Changes in Antioxidant Activity of Alcalase-Hydrolyzed Soybean Hydrolysate under Simulated Gastrointestinal Digestion and Transepithelial Transport

Peptides from Alcalase-hydrolyzed soybean protein hydrolysate(SPH)may hold the potential as natural antioxidants.In addition,the effect of human gastrointestinal(GI)tract on peptide bioavailability needs to be explored.In this study,the impact of simulated GI digestion and transepithelial transport on various antioxidant properties of SPH were investigated.SPH displayed DPPH radical scavenging(IC50=4.22 mg/m L),ABTS·+radical scavenging(IC50=2.93 mg/m L),reducing power and metal ion-chelating activities(IC50=0.67 mg/m L).Furthermore,SPH significantly(P<0.05)inhibited the generation of intracellular reactive oxygen species(ROS)in Caco-2 cells.After simulated GI digestion,the antioxidant properties of SPH were enhanced,except for a decrease in ABTS·+radical scavenging activity.After transepithelial transport,the permeates maintained partial antioxidant activity and the LC-MS/MS data further identified the absorbed soybean peptides.These results suggest that SPH contains the antioxidant peptides that are potentially bioavailable and can be regarded as a promising source of functional food ingredients.

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.

An Ultrastructural Study of Phagocytosis and Transport of Formalized Campylobacter jejuni By M Cells into Mouse Peyer's Patches

Suspension of formalized Campylobacter jejunt (2×10 CFU/ml)was injected into a bothend-ligated intestinal loop of ileum which contained some Peyer's patches from non-immunized adult mice after laparotomy under anesthesia.After 1-hour post inoculation, the specimen was taken out and prepared for TEM and SEM observation.The results showed that bacteria adhered specifically on the surface of M cells of Peyer's patches.The microvilli and microfolds of the M cells fused to capture the bacteria and to form a large endocytotic vesicle in the cytoplasm of the M cell,then transported inward,and, at last.released into the central cavity between lymphocytes.Occasionally, we found some of them were phagocytosed by lymphocytes.

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,CIPC@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.

Regulation of epithelial function, differentiation, and remodeling in the epididymis

The epididymis is a single convoluted tubule lined by a pseudostratified epithelium. Specialized epididymal epithelial cells, the so-called principal, basal, narrow, and clear cells, establish a unique luminal environment for the maturation and storage of spermatozoa. The epididymis is functionally and structurally divided into several segments and sub-segments that create regionally distinct luminal environments. This organ is immature at birth, and epithelial cells acquire their fully differentiated phenotype during an extended postnatal period, but the factors involved in this complex process remain incompletely characterized. In the adult epididymis, the establishment of an acidic luminal pH and low bicarbonate concentration in the epididymis contributes to preventing premature activation of spermatozoa during their maturation and storage. Clear cells are proton-secreting cells throughout the epididymis, but principal cells have distinct acid/base transport properties, depending on their localization within the epididymis. Basal cells are located in all epididymal segments, but they have a distinct morphology depending on the segment and species examined. How this structural plasticity of basal cells is regulated is discussed here. Also, the role of luminal factors and androgens in the regulation of epithelial cells is reviewed in relation to their respective localization in the proximal versus distal regions of the epididymis. Finally, we describe a novel role for CFTR in tubulogenesis and epithelial cell differentiation.

Protective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B

Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current,clinically approved lipid-based formulations.The objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an in vitro model.Methods:Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at air-liquid interface until well-differentiated.Cultures were exposed to ND-AMB vs AMB and changes in K+ permeability and resistance were measured and recorded via Ussing chamber assay.Ciliary beat frequency (CBF) was analyzed in parallel as well as cytotoxic assay.Potency was assessed using real-time PCR measurement of the Aspergillus fumigatus 18S rRNA.Results:Ussing chamber studies revealed K+ currents that increased rapidly within 30 s of adding AMB (10 μg/mL) to the apical side,indicating apical membranes had become permeable to K+ ions.In contrast,negligible induction of K+ current was obtained following addition of NDAMB [AMB =(107.7 ± 15.9) μA/cm2 AMB vs ND-AMB =(2.3 ± 0.7) μA/cm2 ND-AMB;P =0.005].ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P ＜ 0.05).There was no difference in ciliary beat frequency between the two groups (P =0.96).The expression of A.fumigatus 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB (P ＜ 0.05).Conclusions:Data from the present study suggests ND-AMB protects human nasal epithelia membranes from AMB toxicity by protecting against apical cell K+ permeability while maintaining uncompromised antifungal property compared to AMB.ND-AMB could provide a novel topical therapy for sinonasal fungal diseases.