• IMMUNE NETWORK
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• 제21권6호
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• pp.42.1-42.20
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• 2021

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

• Journal of Gastric Cancer
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• 제18권1호
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• pp.99-107
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• 2018

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory disorder characterized by specific pathological findings and elevated serum IgG4 level. IgG4-RD in the stomach is rare, and occasionally diagnosed as gastric subepithelial tumor (SET) by endoscopy or computed tomography scan. Two female patients in the age group of 40-50 years were diagnosed with 4 cm sized gastric SET. One underwent laparoscopic gastric wedge resection. Another one had a history of subtotal gastrectomy for early gastric cancer and idiopathic thrombocytopenic purpura with oral steroids administration. She underwent a completion total gastrectomy with splenectomy for the gastric SET and ITP. The pathology showed storiform fibrosis, and IgG4 was positive in immunohistochemistry (IHC) stain. IgG4-RD is known as a medical disease that could be treated with oral steroids. The difficulty in preoperative diagnosis of the disease occasionally causes unnecessary gastric resection. Thus, preoperative diagnostic methods for IgG4-RD such as deep biopsy with IHC stain or magnetic resonance imaging are needed.

• BMB Reports
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• 제55권5호
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• pp.205-212
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• 2022

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disorder characterized by suprapubic pain and urinary symptoms such as urgency, nocturia, and frequency. The prevalence of IC/BPS is increasing as diagnostic criteria become more comprehensive. Conventional pharmacotherapy against IC/BPS has shown suboptimal effects, and consequently, patients with end-stage IC/BPS are subjected to surgery. The novel treatment strategies should have two main functions, anti-inflammatory action and the regeneration of glycosaminoglycan and urothelium layers. Stem cell therapy has been shown to have dual functions. Mesenchymal stem cells (MSCs) are a promising therapeutic option for IC/BPS, but they come with several shortcomings, such as immune activation and tumorigenicity. MSC-derived extracellular vesicles (MSC-EVs) hold numerous therapeutic cargos and are thus a viable cell-free therapeutic option. In this review, we provide a brief overview of IC/BPS pathophysiology and limitations of the MSC-based therapies. Then we provide a detailed explanation and discussion of therapeutic applications of EVs in IC/BPS as well as the possible mechanisms. We believe our review will give an insight into the strengths and drawbacks of EV-mediated IC/BPS therapy and will provide a basis for further development.

• Tuberculosis and Respiratory Diseases
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• 제40권2호
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• pp.197-202
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• 1993

저자들은 37세의 여자에서 스테로이드치료에 저항을 보이다가 prednisolone과 cyclophosphamide 병합투여로 치료반응을 보인 간질성폐질환을 동반한 다발성근염 1예를 경험하였기에 이를 문헌 고찰과 함께 보고하는 바이다.

• 한국임상약학회지
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• 제28권4호
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• pp.333-341
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• 2018

Objective: Tumor necrosis factor-alpha (TNF-alpha) inhibitors are used as a treatment in various immune-mediated inflammatory diseases (IMIDs). Tuberculosis (TB) risk is reported in several meta-analyses in patients treated with TNF-alpha inhibitors. The purpose of this study is to collect, review, and evaluate the TB risk in TNF-alpha inhibitors according to IMIDs indications and between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors. Methods: A systematic literature search on systematic reviews and meta-analyses was performed in PubMed, MEDLINE, Cochrane library, and EMBASE. We identified meta-analyses that evaluated TB infection risk of TNF-alpha inhibitors in IMIDs patients. Results: Thirteen meta-analyses including 41 study results were included in this umbrella review. IMIDs patients treated with TNF-alpha inhibitors had an increased risk of TB than control group (placebo with or without standard therapy patients) (relative risk ratio (RR) 2.057, 95% confidence interval (CI) 1.697 to 2.495). Among them, RA patients with TNF-alpha inhibitors had a higher risk of TB than control group (RR 1.847, 95% CI 1.385 to 2.464), and non-RA patients with TNF-alpha inhibitors had an increased risk of TB (RR 2.236, 95% CI 1.284 to 3.894). In subgroup analysis on TB risk between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors in RA patients, the analysis indicated that monoclonal-antibody TNF-alpha inhibitors had higher risk of TB than soluble-receptor TNF-alpha inhibitor (RR 2.880, 95% CI 1.730 to 4.792). Conclusion: This umbrella review confirms that the risk of TB is significantly increased in TNF-alpha inhibitor treated patients compared to control group.

• Journal of Periodontal and Implant Science
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• 제40권3호
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• pp.119-124
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• 2010

Purpose: In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-$\alpha$ production in differentiated THP-1 cells, a human monocytic cell line. Methods: LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-$\alpha$ and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-$\alpha$ and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Results: Leptin enhanced P. intermedia LPS-induced TNF-$\alpha$ production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-$\alpha$ expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-$\alpha$ production was not mediated by the leptin receptor. Conclusions: The ability of leptin to enhance P. intermedia LPS-induced TNF-$\alpha$ production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

• 한국임상수의학회지
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• 제41권3호
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• pp.143-149
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• 2024

Circulating cell-free DNA (cfDNA) constitutes a fragment of DNA released into the blood through cellular apoptosis or necrosis. In human medicine, cfDNA has been studied as a disease severity biomarker. Recent studies have shown that concentrations of cfDNA in dogs with immune-mediated and tumor-related diseases are increased. Pancreatitis is known to be caused by excessive release of trypsin, which leads to edema, inflammation, necrosis, and apoptosis in the pancreas. Based on the results of research showing an increase of cfDNA due to apoptosis and necrosis of cells, we hypothesized that cfDNA concentration would increase in the presence of pancreatitis. A total of 35 dogs were studied, including 21 with pancreatitis and 14 without any inflammatory diseases (normal group). The results showed that the concentration of cfDNA in dogs with pancreatitis was approximately twice that of normal dogs (median 0.0912 ng/μL. p-value 0.028). This result suggests that cfDNA can serve as a new biomarker for estimating pancreatitis severity.

• Nutrition Research and Practice
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• 제6권6호
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• pp.513-519
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• 2012

Aged garlic extract (AGE) is known to have a protective effect against immune system, endothelial function, oxidative stress and inflammation. We examined the effects of exercise with and without aged garlic extract administration on body weight, lipid profiles, inflammatory cytokines, and oxidative stress marker in high-fat diet (HFD)-induced obese rats. Forty-five Sprague-Dawley rats were fed either a HFD (HFD, n = 40) or a normal diet (ND, n = 5) for 6 weeks and thereafter randomized into ND (n = 5), HFD (n = 10), HFD with AGE (n = 10), HFD with Exercise (n = 10), or HFD with Exercise+AGE (n = 10) for 4 weeks. AGE groups were administered at a dose of 2.86 g/kg body weight, orally. Exercise consisted of running 15-60 min 5 days/week with gradually increasing intensity. AGE (P<0.01), Exercise, and Exercise+AGE (P<0.001) attenuated body weight gain and food efficiency ratio compared to HFD. Visceral fat and liver weight gain were attenuated (P<0.05) with all three interventions with a greater effect on visceral fat in the Exercise+AGE than AGE (P<0.001). In reducing visceral fat (P<0.001), epididymal fat (P<0.01) and liver weight (P<0.001), Exercise+AGE was effective, but exercise showed a stronger suppressive effect than AGE. Exercise+AGE showed further additive effects on reducing visceral fat and liver weight (P<0.001). AGE significantly attenuated the increase in total cholesterol and low-density lipoprotein-cholesterol compared with HFD (P<0.05). Exercise+AGE attenuated the increase in triglycerides compared with HFD (P<0.05). Exercise group significantly decrease in C-reactive protein (P<0.001). These results suggest that AGE supplementation and exercise alone have anti-obesity, cholesterol lowering, and anti-inflammatory effects, but the combined intervention is more effective in reducing weight gain and triglycerides levels than either intervention alone.

• Journal of Dental Anesthesia and Pain Medicine
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• 제22권6호
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• pp.405-417
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• 2022

Oral lichen planus (OLP) is a chronic inflammatory immune-mediated condition that has been identified as a potentially malignant oral disorder. Various therapies have been proposed for its management as alternative to corticosteroids. However, no definitive treatment has been identified that can result in complete remission or minimal recurrence. Hyaluronic acid has recently been used as an alternative therapy for the management of OLP. This study aimed to systematically review the effectiveness of Hyaluronic acid in the management of symptomatic OLP. Online electronic databases and manual searches were performed for randomized controlled trials (RCTs) published in English between January 2010 and April 2022. RCTs were identified that compared the efficacy of hyaluronic acid and other interventional therapies at baseline and during follow-up. The Cochrane Risk of Bias tool was used to assess the quality of the included studies. Visual analog scale (VAS) scores, Thongprasom sign scores, lesion size, degree of erythema, clinical severity, and disease severity were assessed both quantitatively and qualitatively. Seven studies were analyzed. Five studies reported a high risk of bias while the remaining two studies reported an unclear risk of bias. The overall quantitative assessment of size, symptoms, degree of erythema, and sign score in OLP lesions treated with HA was not statistically significant compared to that in the control group (P > 0.05). In addition, subgroup analysis comparing HA with placebo or corticosteroids did not yield statistically significant (P > 0.05) results. Qualitatively, both HA and tacrolimus resulted in an effective reduction in signs and symptoms. Clinical/disease severity index/scores were inconsistent. A high degree of heterogeneity was observed among the included studies. None of the included studies reported the side effects of HA. These findings suggest that corticosteroids, tacrolimus, placebo, and HA could be equally effective in OLP management. The clinical/disease severity index or score reduction cannot be determined with certainty. Thus, OLP can be treated with HA as an alternative therapy. Owing to limited clinical trials on HA, high heterogeneity, and high risk of bias in the included studies, definitive conclusions cannot be derived.

• 셀메드
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• 제11권1호
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• pp.1.1-1.4
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• 2021

Background: Amavata is a disease that occurs as a result of the error of metabolism. Poor dietary habits and faulty Dincharya (daily regimen) and ritucharya (seasonal regimen) leading to deranged metabolism and Agni (metabolic fire) which results in the formation of Ama(undigested product of metabolism). When Amaconceals with Vata(subtle energy associated with movement) and circulates in the body under the influence of Vyana Vayu (omnipresent air)it clogs the srotasas (microchannels) and initiates the inflammatory cascade. Amavata is commonly correlated with rheumatoid arthritis (RA) while other forms of auto-immune disorders can also be included in Amavata.Dysbiosis of the gut microbiota (GM) has been connected to the onset of diverse autoimmune diseases. In this study, it was hypothesized that Panchakarma (bio-purificatory methods) based intervention such as Virechana Karma (therapeutic purgation) may influence microbiota. Materials and Methods: Various Ayurvedic literature were reviewed for the etiopathogenesis of Amavata. Different databases were searched with research papers related to Gut Dysbiosis and autoimmunity and management of RA. A connecting link between Intestinal Dysbiosis with the autoimmune mechanisms was established and it was also found that the bowel cleansing introduced a change to the GM. Conclusion: It was concluded that Virechana karma is effective in gut flora Dysbiosis. This study aims to correlate the ancient Ayurvedic principles related to Agni Bala(metabolic energy) and biopurificatory treatment modalities like Virechana karma (therapeutic purgation)with the modern concept of gut microbiota and its role in the pathogenesis of various autoimmune disorders such as rheumatoid arthritis. The article creates an understanding about principles of Ayurveda and its rationality in today's scientific world and thereby opens newer vistas of research in therapeutics from Ayurveda, which may be helpful in the management of various immune-mediated Diseases through Ayurveda.