Rat Esophagus Research Articles

Purinergic inhibitory regulation of esophageal smooth muscle is mediated by P2Y receptors and ATP-dependent potassium channels in rats

Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10–100 μM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 μM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 μM), and a P2Y receptor antagonist, cibacron blue F3GA (200 μM), inhibited the ATP (100 μM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 μM), did not affect it. A blocker of ATP-dependent potassium channels (KATP channels), glibenclamide (200 μM), inhibited the ATP-induced relaxation and application of an opener of KATP channels, nicorandil (50 μM), produced relaxation. The findings suggest that ATP is involved in inhibitory regulation of the longitudinal smooth muscle in the muscularis mucosae of the rat esophagus via activation of P2Y receptors and then opening of KATP channels.

Localization of sensory nerve terminals containing calcitonin gene-related peptide (CGRP) on striated muscle fibers in the rat esophagus: Evidence for triple innervation via motor endplates

BackgroundMany esophageal striated muscles of mammals are dually innervated by the vagal and enteric nerves. Recently, substance P (SP)-sensory nerve terminals with calcitonin gene-related peptide (CGRP) were found on a few striated muscle fibers in the rat esophagus, implying that these muscle fibers are triply innervated. In this study, we examined the localization and origin of CGRP-nerve endings in striated muscles to consider their possible roles in the esophagus regarding triple innervation. MethodsWholemounts of the rat esophagus were immunolabeled to detect CGRP-nerve endings in striated muscles. Also, retrograde tracing was performed by injecting Fast Blue (FB) into the esophagus, and cryostat sections of the medulla oblongata, nodose ganglion (NG), and the tenth thoracic (T10) dorsal root ganglion (DRG) were immunostained to identify the origin of the CGRP-nerve endings. ResultsCGRP-fine, varicose nerve endings were localized in motor endplates on a few esophageal striated muscle fibers (4 %), most of which received nitric oxide (NO) synthase nerve terminals, and most of the CGRP nerve endings were SP- and transient receptor potential vanilloid member 1 (TRPV1)-positive. Retrograde tracing showed many FB-labeled CGRP-neurons positive for SP and TRPV1 in the NG and T10 DGR. ConclusionsThis study suggests that the CGRP-varicose nerve endings containing SP and TRPV1 in motor endplates are sensory, and a few esophageal striated muscle fibers are triply innervated. The nerve endings may detect acetylcholine-derived acetic acid from the vagal motor nerve endings and NO from esophageal intrinsic nerve terminals in the motor endplates to regulate esophageal motility.

Local hyperthermia mediated by gold nanoparticle-integrated silicone-covered stent: feasibility and tissue response in a rat esophageal model

BackgroundTo assess the feasibility and tissue response of using a gold nanoparticle (AuNP)-integrated silicone-covered self-expandable metal stent (SEMS) for local hyperthermia in a rat esophageal model.MethodsThe study involved 42 Sprague–Dawley rats. Initially, 6 animals were subjected to near-infrared (NIR) laser irradiation (power output from 0.2 to 2.4 W) to assess the in vitro heating characteristics of the AuNP-integrated SEMS immediately after its placement. The surface temperature of the stented esophagus was then measured using an infrared thermal camera before euthanizing the animals. Subsequently, the remaining 36 animals were randomly divided into 4 groups of 9 each. Groups A and B received AuNP-integrated SEMS, while groups C and D received conventional SEMS. On day 14, groups A and C underwent NIR laser irradiation at a power output of 1.6 W for 2 min. By days 15 (3 animals per group) or 28 (6 animals per group), all groups were euthanized for gross, histological, and immunohistochemical analysis.ResultsUnder NIR laser irradiation, the surface temperature of the stented esophagus quickly increased to a steady-state level. The surface temperature of the stented esophagus increased proportionally with power outputs, being 47.3 ± 1.4 °C (mean ± standard deviation) at 1.6 W. Only group A attained full circumferential heating through all layers, from the epithelium to the muscularis propria, demonstrating marked apoptosis in these layers without noticeable necroptosis.ConclusionsLocal hyperthermia using the AuNP-integrated silicone-covered SEMS was feasible and induced cell death through apoptosis in a rat esophageal model.Relevance statementA gold nanoparticle-integrated silicone-covered self-expanding metal stent has been developed to mediate local hyperthermia. This approach holds potential for irreversibly damaging cancer cells, improving the sensitivity of cancer cells to therapies, and triggering systemic anticancer immune responses.Key points• A gold nanoparticle-integrated silicone-covered self-expanding metal stent was placed in the rat esophagus.• Upon near-infrared laser irradiation, this stent quickly increased the temperature of the stented esophagus.• Local hyperthermia using this stent was feasible and resulted in cell death through apoptosis.Graphical

Evaluation of effects of curcumin on acute esophagitis in the corrosive esophagitis model in rats

Ingestion of a corrosive substance may cause corrosive esophagitis. Curcumin has anti-inflammatory and mucosal protective effects. In this study, the effects of curcumin on the acute phase of corrosive esophagitis were investigated. Twenty-seven Wistar Albino rats were divided into four groups; sham (group I), control (group II), and experiment groups (group III, 100 mg/kg curcumin; group IV, 200 mg/kg curcumin). Forty percent sodium hydroxide solution was used to erode the esophagi of rats in groups other than the sham group. Curcumin was applied to animals in the experiment groups 10 min after the corrosion. After 24 h, animals were sacrificed, and esophagus samples were collected. According to the histopathological examination, the muscularis mucosa damage was regressed from 100% in group II to 71.4% in group III and 50% in group IV. Mild level of damage and collagen deposition in the tunica muscularis regressed from 66.7% of the animals in the control group to 42.9% in group III and to none in group IV. Further, an increase in submucosal collagen was present in all samples from groups II and III, while 83.3% of samples had an increase in submucosal collagen in group IV. There was a significant difference in the histopathological total score between the control group and group IV (p=0.02). The results showed that the administration of curcumin in a dose-dependent manner can relieve the acute phase of corrosive esophagitis.

Localized Photodynamic Therapy Using a Chlorin e6-Embedded Silicone-Covered Self-Expandable Metallic Stent as a Palliative Treatment for Malignant Esophageal Strictures.

Localized photodynamic therapy (PDT) uses a polymeric-photosensitizer (PS)-embedded, covered self-expandable metallic stent (SEMS). PDT is minimally invasive and a noteworthy potential alternative for treating esophageal strictures, where surgery is not a viable option. However, preclinical evidence is insufficient, and optimized irradiation energy dose ranges for localized PDT are unclear. Herein, we validated the irradiation energy doses of the SEMS (embedded in a PS using chlorin e6 [Ce6] and covered in silicone) and PDT-induced tissue changes in a rat esophagus. Cytotoxicity and phototoxicity in the Ce6-embedded SEMS piece with laser irradiation were significantly higher than that of the silicone-covered SEMS with or without laser and the Ce6-embedded silicone-covered SEMS without laser groups (all p < 0.001). Moreover, surface morphology, atomic changes, and homogeneous coverage of the Ce6-embedded silicone-covered membrane were confirmed. The ablation range of the porcine liver was proportionally increased with the irradiation dose (all p < 0.001). The ablation region was identified at different irradiation energy doses of 50, 100, 200, and 400 J/cm2. The in vivo study in the rat esophagus comprised a control group and 100, 200, and 400 J/cm2 energy-dose groups. Finally, histology and immunohistochemistry (TUNEL and Ki67) confirmed that the optimized Ce6-embedded silicone-covered SEMS with selected irradiation energy doses (200 and 400 J/cm2) effectively damaged the esophageal tissue without ductal perforation. The polymeric PS-embedded silicone-covered SEMS can be easily placed via a minimally invasive approach and represents a promising new approach for the palliative treatment of malignant esophageal strictures.

Cranberry Proanthocyanidins Mitigate Reflux-Induced Transporter Dysregulation in an Esophageal Adenocarcinoma Model.

We recently reported that cranberry proanthocyanidins (C-PACs) inhibit esophageal adenocarcinoma (EAC) by 83% through reversing reflux-induced bacterial, inflammatory and immune-implicated proteins and genes as well as reducing esophageal bile acids, which drive EAC progression. This study investigated whether C-PACs' mitigation of bile reflux-induced transporter dysregulation mechanistically contributes to EAC prevention. RNA was isolated from water-, C-PAC- and reflux-exposed rat esophagi with and without C-PAC treatment. Differential gene expression was determined by means of RNA sequencing and RT-PCR, followed by protein assessments. The literature, coupled with the publicly available Gene Expression Omnibus dataset GSE26886, was used to assess transporter expression levels in normal and EAC patient biopsies for translational relevance. Significant changes in ATP-binding cassette (ABC) transporters implicated in therapeutic resistance in humans (i.e., Abcb1, Abcb4, Abcc1, Abcc3, Abcc4, Abcc6 and Abcc10) and the transport of drugs, xenobiotics, lipids, and bile were altered in the reflux model with C-PACs' mitigating changes. Additionally, C-PACs restored reflux-induced changes in solute carrier (SLC), aquaporin, proton and cation transporters (i.e., Slc2a1, Slc7a11, Slc9a1, Slco2a1 and Atp6v0c). This research supports the suggestion that transporters merit investigation not only for their roles in metabolism and therapeutic resistance, but as targets for cancer prevention and targeting preventive agents in combination with chemotherapeutics.

Comprehensive analysis of transcriptome-wide N6-methyladenosine methylomes in the Barrett's esophagus in rats

PurposeAs the most abundant RNA modification, N6-methyladenosine (m6A) methylation plays crucial roles in various diseases. The aim of this study is to comprehensively map the landscape of the mRNA m6A modification pattern in Barrett's esophagus (BE) in order to find key genes and potential therapy for BE and even esophageal adenocarcinoma (EAC). MethodsMethylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequencing (RNA-seq) were performed to compare the difference in mRNA m6A methylation and differentially expressed mRNAs between BE and normal control (NC) tissues. Bioinformatics analysis was used to describe the m6A modification pattern and specific genes in BE and NC tissues. ResultsThrough MeRIP-seq, we obtained m6A methylation profiling in BE and NC tissues. In total, 11,026 unique peaks were detected in the BE groups, whereas 8564 unique peaks were detected in the NC groups. Peaks were primarily enriched within CDS with GGACU motifs and most of the peaks were within 1000 bp in width. Moreover, functional enrichment analysis demonstrated that hypermethylated and hypomethylated genes were significantly enriched in coronavirus disease pathway, calcium signaling pathway and MAPK signaling pathways. Furthermore, PPI network was conducted and 18 hub genes were identified via STRING database and Cystoscope. Among them, ACTA1, CDC20, CKM, KIF20a, MYH11, TPM2, MYL9, DES, TNNT3 were overexpressed in EAC in the GEPIA gene bank and TPM1, KIF20a impaired patients' survival in the Kaplan-Meier plotter database. Finally, functional enrichment analysis demonstrated that co-expressed genes of TPM1 were significantly enriched in calcium signaling pathway, cGMP-PKG signaling pathway and PI3K-Akt signaling pathway. ConclusionOur study is the first to perform comprehensive and transcriptome-wide maps to identify the potential roles played by m6A methylation in BE, which widely involved in oxidative stress. This foresees a guiding role in revealing the molecular mechanism of m6A-mediated genes that govern the pathogenesis and progression of BE and EAC.

Investigation of the histopathological level of Ki-67, caspase-3 expressions of the effects of hesperidin on wound healing in the rat esophagus

The effects of hesperidin application on the wound caused by esophageal burns were investigated in this study. Wistar albino rats were divided into three groups: Control group: only 1 mL of 0.09% NaCl was administered i.p. for 28 days; Burn group: An alkaline esophageal burn model was created with 0.2 mL of 25% NaOH orally by gavage-1 mL of 0.09% NaCl was administered i.p. for 28 days; Burn+Hesperidin group: 1 mL of 50 mL/kg of hesperidin was given i.p. for 28 days to rats after burn injury. Blood samples were collected for biochemical analysis. Esophagus samples were processed for histochemical staining and immunohistochemistry. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly increased in Burn group. Glutathione (GSH) content and histological scores of epithelialization, collagen formation, neovascularization was decreased. After hesperidin treatment, these values were significantly improved in the Burn+Hesperidin group. In the Burn group, epithelial cells and muscular layers were degenerated. Hesperidin treatment restored these pathologies in Burn+Hesperidin group. Ki-67 and caspase-3 expressions were mainly negative in control group; however, the expression was increased in the Burn group. In the Burn+Hesperidin group, Ki-67 and caspase-3 immune activities were reduced. Hesperidin dosage and application methods can be developed as an alternative treatment for burn healing and treatment.

Chronic Inflammatory Changes In Esophageal Mucosa of Albino Rats Following Prolonged Intake of Carbonated Drinks.

Abstract&#x0D; Background: Carbonated beverages include soft drinks or sodas which contain carbondioxide and that when ingested for prolonged period of time lowers the intra-esophageal pH and can lead to histopathological changes in the mucosa.&#x0D; Objective: To study the effects of prolonged intake of carbonated drinks on the oesophagus of albino rats.&#x0D; Method: This experimental study was carried out at Shaheed Mohtarma Benazir Bhutto Medical College for a period of six months. Seventy five rats of wistar strain (gender non specific) were divided into ‘control groups ‘A1 n=10, A2 n=10, A3 n=10 &amp; ‘exposed groups’ B n=15, C n=15 and D n=15.The controls and the exposed animals were fed the same balanced diet, prepared at the lab’s kitchen. The fluid intake of exposed animals was restricted to carbonated drinks only, whereas, the controls were fed water.At the end of the first, third and sixth months, groups A1&amp;B, A2&amp;C and A3&amp;D were sacrificed and histological section of oesophagus were obtained for histomorphological studies.&#x0D; Results:&#x0D; On micrometry, width of the oesophagus of the exposed animals for one month;Group B was higher (17.87) than those of Group A1 (5.70). Those rats sacrificed at the end of the third month; Group C had significantly enlarged wall thickness of the oesophagus compared to A2 group. The average oesophageal wall thickness 13.60?m was found to be more in the exposed group ‘D’, as compared to 4.50?m measured in Control Group A3 (p&lt;0.01).&#x0D; Conclusion: Prolonged consumption of carbonated drinks resulted in gross and histomorphological changes in the esophageal mucosa. The results of this research will help provide awareness to the general public of the adverse effects afflicted by these beverages.&#x0D;

Image-guided stent-directed irreversible electroporation for circumferential ablation in the rat esophagus.

Background: Irreversible electroporation (IRE) has been investigated in the alimentary tract; however, the lack of dedicated electrodes and insufficient tissue responses made its application limited. The aim of this study was to investigate the efficacy and safety of image-guided stent-directed IRE in the rat esophagus. Methods: The bipolar self-expandable electrode (SE) was developed using the braiding technique. A finite element analysis was performed to validate optimal electrical field strength for the rat esophagus. A total of 40 out of 50 rats received stent-directed IRE and were sacrificed at 10h, 3days, 7days, and 28days of 10 each. The remaining ten rats underwent a sham procedure. The outcomes of stent-directed IRE were assessed by esophagography and histological responses. Results: Stent-directed IRE was technically successful in all rats with mild muscle contraction. The heart rate dropped immediately and gradually recovered at 180s. TUNEL and caspase-3 with submucosal thickness significantly increased at 10h and Day 3 compared with those of the sham control (all p < 0.001). The thickness of epithelial layers with collagen deposition significantly decreased at 10h and Day 3 (all p < 0.001), however, increased at Day 7 compared with that of the sham control (all p < 0.05). The Ki67-positive deposition significantly increased at Day 3 and 7 compared with that of the sham control (all p < 0.001). All variables were similar to those of the sham control at Day 28. Conclusion: Image-guided stent-directed IRE was effective and safe in the rat esophagus. It seems to have effectively and evenly induced cell death and gradually recovered with cellular regeneration.

Stent-based electrode for radiofrequency ablation in the rat esophagus: a preliminary study

Endoluminal radiofrequency (RF) ablation has been widely used as a safe and effective treatment for Barrett’s esophagus. However, inadequate RF ablation may occur due to insufficient contact between the electrode and target tissues. Herein, a stent-based monopolar RF electrode (SE) was developed to evenly deliver RF energy to the inner wall of the rat esophagus. The optimal RF parameters were evaluated in the exposed rat esophagus. The temperature in the rat esophagus reached 70 ℃ in 89 s at 30 W, 59 s at 40 W, and 34 s at 50 W. The technical feasibility and efficacy of RF ablation using SE were evaluated based on changes in histological transformation and immunohistochemical parameters of tissues compared at immediately, 1 and 2 weeks after the procedure. The degrees of inflammatory cell infiltration, fibrotic changes, TUNEL, and HSP70 in the RF-ablated rat esophagus were significantly higher than compared with sham control (all p < 0.05). TUNEL-positive deposition gradually decreased, but HSP 70-positive deposition maintained a similar level for 2 weeks. The stent-based RF ablation was technically feasible and effective in evenly inducing thermal damages to the rat esophagus. The RF ablation system using the SE may represent a promising treatment for endoluminal malignancies.

N-nitrosamines-mediated downregulation of LncRNA-UCA1 induces carcinogenesis of esophageal squamous by regulating the alternative splicing of FGFR2

Concerns are raised over the risk to digestive system's tumors from the N-nitrosamines (NAs) exposure in drinking water. Albeit considerable studies are conducted to explore the underlying mechanism responsible for NAs-induced esophageal squamous cell carcinoma (ESCC), the exact molecular mechanisms remain largely unknown, especially at the epigenetic regulation level. In this study, it is revealed that the urinary concentration of N-Nitrosodiethylamine is higher in high incidence area of ESCC, and the lncRNA-UCA1(UCA1) is significantly decreased in ESCC tissues. In vitro and in vivo experiments further show that UCA1 is involved in the malignant transformation of Het-1A cells and precancerous lesions of the rat esophagus induced by N-nitrosomethylbenzylamine (NMBzA). Functional gain and loss experiments verify UCA1 can affect the proliferation, migration, and invasion of ESCC cells in vitro and in vivo. Mechanically, through binding to heterogeneous nuclear ribonucleoprotein F (hnRNP F) protein, UCA1 regulates alternative splicing of fibroblast growth factor receptor 2 (FGFR2), which promotes the FGFR2IIIb isoform switching to FGFR2 IIIc isoform, and the latter activates epithelial-mesenchymal transition via PI3K-AKT signaling pathways impacting tumorigenesis. Therefore, NAs-mediated downregulation of UCA1 promotes ESCC progression through targeting hnRNP F/FGFR2/PI3k-AKT axis, which provides a new chemical carcinogenic target and establishes a previously unknown mechanism for NAs-induced ESCC.

Proteomic analysis reveals that ACSL4 activation during reflux esophagitis contributes to ferroptosis-mediated esophageal mucosal damage

Ferroptosis has been shown to be involved in the pathological process of many diseases. However, the function and mechanism of ferroptosis in reflux esophagitis (RE), especially in the esophageal mucosal damage, remains unknown. The purpose of this study was to screen potential therapeutic target genes that mediate RE esophageal mucosal damage and regulate ferroptosis. RE rats were established by our previous protocol and proteomic analysis of esophageal mucosa was performed. In addition, the ferroptosis-related genes were retrieved from the FerrDb database and were cross analyzed with the differential proteins of proteomics to obtain potential therapeutic target genes Acyl-CoA synthetase long-chain family 4 (ACSL4), a key enzyme for ferroptosis. In the present study, we used the ACSL4 inhibitor rosiglitazone (ROSI) and the ferroptosis inhibitor ferrostatin-1 to intervene with RE rats, and evaluate the levels of protein, histological changes, lipid peroxidation levels, iron accumulation and morphological changes in esophageal tissue by HE staining, Western blot, related kit tests, and transmission electron microscope. The results showed that both ferrostatin-1 and ROSI treatment significantly reduced the levels of iron accumulation and lipid peroxidation, and protected against ferroptosis and esophageal tissue injury in RE rats. Through Immunohistochemical staining, 16SrDNA sequencing, Enzyme linked immunosorbent assay (ELISA), Western blot and other tests on the esophagus, gut, spleen and serum of RE rats, we further found that the changes of esophageal and intestinal microbiota and the increase of peripheral blood LPS were the key factors regulating ferroptosis in esophageal epithelial tissue. On the one hand, LPS could increase the expression of ACSL4 in esophageal tissue by up-regulating special protein 1 (Sp1). On the other hand, LPS could increase the secretion of serum ferritin in spleen and the accumulation of iron in esophageal tissue by activating Capase11/GSDMD pyroptosis pathway. Collectively, this study suggests that ACSL4 and ferroptosis are potential therapeutic targets for RE esophageal mucosal damage, and esophageal and gut microecology play a critical role in this process.

Flexible 3D Nanonetworked Silica Film as a Polymer‐Free Drug‐Eluting Stent Platform to Effectively Suppress Tissue Hyperplasia in Rat Esophagus (Adv. Healthcare Mater. 14/2022)

Nanonetworked Films In article number 2200389 by Wooram Park, Jung-Hoon Park, Joonseok Lee, and co-workers, a large scale 3D nanonetworked silica film (NSF) is constructed on an entire metallic stent surface to function as a drug delivery platform, which shows excellent mechanical stability, flexibility, and adhesion. The NSF with an antiproliferative agent allows in vivo drastic suppression of stentinduced tissue hyperplasia and restenosis.

Examining Gongylonema Neoplasticum From Rats in Tabriz City (Northwest of Iran): A Case Report

Aims Different species of gongylonema are common parasites of rats that can be accidentally transmitted to humans and cause disease. This study aims to identify and investigate the morphology of Gongylonema neoplasticum and its zoonotic significance in Tabriz rats. Methods &amp; Materials In this study, 100 rats (29 Rattus rattus and 71 Rattus norvegicus) were caught from different parts of Tabriz City in northwestern Iran using live traps. In the study areas, edible beetles are abundant and in almost all trapping areas local people complained about the presence of beetles. These beetles host the mediator of gongylonema parasites and easily infect animals, such as mice, rabbits, cats, cattle, and accidentally humans. Findings In this study, the esophagus and stomach of rats were carefully examined for infection with gongylonema and only one of the following species was isolated from them, Gongylonema neoplasticum. Conclusion Due to the high abundance of beetles, high levels of Gongylonema neoplasticum were not reported, which can be considered in terms of human infections. More parasitological studies should be done in different geographical regions of Iran and other countries.

Endoscopic Injections of Botulinum Toxin Type A in the Piglet Esophagus Is Safe and Feasible but Did Not Result in any Significant Structural Changes 3 Days after Injection.

Treatment for long-gap esophageal atresia (LGEA) aims at achieving primary anastomosis with minimal tension. Previous studies have shown that intramural injections with botulinum toxin type-A (BTX-A) from the adventitial side can increase the elongation of the piglet and rat esophagus before bursting, and that this effect is dose and time dependent. Our aim was to determine if endoscopic injections would be feasible, safe, and with an effect on the mechanical properties of the esophagus. Twenty-two male piglets (5.15 kg) were randomized into two groups, one receiving 2 units/kg BTX-A, the other equal volume 0.9% NaCl. On day 3, the esophagus was harvested and tested in a stretch-tension machine to evaluate elongation and maximum load, followed by histological examination. No adverse effects to the procedure were observed. No statistically significant difference in elongation or maximum load before bursting between the treatment and placebo group was found. In histopathological analysis, inflammation and abscess formation were observed with no statistically significant difference between the two groups. Endoscopic placement of BTX-A injections in the piglet esophagus was safe and feasible but did not result in any difference in the mechanical properties or histology of the esophagus.

Flexible 3D Nanonetworked Silica Film as a Polymer-Free Drug-Eluting Stent Platform to Effectively Suppress Tissue Hyperplasia in Rat Esophagus.

Loading and eluting drugs on self-expandable metallic stents (SEMSs) can be challenging in terms of fabrication, mechanical stability, and therapeutic effects. In this study, a flexible 3D nanonetworked silica film (NSF) capable of withstanding mechanical stress during dynamic expansion is constructed to function as a drug delivery platform on an entire SEMS surface. Despite covering a broad curved area, the synthesized NSF is defect-free and thin enough to increase the stent strut diameter (110µm) by only 0.4 percent (110.45µm). The hydrophobic modification of the surface enables loading of 4.7 times the sirolimus (SRL) concentration in NSF than Cypher, polymer-coated commercial stent, which is based on the same thickness of coating layer. Furthermore, SRL-loaded NSF exhibits a twofold delay in release compared to the control group without NSF. The SRL-loaded NSF SEMS significantly suppresses stent-induced tissue hyperplasia than the control SEMS in the rat esophagus (all variables, p <0.05). Thus, the developed NSF is a promising polymer-free drug delivery platform to efficiently treat esophageal stricture.

Localization of substance P (SP)-immunoreactivity in the myenteric plexus of the rat esophagus.

The present immunohistochemical study was performed to examine the number, distribution, and chemical coding of intrinsic substance P (SP) neurons and nerve fibers within the esophagus and discuss their functional roles. Many SP neurons and nerve fibers were found in the myenteric plexus, and the SP neurons gradually decreased from the oral side toward the aboral side of the esophagus. Double-immunolabeling showed that most SP neurons were cholinergic (positive for choline acetyltransferase), and few were nitrergic (positive for nitric oxide synthase). Some cholinergic SP nerve terminals surrounded cell bodies of several myenteric neurons. In the muscularis mucosa and lower esophageal sphincter, and around blood vessels, numerous SP nerve endings were present, and many of them were cholinergic. Also, SP nerve endings were found on only a few motor endplates of the striated muscles, and most of them were calcitonin gene-related peptide (CGRP)-positive. Retrograde tracing using Fast Blue (FB) showed that numerous sensory neurons in the dorsal root ganglia (DRGs) and nodose ganglion (NG) projected to the esophagus, and most FB-labeled SP neurons were CGRP-positive. These results suggest that the intrinsic SP neurons in the rat esophagus may play roles as, at least, motor neurons, interneurons, and vasomotor neurons, which are involved in local regulation of smooth muscle motility, neuronal transmission, and blood circulation, respectively. Moreover, SP nerve endings on only a minority of motor endplates may be extrinsic, derived from DRGs or NG, and possibly detect chemical circumstances within motor endplates to modulate esophageal motility.

Normal Macroscopic, Morphological, and Morphometric Parameters of the Esophagus of Whiterats

Histological methods of analysis of the morphofunctional status of the esophagus are widely used in the diagnosis and differential diagnosis of diseases of the gastrointestinal tract of various etiologies. However, their results do not always reflect the disruption of the entire organ structure. All this together increases the interest of researchers in the application of new methods of assessing esophageal pathology, which may be associated with microscopic evaluation of criteria for changes in esophageal pathomorphological structures, several anti-inflammatory agents, i.e. help detect changes in polypragmasic state. Therefore, macroscopic and microscopic studies of white esophageal rat esophagus were aimed at studying the normal data of esophageal tissue and comparing them with pathological processes, and 12 white non-white rat esophageal macroscopic and microscopic studies were performed.

Transcriptome Profiling Unveils a Critical Role of IL-17 Signaling-Mediated Inflammation in Radiation-Induced Esophageal Injury in Rats.

Elucidation of the molecular mechanisms involving the initiation and progression of radiation-induced esophageal injury (RIEI) is important for prevention and treatment. Despite ongoing advances, the underlying mechanisms controlling RIEI remain largely unknown. In the present study, RNA-seq was performed to characterize mRNA profiles of the irradiated rat esophagus exposed to 0, 25, or 35 Gy irradiation. Bioinformatics analyses including dose-dependent differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, protein-protein interaction (PPI) network, and immune infiltration were performed. 134 DEGs were screened out with a dose-dependent manner (35 Gy > 25 Gy > control, or 35 Gy < 25 Gy < control). GO and KEGG analyses showed that the most significant mechanism was IL-17 signaling-mediated inflammatory response. 5 hub genes, Ccl11, Cxcl3, Il17a, S100a8, and S100a9, were identified through the intersection of the DEGs involved in inflammatory response, IL-17 pathway, and PPI network. Additionally, immune infiltration analysis showed the activation of macrophages, monocytes, T cells, NKT cells, and neutrophils, among which macrophages, monocytes, and neutrophils might be the main sources of S100a8 and S100a9. Thus, these findings further our understanding on the molecular biology of RIEI and may help develop more effective therapeutic strategies.