염증 해소를 통한 발암 억제

이하나,서영준 대한암예방학회 2012 Journal of cancer prevention Vol.17 No.1

Uncontrolled and excessive inflammation results in chronic inflammation, which has long been thought to contribute to the development of cancer. Chronic inflammatory conditions predispose susceptible cells to malignant transformation. To prevent the inflammation-associated cancer, resolution of inflammation is essential. Resolution of inflammation is an active coordinated process regulated by a distinct set of anti-inflammatory and pro-resolving mediators, such as resolvins. However, the ‘inflammation-cancer’ connection is not limited to an increased risk for tumorigenesis. Recently, it has also been suggested that oncogenic changes can induce inflammation that stimulates the development of tumors. In the tumor microenvironment, cancer-associated inflammation contributes to proliferation and survival of malignant cells, angiogenesis, metastasis, immunesuppression, and reduced response to chemotherapeutic agents. Paradoxically, there are parallels between the resolution of inflammation and the inflammatory microenvironment in cancer. Although resolution of inflammation prevents carcinogenesis, the precise roles of anti-inflammatory and pro-resolving signaling pathways in tumor progression are still unclear. To find novel preventive and therapeutic targets for management of cancer, the molecular pathways linking resolution of inflammation and cancer should be unraveled.

The Severity of Portal Inflammation Is Associated with Hepatic Fibrosis Stage and Components of Metabolic Syndrome in NAFLD

( Sae Kyung Joo ),( Yong Jin Jung ),( Dong Hyeon Lee ),( Won Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Portal inflammation is considered significant marker in pediatric NAFLD with severe liver disease and fibrosis. However, the prognostic significance of portal inflammation remains unclear in adult patients with NAFLD. Therefore, we assessed the relationship between portal inflammation, hepatic fibrosis and metabolic syndrome in adult NAFLD. Methods: Three hundred ninety nine patients with biopsy-proven NAFLD were prospectively included. Histology assessed using Kleiner classification for fibrosis and the Nonalcoholic Steatohepatitis Clinical Research Network system for portal inflammation. All enrolled patients were assessed for the presence of the metabolic syndrome. Patients were categorized according to severity of portal inflammation (no/mild/more than mild). Results: Approximately one-third of the patients had either diabetes mellitus (DM) or hypertension, and more than half had metabolic syndrome. Fibrosis was presented in 291 (72.9%) patients and significant fibrosis was seen in 67 (16.8%) patients. Almost half of the patients had mild portal inflammation. In terms of the NAFLD activity score (NAS), approximately one-third had definite NASH (NAS ≥5). Those with mild portal inflammation subgroup had more severe metabolic phenotype, with higher body mass index, waist circumference, and lower high-density lipoprotein than in no portal inflammation subgroup. Similarly, those with moderate to severe portal inflammation subgroup had more severe metabolic phenotype than in mild or no portal inflammation subgroup. Portal inflammation was associated with the severity of steatosis (P < 0.001), presence of ballooning (P < 0.001), lobular inflammation (P < 0.001) on logistic regression analysis. Moreover, stage of fibrosis is significantly increased with increasing portal inflammation severity (P < 0.001). Fibrosis was associated with portal inflammation (95% confidence interval 3.64-6.03, odds ratio = 4.69). Diabetes was also associated with portal inflammation (95% confidence interval 1.94-4.49, odds ratio = 2.95). Conclusions: Portal inflammation is associated with histological and clinical features in NAFLD patients. It suggests portal inflammation is a significant predictor of disease progression in patients with NAFLD.

전립선비대증으로 인한 하부요로증상을 호소하는 환자에서 전립선 조직 내 염증의 의미

정원호,최미선,장혁수,박철희,김천일 대한비뇨의학회 2009 Investigative and Clinical Urology Vol.50 No.8

Purpose: Histological evidence of intraprostatic inflammation is a common finding of transrectal ultrasonography (TRUS)-guided needle biopsy of the prostate in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH). The aim of this study was to evaluate the relationship between intraprostatic inflammation and lower urinary tract symptoms depending on the severity of intraprostatic inflammation. Materials and Methods: Between January 2002 and December 2006, 141 BPH patients with prostate-specific antigen (PSA) of 4.0-10.0 ng/ml underwent TRUS-guided biopsy of the prostate. The extent and aggressiveness of intraprostatic inflammation were classified into 4 grades. The relationship between the grades of extent and aggressiveness of inflammation and the International Prostate Symptom Score (IPSS) was evaluated. The IPSS was evaluated according to voiding and storage symptom scores. Results: Mean storage symptom scores were increased by grade of the extent of intraprostatic inflammation (grade 0, 6.3; grade 1, 10.1; grade 2, 11.0; and grade 3, 11.3) (p<0.001). The aggressiveness of intraprostatic inflammation also showed increasing storage symptom scores with grade (grade 0, 6.3; grade 1, 10.2; grade 2, 10.9; and grade 3, 11.6) (p<0.001). Voiding symptom scores had no relationship with extent or aggressiveness of intraprostatic inflammation (p=0.942 and p=0.449, respectively). Conclusions: BPH patients with intraprostatic inflammation complained of more severe storage symptoms than did patients without inflammation. Therefore, if storage symptoms are severe, we might consider medical treatment for intraprostatic inflammation in BPH patients. Purpose: Histological evidence of intraprostatic inflammation is a common finding of transrectal ultrasonography (TRUS)-guided needle biopsy of the prostate in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH). The aim of this study was to evaluate the relationship between intraprostatic inflammation and lower urinary tract symptoms depending on the severity of intraprostatic inflammation. Materials and Methods: Between January 2002 and December 2006, 141 BPH patients with prostate-specific antigen (PSA) of 4.0-10.0 ng/ml underwent TRUS-guided biopsy of the prostate. The extent and aggressiveness of intraprostatic inflammation were classified into 4 grades. The relationship between the grades of extent and aggressiveness of inflammation and the International Prostate Symptom Score (IPSS) was evaluated. The IPSS was evaluated according to voiding and storage symptom scores. Results: Mean storage symptom scores were increased by grade of the extent of intraprostatic inflammation (grade 0, 6.3; grade 1, 10.1; grade 2, 11.0; and grade 3, 11.3) (p<0.001). The aggressiveness of intraprostatic inflammation also showed increasing storage symptom scores with grade (grade 0, 6.3; grade 1, 10.2; grade 2, 10.9; and grade 3, 11.6) (p<0.001). Voiding symptom scores had no relationship with extent or aggressiveness of intraprostatic inflammation (p=0.942 and p=0.449, respectively). Conclusions: BPH patients with intraprostatic inflammation complained of more severe storage symptoms than did patients without inflammation. Therefore, if storage symptoms are severe, we might consider medical treatment for intraprostatic inflammation in BPH patients.

Propolis Protects Endotoxin Induced Acute Lung and Liver Inflammation Through Attenuating Inflammatory Responses and Oxidative Stress

Berat Yangi,Mehmet Cengiz Ustuner,Murat Dincer,Cansu Ozbayer,Neslihan Tekin,Derya Ustuner,Emine Colak,Umut Kerem Kolac,Emre Entok 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.11

Propolis is a natural bee product, and it has many effects, including antioxidant, anti-inflammatory, antihepatotoxic, and anticancer activity. In this study, we aimed to explore the potential in vivo anti-inflammatory, antioxidant, and antiapoptotic properties of propolis extract on lipopolysaccharide (LPS)-induced inflammation in rats. Forty-two, 3- to 4-month-old male Sprague Dawley rats were used in six groups. LPS (1 mg/kg) was administered intraperitoneally to rats in inflammation, inflammation + propolis30, and inflammation+propolis90 groups. Thirty milligram/kilogram and 90 mg/kg of propolis were given orally 24 h after LPS injection. After the determination of the inflammation in lung and liver tissues by 18F-fluoro-deoxy-d-glucose–positron emission tomography (18FDG-PET), samples were collected. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), nitric oxide (NO), and DNA fragmentation were determined. The decrease of MDA levels in inflammation + propolis30 and inflammation + propolis90 groups was determined compared to the inflammation group in lung and liver tissues. The increase of SOD% inhibition in inflammation + propolis90 group was determined in liver, lung, and hemolysate compared to the inflammation group. Increased CAT activities in inflammation + propolis30 and inflammation + propolis90 groups were observed in liver tissue and hemolysate compared to inflammation group. In lung tissue, NO levels were lower in inflammation group compared to the control group, but DNA fragmentation levels were higher. 18F-FDG uptake of tissues in inflammation + propolis30 and inflammation + propolis90 groups was decreased compared to the inflammation group. In conclusion, the data of this study indicate that the propolis application may serve as a potential approach for treating inflammatory diseases through the effect of reducing inflammation and free oxygen radical production.

Effect of Histological Inflammation on Total and Free Serum Prostate-Specific Antigen Values in Patients Without Clinically Detectable Prostate Cancer

Goran Stimac,Borislav Spajic,Ante Reljic,Josip Katusic,Alek Popovic,Igor Grubisic,Davor Tomas 대한비뇨의학회 2014 Investigative and Clinical Urology Vol.55 No.8

Purpose: We are often confronted with patients in the “gray zone” (prostate-specific antigen[PSA]<10 ng/mL) whose biopsies reveal no malignancy but only inflammation. We investigated the relationship between histological inflammation and total PSA(tPSA), free PSA (fPSA), and percentage of free PSA (f/tPSA) levels in patients withoutprostate cancer (PC). Materials and Methods: We studied 106 men with tPSA<10 ng/mL who had undergonebiopsy that was negative for PC and who had no clinical prostatitis. Inflammation observedat biopsies was scored for inflammation type in each biopsy core by use of afour-point scale and was then correlated with tPSA, fPSA, and f/tPSA. Results: Different patterns of inflammation were found in each set of biopsies. Regression factor analysis was used to form two groups according to inflammation type:more chronic and more acute. Median tPSA, fPSA, and f/tPSA levels in the more chronicand more acute inflammation groups were 6.4 ng/mL, 1.09 ng/mL, and 15%, and 7.3ng/mL, 0.79 ng/mL, and l2%, respectively. A significant difference was found in fPSA(p=0.003) and f/tPSA (p<0.001), whereas the difference in tPSA was not significant(p=0.200). Total PSA correlated with fPSA (r=0.4, p<0.001) but not with inflammationtype (r=0.12, p>0.010). A correlation existed between inflammation type and fPSA(r=–0.31, p=0.001) and f/tPSA (r=–0.43, p<0.001) in that the fPSA and f/tPSA were lowerin the group with more acute inflammation. Conclusions: Subclinical inflammation has a significant influence on fPSA in patientswith tPSA<10 ng/mL but without PC or clinical prostatitis. Subclinical inflammationis not characterized by elevated tPSA alone but also by a decreased fPSA, a tendencysimilar to that in PC.

15-lipoxygenase metabolites play an important role in the development of a T-helper type 1 allergic inflammation induced by double-stranded RNA

Jeon, S. G.,Moon, H.-G.,Kim, Y.-S.,Choi, J.-P.,Shin, T.-S.,Hong, S.-W.,Tae, Y.-M.,Kim, S.-H.,Zhu, Z.,Gho, Y. S.,Kim, Y.-K. Blackwell Publishing Ltd 2009 Clinical and experimental allergy Vol.39 No.6

<P>Summary</P><P>Background</P><P>We recently demonstrated that the T-helper type 1 (Th1) immune response plays an important role in the development of non-eosinophilic inflammation induced by airway exposure of an allergen plus double-stranded RNA (dsRNA). However, the role of lipoxygenase (LO) metabolites in the development of Th1 inflammation is poorly understood.</P><P>Objective</P><P>To evaluate the role of LO metabolites in the development of Th1 inflammation induced by sensitization with an allergen plus dsRNA.</P><P>Methods</P><P>A Th2-allergic inflammation mouse model was created by an intraperitoneal injection of lipopolysaccharide-depleted ovalbumin (OVA, 75 μg) and alum (2 mg) twice, and the Th1 model was created by intranasal application of OVA (75 μg) and synthetic dsRNA [10 μg of poly(I : C)] four times, followed by an intranasal challenge with 50 μg of OVA four times. The role of LO metabolites was evaluated using two approaches: a transgenic approach using 5-LO<SUP>−/−</SUP> and 15-LO<SUP>−/−</SUP> mice, and a pharmacological approach using inhibitors of cysteinyl leucotriene receptor-1 (cysLTR1), LTB4 receptor (BLT1), and 15-LO.</P><P>Results</P><P>We found that the Th1-allergic inflammation induced by OVA+dsRNA sensitization was similar between 5-LO<SUP>−/−</SUP> and wild-type (WT) control mice, although Th2 inflammation induced by sensitization with OVA+alum was reduced in the former group. In addition, dsRNA-induced Th1 allergic inflammation, which is associated with down-regulation of 15-hydroxyeicosateraenoic acids production, was not affected by treatment with cysLTR1 or BLT1 inhibitors, whereas it was significantly lower in 12/15-LO<SUP>−/−</SUP> mice compared with WT control mice. Moreover, dsRNA-induced allergic inflammation and the recruitment of T cells following an allergen challenge were significantly inhibited by treatment with a specific 15-LO inhibitor (PD146176).</P><P>Conclusion</P><P>15-LO metabolites appear to be important mediators in the development of Th1-allergic inflammation induced by sensitization with an allergen plus dsRNA. Our findings suggest that the 15-LO pathway is a novel therapeutic target for the treatment of virus-associated asthma characterized by Th1 inflammation.</P>

Hypothalamic inflammation and malfunctioning glia in the pathophysiology of obesity and diabetes: Translational significance

Rahman, Md Habibur,Bhusal, Anup,Lee, Won-Ha,Lee, In-Kyu,Suk, Kyoungho Elsevier 2018 Biochemical pharmacology Vol.153 No.-

<P><B>Abstract</B></P> <P>Preclinical studies have suggested that chronic inflammation in the brain might be associated with multiple metabolic disorders, including obesity and diabetes. In particular, hypothalamic inflammation interferes with the endocrine system and modulates nutritional homeostasis, leading to metabolic alterations and consequent pathologies. With regard to the mechanisms underlying molecular and cellular pathogenesis, neurons, non-neuronal cells, and the crosstalk between them have gained particular attention. Specifically, malfunctioning glia have recently been implicated as an important component of pathological hypothalamic inflammation. Hypothalamic inflammation modulates food intake, energy expenditure, insulin secretion, hepatic glucose production, and glucose and fatty acid metabolism. Moreover, growing evidence suggests that hypothalamic inflammation is intrinsically associated with the pathogenesis of obesity, diabetes, and their dysfunctional consequences. However, the translational significance of hypothalamic inflammation has not yet been fully explored. In this review, we cover recent advances suggesting that hypothalamic inflammation and glia play a central role in the ontology of obesity, diabetes, and their complications. Finally, we explore the possibilities and challenges of targeting hypothalamic inflammation as a potential therapeutic strategy.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Histological inflammation increases the risk of colorectal neoplasia in ulcerative colitis: a systematic review

( Ruben J. Colman ),( David T. Rubin ) 대한장연구학회 2016 Intestinal Research Vol.14 No.3

Background/Aims: Ulcerative colitis (UC) patients are at greater risk for the development of colorectal neoplasia. Several individual studies have demonstrated associations between severity of histologic inflammation and colorectal neoplasia. However, a comprehensive systematic review has not been completed. We performed a systematic review and meta-analysis to explore the relationship between histologic inflammation and risk for neoplasia among available observational studies. Methods: Three databases (EMBASE, MEDLINE and the Cochrane Library) were systematically searched. Studies were included if they included UC patients who underwent colonoscopic assessment and when histologic inflammation and colorectal neoplasia were both reported. Colorectal neoplasia rates were compared. Quantitative meta-analysis was attempted. Results: Four of 1,422 records found were eligible. Results from 2 case-control studies reported a 3.5-fold increased risk for colorectal neoplasia associated with a single point increase in histologic inflammation. This result was further corroborated by one cohort study that demonstrated increased hazard ratios. The second cohort study reported outcomes for patients with normal gross endoscopy, but had increased histological inflammation when neoplasia was assessed. Finally, this study reported increased risk for neoplastic progression by histological inflammation among patients who were normal by gross endoscopic evaluation. Quantitative meta-analysis was unsuccessful due to heterogeneity between study measures. Conclusions: There is strong evidence that histologic inflammation among patients with UC increases the risk of colorectal neoplasia. The depth and nature of assessment of additional clinical variables was varied and may have resulted in greater outcome discrepancy. Additional study related to mechanisms of inflammation-related neoplasia and therapeutic modification is needed.

Active Molecular Chitosan alleviate Bleomycin-induced Acute Pulmonary Inflammation in Mice

( Seong-bo Yun ),( Dong-hun Kang ),( Ji-sun Choi ),( Dae-young Kim ) 한국키틴키토산학회 2019 한국키틴키토산학회지 Vol.24 No.3

Generally acute pulmonary inflammation is triggered by damage to alveolar epithelial cells due to the pollutants, viral infection, allergens and toxic substances. The active molecular chitosan (AMC, 5~8 kDa) is known to have non-toxic, bio-degradable, and biological activities including anti-tumor, anti-viral, and anti-inflammatory activities. The purpose of this study was to observe AMC’s preclinical efficacy to acute pulmonary inflammation and evaluate the therapeutic effect of a bleomycin (BLM) induced mouse model using AMC, a final product made by the hydrolysis of chitosan. Our experiments were conducted using male C57BL/6 mouse and BLM (5 mg/kg) was injected once with the intratracheal instillation (IT) method to induce pulmonary inflammation. Each group was conducted with prednisolone (PDS, 6.5 mg/kg) or AMC (100 mg/kg and 200 mg/kg, respectively) for 10 days with oral gavage. The relative lung weight measurements, histological findings in lung tissue specimens and cell counts through bronchoalveolar lavage fluid (BALF) were performed to determine the anti-inflammatory effects of AMC. The AMC treated groups with BLM induction had a decreased tendency of inflammation on our experiments. A dose of 100 mg/kg AMC induce group showed that similar aspect with control group on histological results. In addition, the lymphocyte rate appeared a noticeable on this group. The degree of lymphocyte was remarkably lower. It was inferred that inflammatory improvement in the AMC treated group. We confirmed that the BLM-induced lung disease model that progressed inflammation was inhibited by AMC. Furthermore, AMC performs an anti-inflammation function and has the possibility of use for the treatment of inflammatory disease.

Interstitial Inflammation in the ISN/RPS 2018 Classification of Lupus Nephritis Predicts Renal Outcomes and is Associated With Bcl-2 Expression

이상진,남언정,한만훈,김용진 대한류마티스학회 2022 대한류마티스학회지 Vol.29 No.4

Objective: To investigate the histopathological characteristics of patients with lupus nephritis in the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification and assess the prognostic factors. Methods: This study enrolled 92 patients with lupus nephritis, who had conventional treatment and renal biopsy. Each renal tissue was evaluated according to 2018 ISN/RPS classification, and quantified apoptotic regulator protein, the B-cell lymphoma-2 protein (Bcl-2), expressions in selected lymphocyte subsets were measured using novel computational approaches using multicolor confocal images. Histopathological characteristics and prognostic factors of end-stage renal disease (ESRD) and chronic kidney disease (CKD) were compared. Follow-up data were obtained, and survival analysis was conducted. Results: During follow-up period (average: 74.3 months), 16 and 18 patients progressed ESRD and CKD, respectively. Multivariable analysis of age, sex, disease activity and pathological features in ISN/RPS demonstrated the extent of interstitial inflammation (grade 0~3) was significantly associated with both ESRD and CKD. When interstitial inflammation was divided into mild (grade 0, 1) and severe (grade 2, 3), Cox regression analysis showed that patients with severe interstitial inflammation were significantly increased risk of both ESRD and CKD (hazard ratio: 4.67 and 3.8, respectively). Bcl-2 expression in CD4+ and CD20 cells was significantly higher in the severe interstitial inflammation group compared to in mild interstitial inflammation patients (p=0.006 and 0.010, respectively). Conclusion: The extent of interstitial inflammation can predict clinical renal outcomes. Significantly elevated Bcl-2 expression in both CD4+ and CD20 cells was found in severe interstitial inflammation compared with mild interstitial inflammation.