Rat Small Intestine Research Articles

Rat small intestine extract as a source of mammalian α- and β-glycosidases to study polyphenol bioaccessibility and deglycosylation in vitro: A case study with matrix-devoid and matrix-defined apple fractions

Most polyphenols are glycosylated, affecting their uptake, metabolism, and biological activity. However, the attached sugar must be removed before absorption and functionality can take place. Yet, despite the biological and chemical implications of polyphenol (de-)glycosylation, most in vitro digestion assays omit the utilization of intestinal brush border α- and/or β-glycosidases to study polyphenol bioaccessibility and deglycosylation. This study investigated the effect of rat small intestine extract (RSIE) as an affordable source of mammalian α- and β-glycosidases in different food matrices: matrix-devoid whole apple extract, whole apple, apple juice, and apple pomace. Using the INFOGEST 2.0 model, transepithelial polyphenol absorption, UHPLC-ESI-QTOF-MS/MS, and the inclusion of RSIE at the 15 U*mL−1 maltase activity reported in the human epithelium, the role of RSIE in polyphenol bioaccessibility and deglycosylation was explored. Moreover, the effect of the plant cell wall (PCW) matrix on the role of RSIE was mechanistically investigated by comparing whole apple (or pomace) with their respective extracts. 36 glycosylated polyphenols were identified, including 33 β-O-glycosides and 3 α-O-glycosides. The content of bioaccessible polyphenol β-O-glycosides and α-O-glycosides was significantly lower (p < 0.001) when RSIE was present, which resulted in a concomitant generation of the aglycone forms (phloretin, quercetin, ferulic acid, caffeic acid and p-coumaric acid). However, the concentration of aglycones was much lower than the reduction in the concentration of glycosylated polyphenols, strongly suggesting that polyphenols bind to RSIE. Matrix-devoid whole apple extract, or pomace extract, exhibited higher polyphenol bioaccessibility than whole apple or pomace, likely due to reduced interactions between polyphenols and the food matrix. Importantly, these differences in bioaccessibility diminished with RSIE, suggesting that RSIE α-glycosidases cleaved α-glucans and disrupted the PCW structure.

Case Report: Hymenolepis diminuta in an asymptomatic Ecuadorian child.

Background The cestode Hymenolepis diminuta is a cosmopolitan parasite, which in the adult stage is usually found in the small intestine of rats and accidentally in humans. Case report We describe the finding of eggs of this parasite in an asymptomatic 3-year-old child. The child had extremely high IgE values of 1,376 IU/ml. After receiving treatment with Albendazole suspension 400mg/20mL, on the 10th day post-treatment, he showed no H. diminuta eggs in his fecal matter Conclusions Detailed morphological review of Hymenolepis nana-like eggs is recommended to distinguish them from H. diminuta eggs.

Apoptotic and proliferative processes in the small intestine of rats with type 2 diabetes mellitus after metformin and propionic acid treatment.

Propionic acid (PA) is an intermediate product of metabolism of intestinal bacteria and may protect the intestinal barrier from disruption. The aim of the study was to investigate the apoptotic and proliferative processes in the small intestine (SI) of rats with type 2 diabetes mellitus (T2DM) on the background of metformin monotherapy and its combination with PA. Male Wistar rats were divided: 1) control; 2) T2DM (3-month high-fat diet followed by streptozotocin injection of 25mg/kg of body weight); 3) T2DM + metformin (60mg/kg, 14days, orally); 4) T2DM + PA (60mg/kg, 14days, orally); 5) T2DM + PA + metformin. Western blotting, RT-PCR, and scanning electron microscopy were performed. We observed profound changes in the SI of diabetic rats suggesting the disturbed intestinal homeostasis: impaired mitochondrial ultrastructure, increased cristae volume, and decreased content of proliferative marker Ki67 with almost unchanged proapoptotic caspase-3 and its p17 subunit levels. Metformin and PA monotherapies also led to an increased cristae volume, however, after their combination, a tendency to normalization of ultrastructure of mitochondria was observed. While there was a significant inhibition of proliferation in T2DM and, in greater extent, after metformin and PA monotherapies, differential influence on apoptosis in the SI was observed. While metformin inhibited apoptosis via Bax declining, PA mainly acted via caspase-3-dependent mechanism elevating its active p17 subunit. PA supplementation for the improvement of diabetes-induced gastrointestinal complications concurrently with metformin may be consider as a perspective supportive therapy. Data related to PA action on SI may be valuable during the development of new treatment strategies for diabetes-induced intestinal disturbances raised after metformin treatment.

Case Report: Hymenolepis diminuta in an asymptomatic Ecuadorian child.

Background The cestode Hymenolepis diminuta is a cosmopolitan parasite, which in the adult stage is usually found in the small intestine of rats and accidentally in humans. Case report We describe the finding of eggs of this parasite in an asymptomatic 3-year-old child. The child had extremely high IgE values of 1,376 IU/ml. After receiving treatment with Albendazole suspension 400mg/20mL, on the 10th day post-treatment, he showed no H. diminuta eggs in his fecal matter Conclusions Detailed morphological review of Hymenolepis nana-like eggs is recommended to distinguish them from H. diminuta eggs.

Electroacupuncture Promotes the Generation of Intestinal Treg Cells After Ischemic Stroke by Foxp3 Acetylation Regulation.

Electroacupuncture (EA) has been shown to ameliorate brain injury and protect against intestinal injury after ischemic stroke. These protective effects are closely associated with the enhancement of regulatory T (Treg) cell numbers and function in the intestine, as well as the inhibition of intestinal γδ T cell production and their migration to the brain. This study aimed to elucidate the potential mechanism by which EA regulates intestinal Treg cell differentiation after stroke. Sprague-Dawley rats were divided into three groups: the sham group, the middle cerebral artery occlusion (MCAO) group, and the MCAO plus EA (MEA) group. The MCAO model was generated by occluding the middle cerebral artery. EA was applied to Baihui (GV20) acupoint once daily. Samples were collected 3days after reperfusion. Our results showed that EA reduced the inflammatory response in the brain and intestine after ischemic stroke. EA treatment increased the percentage of Treg cells in the small intestine of rats. EA increased the levels of SCFAs, while also inhibiting histone deacetylase activity (HDAC). Additionally, acetylated Foxp3 protein in the small intestine was increased after EA treatment. These results suggest that EA at GV20 alleviates brain and intestinal inflammatory injury in stroke rats, potentially through the enhancement of SCFA-mediated Foxp3 acetylation in Treg cells.

Curcumin-loaded microcapsules with soy and whey protein as wall material: In vitro release, and ex vivo absorption based on the rat small intestine

Plant proteins, serving as an environmentally friendly and cost-effective alternative to animal proteins, have gained widespread usage in encapsulating various bioactive compounds like curcumin. However, understanding how plant protein-based microcapsules compare to those made with animal proteins in terms of disintegration, release, and absorption in the gastrointestinal tract (GIT) remains limited. This study aims to investigate the impact of soy protein isolate (SPI) and whey protein isolate (WPI) as wall materials on the release, stability, and absorption of curcumin. Spray-dried SPI-based microcapsules (SPI–C) exhibited significantly lower encapsulation efficiency (77.1%) and loading efficiency (3.6%) compared to WPI-based microcapsules (WPI–C) (97.6% and 9.6%, respectively). Structural analysis revealed pleated hollow spherical structures for SPI-C and a concave surface with a single-chamber structure for WPI-C. SPI-C demonstrated higher proteolysis (55.8% vs. 44.1%) during in vitro digestion, leading to greater curcumin release ratio (67.9% vs. 59.2%) and digestive stability (97.9% vs. 93.7%) compared to WPI-C. Notably, SPI-C exhibited higher apparent permeability (0.97 × 10−6 cm/s) to the ex vivo rat small intestine than WPI-C (0.44 × 10−6 cm/s). These findings suggest improved gastrointestinal stability and absorption of curcumin encapsulated by SPI, indicating the potential for enhanced utilization of plant-derived proteins in encapsulating bioactive compounds.

Distraction Enterogenesis in Rats: A Novel Approach for the Treatment of Short Bowel Syndrome.

Surgeons often encounter patients with intestinal failure due to inadequate intestinal length ("short bowel syndrome"/SBS). Treatment in these patients remains challenging and the process of physiologic adaptation may take years to complete, which frequently requires parenteral nutrition. We propose a proof-of-concept mechanical bowel elongation approach using a self-expanding prototype of an intestinal expansion sleeve (IES) for use in SBS to accelerate the adaptation process. IESs were deployed in the small intestines of Sprague Dawley rats. Mechanical characterization of these prototypes was performed. IES length-tension relationships and post-implant bowel expansion were measured ex vivo. Bowel histology before and after implantation was evaluated. IES mechanical studies demonstrated decreasing expansive force with elongation. The deployment of IES devices produced an immediate 21 ± 8% increase in bowel length (p < 0.001, n = 11). Mechanical load testing data showed that the IESs expressed maximum expansive forces at 50% compression of the initial pre-contracted length. The small-intestine failure load in the rats was 1.88 ± 21 N. Intestinal histology post deployment of the IES showed significant expansive changes compared to unstretched bowel tissue. IES devices were scalable to the rat intestinal model in our study. The failure load of the rat small intestine was many times higher than the force exerted by the contraction of the IES. Histology demonstrated preservation of intestinal structure with some mucosal erosion. Future in vivo rat studies on distraction enterogenesis with this IES should help to define this organogenesis phenomenon.

Physiological evaluation of PVP-coated AgNP in the rat small intestine: an ex vivo approach

Physiological evaluation of PVP-coated AgNP in the rat small intestine: an ex vivo approach

Improved Preservation of Rat Small Intestine Transplantation Graft by Introduction of Mesenchymal Stem Cell-Secreted Fractions.

Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24h in University of Wisconsin (UW) solution containing MSC-CM with 50-100kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.

L-valine is a powerful stimulator of GLP-1 secretion in rodents and stimulates secretion through ATP-sensitive potassium channels and voltage-gated calcium channels

BackgroundWe previously reported that, among all the naturally occurring amino acids, l-valine is the most powerful luminal stimulator of glucagon-like peptide 1 (GLP-1) release from the upper part of the rat small intestine. This makes l-valine an interesting target for nutritional-based modulation of GLP-1 secretion. However, the molecular mechanism of l-valine-induced secretion remains unknown.MethodsWe aimed to investigate the effect of orally given l-valine in mice and to identify the molecular details of l-valine stimulated GLP-1 release using the isolated perfused rat small intestine and GLUTag cells. In addition, the effect of l-valine on hormone secretion from the distal intestine was investigated using a perfused rat colon.ResultsOrally given l-valine (1 g/kg) increased plasma levels of active GLP-1 comparably to orally given glucose (2 g/kg) in male mice, supporting that l-valine is a powerful stimulator of GLP-1 release in vivo (P > 0.05). Luminal l-valine (50 mM) strongly stimulated GLP-1 release from the perfused rat small intestine (P < 0.0001), and inhibition of voltage-gated Ca2+-channels with nifedipine (10 μM) inhibited the GLP-1 response (P < 0.01). Depletion of luminal Na+ did not affect l-valine-induced GLP-1 secretion (P > 0.05), suggesting that co-transport of l-valine and Na+ is not important for the depolarization necessary to activate the voltage-gated Ca2+-channels. Administration of the KATP-channel opener diazoxide (250 μM) completely blocked the l-valine induced GLP-1 response (P < 0.05), suggesting that l-valine induced depolarization arises from metabolism and opening of KATP-channels. Similar to the perfused rat small intestine, l-valine tended to stimulate peptide tyrosine-tyrosine (PYY) and GLP-1 release from the perfused rat colon.Conclusionsl-valine is a powerful stimulator of GLP-1 release in rodents. We propose that intracellular metabolism of l-valine leading to closure of KATP-channels and opening of voltage-gated Ca2+-channels are involved in l-valine induced GLP-1 secretion.

A Novel Dimeric Short Peptide Derived from α-Defensin-Related Rattusin with Improved Antimicrobial and DNA-Binding Activities.

Rattusin, an α-defensin-related antimicrobial peptide isolated from the small intestine of rats, has been previously characterized through NMR spectroscopy to elucidate its three-dimensional structure, revealing a C2 homodimeric scaffold stabilized by five disulfide bonds. This study aimed to identify the functional region of rattusin by designing and synthesizing various short analogs, subsequently leading to the development of novel peptide-based antibiotics. The analogs, designated as F1, F2, F3, and F4, were constructed based on the three-dimensional configuration of rattusin, among which F2 is the shortest peptide and exhibited superior antimicrobial efficacy compared to the wild-type peptide. The central cysteine residue of F2 prompted an investigation into its potential to form a dimer at neutral pH, which is critical for its antimicrobial function. This activity was abolished upon the substitution of the cysteine residue with serine, indicating the necessity of dimerization for antimicrobial action. Further, we synthesized β-hairpin-like analogs, both parallel and antiparallel, based on the dimeric structure of F2, which maintained comparable antimicrobial potency. In contrast to rattusin, which acts by disrupting bacterial membranes, the F2 dimer binds directly to DNA, as evidenced by fluorescence assays and DNA retardation experiments. Importantly, F2 exhibited negligible cytotoxicity up to 515 μg/mL, assessed via hemolysis and MTT assays, underscoring its potential as a lead compound for novel peptide-based antibiotic development.

SOURCES OF SUPEROXIDE ANION RADICAL IN SMALL INTESTINE TISSUES IN RATS SUBJECTED TO SURGICAL TRAUMA SIMULATED UNDER EXPERIMENTAL MODEL OF POSTTRAUMATIC STRESS DISORDER

The sources of superoxide anion radical (.О ) in the tissues of the small intestine in rats subjected to surgical trauma simulated under an experimental model of posttraumatic stress disorder (PTSD) were investigated. The study involved 42 white Wistar rats weighing 210-230 g, divided into 6 groups: group 1 comprised intact animals, group 2 included animals with the PTSD induced through single-prolonged stress (SPS), group 3 consisted of rats subjected to a sham surgical operation, group 4 comprised animals undergoing laparotomy, group 5 involved rats undergoing a sham surgical operation following SPS, and group 6 included animals undergoing laparotomy under modeled SPS. The rate of .О generation in the small intestine homogenate was measured spectrophotometrically using the nitroblue tetrazolium test. The .О production by NADPH-dependent (microsomal and NO synthase) electron transport chains (ETC), NADH-dependent (mitochondrial) ETC and leukocyte NADPH oxidase was assessed. The findings obtained have demonstrated that experimental SPS modeling leads to an increase in oxidative stress in the small intestine tissues of rats. This is manifested by an increase in the rate of .О formation with the participation of microsomes, mitochondria and leukocyte NADPH oxidase. On the 7th day after laparotomy under the experimental PTSD model, the .О production in the tissues of the small intestine by different sources (microsomes, mitochondria and leukocyte NADPH oxidase) exceeds their values obtained after a single laparotomy or after performing a sham operation under single long-term stress.

Astragaloside IV ameliorates indomethacin-induced intestinal inflammation in rats through inhibiting the activation of NLRP3 inflammasome

The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may cause significant intestinal alteration and inflammation and lead to the occurrence of inflammatory diseases resembling duodenal ulcers. Astragaloside IV (AS-IV) is a glycoside of cycloartane-type triterpene isolated from the dried root of Astragalus membranaceus (Fisch.) Bge. (family Fabaceae), and has been used for ameliorating the NSAID-induced inflammation in the small intestine. The present study aimed to investigate the effects of AS-IV on indomethacin (IND)-induced inflammation in the small intestine of rats and its underlying mechanisms. Hematoxylin-eosin (H&E) staining, transmission and scanning electron microscopy were carried out to observe the surface morphology and ultrastructure of the small intestinal mucosa. Immunofluorescence and ELISA tests were employed to detect the expressions of NLRP3, ASC, caspase-1, and NF-κB proteins, as well as inflammatory factors IL-1β and IL-18, to uncover potential molecular mechanisms responsible for mitigating small intestinal inflammation. The results demonstrated that AS-IV significantly decreased the ulcer index, improved the surface morphology and microstructure of the small intestinal mucosa, and increased mucosal blood flow. Molecular docking revealed a strong and stable binding capacity of AS-IV to NLRP3, ASC, caspase-1, and NF-κB proteins. Further experimental validation exhibited that AS-IV markedly decreased levels of IL-1β and IL-18, and inhibited the protein expression of NLRP3, ASC, caspase-1, and NF-κB. Our data demonstrate that AS-IV ameliorates IND-induced intestinal inflammation in rats by inhibiting the activation of NLRP3 inflammasome and reducing the release of IL-1β and IL-18, thereby representing a promising therapy for IND-induced intestinal inflammation.

Herb–drug interactions: Quantitative analysis of levofloxacin absorption and transporter expression in the rat intestine following combined treatment with Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross

Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, a traditional Chinese medicinal plant, is often used to treat various urologic disorders in China. P. capitata extracts (PCE) have been used in combination with levofloxacin (LVFX) to treat urinary tract infections (UTIs) for a long time. However, little is known about the absorption of LVFX and transporter expression in the intestine after combined treatment with PCE, restricting the development and utilization of PCE. In view of this, a UPLC-MS/MS method was established for the determination of LVFX in intestinal sac fluid samples and in situ intestinal circulation perfusate samples to explore the effect of PCE on the intestinal absorption characteristics of LVFX ex vivo and in vivo. To further evaluate the interaction between LVFX and PCE, western blotting, immunohistochemistry, and RT-qPCR were utilized to determine the expression levels of drug transporters (OATP1A2, P-gp, BCRP, and MRP2) involved in the intestinal absorption of LVFX after combined treatment with PCE. Using the everted intestinal sac model, the absorption rate constant (Ka) and cumulative drug absorption (Q) of LVFX in each intestinal segment were significantly lower in groups treated with PCE than in the control group. Ka at 2 h decreased most in the colon segment (from 0.088 to 0.016 µg/h·cm2), and Q at 2 h decreased most in the duodenum (from 213.29 to 33.92 µg). Using the intestinal circulation perfusion model, the Ka value and percentage absorption rate (A) of LVFX in the small intestine decreased significantly when PCE and LVFX were used in combination. These results showed that PCE had a strong inhibitory effect on the absorption of LVFX in the rat small intestine (ex vivo and in vivo intestinal segments). In addition, PCE increased the protein and mRNA expression levels of efflux transporters (P-gp, BCRP, and MRP2) and decreased the expression of the uptake transporter OATP1A2 significantly. The effects increased as the PCE concentration increased. These findings indicated that PCE changed the absorption characteristics of levofloxacin, possibly by affecting the expression of transporters in the small intestine. In addition to revealing a herb–drug interaction (HDI) between PCE and LVFX, these results provide a basis for further studies of their clinical efficacy and mechanism of action.

Hypoglycemic effects of mountain caviar extract and inhibitory mechanism of saponins, including momordin Ic, on glucose absorption.

Mountain caviar is a fruit of Kochia scoparia that contains momordin Ic as a major saponin constituent. Its extract (MCE) has been shown to suppress blood glucose elevations in the human oral glucose tolerance test (OGTT) as well as increases in blood glucose in OGTT, gastric emptying (GE), and glucose incorporation in the small intestine in rats. However, the effects of MCE and momordin Ic on glucose absorption in mice and these action mechanisms have not been examined for more than 2 decades. Therefore, we herein investigated the effects of MCE, its saponin fraction, and momordin Ic on blood glucose elevations in mice. Mouse blood glucose elevation tests were performed on carbohydrate-loaded mice. The mountain caviar saponin fraction significantly delayed blood glucose elevations in glucose-, sucrose-, and soluble starch-loaded mice. In glucose-loaded mice, the saponin fraction, MCE, and momordin Ic significantly suppressed rapid glucose elevations after glucose loading, but not sucrose loading. A mouse GE study was performed by loading with glucose and phenolphthalein solution. Momordin Ic and MCE strongly suppressed mouse GE. Intestinal glucose absorption was evaluated by the incorporation of 2-deoxyglucose (2-DG) into Caco-2 cell layers and mouse duodenum wall vesicles. The results obtained showed that momordin Ic inhibited the incorporation of 2-DG into Caco-2 cells and mouse duodenum vesicles. Collectively, these results suggest that MCE, particularly the principal saponin, momordin Ic, preferably suppressed glucose-induced blood glucose elevations and delayed carbohydrate-induced glucose elevations in mice. The underlying mechanism was found to involve the suppression of GE and intestinal glucose absorption.

FEATURES OF THE METABOLISM OF SIALOGLYCOPROTEINS IN THE TISSUES OF THE LIVER, STOMACH AND SMALL INTESTINE OF RATS UNDER IMMOBILIZATION STRESS

Introduction. Immobilization stress leads to the intensification of free-radical reactions leading to the destruction of sialoglycoproteins of the gastroduodenal zone. The aim of the study. To evaluate the features of the metabolism of sialoglycoproteins in the tissues of the liver, stomach and small intestine of rats under immobilization stress. Methods. Total sialic acids (TSA) and levels of sialidase activity (SA) were determined in the serum, liver, stomach, and small intestine tissues of rats by standard testing systems in dynamics on the 21st, 35th, 60th and 90th days of observation. Results. The blood serum of laboratory rats showed a maximum increase in total sialic acids and sialidases by 35 days of stress exposure, while in the liver, on the contrary, a decrease in the above-mentioned indicators. In the mucous overlays of the stomach and small intestine, the number of TSA increased throughout the dynamics of observation, and the activity of sialidase decreased by day 21 and increased in the following days of the experiment. In the wall of the stomach and small intestine of experimental rodents, the level of TSA increased by the 35th day of observation. Conclusion. During immobilization stress in the exchange of sialoglycoproteins, a compensatory predominance of anabolic processes in liver tissues was noted against the background of the prevalence of catabolism in the mucosal layer of the stomach and small intestine on days 21, 35 of observation, changes in the walls of the above organs are less pronounced and manifest themselves at a later date.

Characterizing interregional differences in the rheological properties and composition of rat small intestinal mucus.

The mucus layer in the small intestine is generally regarded as a barrier to drug absorption. However, the mucus layer is a complex system, and presently, only a few studies have been conducted to elucidate its physicochemical properties. The current study hypothesizes that the mucus layer contains solubility-enhancing surfactants and thus might aid the oral absorption of poorly water-soluble drugs.Mucus was sampled from sections of the small intestine of fasted rats to analyze the rheological properties and determine the mucus pH and concentrations of proteins and endogenous surfactants, i.e., bile salts, polar lipids, and neutral lipids.The mucus layer in the two proximal sections of the small intestine exhibited different rheological properties such as higher zero-shear viscosity and lower loss tangent and higher protein concentrations compared to all subsequent sections of the small intestine. The pH of the mucus layer was stable at ~ 6.5 throughout most of the small intestine, but increased to 7.5 in the ileum.The bile salt concentrations increased from the duodenum (16.0 ± 2.2mM) until the mid jejunum (55.1 ± 9.5mM), whereas the concentrations of polar lipids and neutral lipids decreased from the duodenum (17.4 ± 2.2mM and 37.8 ± 1.6mM, respectively) until the ileum (4.8 ± 0.4mM and 10.7 ± 1.1mM, respectively).In conclusion, the mucus layer of the rat small intestine contains endogenous surfactants at levels that might benefit solubilization and absorption of orally administered poorly water-soluble drugs.

Regional differences in the ultrastructure of mucosal macrophages in the rat large intestine.

We previously clarified the histological characteristics of macrophages in the rat small intestine using serial block-face scanning electron microscopy (SBF-SEM). However, the regional differences in the characteristics of macrophages throughout the large intestine remain unknown. Here, we performed a pilot study to explore the regional differences in the ultrastructure of mucosal macrophages in the large intestine by using SBF-SEM analysis. SBF-SEM analysis conducted on the luminal side of the cecum and descending colon revealed macrophages as amorphous cells possessing abundant lysosomes and vacuoles. Macrophages in the cecum exhibited a higher abundance of lysosomes and a lower abundance of vacuoles than those in the descending colon. Macrophages with many intraepithelial cellular processes were observed beneath the intestinal superficial epithelium in the descending colon. Moreover, macrophages in contact with nerve fibers were more prevalent in the cecum than in the descending colon, and a subset of them surrounded a nerve bundle only in the cecum. In conclusion, the present pilot study suggested that the quantity of some organelles (lysosomes and vacuoles) in macrophages differed between the cecum and the descending colon and that there were some region-specific subsets of macrophages like nerve-associated macrophages in the cecum.

Polymeric nanoparticles for oral delivery of biopharmaceuticals: an overview

Biopharmaceuticals, cutting-edge medications sourced from living organisms, embody the zenith of therapeutic progress driven by biotechnological breakthroughs. While oral drug delivery is convenient, it proves challenging for biopharmaceuticals due to the complex barriers in the gastrointestinal tract. Their delicate structure and susceptibility to degradation in the gut pose formidable obstacles. This scientific conundrum necessitates innovative solutions to ensure their effectiveness. Pseudomonas aeruginosa's Exotoxin A demonstrates the difficulty in traversing the intestinal epithelium, necessitating innovative strategies. Researchers utilize mucoadhesive, biodegradable polymers like alginate and chitosan to create nanoparticles. These nanoparticles form a protective gel in the stomach's acidic environment, enhancing drug stability and absorption. Chitosan and alginate collaborate in nanoparticle formulations, improving mucosal adhesion and prolonging drug retention. Introducing non-toxic Exotoxin A enhances trans-epithelial transport, validated by in vitro studies on Caco-2 cell monolayers and accumulation in the rat small intestine's lamina propria. Utilizing green fluorescent protein as a model within alginate-chitosan nanoparticles showcases their potential for oral drug delivery. Bacterial toxins play a crucial role in enhancing trans-epithelial transport, endorsing these nanoparticles. This fusion of biotechnology and polymer science offers a promising solution for biopharmaceutical oral delivery challenges, highlighting alginate-chitosan nanoparticles as versatile carriers for transformative drug delivery advancements.

Preferential meropenem absorption activated by 1α,25-dihydroxyvitamin D3 and shared with foscarnet, a phosphate transporter substrate, in the rat ileum

Meropenem (MEPM) is used for the treatment of serious infectious diseases solely as. InjectableTherefore, the development of an oral formulation would expand its clinical utility. To this end, an exact understanding of the absorption characteristics of MEPM is essential. In this study, MEPM absorption in the rat small intestine was investigated using an in situ loop technique and an in vitro diffusion chamber method. The disappearance ratios of MEPM (0.1 mM) were in the order of ileum > duodenum > jejunum. The extensive MEPM disappearance in the ileum was significantly reduced in the presence of foscarnet, a Na+-dependent phosphate transporter (NaPi-T) substrate, whereas glycylsarcosine, thiamine, taurocholic acid, and biapenem had no effects. The mucosal-to-serosal (M-to-S) permeation of MEPM across the rat ileal segments was very small under normal experimental conditions. However, on addition of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) to the experimental medium, the M-to-S permeation of MEPM markedly increased, showing a more than 7-fold greater apparent permeation coefficient. The present results suggest that MEPM is preferentially absorbed in the rat ileum, sharing with foscarnet, and that 1,25(OH)2D3 potentially activates the absorption of MEPM there. A likely candidate for involvement in MEPM absorption was NaPi-T or a related transporter.