• Journal of Animal Science and Technology
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• v.63 no.2
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• pp.211-247
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• 2021

Livestock species experience several stresses, particularly weaning, transportation, overproduction, crowding, temperature, and diseases in their life. Heat stress (HS) is one of the most stressors, which is encountered in livestock production systems throughout the world, especially in the tropical regions and is likely to be intensified due to global rise in environmental temperature. The gut has emerged as one of the major target organs affected by HS. The alpha- and beta-diversity of gut microbiota composition are altered due to heat exposure to animals with greater colonization of pathogenic microbiota groups. HS also induces several changes in the gut including damages of microstructures of the mucosal epithelia, increased oxidative insults, reduced immunity, and increased permeability of the gut to toxins and pathogens. Vulnerability of the intestinal barrier integrity leads to invasion of pathogenic microbes and translocation of antigens to the blood circulations, which ultimately may cause systematic inflammations and immune responses. Moreover, digestion of nutrients in the guts may be impaired due to reduced enzymatic activity in the digesta, reduced surface areas for absorption and injury to the mucosal structure and altered expressions of the nutrient transport proteins and genes. The systematic hormonal changes due to HS along with alterations in immune and inflammatory responses often cause reduced feed intake and production performance in livestock and poultry. The altered microbiome likely orchestrates to the hosts for various relevant biological phenomena occurring in the body, but the exact mechanisms how functional communications occur between the microbiota and HS responses are yet to be elucidated. This review aims to discuss the effects of HS on microbiota composition, mucosal structure, oxidant-antioxidant balance mechanism, immunity, and barrier integrity in the gut, and production performance of farm animals along with the dietary ameliorations of HS. Also, this review attempts to explain the mechanisms how these biological responses are affected by HS.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.4
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• pp.388-396
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• 2020

Purpose: Impaired intestinal mucosal integrity may affect the gastrointestinal function, especially in relation to nutrition, absorption, and barrier function. The purpose of this study was to measure the prevalence of impaired intestinal mucosal integrity in presumed healthy children aged 1-3 years and assess the effects of zinc, glutamine, fiber, and prebiotic supplementation in them. Methods: A cross-sectional study was conducted in 200 children aged 1-3 years in Pasar Minggu, South Jakarta, Indonesia. A randomized double-blind parallel group method clinical trial was then performed to assess the effects of zinc, glutamine, fiber, and prebiotic supplementation. Results: Elevated calprotectin was found in 91/200 subjects (45.5%) at the onset of the study. After 10 months, 144 subjects completed the study: 72 subjects received the trial formula, whereas the other 72 received the standard formula. A transitory decrease in fecal calprotectin (FC) was observed after 6 months in the subgroup with normal FC levels, who were fed the test formula (p=0.012). Conclusion: The prevalence of impaired intestinal mucosal integrity in this group of Indonesian children aged 1-3 years was high. Supplementation with zinc, glutamine, fiber, and prebiotics during 6 months reduced FC only in those who had low levels at baseline but not in those with impaired integrity.

• Microbiology and Biotechnology Letters
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• v.50 no.1
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• pp.51-62
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• 2022

Lactobacillus rhamnosus SKG34 (LrSKG34), a potential probiotic strain, was successfully isolated from Sumbawa Mare's milk. Our previous studies showed that the strain is resistant to gastrointestinal conditions, possesses antioxidant activity, and lowers blood cholesterol levels. Further clarification of the potential probiotic characteristics and safety assessment are necessary. This study aimed to evaluate the adhesion of LrSKG34 to Caco-2 cell monolayers and its effect on mucosal integrity in vitro. We also examined the LrSKG34 safety profile based on antimicrobial susceptibility testing, haemolytic activity determination, Caco-2 cell monolayer translocation evaluation, and in vivo investigation of the effect of LrSKG34 on the physiology, biochemical markers, and histopathological appearance of major organs in an animal model. LrSKG34 attached to Caco-2 cell monolayers and maintained mucosal integrity in vitro. The typical resistance of lactobacilli to ciprofloxacin, gentamicin, vancomycin, trimethoprim-sulfamethoxazole, and metronidazole was confirmed for LrSKG34. No haemolytic activity was observed on blood agar plates, and no LrSKG34 translocation was observed in Caco-2 cell monolayers. Administration of LrSKG34 to Sprague-Dawley rats did not adversely affect body weight. No abnormalities in hematological parameters, serum biochemistry levels, or histopathological structures of major organs were observed in LrSKG34-treated rats. Collectively, the results implicate LrSKG34 as a promising and potentially safe probiotic candidate for further development.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.175-183
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• 2021

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

• Journal of Yeungnam Medical Science
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• v.38 no.1
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• pp.27-33
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• 2021

The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.

• IMMUNE NETWORK
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• v.13 no.3
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• pp.102-106
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• 2013

Emerging evidence suggests that gap formation and opening of the endothelial junctions during leukocyte extravasation is actively controlled to maintain the integrity of the vascular barrier. While the role for endothelial cells to this process has been well defined, it is not clear whether leukocytes are also actively contributing to endothelial barrier function. We have recently showed that extravasating leukocytes deposit microparticles on the subendothelium during the late stages of extravasation, which is LFA-1 dependent. Using multiphotonintravital microscopy (MP-IVM) of mouse cremaster muscle vessels in the current work, we show that microparticle formation and deposition maintains the integrity of the microvascular barrier during leukocyte extravasation. Inhibition of neutrophil-derived microparticle formation resulted in dramatically increased vascular leakage. These findings suggest that deposition of microparticles during neutrophil extravasation is essential for maintaining endothelial barrier function and may result in temporal difference between neutrophil extravasation and an increase in vascular leakage.

• Journal of Pharmaceutical Investigation
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• v.27 no.1
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• pp.11-14
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• 1997

This laboratory has recently reported the solubility and in vivo absorption enhancement of diclofenac sodium by ${\beta}-cyclodextrin$ complexation. The acute gastroduodenal mucosa injury provoked by administration of 34 mg/kg and 68 mg/kg of a diclofenac sodium (DS) and equivalent dose of new formulation [diclofenac sodium-beta-cyclodextrin complexation$(DS-{\beta}-CD)$] was evaluated and compared. Microscopic examinations, performed after 18-hrs treatment, demonstrated that $DS-{\beta}-CD$ was less gastrolesive than DS. The drop in gastrophy after a single dose of the assigned drug was considerably greater for DS than for $DS-{\beta}-CD$, which registered similar values to control. Since gastrophy is an expression of the anatomy-functional integrity of the gastric barrier, the results indicate that $DS-{\beta}-CD$ exerts less direct acute damage on the gastric mucosa. Therefore, when administered short-term, $DS-{\beta}-CD$ appears to be less gastrolesive than the standard DS formulation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.71-77
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• 2011

Gastric ulcer has multifactorial etiology, and the development of ulcer is known to be caused by gastric acidity, pepsin secretion, gastric motility and gastric mucosal blood flow. The ulcer results from the tissue necrosis and apoptotic cell death triggered by mucosal ischemia, free radical formation and cessation of nutrient delivery. The gastric mucosa is usually exposed to a wide range of aggressive insults, and has developed efficient mechanisms to repair tissue injury. The apoptotic process of gastric mucosa is triggered by the induction of such proapoptotic gene expression, such as BAX. The Bcl-2 family of proteins plays a pivotal role in the regulation of apoptosis. The maintenance of gastric mucosa integrity depends upon the ratio between cell proliferation and cell death. Stress-inducing factors may affect Bcl-2/BAX ratio and thus the rate of apoptosis through modulation of the expression of both proteins depends upon the experimental model. In addition to the regulation of apoptosis, new vessels have to be generated in order to ensure an adequate supply of oxygen and nutrients to the healing gastric mucosa. This events are regulated by several factors. Among them, such polypeptide growth factors, such as vascular endothelial growth factor (VEGF) regulates essential cell functions involved in tissue healing including cell proliferation and differentiation. The purpose of this study was carried to investigate whether Rhei Rhizoma administration might protect apoptotic cell death and promote angiogenesis in gastric mucosa. Sprague-Dawley rats were randomly divided into 4 groups; normal, saline, cimetidine and Rhei Rhizoma-treated group. The saline, cimetidine and Rhei Rhizoma extracts were orally administrated to each group and gastric ulcer was induced by HCl-EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In results, Rhei Rhizoma proves to promote to heal wound in gastric ulcer in conclusion and the significant changes of BAX, Bcl-2 and VEGF quantity in gastric mucosa were observed. These results suggest that Rhei Rhizoma extract may promote incision wound healing and has protective effects on gastric ulcer in rats.

• Imaging Science in Dentistry
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• v.51 no.3
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• pp.243-250
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• 2021

Purpose: The objective of this study was to evaluate the amount of height available for a maxillary sinus augmentation procedure without blocking the ostium and jeopardizing the drainage of the ostiomeatal complex using cone-beam computed tomography (CBCT) imaging. Materials and Methods: A total of 200 sinonasal complexes comprising 100 dentate and 100 edentulous scans were retrospectively assessed using CBCT. Invivo 5.0, a CBCT reconstruction program, was used for image evaluation. The coronal section demonstrating the ostiomeatal complex was selected as a reference view to perform measurements of the sinus. The measurements were done by 2 evaluators in separate sessions. Comparative analyses of measurements were performed between dentate and edentulous patients and between male and female patients. Results: The safe height to which the sinus can be elevated without compromising the integrity of the ostiomeatal complex was calculated for each sinus. In the presence of significant mucosal thickening, the height available for augmentation was calculated by subtracting the height of mucosal thickening from the sinus floor to the location of the ostium. In this study, the available height was approximately 27.05 mm for dentate and 23.40 mm for edentulous patients. The inter-operator reliability was excellent for all the parameters evaluated. Conclusion: This retrospective study with a limited number of patients from a single university-based site shows that CBCT is valuable in evaluating the location and patency of the ostium for planning sinus augmentation procedures for dental implant placement.

• Animal Bioscience
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• v.35 no.6
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• pp.869-883
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• 2022

Objective: The aim of study was to investigate the effects of in-feed supplementation of Bacillus amyloliquefaciens (BA) and Saccharomyces cerevisiae (SC) on growth performance, gut integrity, and microbiota modulations in red-feathered native chickens (RFCs). Methods: A total of 18,000 RFCs in a commercial farm were evenly assigned into two dietary treatments (control diet; 0.05% BA and 0.05% SC) by randomization and raised for 11 weeks in two separate houses. Fifty RFCs in each group were randomly selected and raised in the original house with the partition for performance evaluations at the age of 9 and 11 weeks. Six non-partitioned RFCs per group were randomly selected for analyses of intestinal architecture and 16S rRNA metagenomics. Results: Feeding BA and SC increased the body weight and body weight gain, significantly at the age of 11 weeks (p<0.05). The villus height/crypt ratio in the small intestines and Firmicutes to Bacteroidetes ratio were also notably increased (p<0.05). The supplementation did not disturb the microbial community structure but promote the featured microbial shifts characterized by the significant increments of Bernesiella, Prevotellaceae_NK3B31_group, and Butyrucimonas, following remarkable decrements of Bacteroides, Rikenellaceae_RC9_gut_group, and Succinatimonas in RFCs with growth benefits. Besides, functional pathways of peptidoglycan biosynthesis, nucleotide excision repair, glycolysis/gluconeogenesis, and aminoacyl transfer ribonucleic acid (tRNA) biosynthesis were significantly promoted (p<0.05). Conclusion: In-feed supplementation of BA and SC enhanced the growth performance, improved mucosal architectures in small intestines, and modulated the cecal microbiota and metabolic pathways in RFCs.