC) are increasing worldwide. Hydrocortisone enema (HC) is widely used in UC treatment; however, this approach is limited by the easy degradation of HC in the intestinal environment and low intestinal uptake efficiency. Accordingly, the development of methods to improve the targeting efficiency of corticosteroids is an important issue. Mesoporous silica nanoparticles (MSN) and biomimetic nanovesicles (derived from the natural cell membrane structure) provide a basis for improved drug delivery and uptake. In this research, we constructed neutrophil membrane-coated MSN loaded with HC for the treatment of UC. MSN-HC and neutrophil-derived membrane nanoparticles (MSN-HC@NM NPs) were obtained by mechanical extrusion and characterized. The effects of free HC, MSN, MSN-HC, and MSN-HC@NM NPs were compared using dextran sodium sulfate (DSS)-induced colitis model, including terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays and inflammatory factors in colon tissues. The MSN-HC@NM NPs alleviated DSS-induced colitis by reducing colon apoptosis and ameliorating the destruction of the colonic barrier and inflammation in mice. This research provides a hydrocortisone delivery system with good biosafety and the potential for clinical translation.

The Contribution of Phytate-Degrading Enzymes to Chicken-Meat Production.

The contribution that exogenous phytases have made towards sustainable chicken-meat production over the past two decades has been unequivocally immense. Initially, their acceptance by the global industry was negligible, but today, exogenous phytases are routine additions to broiler diets, very often at elevated inclusion levels. The genesis of this remarkable development is based on the capacity of phytases to enhance phosphorus (P) utilization, thereby reducing P excretion. This was amplified by an expanding appreciation of the powerful anti-nutritive properties of the substrate, phytate (myo-inositol hexaphosphate; IP6), which is invariably present in all plant-sourced feedstuffs and practical broiler diets. The surprisingly broad spectra of anti-nutritive properties harbored by dietary phytate are counteracted by exogenous phytases via the hydrolysis of phytate and the positive consequences of phytate degradation. Phytases enhance the utilization of minerals, including phosphorus, sodium, and calcium, the protein digestion, and the intestinal uptakes of amino acids and glucose to varying extents. The liberation of phytate-bound phosphorus (P) by phytase is fundamental; however, the impacts of phytase on protein digestion, the intestinal uptakes of amino acids, and the apparent amino acid digestibility coefficients are intriguing and important. Numerous factors are involved, but it appears that phytases have positive impacts on the initiation of protein digestion by pepsin. This extends to promoting the intestinal uptakes of amino acids stemming from the enhanced uptakes of monomeric amino acids via Na+-dependent transporters and, arguably more importantly, from the enhanced uptakes of oligopeptides via PepT-1, which is functionally dependent on the Na+/H+ exchanger, NHE. Our comprehension of the phytate-phytase axis in poultry nutrition has expanded over the past 30 years; this has promoted the extraordinary surge in acceptance of exogenous phytases, coupled with the development of more efficacious preparations in combination with the deflating inclusion costs for exogenous phytases. The purpose of this paper is to review the progress that has been made with phytate-degrading enzymes since their introduction in 1991 and the underlying mechanisms driving their positive contribution to chicken-meat production now and into the future.