Inflammatory bowel disease (IBD) is a global disease that is in increasing incidence. The gut, which contains the largest amount of lymphoid tissue in the human body, as well as a wide range of nervous system components, is integral in ensuring intestinal homeostasis and function. By interacting with gut microbiota, immune cells, and the enteric nervous system, the intestinal barrier, which is a solid barrier, protects the intestinal tract from the external environment, thereby maintaining homeostasis throughout the body. Destruction of the intestinal barrier is referred to as developing a "leaky gut," which causes a series of changes relating to the occurrence of IBD. Changes in the interactions between the intestinal barrier and gut microbiota are particularly crucial in the development of IBD. Exploring the leaky gut and its interaction with the gut microbiota, immune cells, and the neuroimmune system may help further explain the pathogenesis of IBD and provide potential therapeutic methods for future use.
Heeyeon Ryu;Hyeon Hak Jeong;Seungjun Lee;Min-Kyeong Lee;Myeong-Jin Kim;Bonggi Lee
Journal of Microbiology and Biotechnology
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v.34
no.2
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pp.270-279
/
2024
Macrophages are versatile immune cells that play crucial roles in tissue repair, immune defense, and the regulation of immune responses. In the context of skeletal muscle, they are vital for maintaining muscle homeostasis but macrophage-induced chronic inflammation can lead to muscle dysfunction, resulting in skeletal muscle atrophy characterized by reduced muscle mass and impaired insulin regulation and glucose uptake. Although the involvement of macrophage-secreted factors in inflammation-induced muscle atrophy is well-established, the precise intracellular signaling pathways and secretion factors affecting skeletal muscle homeostasis require further investigation. This study aimed to explore the regulation of macrophage-secreted factors and their impact on muscle atrophy and glucose metabolism. By employing RNA sequencing (RNA-seq) and proteome array, we uncovered that factors secreted by lipopolysaccharide (LPS)-stimulated macrophages upregulated markers of muscle atrophy and pro-inflammatory cytokines, while concurrently reducing glucose uptake in muscle cells. The RNA-seq analysis identified alterations in gene expression patterns associated with immune system pathways and nutrient metabolism. The utilization of gene ontology (GO) analysis and proteome array with macrophage-conditioned media revealed the involvement of macrophage-secreted cytokines and chemokines associated with muscle atrophy. These findings offer valuable insights into the regulatory mechanisms of macrophage-secreted factors and their contributions to muscle-related diseases.
BACKGROUND/OBJECTIVES: The anti-diabetic activity of pear through inhibition of ${\alpha}-glucosidase$ has been demonstrated. However, little has been reported about the effect of pear on insulin signaling pathway in obesity. The aims of this study are to establish pear pomace 50% ethanol extract (PPE)-induced improvement of insulin sensitivity and characterize its action mechanism in 3T3-L1 cells and high-fat diet (HFD)-fed C57BL/6 mice. MATERIALS/METHODS: Lipid accumulation, monocyte chemoattractant protein-1 (MCP-1) secretion and glucose uptake were measure in 3T3-L1 cells. Mice were fed HFD (60% kcal from fat) and orally ingested PPE once daily for 8 weeks and body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and serum lipids were measured. The expression of proteins involved in insulin signaling pathway was evaluated by western blot assay in 3T3-L1 cells and adipose tissue of mice. RESULTS: In 3T3-L1 cells, without affecting cell viability and lipid accumulation, PPE inhibited MCP-1 secretion, improved glucose uptake, and increased protein expression of phosphorylated insulin receptor substrate 1 [p-IRS-1, ($Tyr^{632})$)], p-Akt, and glucose transporter type 4 (GLUT4). Additionally, in HFD-fed mice, PPE reduced body weight, HOMA-IR, and serum lipids including triglyceride and LDL-cholesterol. Furthermore, in adipose tissue, PPE up-regulated GLUT4 expression and expression ratio of p-IRS-1 ($Tyr^{632})/IRS$, whereas, down-regulated p-IRS-1 ($Ser^{307})/IRS$. CONCLUSIONS: Our results collectively show that PPE improves glucose uptake in 3T3-L1 cells and insulin sensitivity in mice fed a HFD through stimulation of the insulin signaling pathway. Furthermore, PPE-induced improvement of insulin sensitivity was not accompanied with lipid accumulation.
Stress is a global menace exacerbated by the advancement of industrialization. Failure of stress management is to a breakdown of the psychological and physiological protection mechanisms against stress. The aim of present study was to investigate the anti-stress potential of ginseng against immobilization stress. Male Sprague-Dawley rats (n=24) were divided into three groups; (i) control, (ii) immobilization stress (2hr daily, for 2 weeks), and (iii) immobilization stress (2 hr daily, for 2 weeks) plus oral administration of ginseng (200 mg/kg BW Id). Immobilization stress resulted in a significant inhibition of body weight gain by 45 % and a significant decrease in the tissue weights of thymus and spleen (p < 0.05). The concentrations of blood GOT and GPT were significantly increased in the immobilization-stressed group compared to the control group (p < 0.05). There were no differences in the blood cholesterol levels among groups. Ginseng administration in the immobilization-stressed group tended to reverse the lack of body weight gain and food intake, though not significantly. The ginseng-administered group showed a significant reversal in the stress-induced effect on spleen and thymus weight, increasing the tissue weights by 16% and 20%, respectively, compared to immobilization-stressed group (p<0.05). The plasma corticosterone level was significantly increased in the stressed group by 39 % compared to the control group (p<0.05), but ginseng administration significantly reversed the stress-induced increase in plasma corticosterone by 15 % compared to the immobilization-stressed group. The present study suggests that the anti-stress effect of ginseng is mediated by normalization of stress-induced changes in the circulating hormones and a reversal of tissue weight loss, thereby returning the body to normal homeostasis.
Ayala-Cuellar, Ana Patricia;Kang, Ji-Houn;Jeung, Eui-Bae;Choi, Kyung-Chul
Biomolecules & Therapeutics
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v.27
no.1
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pp.25-33
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2019
Mesenchymal stem cells are classified as multipotent stem cells, due to their capability to transdifferentiate into various lineages that develop from mesoderm. Their popular appeal as cell-based therapy was initially based on the idea of their ability to restore tissue because of their differentiation potential in vitro; however, the lack of evidence of their differentiation to target cells in vivo led researchers to focus on their secreted trophic factors and their role as potential powerhouses on regulation of factors under different immunological environments and recover homeostasis. To date there are more than 800 clinical trials on humans related to MSCs as therapy, not to mention that in animals is actively being applied as therapeutic resource, though it has not been officially approved as one. But just as how results from clinical trials are important, so is to reveal the biological mechanisms involved on how these cells exert their healing properties to further enhance the application of MSCs on potential patients. In this review, we describe characteristics of MSCs, evaluate their benefits as tissue regenerative therapy and combination therapy, as well as their immunological properties, activation of MSCs that dictate their secreted factors, interactions with other immune cells, such as T cells and possible mechanisms and pathways involved in these interactions.
Chae, Yong Kwon;Shin, Seo Young;Kang, Sang Wook;Choi, Sung Chul;Nam, Ok Hyung
Journal of Periodontal and Implant Science
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v.52
no.2
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pp.127-140
/
2022
Purpose: In dental avulsion, delayed replantation usually has an uncertain prognosis. After tooth replantation, complex inflammatory responses promote a return to periodontal tissue homeostasis. Various types of cytokines are produced in the inflammatory microenvironment, and these cytokines determine the periodontal tissue response. This study aimed to identify the gene expression profiles of replanted teeth and evaluate the functional differences between immediate and delayed replantation. Methods: Maxillary molars from Sprague-Dawley rats were extracted, exposed to a dry environment, and then replanted. The animals were divided into 2 groups according to the extra-oral time: immediate replantation (dry for 5 minutes) and delayed replantation (dry for 60 minutes). Either 3 or 7 days after replantation, the animals were sacrificed. Periodontal soft tissues were harvested for mRNA sequencing. Hallmark gene set enrichment analysis was performed to predict the function of gene-gene interactions. The normalized enrichment score (NES) was calculated to determine functional differences. Results: The hallmark gene sets enriched in delayed replantation at 3 days were oxidative phosphorylation (NES=2.82, Q<0.001) and tumor necrosis factor-alpha (TNF-α) signaling via the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway (NES=1.52, Q=0.034). At 7 days after delayed replantation, TNF-α signaling via the NF-κB pathway (NES=-1.82, Q=0.002), angiogenesis (NES=-1.66, Q=0.01), and the transforming growth factor-beta signaling pathway (NES=-1.46, Q=0.051) were negatively highlighted. Conclusions: Differentially expressed gene profiles were significantly different between immediate and delayed replantation. TNF-α signaling via the NF-κB pathway was marked during the healing process. However, the enrichment score of this pathway changed in a time-dependent manner between immediate and delayed replantation.
Jeewan Chun;Ji-Hoi Moon;Kyu Hwan Kwack;Eun-Young Jang;Saebyeol Lee;Hak Kyun Kim;Jae-Hyung Lee
BMB Reports
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v.57
no.5
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pp.232-237
/
2024
This study investigated how adipose tissue-derived mesenchymal stem cells (AT-MSCs) respond to chondrogenic induction using droplet-based single-cell RNA sequencing (scRNA-seq). We analyzed 37,219 high-quality transcripts from control cells and cells induced for 1 week (1W) and 2 weeks (2W). Four distinct cell clusters (0-3), undetectable by bulk analysis, exhibited varying proportions. Cluster 1 dominated in control and 1W cells, whereas clusters (3, 2, and 0) exclusively dominated in control, 1W, and 2W cells, respectively. Furthermore, heterogeneous chondrogenic markers expression within clusters emerged. Gene ontology (GO) enrichment analysis of differentially expressed genes unveiled cluster-specific variations in key biological processes (BP): (1) Cluster 1 exhibited up-regulation of GO-BP terms related to ribosome biogenesis and translational control, crucial for maintaining stem cell properties and homeostasis; (2) Additionally, cluster 1 showed up-regulation of GO-BP terms associated with mitochondrial oxidative metabolism; (3) Cluster 3 displayed up-regulation of GO-BP terms related to cell proliferation; (4) Clusters 0 and 2 demonstrated similar up-regulation of GO-BP terms linked to collagen fibril organization and supramolecular fiber organization. However, only cluster 0 showed a significant decrease in GO-BP terms related to ribosome production, implying a potential correlation between ribosome regulation and the differentiation stages of AT-MSCs. Overall, our findings highlight heterogeneous cell clusters with varying balances between proliferation and differentiation before, and after, chondrogenic stimulation. This provides enhanced insights into the single-cell dynamics of AT-MSCs during chondrogenic differentiation.
Han, Hyung-Chul;So, Hye-Jin;Domby, Elizabeth;Engle, Terry
Asian-Australasian Journal of Animal Sciences
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v.25
no.2
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pp.194-199
/
2012
Liver and pulmonary artery tissue from 5 Angus cross bred steers, 6 goats, and 6 pigs were collected at a commercial abattoir to examine the relationship of pulmonary artery copper (Cu) concentrations and genes involved in copper homeostasis. Liver and pulmonary artery samples were collected at the time of harvest and snap frozen. Liver and pulmonary artery Cu concentrations were determined via flame atomic absorption spectrophotometry and gene expression was determined via real time PCR. Liver Cu concentrations (mg Cu/kg DM${\pm}$SE) were higher (p<0.01) in cows ($396.4{\pm}109.1$) and goats ($181.4{\pm}37.0$) than in pigs ($19.2{\pm}3.5$). All liver Cu concentrations were within normal ranges and considered adequate for each species. Liver Cu concentration was more variable in cows and goats compared to pig liver Cu concentrations. Pulmonary artery ${\beta}$-hydroxylproline was higher (p<0.01) in cow and pig than goat. Real Time PCR revealed that goat liver atp7a was positively correlated ($r^2$ = 0.92; p<0.01) to liver Cu concentrations while cow and pig atp7a was not correlated to liver Cu concentration. In the pig, liver atp7a concentration was positively correlated to atp7b ($r^2$ = 0.66; p<0.05). Pulmonary artery Cu concentration was highest in cows ($14.9{\pm}4.7$), intermediate in pigs ($8.9{\pm}3.3$), and lowest in goats ($3.9{\pm}1.1$). Goat pulmonary artery Cu concentration was not correlated to ctr1 concentration, however, atp7a concentration was positively correlated with ctr1 ($r^2$ = 0.90; p<0.01). In cow pulmonary artery, loxl1 concentration was positively correlated to eln mRNA concentration ($r^2$ = 0.91; p<0.02). Pulmonary artery CTR1 protein concentration was positively correlated to pulmonary artery Cu ($r^2$ = 0.85; p = 0.03) concentration while negatively correlated to liver Cu ($r^2$ = -0.79; p<0.04). Pulmonary artery Cu concentration was not correlated to concentration of Cu homeostatic genes in the pig. These data indicate that genes involved in Cu homeostasis (ctr1, atp7A, atp7B, loxl1 and eln) are differently regulated in different species.
Objective: Stocking density (SD) is an important issue in the poultry industry, which is related to the production performance, intestinal health and immune status. In the present study, the effects of SD on the metabolism and homeostasis of uric acid as well as the related functions of the liver and kidney in ducks were examined. Methods: A total of 360 healthy 56-day-old Shan-ma ducks were randomly divided into the low stocking density (n = 60, density = 5 birds/m2), medium stocking density (n = 120, density = 10 birds/m2) and high stocking density groups (HSD; n = 180, density = 15 birds/m2). Samples were collected in the 3rd, 6th, and 9th weeks of the experiment for analysis. Results: The serum levels of uric acid, lipopolysaccharide and inflammatory cytokines (interleukin-1β [IL-1β], IL-8, and tumor necrosis factor-α [TNF-α]) were increased significantly in the HSD group. Serious histopathological lesions could be seen in both the livers and kidneys in the HSD group in the 9th week. The mRNA expression levels of inflammatory cytokines (IL-8 and TNF-α) and related pathway components (toll-like receptor 4, myeloid differentiation primary response gene 88, and nuclear factor-κB) were increased significantly in both the livers and kidneys in the HSD group. The mRNA expression levels of enzymes (adenosine deaminase, xanthine oxidase, phosphoribosyl pyrophosphate amidotransferase, and phosphoribosyl pyrophosphate synthetase 1) related to the synthesis of uric acid increased significantly in the livers in the HSD group. However, the mRNA expression level of solute carrier family 2 member 9, which plays an important role in the excretion of uric acid by the kidney, was decreased significantly in the kidneys in the HSD group. Conclusion: These results indicated that a higher SD could cause tissue inflammatory lesions in the liver and kidney and subsequently affect the metabolism and homeostasis of uric acid, and is helpful for guiding decisions related to the breeding and production of ducks.
Kim, Ha-Rang;Yoo, Jae-Ha;Choi, Byung-Ho;Sul, Sung-Han;Mo, Dong-Yub;Lee, Chun-Ui
Maxillofacial Plastic and Reconstructive Surgery
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v.31
no.6
/
pp.544-549
/
2009
Failure to use effective methods of reduction, fixation and immobilization may lead to osteomyelitis with the exposed necrotic bone, as the overzealous use of transosseous wires & plates that devascularizes bone segments in the compound comminuted fractures of mandible. Once osteomyelitis secondary to fractures has become established, intermaxillary fixation should be instituted as early as possible. Fixation enhances patient comfort and hinders ingress of microorganisms and debris by movement of bone fragments. Teeth and foreign materials that are in the line of fracture should be removed and initial debridement performed at the earliest possible time. Grossly necrotic bone should be excised as early as possible ; no attempt should be made to create soft tissue flaps to achieve closure over exposed bone. The key to treatment of chronic osteomyelitis of the mandible is adequate and prolonged soft tissue drainage. If good soft tissue drainage is provided over a long period, sequestration of infected bone followed by regeneration or fibrous tissue replacement will occur so that appearance and function are not seriously altered. Localization and sequestration of infected mandible are far better performed by natural mechanism of homeostasis than by cutting across involved bone with a cosmetic or functional defect. As natural host defenses and conservative therapy begin to be effective, the process may become chronic, inflammation regresses, granulation tissue is formed, and new blood vessels cause lysis of bone, thus separating fragments of necrotic bone(sequestra) from viable bone. The sequestra may be isolated by a bed of granulation tissue, encased in a sheath of new bone(involucrum), and removed easily with pincettes. This is a case report of the long-term conservative drainage care in osteomyelitis associated with mandibular fractures.
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