Transepithelial transport of nanoparticles in oral drug delivery: From the perspective of surface and holistic property modulation.

Despite the promising prospects of nanoparticles in oral drug delivery, the process of oral administration involves a complex transportation pathway that includes cellular uptake, intracellular trafficking, and exocytosis by intestinal epithelial cells, which are necessary steps for nanoparticles to enter the bloodstream and exert therapeutic effects. Current researchers have identified several crucial factors that regulate the interaction between nanoparticles and intestinal epithelial cells, including surface properties such as ligand modification, surface charge, hydrophilicity/hydrophobicity, intestinal protein corona formation, as well as holistic properties like particle size, shape, and rigidity. Understanding these properties is essential for enhancing transepithelial transport efficiency and designing effective oral drug delivery systems. Therefore, this review provides a comprehensive overview of the surface and holistic properties that influence the transepithelial transport of nanoparticles, elucidating the underlying principles governing their impact on transepithelial transport. The review also outlines the chosen of parameters to be considered for the subsequent design of oral drug delivery systems.

Acidocin A and Acidocin 8912 Belong to a Distinct Subfamily of Class II Bacteriocins with a Broad Spectrum of Antimicrobial Activity.

Within class II bacteriocins, we assume the presence of a separate subfamily of antimicrobial peptides possessing a broad spectrum of antimicrobial activity. Although these peptides are structurally related to the subclass IIa (pediocin-like) bacteriocins, they have significant differences in biological activities and, probably, a mechanism of their antimicrobial action. A representative of this subfamily is acidocin A from Lactobacillus acidophilus TK9201. We discovered the similarity between acidocin A and acidocin 8912 from Lactobacillus acidophilus TK8912 when analyzing plasmids from lactic acid bacteria and suggested the presence of a single evolutionary predecessor of these peptides. We obtained the C-terminally extended homolog of acidocin 8912, named acidocin 8912A, a possible intermediate form in the evolution of the former. The study of secondary structures and biological activities of these peptides showed their structural similarity to acidocin A; however, the antimicrobial activities of acidocin 8912 and acidocin 8912A were lower than that of acidocin A. In addition, these peptides demonstrated stronger cytotoxic and membranotropic effects. Building upon what we previously discovered about the immunomodulatory properties of acidocin A, we studied its proteolytic stability under conditions simulating those in the digestive tract and also assessed its ability to permeate intestinal epithelium using the Caco-2 cells monolayer model. In addition, we found a pronounced effect of acidocin A against fungi of the genus Candida, which might also expand the therapeutic potential of this bacterial antimicrobial peptide.

Evaluating intestinal absorption of peptide Met-Lys-Pro in casein hydrolysate using Caco-2 and human iPS cell-derived small intestinal epithelial cells.

High blood pressure is a major risk factor for cardiovascular disease. Our previous study confirmed that daily intake of casein hydrolysate that contained Met-Lys-Pro (MKP) can safely lower mildly elevated blood pressure. The present study aimed to evaluate the intestinal absorption differences between peptide MKP as a casein hydrolysate and synthetic MKP alone using Caco-2 cells and human iPS cell-derived small intestinal epithelial cells (hiSIECs). MKP was transported intact through Caco-2 cells and hiSIECs with permeability coefficient (Papp) values of 0.57 ± 0.14 × 10-7 and 1.03 ± 0.44 × 10-7 cm/s, respectively. This difference in Papp suggests differences in the tight junction strength and peptidase activity of each cell. Moreover, the transepithelial transport and residual ratio of intact MKP after adding casein hydrolysate containing MKP was significantly higher than that after adding synthetic MKP alone, suggesting that other peptides in casein hydrolysate suppressed MKP degradation and increased its　transport. These findings suggest that hiSIECs could be useful for predicting the human intestinal absorption of bioactive peptides; ingesting MKP as a casein hydrolysate may also improve MKP bioavailability.

Bioaccessibility and Antioxidant Activity of Faba Bean Peptides in Comparison to those of Pea and Soy after In Vitro Gastrointestinal Digestion and Transepithelial Transport across Caco-2 and HT29-MTX-E12 Cells.

In this study, the transepithelial transport of bioactive peptides derived from faba bean flour gastrointestinal digestates was investigated, in vitro, using a Caco-2 and HT29-MTX-E12 coculture monolayer, in comparison to those of pea and soy. The profile of transported peptides was determined by mass spectrometry, and the residual antioxidant activity was assessed. The ORAC value significantly (p < 0.05) decreased after transepithelial transport (24-36% reduction) for all legumes, while the antioxidant activity in ABTS assay significantly (p < 0.05) increased, as shown by the EC50 decrease of 26-44%. Five of the nine faba bean peptides that crossed the intestinal cell monolayer exhibited antioxidant activity. Two of these peptides, TETWNPNHPEL and TETWNPNHPE, were further hydrolyzed by the cells' brush border peptidases to smaller fragments TETWNPNHP and TWNPNHPE. These metabolized peptides were synthesized, and both maintained high antioxidant activity in both ABTS (EC50 of 1.2 ± 0.2 and 0.4 ± 0.1 mM, respectively) and ORAC (2.5 ± 0.1 and 3.4 ± 0.2 mM of Trolox equivalent/mM, respectively) assays. These results demonstrated for the first time the bioaccessibility of faba bean peptides produced after in vitro gastrointestinal digestion and how their bioactive properties can be modulated during transepithelial transport.

Oral In-Situ Nanoplatform with Balanced Hydrophobic-Hydrophilic Property for Transport Across Gastrointestinal Mucosa.

Transport of oral nanocarriers across the GI epithelium necessitates transport across hydrophilic mucus layer and the hydrophobic epithelium. Based on hydrophobic-hydrophilic balance, Curcumin-Lipomer (lipid-polymer hybrid nanoparticles) comprising hydrophobic stearic acid and hydrophilic Gantrez™ AN 119 (Gantrez) were developed, by a radical in-situ approach, to successfully traverse both barriers. A monophasic preconcentrate (Cur-Pre) comprising Cur (Curcumin), stearic acid, Gantrez and stabilizers, prepared by simple solution, was added to an aqueous phase to instantaneously generate Curcumin-Lipomer (Cur-Lipo) of nanosize and high entrapment efficiency (EE). Cur-Lipo size and EE was optimized by Box-Behnken Design. Cur-Lipomers of varying hydrophobic-hydrophilic property obtained by varying the stearic acid: Gantrez ratio exhibited size in the range 200-400 nm, EE > 95% and spherical morphology as seen in the TEM. A decrease in contact angle and in mucus interaction, evident with increase in Gantrez concentration, indicated an inverse corelation with hydrophilicity, while a linear corelation was observed for mucopenetration and hydrophilicity. Cur-SLN (solid lipid nanoparticles) which served as the hydrophobic reference revealed contact angle > 90°, maximum interaction with mucus and minimal mucopenetration. The ex-vivo permeation study through chicken ileum, revealed maximum permeation with Cur-Lipo1 and comparable and significantly lower permeation of Cur-Lipo1-D and Cur-SLN proposing the importance of balancing the hydrophobic-hydrophilic property of the nanoparticles. A 1.78-fold enhancement in flux of hydrophobic Cur-SLN, with no significant change in permeation of the hydrophilic Cur-Lipomers (p > 0.05) following stripping off the mucosal layer was observed. This reiterated the significance of hydrophobic-hydrophilic balance as a promising strategy to design nanoformulations with superior permeation across the GI barrier.

Understanding the Transepithelial Transport and Transbilayer Diffusion of the Antihypertensive Peptide Asn-Cys-Trp: Insights from Caco-2 Cell Monolayers and the DPPC Model Membrane.

Understanding the transport mechanism of the peptide Asn-Cys-Trp (NCW) is crucial to improving its intestinal absorption and bioavailability. This study investigated the absorption of NCW through Caco-2 cell monolayers and its interaction with the DPPC bilayers. Results revealed that after a 3 h incubation, the Papp (AP-BL) and Papp (BL-AP) values of NCW at a concentration of 5 mmol/L were (22.24 ± 4.52) × 10-7 and (6.63 ± 2.31) × 10-7 cm/s, respectively, with the transport rates of 1.59 ± 0.32 and 0.62 ± 0.20%, indicating its moderate absorption. NCW was found to be transported via PepT1 and paracellular transport pathways, as evidenced by the significant impact of Gly-Pro and cytochalasin D on the Papp values. Moreover, NCW upregulated ZO-1 mRNA expression. Further investigation of the ZO-1-mediated interaction between NCW and tight junction proteins will contribute to a better understanding of the paracellular transport mechanism of NCW. The interaction between NCW and the DPPC bilayers was predominantly driven by entropy. NCW permeated the bilayers through electrostatic, hydrogen bonding, and hydrophobic interactions, resulting in increased fluidity, flexibility, and disorder as well as phase transition and phase separation of the bilayers.

Impact of dietary plant flavonoids on 7,8-dihydroxyflavone transepithelial transport in human intestinal Caco-2 cells.

7,8-dihydroxyflavone (7,8-DHF) is a biologically active flavone with various physiological activities, including neuroprotection, anti-inflammation, and weight loss. Previous studies have found that the efflux protein P-glycoprotein (P-gp) significantly affects the transepithelial transport of 7,8-DHF in the intestine, resulting in its low oral bioavailability. Based on this, in this study, a Caco-2 monolayer cell model was used to investigate 14 dietary plant flavonoids as potential P-gp inhibitors, and their effects on the transepithelial transport and in vitro digestion of 7,8-DHF were explored. The results showed that among the 14 plant flavonoids, hesperetin, epigallocatechin gallate, fisetin, kaempferol, quercetin, and isoorientin increased and the apparent permeability coefficients (P app) of 7,8-DHF at AP → BL direction and lowered P app value at BL → AP direction to varying degrees, reducing the efflux ratio of 7,8-DHF less than 1.5. In particular, kaempferol and quercetin exhibited the best effect on promoting the transepithelial transport of 7,8-DHF, especially when used at molar concentration ratios of 1:1 and 1:2 with 7,8-DHF. This is beneficial for improving the oral bioavailability of 7,8-DHF. Meanwhile, 7,8-DHF was found to maintain structural stability in simulated saliva, gastric juice, and intestinal juice, and its stability was not affected by the coexistence of quercetin and kaempferol. Overall, this study provided a theoretical basis for seeking natural and safe P-gp inhibitors to improve the oral absorption of natural products.

A Shared Perspective on in Vitro and in Vivo Models to Assay Intestinal Transepithelial Transport of Food Compounds.

Assessing nutrient bioavailability is complex, as the process involves multiple digestion steps, several cellular environments, and regulatory-metabolic mechanisms. Several in vitro models of different physiological relevance are used to study nutrient absorption, providing significant challenges in data evaluation. However, such in vitro models are needed for mechanistic studies as well as to screen for biological functionality of the food structures designed. This collaborative work aims to put into perspective the wide-range of models to assay the permeability of food compounds considering the particular nature of the different molecules, and, where possible, in vivo data are provided for comparison.

Modulation of soy protein immunoreactivity by different matrix structures of lactic acid bacterium-induced soy protein gels: Epitope destruction during in vitro gastroduodenal digestion and absorption.

Soy allergy is a common health problem. Food structure may change the gastroduodenal digestion and absorption of soy proteins, thus leading to the modulation of the immunoreactivity of soy proteins. In this study, lactic acid bacterium (LAB)-fermented soy protein isolates (FSPIs) were prepared at four concentrations (0.2 %-5.0 %, w/v) to present various matrix structures (nongel, NG; weak gel, WG; medium gel, MG; and firm gel, FG) and subjected to in vitro dynamic gastroduodenal digestion model. The results of sandwich enzyme-linked immunosorbent and human serum IgE binding capacity assays demonstrated that FSPI gels, especially the FSPI-MG/WG digestates obtained at the early and medium stages of duodenal digestion (D-5 and D-30), possessed greater potency in immunoreactivity reduction than FSPI-NG and reduced to 1.9 %-68.3 %. The transepithelial transport study revealed that the immunoreactivity of FSPI-MG/WG D-5 and D-30 digestates decreased through the stimulation of interferon-γ production and the induction of dominant Th1/Th2 differentiation. Peptidomics and bioinformatics analyses illustrated that compared with FSPI-NG, the FSPI-gel structure promoted the epitope degradation of the major allergens glycinin G2/G5, ß-conglycinin α/ß subunit, P34, lectin, trypsin inhibitor, and basic 7S globulin. Spatial structure analysis showed that FSPI-gel elicited an overall promotion in the degradation of allergen epitopes located in interior and exterior regions and was dominated by α-helix and ß-sheet secondary structures, whereas FSPI-MG/WG promoted the degradation of epitopes located in the interior region of glycinin/ß-conglycinin and exterior region of P34/basic 7S globulin. This study suggested that the FSPI-gel structure is a promising food matrix for decreasing the allergenic potential of allergenic epitopes during gastroduodenal digestion and provided basic information on the production of hypoallergenic soy products.

Bioaccessibility and Genoprotective Effect of Melanoidins Obtained from Common and Soft Bread Crusts: Relationship between Melanoidins and Their Bioactivity.

Bread crust constitutes an important by-product of the bakery industry, and its utilization for the isolation of melanoidins to be used as a functional ingredient can enhance its added value and contribute to health. The aim of this study was to evaluate the bioaccessibility, bioactivity, and genoprotective effect of melanoidins derived from bread crust. Bioaccessibility was assessed in gastric, intestinal digestion, and colonic fermentation fractions. The results revealed a relationship between bioaccessible melanoidins and their type (common or soft bread). No cytotoxicity effects were observed for bioaccessible fractions, as assessed by MTT and RTA methods, and they did not affect the distribution of E-cadherin in Caco-2 cells, confirming their ability to maintain membrane integrity. Furthermore, our study demonstrated that the gastrointestinal and colonic fermentation fractions successfully transported across the intestinal barrier, without affecting cell permeability, and showed antioxidant activity on the basolateral side of the cell monolayer. Remarkably, both fractions displayed a significant genoprotective effect in Caco-2 cells. Our findings provide crucial insights into the relationship between the melanoidins and their bioactivity and genoprotective effect. These results demonstrated the potential of bioaccessible melanoidins as valuable bioactive compounds for the development of functional foods, without showing toxic effects on gastrointestinal cells.

Disease-specific protein corona formed in pathological intestine enhances the oral absorption of nanoparticles.

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract. We prepared polystyrene nanoparticles (PS) adsorbed with different IPC derived from the intestinal tract of healthy, diabetic, and colitis rats (H-IPC@PS, D-IPC@PS, C-IPC@PS). Proteomics analysis revealed that, compared with healthy IPC, the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the intestine. Consequently, both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking, which increased the transcytosis from the epithelium. Together, disease-specific IPC endowed NPs with higher intestinal absorption. D-IPC@PS posed "positive effect" on intestinal absorption into blood circulation for diabetic therapy. Conversely, C-IPC@PS had "negative effect" on colitis treatment because of unfavorable absorption in the intestine before arriving colon. These results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases.

Transepithelial Transport of the Bifunctional Peptide IPYWTY Indirectly Induced Insulin Release Mediated by Active GLP-1.

There is currently no appropriate cell model suitable for evaluating the insulinotropic effects of DPP-4 inhibitory peptides (DPP-4IPs) mediated by active glucagon-like peptide-17-36 (active GLP-1). The study aims to evaluate the transepithelial transport of IPYWTY on its in situ insulinotropic effects by using a 2D and dual-layered coculture cell model that consists of Caco-2 and NCI-H716 cells on the apical (AP) side and ß-TC-6 cells on the basolateral (BL) side. During transportation, IPYWTY was absorbed in its intact form through PepT1 and paracellular transport. Meanwhile, it was degraded to several peptide fragments, including PYWTY, YWTY, WTY, and IPY, which decreased its in situ DPP-4 inhibitory activity. IPYWTY does not directly stimulate insulin release in ß-TC-6 cells, while it increased the active GLP-1 level from 76.57 ± 15.16 to 95.63 ± 1.99 pM (1.25 times) in NCI-H716 cells. Interestingly, IPYWTY indirectly increased insulin levels from 426.91 ± 6.07 to 573.94 ± 2.97 µIU/mL (1.34 times) in the 2D and dual-layered coculture cell model for its dual function of stimulating active GLP-1 secretion and DPP-4 inhibition. These results suggested that the 2D and dual-layered coculture cell model is an alternative strategy for effectively evaluating the insulinotropic effects of DPP-4IPs mediated by active GLP-1.

Decaying kidney function during cirrhosis correlates with remodeling of distal colon aldosterone target gene expression.

Liver cirrhosis is associated to circulatory abnormalities leading to hypovolemia and stimulation of the renin-angiotensin-aldosterone system (RAAS). Advanced stages of the disease cause renal failure, impairing K+ and Na+ homeostasis. It has been proposed that the distal colon undergoes functional remodeling during renal failure, in particular by aldosterone-driven increased K+ excretion. In this study, we compared the transcriptional response of aldosterone target genes in the rat distal colon under two models of increased circulating aldosterone (one with concomitant RAAS activation) and in a model of secondary hyperaldosteronism induced by cirrhosis. The expression of a subset of these genes was also tested in distal colon biopsies from control subjects or patients with cirrhosis with varying levels of disease progression and treated or not with mineralocorticoid receptor inhibitor spironolactone. We examined known aldosterone-regulated transcripts involved in corticosteroid signaling and transepithelial ion transport. In addition, we included aldosterone-regulated genes related to cell proliferation. Our comparison revealed multiple aldosterone target genes upregulated in the rat distal colon during decompensated cirrhosis. Epithelial Na+ channel ß and γ subunit expression correlated positively with plasma aldosterone concentration and negatively with glomerular filtration rate. Patients with cirrhosis showed increased expression of 11-ß-hydroxysteroid-dehydrogenase 2 (11ßHSD2), which was reverted by spironolactone treatment, suggesting a sensitization of the distal colon to aldosterone action. In summary, our data show that decaying kidney function during cirrhosis progression toward a decompensated state with hypovolemia correlates with remodeling of distal colon ion transporter expression, supporting a role for aldosterone in the process.NEW & NOTEWORTHY Liver cirrhosis progression significantly alters ion transporter subunit expression in the rat distal colon, a change that correlated well with declining kidney function and the severity of the disease. Our data suggest that the steroid hormone aldosterone participates in this homeostatic response to maintain electrolyte balance.

Novel Casein-Derived Peptide-Zinc Chelate: Zinc Chelation and Transepithelial Transport Characteristics.

Casein-derived peptides are recognized as promising candidates for improving zinc bioavailability through the form of a peptide-zinc chelate. In the present work, a novel 11-residue peptide TEDELQDKIHP identified from casein hydrolysate in our previous study was synthesized to investigate the zinc chelation characteristics. Meanwhile, the digestion stability and transepithelial transport of TEDELQDKIHP-Zn were also investigated. The obtained results indicated that the carboxyl groups (from Asp and Glu), amino groups (from Lys and His), pyrrole nitrogen group of Pro, and imidazole nitrogen group of His were responsible for zinc chelation. The complexation with zinc resulted in a more ordered structure of TEDELQDKIHP-Zn. In terms of digestion stability, the chelate of TEDELQDKIHP-Zn could remain stable to a large extent after gastric (78.54 ± 0.14%) and intestinal digestion (70.18 ± 0.17%). Moreover, TEDELQDKIHP-Zn was proven to be a well-absorbed biological particle with a Papp value higher than 1 × 10-6 cm/s, and it could be transported across the intestine epithelium through transcytosis. TEDELQDKIHP-Zn exhibited more bioavailable effects on zinc absorption and ALP activity than inorganic zinc sulfate.

Novel Hypocholesterolemic Peptides Derived from Silver Carp Muscle: The Modulatory Effects on Enterohepatic Cholesterol Metabolism In Vitro and In Vivo.

This research aimed to investigate the effect of silver carp hydrolysates (SCHs) on hypercholesterolemia and enterohepatic cholesterol metabolism. Results showed that in vitro gastrointestinal digestion products of Alcalase-SCH (GID-Alcalase) exhibited the highest inhibitory activity of cholesterol absorption mainly through downregulating the expression of essential genes related to cholesterol transport in a Caco-2 monolayer. After being absorbed by the Caco-2 monolayer, GID-Alcalase increased the low-density lipoprotein (LDL) uptake in HepG2 cells by enhancing the protein level of the LDL receptor (LDLR). The in vivo experiment showed that long-term intervention of Alcalase-SCH ameliorated hypercholesterolemia in ApoE-/- mice fed with a Western diet (WD). After transepithelial transport, four novel peptides (TKY, LIL, FPK, and IAIM) were identified, and these peptides possessed dual hypocholesterolemic functions including inhibition of cholesterol absorption and promotion of peripheric LDL uptake. Our results indicated for the first time the potential of SCHs as functional food ingredients for the management of hypercholesterolemia.

An ex vivo intestinal absorption model is more effective than an in vitro cell model to characterise absorption of dietary carotenoids following simulated gastrointestinal digestion.

To get the most accurate food digestion-related data, and how this affects nutrient absorption, it is critical to carefully simulate human digestion systems using model settings. In this study, the uptake and transepithelial transportation of dietary carotenoids was compared using two different models that have previously been used to assess nutrient availability. The permeability of differentiated Caco-2 cells and murine intestinal tissue were tested using all-trans-ß-carotene and lutein prepared in artificial mixed micelles and micellar fraction from orange-fleshed sweet potato (OFSP) gastrointestinal digestion. Transepithelial transport and absorption efficiency were then determined using liquid chromatography tandem-mass spectrometry (LCMS-MS). Results showed that the mean uptake for all-trans-ß-carotene in the mouse mucosal tissue was 60.2 ± 3.2% compared to 36.7 ± 2.6% in the Caco-2 cells with the mixed micelles as the test sample. Similarly, the mean uptake was higher in OFSP with 49.4 ± 4.1% following mouse tissue uptake compared to 28.9 ± 4.3% using Caco-2 cells for the same concentration. In relation to the uptake efficiency, the mean percentage uptake for all-trans-ß-carotene from artificial mixed micelles was 1.8-fold greater in mouse tissue compared to Caco-2 cells (35.4 ± 1.8% against 19.9 ± 2.6%). Carotenoid uptake reached saturation at 5 µM when assessed with the mouse intestinal cells. These results demonstrate the practicality of employing physiologically relevant models simulating human intestinal absorption processes that compares well with published human in vivo data. When used in combination with the Infogest digestion model, the Ussing chamber model, using murine intestinal tissue, may thus be an efficient predictor of carotenoid bioavailability in simulating human postprandial absorption ex vivo.

Digestion, absorption, and transport properties of soy-fermented douchi hypoglycemic peptides VY and SFLLR under simulated gastrointestinal digestion and Caco-2 cell monolayers.

Two novel hypoglycemic peptides VY and SFLLR were identified from douchi as the major peptides responsible for the glucose uptake activity. The present work aimed to elucidate their digestion, absorption and transport properties using simulated digestion and Caco-2 cell monolayers transport models. Besides, the effects of digestion and absorption on the structure and activity were also studied. The results showed that VY was resistant to gastrointestinal tract digestion and could cross Caco-2 cell monolayers intactly via both TJs-mediated passive paracellular pathway and PepT1-mediated active route. In comparison, SFLLR was partially degraded into small fragments of SFLL, SFL, and SF by the digestive system, leading to increased glucose uptake activity. Notably, SFLLR, SFLL, and SFL were partly hydrolyzed by aminopeptidase N or dipeptidyl peptidase IV during transport, but they were transported intact. SFL was transported via both paracellular diffusion and PepT1-mediated routes, while SFLLR and SFLL were via paracellular route only.

Prumnopitys Andina Fruit Extract Activates Liver X Receptors after In Vitro Digestion.

SCOPE: 20-Hydroxyecdysone (20E) is the main phytochemical present in the fresh arils of Prumnopitys andina. 20E is reported to have anabolic effects by modulation of gene transcription by interaction with nuclear receptors. Our aim is to evaluate the in vitro bioaccessibility, transepithelial transport of 20E, and the capacity of P. andina fruit extract and 20E to activate selected mammalian nuclear receptors in transiently transfected human cells after simulated gastrointestinal digestion. RESULTS: 20E shows good stability, solubility, and micellization after in vitro digestion. 20E is taken up by Caco-2 cells, but poorly transported through the epithelial cell membrane, possibly due to P-glycoprotein-mediated efflux. In transiently transfected HepG2 cells, the fruit extract significantly induces the signal intensity for the liver X receptor (LXR)-α and -ß by 1.6 and 1.4-fold, respectively. In contrast, the treatment with 20E, irrespective of its concentration, did not change the activity of both LXR receptors. No effects are observed for the pregnane X receptor or the constitutive androstane receptor. CONCLUSION: Our findings show that components of the digested P. andina extract other than 20E are responsible for the effects on LXR-α and -ß. Our findings open new perspectives on the potential role of P. andina fruits in cholesterol metabolism and inflammatory diseases.

Is there a molecular basis for solvent drag in the renal proximal tubule?

The concept of solvent drag, i.e., water and solutes sharing the same pore and their transport being frictionally coupled, was first proposed in the early 1950s. During the following decades, it was applied to transport processes across cell membranes as well as transport along the paracellular pathway. Water-driven solute transport was proposed as the major mechanism for electrolyte and nutrient absorption in the small intestine and for Cl- and HCO3- reabsorption in the renal proximal tubule. With the discovery of aquaporins as transcellular route for water transport and the claudin protein family as the major determinant of paracellular transport properties, new mechanistic insights in transepithelial water and solute transport are emerging and call for a reassessment of the solvent drag concept. Current knowledge does not provide a molecular basis for relevant solvent drag-driven, paracellular nutrient, and inorganic anion (re-)absorption. For inorganic cation transport, in contrast, solvent drag along claudin-2-formed paracellular channels appears feasible.

Generation of novel antioxidant peptides from silver carp muscle hydrolysate: Gastrointestinal digestion stability and transepithelial absorption property.

Oxidative stress is a major cause of cardiovascular diseases (CVDs). Antioxidant peptides have potential to improve CVDs. The aim of this study was to develop novel antioxidant peptides from silver carp muscle hydrolysates (SCHs) and investigate their gastrointestinal digestion (GID) stability, and bioavailability. Results showed that SCHs generated by Alcalase and Papain exhibited the highest free radical scavenging activity, peroxynitrite scavenging activity and low density lipoprotein (LDL) oxidation inhibitory capacity. All these antioxidant activities were enhanced in different SCHs after GID. Notably, the GID products of Papain-SCH and Alcalase-SCH possessed potent ameliorating effects on oxidative stress injury in endothelial cells. After transepithelial transport, total of nine peptides was identified from permeates of GID products of Papain-SCH and Alcalase-SCH. The VKVGNEF and MEAPPH were both novel peptides in the current study that possess the highest activities in scavenging free radicals, inhibiting LDL oxidation and alleviating oxidative stress injury in endothelial cells.