Mucosal Repair Research Articles

Interleukin-1α inhibits transforming growth factor-β1 and β2-induced extracellular matrix production, remodeling and signaling in human lung fibroblasts: Master regulator in lung mucosal repair

BackgroundLung fibroblasts play a central role in maintaining lung homeostasis and facilitating repair through the synthesis and organization of the extracellular matrix (ECM). This study investigated the cross-talk between interleukin-1 alpha (IL-1α) and transforming growth factor-β (TGF-β) signaling, two key regulators in tissue repair and fibrosis, in the context of lung fibroblast repair in the healthy lung. ResultsStimulation of lung fibroblasts with TGF-β1 and TGF-β2 induced collagen-I and fibronectin protein expression (p < 0.05), a response inhibited with co-treatment with IL-1α (p < 0.05). Additionally, TGF-β1 and TGF-β2 induced myofibroblast differentiation, and collagen-I gel contraction, which were both suppressed by IL-1α (p < 0.05). In contrast, interleukin (IL)-6, IL-8 and thymic stromal lymphopoietin induced by IL-1α, were unaffected by TGF-β1 or TGF-β2. Mechanistically, IL-1α administration led to the suppression of TGF-β1 and TGF-β2 signaling, through downregulation of mRNA and protein for TGF-β receptor II and the downstream adaptor protein TRAF6, but not through miR-146a that is known to be induced by IL-1α. DiscussionIL-1α acts as a master regulator, modulating TGF-β1 and TGF-β2-induced ECM production, remodeling, and myofibroblast differentiation in human lung fibroblasts, playing a vital role in balancing tissue repair versus fibrosis. Further research is required to understand the dysregulated cross-talk between IL-1α and TGF-β signaling in chronic lung diseases and the exploration of therapeutic opportunities. MethodsPrimary human lung fibroblasts (PHLF) were treated with media control, or 1 ng/ml IL-1α with or without 50 ng/ml TGF-β1 or TGF-β2 for 1, 6 and 72 h. Cell lysates were assessed for the expression of ECM proteins and signaling molecules by western blot, miRNA by qPCR, mRNA by RNA sequencing and cell supernatants for cytokine production by ELISA. PHLFs were also seeded in non-tethered collagen-I gels to measure contraction, and myofibroblast differentiation using confocal microscopy.

Gastroduodenal injury and repair mechanisms.

Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper, persistent lesions that if not healed, can be the site of increased permeability to luminal antigens, inflammation, and/or neoplasia development. Studies on acute superficial lesions have been sparse in the past year, with more focus given to novel mechanisms of mucosal protection, and the way in which mature epithelial cells or committed stem cells dedifferentiate, reprogram, proliferate, and then regenerate the gastroduodenal mucosa after injury. For this, adenoviral therapy showed organ specific targeting with mRNA and protein expression of effectors to protect against mucosal injury and ulceration. A large database of plant-based agents known to protect against injury and ulceration was published, along with studies using plant-based compounds delivered with alginates, polysaccharide/gel floating rafts, or incorporated into nanoparticles or green carbon dots to improve targeting and retention at the ulcerated lesion. With RNA technology developing rapidly, particularly single-cell RNA sequencing, important and novel data was forthcoming on mucosal regeneration. In particular, the role of interleukin-17 hub proteins in mucosal healing was highlighted. The presence and role of injury reserve cells was determined, as was the composition of ligand gradients for cell differentiation in both stomach and duodenum. The role of amphiregulin in parietal cell differentiation from lineage-restricted stem cells and the Yap1 gene signature in metaplasia vs. healing ulcers were of particular importance. Additionally, studies unveiled the important role of mesenchymal stromal cells in differentiation and repair mechanisms, in Muse cells as an exciting new therapy for mucosal repair after injury, and the role of sympathetic neurons in activating the immune system to regulate mucosal repair mechanisms. Recent studies highlight novel mechanisms that promote mucosal regeneration after injury of the gastroduodenal mucosa.

Morphological aspects of small intestinal mucosal injury and repair after electron irradiation.

Morphological evaluation of the small intestine mucosa and apoptosis activity (caspase-3) is necessary to assess the severity of damage to the small intestine. At the same time, proliferative index based on Ki-67 can be used to assess the regenerative potential of the small intestine. Fragments of small intestine of Wistar rats (n=60) of three groups: I) control (n=20); II) experimental group (n=20; local single electron irradiation at a dose of 2 Gy), III) experimental group (n=20; local single electron irradiation at a dose of 8 Gy) were studied by light microscopy using hematoxylin and eosin staining and immunohistochemical reactions with antibodies to Ki-67 and caspase-3. In all samples of the experimental groups, a decrease in all morphometric indices was observed on day 1 with a tendency to recover on day 3. Small intestinal electron irradiation led to disturbances in the histoarchitecture of varying severity, and an increase in cell apoptosis was observed (increased expression of caspase-3 and decrease in Ki-67). In addition, modulation of the PI3K/AKT and MAPK/ERK signaling pathways was detected. The most pronounced destructive changes were observed in the group of 8 Gy single electron irradiation. Local irradiation of the small intestine with electrons at a dose of 2 and 8 Gy results in a decrease in the number of enterocytes, mainly stem cells of the intestinal crypts.

Clinical classification, staging and treatment strategy of radionecrosis of the nasopharynx and skull base

Objective:To establish a staging system for guiding clinical treatment and prognostic risk assessment by retrospectively analyzing the cases with radionecrosis of the nasopharynx and skull base （RNSB） after radiotherapy for nasopharyngeal carcinoma. Methods:A total of 86 cases of RNSB from January 2019 to December 2022 visited Department of Otorhinolaryngology Head and Neck, the People's Hospital of Guangxi Zhuang Autonomous Region. Seventeen patients gave up the treatment, and 69 patients who underwent treatment were included for analysis. By analyzing the results of electronic nasopharyngolaryngoscopy combined with magnetic resonance （MR）, CT, and other imaging examinations, a staging system for RNSB was proposed. The relationship between the staging system and the surgical effectiveness and clinical prognosis was further analyzed. Results:According to the severity and extent of destruction of soft tissue, bone, and the adjacent neurovascular structures, the RNSB was categorized into closed type （n=5） and open type （n=64）, of which the open type was subdivided into five types: type Ⅰ（n=4）, type Ⅱ（n=6）, type Ⅲ（n=39, of which 21 cases were type Ⅲa and 18 cases were type Ⅲb）, type Ⅳ（n=12）, and type Ⅴ（n=8）. The clinical stage of RNSB were classified based on nasopharyngolaryngoscopy and imaging examinations, receiving the second course of radiotherapy or not, the involvement of the infection site, the extent of bone destruction, the degree of internal carotid artery involvement, and the degree of brain tissue necrosis: stageⅠ（1-2 scores）, 11 cases at stageⅡ（3-4 scores）, 24 cases at stage Ⅲ（5-6 scores）, and 30 cases at stage Ⅳ（ ≥ 7 scores or more）. Twenty-two patients chose conservative treatment （2 patients at stage Ⅰ, 3 patients at stage Ⅱ, 7 patients at stage Ⅲ, and 10 patients at stage Ⅳ）. Forty-seven patients chose nasal endoscopic surgical treatment （2 patients at stage Ⅰ, 8 patients at stage Ⅱ, 17 patients at stage Ⅲ, and 20 patients at stage Ⅳ）, of which 16 cases had received free mucosal flap and/or stented septum mucosal flap repair. Patients at stages Ⅰ, Ⅱ, and Ⅲ achieved satisfactory efficacy after surgical treatment. In addition, higher clinical stage was found to correlate with the worse prognosis and higher incidence of perioperative complications, which included failure of healing because of surgical site infection, cerebrospinal fluid nasal leakage, progressive osteonecrosis, nasopharyngeal hemorrhage, and death. Conclusion:The staging system proposed in our study can be used for early detection of RNSB during regular follow-up, and is also valuable for clinical treatment guidance and prognosis assessment.

Molecular Mechanisms of Intestinal Protection by Levilactobacillus brevis 23017 against Salmonella typhimurium C7731-Induced Damage: Role of Nrf2.

The treatment and prevention of pathogenic diseases by lactic acid bacteria (LAB) has attracted more and more attention. As a special LAB, Levilactobacillus brevis (L. brevis) has relatively less research on its antibacterial infection in vivo, and its protective effect and mechanism still need to be fully studied. In this study, we selected L. brevis 23017, which can regulate the intestinal immunity of the host animal and resist pathogen infection, to evaluate its protective role and potential molecular mechanisms in the mouse model of S. typhimurium C7731 infection. As expected, we confirmed that L. brevis 23017 reduced the diarrhea rate and increased the daily weight gain and survival rate of the mouse model, and inhibited S. typhimurium colonization in the jejunum and liver. It also reduced the level of oxidative damage and protected the integrity of intestinal tissue by increasing the activity of intestinal antioxidant enzymes (SOD, GSH-Px and T-AOC). From the perspective of intestinal mucosal barrier injury and repair, it was confirmed that L. brevis 23017 could increase the expression levels of intestinal tight junction proteins (ZO-1 and OCLN). Our research results also show that L. brevis 23017 inhibits the inflammatory response and promotes the occurrence of cellular immunity in the body by promoting the increase in IL-10 and inhibiting IL-13 in serum and intestinal tissue. Notably, L. brevis 23017 increased total secretory immunoglobulin A (SIgA) levels in the intestine, which were closely associated with elevated levels of IL-5, IL-13, pIgR, j-chain, and IgAα-chain. In addition, L. brevis 23017 increased the expression of antioxidant proteins Nrf2, NQO1, and HO-1 associated with Nrf2 signaling to inhibit intestinal oxidative damage. This mechanism may be responsible for its protective effect against S. typhimurium-infected intestine. Our study provides new evidence and theoretical support for the analysis of the anti-bacterial infection effect and mechanism of L. brevis, which will contribute to the development of L. brevis and the treatment of pathogenic bacteria intestinal infection.

Identification of peptides from Corneum Galli Gigeri Endothelium and inhibiting H2O2-induced gastric mucosa associated with the Rho signaling pathway

Corneum Galli Gigeri Endothelium (CGGE) is a traditional food material known for its stomach-strengthening and digestive-enhancing functions. However, the mechanism by which CGGE peptides in repairing gastric mucosal damage is still unclear. In this study, we isolated the B1 component from CGGE peptides and demonstrated its significant activity in repairing gastric mucosal injuries. This component is primarily composed of six peptide segments, namely DYPELS, LPPLEH, SFYYGK, DDDGVGF, VVLPR, and LPYPR. Notably, LPPLEH and LPYPR exhibited effective scratch repair abilities. Furthermore, we elucidated the mechanism underlying the protection of gastric mucosal damage by the B1 component using hydrogen peroxide (H2O2)-induced damage in GES-1 cells.The results showed that the B1 component significantly downregulated the secretion of lactate dehydrogenase (LDH) and malondialdehyde (MDA) in GES-1 cells induced by H2O2 injury (P < 0.05), increased the enzyme activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and significantly increased the synthesis of glutathione (GSH), epidermal growth factor (EGF), transforming growth factor (TGF), hepatocyte growth factor (HGF), trefoil factor (TFF), and vascular endothelial growth factor (VEGF) (P < 0.05). Furthermore, the B1 component significantly upregulated the protein expression of recombinant cell division cycle protein 42 (Cdc42), Rac1, and RhoA in a concentration-dependent manner (P < 0.01). The findings demonstrate that the B1 component has a significant effect on repairing gastric mucosal damage, possibly by improving antioxidant activity and being associated with the Rho signaling pathway. This study provides experimental data and theoretical support for the clinical challenge of gastric mucosal injury repair.

The intestinal mucosal immunity in mice enhanced by crosslinked ready-to-eat sea cucumber via regulating the SIgA secretion and gut microbiota

The protective effects of molecular crosslinked ready-to-eat sea cucumber (RSC) against immunosuppression induced by cyclophosphamide in mice were investigated. After gavage of molecular crosslinked RSC, the SIgA levels of intestinal mucosa in mice were significantly increased by 31.6% (P < 0.01), and the terminal differentiation of IgA+ B cell was promoted with the significant up-regulation of IL-6 and IL-10 levels. Moreover, the secretion mechanism of plasma cell was mainly promoted through XBP-1s pathway mediated by IRE1 (P < 0.01), rather than ATF-4 and ATF-6 pathway (P > 0.05). In addition, the diversity of intestinal flora was increased, and the imbalance of intestinal flora was improved. The Lachnospiraceae_NK4A136_group dominated in crosslinked group could promote the repair of intestinal mucosa. Therefore, molecular crosslinked RSC can alleviate the intestinal mucosal damage via promoting SIgA secretion and regulating gut microbiota of mice.

Construction of hyaluronic acid-functionalized magnolol nanoparticles for ulcerative colitis treatment

Oral targeted anti-inflammatory drugs have garnered significant interest in treating ulcerative colitis (UC) due to their potential in reducing medical costs and enhancing treatment efficacy. Magnolol (Mag), a natural anti-inflammatory compound, has demonstrated protective effects against UC. However, its application as an alternative therapeutic agent for UC is limited by poor gastrointestinal stability and inadequate accumulation at inflamed colonic lesions. This study introduces a novel nanoparticle (NPs) formulation based on Mag, functionalized with hyaluronic acid (HA) for targeted UC therapy. Bovine serum albumin (BSA) was modified with 2-thiamine hydrochloride to synthesize BSA·SH. Thiol-ene click reaction with Mag led to the formation of BSA·SH-Mag NPs, which were further modified with HA through dehydration condensation, regular spherical inflammation-targeting HA-BSA·SH-Mag nanoparticles with a charge of −23.6 mV and a particle size of 403 ± 4 nm were formed. In vitro studies revealed significant macrophage targeting and enhanced uptake by colon epithelial cells. Oral administration of HA-BSA·SH-Mag facilitated colon mucosal barrier repair by modulating pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), anti-inflammatory cytokines (IL-10), and tight junction proteins (ZO-1, Claudin, Occludin). Crucially, HA-BSA·SH-Mag was found to inhibit the JAK2/STAT3/NF-κB signaling pathway, reducing DSS-induced colon tissue inflammation. This research provides valuable insights into the oral use of natural compounds in UC therapy, highlighting the therapeutic potential of HA-BSA·SH-Mag NPs.

A Rapid Self-Assembling Peptide Hydrogel for Delivery of TFF3 to Promote Gastric Mucosal Injury Repair.

Self-assembled peptide-based nanobiomaterials exhibit promising prospects for drug delivery applications owing to their commendable biocompatibility and biodegradability, facile tissue uptake and utilization, and minimal or negligible unexpected toxicity. TFF3 is an active peptide autonomously secreted by gastric mucosal cells, possessing multiple biological functions. It acts on the surface of the gastric mucosa, facilitating the repair process of gastric mucosal damage. However, when used as a drug, TFF3 faces significant challenges, including short retention time in the gastric mucosal cavity and deactivation due to degradation by stomach acid. In response to this challenge, we developed a self-assembled short peptide hydrogel, Rqdl10, designed as a delivery vehicle for TFF3. Our investigation encompasses an assessment of its properties, biocompatibility, controlled release of TFF3, and the mechanism underlying the promotion of gastric mucosal injury repair. Congo red/aniline blue staining revealed that Rqdl10 promptly self-assembled in PBS, forming hydrogels. Circular dichroism spectra indicated the presence of a stable β-sheet secondary structure in the Rqdl10 hydrogel. Cryo-scanning electron microscopy and atomic force microscopy observations demonstrated that the Rqdl10 formed vesicle-like structures in the PBS, which were interconnected to construct a three-dimensional nanostructure. Moreover, the Rqdl10 hydrogel exhibited outstanding biocompatibility and could sustainably and slowly release TFF3. The utilization of the Rqdl10 hydrogel as a carrier for TFF3 substantially augmented its proliferative and migratory capabilities, while concurrently bolstering its anti-inflammatory and anti-apoptotic attributes following gastric mucosal injury. Our findings underscore the immense potential of the self-assembled peptide hydrogel Rqdl10 for biomedical applications, promising significant contributions to healthcare science.

The Roles of Polyamines in Intestinal Development and Function in Piglets.

The gastrointestinal tract plays crucial roles in the digestion and absorption of nutrients, as well as in maintenance of a functional barrier. The development and maturation of the intestine is important for piglets to maintain optimal growth and health. Polyamines are necessary for the proliferation and growth of enterocytes, which play a key role in differentiation, migration, remodeling and integrity of the intestinal mucosa after injury. This review elaborates the development of the structure and function of the intestine of piglets during embryonic, suckling and weaning periods, the utilization and metabolism of polyamines in the intestine, as well as the role of polyamines in intestinal development and mucosal repair. The nutritional intervention to improve intestinal development and functions by modulating polyamine metabolism in piglets is also put forward. These results may help to promote the adaption to weaning in pigs and provide useful information for the development and health of piglets.

Turtle peptide and its derivative peptide ameliorated DSS-induced ulcerative colitis by inhibiting inflammation and modulating the composition of the gut microbiota

Ulcerative colitis (UC) is a recurrent intestinal disease with an increasing incidence worldwide that seriously affects the life of patients. Turtle peptide (TP) is a bioactive peptide extracted from turtles that has anti-inflammatory, antioxidant and anti-aging properties. However, studies investigating the effect of TP on the progression of UC are lacking. The aim of this study was to investigate effects and underlying mechanisms of TP and its derivative peptide GPAGPIGPV (GP-9) in alleviating UC in mice. The results showed that 500 mg/kg TP treatment significantly ameliorated colitis symptoms and oxidative stress in UC mice. TP alleviated intestinal barrier damage in UC mice by promoting mucosal repair and increasing the expression of tight junction proteins (ZO1, occludin and claudin-1). TP also modulated the composition of the gut microbiota by increasing the abundance of the beneficial bacteria Anaerotignum, Prevotellaceae_UCG-001, Alistipes, and Lachno-spiraceae_NK4A136_group and decreasing the abundance of the harmful bacteria Prevotella_9 and Parasutterella. Furthermore, we characterized the peptide composition of TP and found that GP-9 ameliorated the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by inhibiting the TLR4/NF-κB signaling pathway. In conclusion, TP and its derivative peptides ameliorated DSS-induced ulcerative colitis by inhibiting the expression of inflammatory factors and modulating the composition of the intestinal microbiota; this study provides a theoretical basis for the application of TP and its derivative peptides for their anti-inflammatory activity.

Construction of Magnolol Nanoparticles for Alleviation of Ethanol-Induced Acute Gastric Injury.

Ethanol (EtOH) has been identified as a potential pathogenic factor in gastric ulcer development primarily due to its association with gastric injury and excessive production of reactive oxygen species. Magnolol (Mag), the principal active compound in Magnolia officinalis extract, is well studied for its notable anti-inflammatory and antioxidant properties. However, its limited solubility, propensity for agglomeration, and low absorption and utilization rates significantly restrict its therapeutic use. This study aims to overcome these challenges by developing a Mag nanoparticle system targeting the treatment and prevention of EtOH-induced gastric ulcers in mice. Utilizing a click chemistry approach, we successfully synthesized this system by reacting thiolated bovine serum albumin (BSA·SH) with Mag. The in vitro analysis revealed effective uptake of the BSA·SH-Mag nanoparticle system by human gastric epithelial cells (GES-1), showcasing its antioxidant and anti-inflammatory capabilities. Additionally, BSA·SH-Mag exhibited gradual disintegration and release in simulated gastric fluid, resulting in a notable reduction of oxidative stress in gastric tissues and mucosal tissue repair and effectively reducing inflammatory expression. Furthermore, BSA·SH-Mag attenuated EtOH-induced gastric inflammation by decreasing the level of NOX4 protein expression and augmenting the level of Nrf2 protein expression. In conclusion, our findings indicate that BSA·SH-Mag represents a promising candidate as an oral therapeutic for gastric ulcer treatment.

Effects of submucoperichondrial application of platelet-rich plasma on nasal mucosal healing after septoplasty

Objective(s)Our aim is to investigate the effects of the submucoperichondrial application of Platelet Rich Plasma (PRP) on nasal mucosal healing after septoplasty surgery. Method(s)This prospective randomized observational study was conducted between July 2019 and February 2021, with 40 patients aged 18–60 years who underwent closed the only septoplasty operation for similar septal deviations. Patient divided into two group; 21 patients were placed in PRP group to which PRP was applied on all mucosal surface and submucoperichondrial area of septum and 19 patients were placed in control group to which saline solution was applied on same regions. Nasal obstruction score, mucociliary clearance time, presence of nasal crusting, and bleeding time were evaluated on 5th, 10th, 15th day after surgery and compared between groups. ResultsIntranasal crusting on day 10 was found to be lower in the PRP group (n:13 68.4 %) than control group (n:7 33.3 %) with a statistically significant difference (p = 0.028). The nasal obstruction score on day 10 and 15 were found to be lower in the PRP group (3,33 ± 2,75, 2,07 ± 2,20) (than the control group (5,44 ± 2,26, 3,37 ± 1,92) with a statistically significant difference (p = 0,003,p = 0,009). The mucociliary clearance rate was found to be higher and the bleeding time was found to be lower in the PRP group, but a statistically significant difference was not observed. ConclusionsApplication of submucoperichondrial PRP could have beneficial effects on nasal mucosal repair, nasal crusting, and congestion after septoplasty surgery.

The Usefulness of Surgical Titanium Microclips for Mucosal Repair in the Frontal Sinus Using ORBEYE: A Technical Note.

Bifrontal craniotomy frequently involves opening the frontal sinus and mucosal injury. We report a new technique for mucosal repair in the frontal sinus using surgical titanium microclips. Six consecutive patients who underwent bifrontal craniotomy with frontal sinus exposure and mucosal injury underwent mucosal repair using surgical titanium microclips between April 2019 and August 2022. In all cases, the frontal sinus mucosa was peeled from the inner walls of the frontal sinus to ensure sufficient mucosal margin for clipping using ORBEYE. The repair was accomplished with the microclips in all cases. We also sealed the mucosal wound using fibrin glue and sufficiently filled the frontal sinus with bone debris, resulting in zero incidence of postoperative liquorrhea in all cases. Repairing the mucosa using surgical titanium microclips using ORBEYE may be a simple and quick technique when the frontal sinus mucosa is injured during craniotomy.

An antibiotic-free platform for eliminating persistent Helicobacter pylori infection without disrupting gut microbiota

Helicobacter pylori (H. pylori) infection remains the leading cause of gastric adenocarcinoma, and its eradication primarily relies on the prolonged and intensive use of two antibiotics. However, antibiotic resistance has become a compelling health issue, leading to H. pylori eradication treatment failure worldwide. Additionally, the powerlessness of antibiotics against biofilms, as well as intracellular H. pylori and the long-term damage of antibiotics to the intestinal microbiota, have also created an urgent demand for antibiotic-free approaches. Herein, we describe an antibiotic-free, multifunctional copper-organic framework (HKUST-1) platform encased in a lipid layer comprising phosphatidic acid (PA), rhamnolipid (RHL), and cholesterol (CHOL), enveloped in chitosan (CS), and loaded in an ascorbyl palmitate (AP) hydrogel: AP@CS@Lip@HKUST-1. This platform targets inflammatory sites where H. pylori aggregates through electrostatic attraction. Then, hydrolysis by matrix metalloproteinases (MMPs) releases CS-encased nanoparticles, disrupting bacterial urease activity and membrane integrity. Additionally, RHL disperses biofilms, while PA promotes lysosomal acidification and activates host autophagy, enabling clearance of intracellular H. pylori. Furthermore, AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu2+ release while preserving the intestinal microbiota. Collectively, this platform presents an advanced therapeutic strategy for eradicating persistent H. pylori infection without inducing drug resistance.

Repair of buccal mucosa and floor of mouth defects using keystone design perforator island flap

ObjectiveTo assess the feasibility of utilizing the keystone design perforator island flap (KDPIF) for the repair of small to medium-sized defects in the buccal mucosa and floor of mouth (cT1-2 stage tumor). Study DesignWe conducted a retrospective analysis of eight patients who underwent KDPIF to address oral defects at the Affiliated Hospital of Qingdao University between June 2021 and September 2022. Patient information, including medical history, defect site, flap size, operative time, hospital stay, complications, and postoperative recovery of oral function, was comprehensively evaluated. ResultsEight patients (6 females and 2 males) underwent reconstruction using KDPIF. The mean operation time was 58.5 minutes (55-63 minutes), with an average length of stay of 3.5 days (3 to 5 days). None of the 8 cases (100%) exhibited flap splitting necrosis or infection. Moreover, no scar contracture was observed, and oral functions, including the degree of opening, type of opening, tongue mobility, speech function, and swallowing function, were successfully restored. One patient (12.5%) experienced bleeding from the incision on the first postoperative day, but following compression, hemostasis was achieved, and the incision healed well. ConclusionsKDPIF demonstrates technical feasibility and suitability for repairing small to medium-sized buccal mucosa and floor of mouth defects (cT1-2).

To Explore the Mechanism of Periplaneta americana Extracts and Rebeprazole Intervention in Gastric Mucosal Injury Based on ERS Pathway

The mechanism of Periplaneta americana extracts and rabeprazole in treating gastric mucosal injury were explored through ER stress pathway. Acute gastric mucosal injury model rats were made by intragastric administration of anhydrous ethanol. The rats were then randomly assigned to different groups: model group, Periplaneta americana extracts group, rabeprazole group and combined drug group of rabeprazole and Periplaneta americana extracts, with 6 rats in each group. A normal control group, comprising of six rats, was fed a standard diet. Drug groups were treated with intragastric administration for 3 days. The apparent morphological changes of gastric mucosal injury repair in each group of rats were observed. The length and width of the damaged erosion bands were measured and recorded by vernier caliper, and the index of gastric mucosal damage of rats was calculated using the Guth 57 standard method. Pathological repair of gastric mucosal damage was visualized using hematoxylin-eosin staining (HE). The protein expression of gastric mucosa glucose regulated protein (GRP 78), transcriptional activator 6 (ATF 6), C/EBP (CHOP) and interleukin-6 (IL-6) by protein immunoblot (Western Blot, WB). The content of prostaglandin 2 (PGE 2) in the gastric mucosa and serum was observed by an enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC). The results were compared between the other groups and the model group. Intervention treatment in each experimental group demonstrated effective improvement of gastric mucosal injury, reduction in the index of gastric mucosal injury, downregulation of the protein expression of GRP 78, ATF 6, CHOP, and IL-6 in the gastric mucosa. Increasing the content of PGE2 in gastric mucosa and serum, and promoting the repair of inflammation. Notably, the combined drug group exhibited the most significant intervention effect, with a statistically significant difference (P &gt; 0.05). Periplaneta americana extracts, Rabeprazole alone and in combination have different degrees of protection and repair effect on gastric mucosal injury. The regulation of endoplasmic reticulum stress (ERS) may affect the mechanism of action, reducing the protein expression of inflammatory factors, increasing the expression level of PGE2, and promoting the recovery of normal physiological metabolic environment of gastric mucosa.

PH-responsive CuS/DSF/EL/PVP nanoplatform alleviates inflammatory bowel disease in mice via regulating gut immunity and microbiota

The clinical treatment of inflammatory bowel disease (IBD) is challenging. We developed copper sulfate (CuS)/disulfiram (DSF)/methacrylic acid-ethyl acrylate copolymer (EL)/polyvinylpyrrolidone (PVP) nanoplatform (CuS/DSF/EL/PVP) and evaluated its efficiency for treating IBD. After oral administration, the pH-sensitive EL protected the CuS/DSF/EL/PVP against degradation by acidic gastric juices. Once the colon was reached, EL was dissolved, releasing DSF and Cu2+. Further, the main in vivo metabolite of DSF can bind to Cu2+ and form copper (II) N, N-diethyldithiocarbamate (CuET), which significantly alleviated acute colitis in mice. Notably, CuS/DSF/EL/PVP outperformed CuS/EL/PVP and DSF/EL/PVP nanoplatforms in reducing colonic pathology and improving the secretion of inflammation-related cytokines (such as IL-4 and IL-10) in the colonic mucosa. RNA-seq analysis revealed that the nanoplatform reduced colonic inflammation and promoted intestinal mucosal repair by upregulating C-type lectin receptor (CLR)-related genes and signaling pathways. Furthermore, CuS/DSF/EL/PVP showed potential for improving colitis Th1/Th17 cells through innate immunity stimulation, down-regulation of inflammatory cytokines, and upregulation of anti-inflammatory cytokines. Additionally, the intervention with CuS/DSF/EL/PVP led to increased intestinal flora diversity, decreased Escherichia–Shigella abundance, and elevated levels of short-chain fatty acid (SCFA)-producing bacteria Prevotella, Lactobacillus, and Bifidobacterium, indicating their potential to modulate the dysregulated intestinal flora and suppress inflammation. Statement of SignificanceOur study introduces the CuS/DSF/EL/PVP nanoplatform as a therapeutic strategy for treating inflammatory bowel disease (IBD). This approach demonstrates significant efficacy in targeting the colon and alleviating acute colitis in mice. It uniquely modulates gut immunity and microbiota, exhibiting a notable impact on inflammation-related cytokines and promoting intestinal mucosal repair. The nanoplatform's ability to regulate gut flora diversity, combined with its cost-effective and scalable production, positions it as a potentially transformative treatment for IBD, offering new avenues for personalized medical interventions.

A tailored series of engineered yeasts for the cell-dependent treatment of inflammatory bowel disease by rational butyrate supplementation

ABSTRACT Intestinal microbiota dysbiosis and metabolic disruption are considered essential characteristics in inflammatory bowel disorders (IBD). Reasonable butyrate supplementation can help patients regulate intestinal flora structure and promote mucosal repair. Here, to restore microbiota homeostasis and butyrate levels in the patient’s intestines, we modified the genome of Saccharomyces cerevisiae to produce butyrate. We precisely regulated the relevant metabolic pathways to enable the yeast to produce sufficient butyrate in the intestine with uneven oxygen distribution. A series of engineered strains with different butyrate synthesis abilities was constructed to meet the needs of different patients, and the strongest can reach 1.8 g/L title of butyrate. Next, this series of strains was used to co-cultivate with gut microbiota collected from patients with mild-to-moderate ulcerative colitis. After receiving treatment with engineered strains, the gut microbiota and the butyrate content have been regulated to varying degrees depending on the synthetic ability of the strain. The abundance of probiotics such as Bifidobacterium and Lactobacillus increased, while the abundance of harmful bacteria like Candidatus Bacilloplasma decreased. Meanwhile, the series of butyrate-producing yeast significantly improved trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice by restoring butyrate content. Among the series of engineered yeasts, the strain with the second-highest butyrate synthesis ability showed the most significant regulatory and the best therapeutic effect on the gut microbiota from IBD patients and the colitis mouse model. This study confirmed the existence of a therapeutic window for IBD treatment by supplementing butyrate, and it is necessary to restore butyrate levels according to the actual situation of patients to restore intestinal flora.

Tannic acid and zinc ion coordination of nanase for the treatment of inflammatory bowel disease by promoting mucosal repair and removing reactive oxygen and nitrogen species

Colon mucosal overexpression of reactive oxygen and nitrogen species (RONS) accelerates the development of inflammatory bowel disease (IBD) and destroys the mucosa and its barrier. IBD can be alleviated by removing RONS from the inflamed colon. The preparation of strong and efficient nanoantioxidants remains a challenge despite the development of numerous nanoantioxidants. In this paper, Zn-TA nanoparticles with fine hollow microstructure (HZn-TA) were successfully prepared and could be effectively used to treat IBD. In the first step, ZIF-8 nanoparticles were synthesized by a one-pot method. On this basis, HZn-TA nanoparticles were etched by TA, and a multifunctional nanase was developed for the treatment of IBD. RONS, including reactive oxygen species (ROS) and nitric oxide (NO), can be eliminated to increase cell survival following Hydrogen peroxide (H2O2) stimulation, including reactive oxygen species (ROS) and nitric oxide (NO with hydrogen peroxide (H2O2). In a model for preventing and delaying acute colitis, clearance of RONS has been shown to reduce intestinal inflammation in mice by reducing colon damage, proinflammatory cytokine levels, the spleen index, and body weight. Intestinal mucosal healing can be promoted by HZn-TA nanoparticles, which can upregulate zonula occludens protein 1 (ZO-1) and claudin-1 expression. Based on the results of this study, HZn-TA nanoparticles were able to effectively treat IBD with minimal adverse effects by being biocompatible, multienzyme active, and capable of scavenging RONS. Therefore, we pioneered the application of HZn-TA nanoparticles for the treatment of IBD, which are capable of clearing RONS without significant adverse effects. Statement of significance➢ HZn-TA nanoparticles were successfully prepared and could be effectively used to treat IBD.➢ Intestinal mucosal healing can be promoted by HZn-TA nanoparticles, which can upregulate ZO-1 and claudin-1 expression.➢ HZn-TA nanoparticles were able to effectively treat IBD with minimal adverse effects by being biocompatible, multienzyme active, and capable of scavenging RONS.