001). We could not find any relationships between OLGA gastritis stage and sex, smoking as well as a familial history of gastric cancer. The severity of EGA significantly correlated with that of OLGA gastritis stage as presented in Table 2 Tamoxifen in vitro (Spearman correlation coefficient = 0.6, P < 0.001). All of the patients with high-stage OLGA gastritis had moderate-to-severe EGA (Fisher's exact test, P < 0.001). Using moderate-to-severe EGA as the diagnostic criterion for high-stage gastritis, the sensitivity, specificity, positive predictive value and negative predictive value were 100% (95% CI 75.3–100%),

57.7% (95% CI 51.5–63.7%), 10.3% (95% CI 5.6–17%), and 100% (95% CI 97.6–100%), respectively. There were 95 patients who were older than 40 years-of-age and had H. pylori infection in the present study (28 with mild EGA and 67 with moderate-to-severe EGA). In this subgroup of

patients, the positive predictive value increased to 19.4% (95% CI 10.8–30.9%). There were seven patients (2.5%) with low-grade CP-868596 in vitro dysplasia (3 in stage I, 3 in stage III and 1 in stage IV according to the OLGA gastritis system). All the dysplastic lesions were not endoscopically visible and were detected by systemic map biopsies according to the updated Sydney system. Dysplastic lesions were frequently detected in patients with high-stage gastritis: 4/13 (30.7%) patients with high-stage gastritis versus 3/267 (1.1%) patients with low-stage gastritis (i.e. stage 0–II; Fisher’s exact test P = 0.0001; OR = 39.1; 95% CI 6.1–270.8). Dysplastic lesions were also clustered in patients with moderate-to-severe EGA: 6/126 (4.76%) with moderate-to-severe EGA versus 1/154 (0.65%) with mild EGA (Fisher’s exact test P = 0.048; OR = 7.7; 95% CI 0.9–170.9). The southern area of Vietnam, where this study was carried out, Verteporfin has

a moderate incidence of gastric cancer. The age-standardized rate per 100 000 is 16.5 in males.16 The gastritis stage of patients in the present study who were under 40 years-of-age was almost between those in the low-risk and high-risk regions.7 Therefore, the result of the present study suggests that OLGA gastritis staging parallels the gastric cancer risk in our population. However, there was a difference between our result and those from other moderate-risk regions; we found a higher proportion of patients with gastritis stage I–II and no patients with high-stage gastritis, whereas Rugge et al. reported a lower proportion of patients with stage I–II, and a few patients with high-stage gastritis in Hong Kong and Taiwan. Gastric atrophy is more severe among patients with H. pylori infection and tends to increase when the infection is prolonged.17 The present study confirmed that high-stage gastritis is significantly associated with H. pylori infection and advanced age as reported in previous studies and in other populations.8,9 It has been reported that the atrophic progression is not invariable and only appeared in a subgroup of patients with H. pylori.

group. Both groups showed marked thrombocytopenia. Overall, IFN therapies tended

to be used more frequently in the Lap-sp. group compared with the PSE group. The operation time for Lap-sp. ranged 200–400 min (average, 237.7 ± 43.5 min). The blood loss ranged 10–1500 mL (average, 138.2 ± 190.6 mL). The mass of the spleen ranged 500–850 g (average, 346.3 ± 108.5 g). None of the patients experienced uncontrolled intraoperative bleeding. None of the patients required a conversion to open surgery. However, four out of 21 patients (19%) underwent hand-assisted laparoscopic surgery with an extension of the skin incision to 4 cm at the upper midline. There were no other major intraoperative complications. All of the patients in both groups tolerated the operations well. All PSE procedures were completed successfully with no intraoperative difficulty and no intraoperative complication. All patients tolerated the operations well. The actual Autophagy Compound Library clinical trial amount of devascularized parenchyma ranged 45–80% (average, 65.1%). Table 2 shows the post-intervention outcomes for both groups. The occurrence of continuing fever over 37°C and the use of anti-inflammatory analgesic drugs

were significantly lower in the Lap-sp. group than in the PSE group (P < 0.05). No major complication occurred in any patient in this study. Portal vein thrombosis occurred in two patients, pancreatic fistula in one patient and wound Decitabine manufacturer infection in one patient in the Lap-sp. group. However, these minor complications were successfully overcome using adequate treatments, including

Selleck Panobinostat administration of anticoagulation drugs, drainage and lavage. An intrasplenic abscess was found in one patient in the PSE group, which was successfully treated using puncture and drainage. There were no episodes of increased ascites or hepatic encephalopathy, which indicates severe liver dysfunction, in either group. The WBC count at 1 week after the interventions had increased significantly in both groups compared with the count prior to the interventions (Lap-sp. 5706 ± 1169 vs 2961 ± 1051/µL; PSE 4986 ± 1311 vs 3447 ± 1576/µL; both P < 0.05), and there was no statistically significant difference in the WBC count at 1 week after the interventions between the two groups. The average duration of hospital stay was shorter in the Lap-sp. group compared with the PSE group, although not statistically significantly. No cases of overwhelming post-splenectomy sepsis were observed in the Lap-sp. group throughout the duration of this study. Figure 1 shows the changes in platelet counts after each intervention. The platelet count 1 week after the interventions had increased significantly in both groups compared with the count prior to the interventions (Lap-sp. 22.0 ± 3.5 vs 6.2 ± 2.5 × 104/µL; PSE 12.9 ± 5.6 vs 5.2 ± 2.4 × 104/µL; both P < 0.05). The platelet count in the Lap-sp.

Although WNT proteins are predominantly associated with embryogenesis, they are also important in disease progression. Previous studies described regulation of WNT-5A by the fibrogenic growth factor TGFβ. This interaction warrants further studies into the role of WNT-5A in liver fibrosis. Although gene-array studies identified increased WNT5 in fibrotic livers, the functional role of WNT-5A in this liver disease is not described yet. Therefore, our aim was to elucidate its role in liver

fibrosis. We studied the expression of WNT-5A in mouse and human livers in more detail and examined the relation between WNT-5A and various fibrosis-associated growth factors, cytokines and extracellular matrix proteins. WNT-5A and collagen I expression in normal and fibrotic mouse and human livers were analyzed with RT-PCR, ubiquitin-Proteasome pathway Western blot, and immuno-histochemistry.

The effects of cytokines/growth factors on WNT-5A and collagen I expression in LX2 cells were analyzed with RT-PCR and Western blot. The effects of WNT-5A on the expression of matrix proteins were determined after incubation of LX2 cells with WNT-5A siRNA in the absence and presence of TGFβ. WNT-5A gene and protein expression was significantly higher in fibrotic mouse and human livers compared to normal. Immunohistochemical analysis showed PD0325901 that WNT-5A expression was found in fibrotic collagen-rich areas of mouse and human livers. WNT-5A staining co-localized with desmin staining in these areas. In vitro studies with myofibroblasts showed that WNT-5A expression was significantly increased after incubation with TGF-β while PDGF-BB and pro-inflammatory cytokines (IL1β and TNFα) did not change WNT-5A expression. After silencing

of WNT-5A in myofibroblasts, using WNT-5A siRNA, reduced levels of collagen I, vimentin, and fibronectin in TGF-β-stimulated LX2 cells were found as compared to transfection controls. Interestingly, the antifibrotic cytokine IFNγ suppressed WNT-5A and collagen type I expressions in vitro. In addition, hepatic WNT-5A and collagen Ievels were significantly Urocanase reduced in CCL4 exposed (8 weeks) mice treated with (targeted) IFNγ as compared to untreated fibrotic mice. In conclusion, WNT-5A is significantly upregulated in fibrotic livers in particular in myofibroblasts in fibrotic bands. WNT-5A expression in myofibroblasts is induced by TGFβ and is involved in the regulation of various fibrotic matrix proteins. Targeted IFNγ therapy reduces hepatic WNT-5A expression and ameliorates liver fibrosis. These results identify WNT-5A as a potential new antifibrotic drug target.

The urease B subunit was recently shown to lead to Th17

responses in the mouse model of H. pylori infection [35]. When recombinant urease B was incubated directly with mouse splenic lymphocytes, IL-17-producing cells were increased, and when macrophages were incubated with recombinant urease B, IL-6 and IL-23 were produced to support Th17 development. H. pylori LPS has been shown to induce weaker immune responses than LPS from other bacteria. Particularly, LPS from H. pylori did not induce strong IL-1β, IL-6, or IL-8 responses [36] as other bacterial LPS does. H. pylori LPS was also shown click here to induce little NF-κB activation through TLR-4, but was shown in this study to induce IL-12 and IL-18 responses, which are thought to be pro-inflammatory. This is in contrast to another study that showed a lack of IL-12 and IL-2 induction by lymphocytes incubated with H. pylori LPS, which was accompanied by decreased cytotoxic PI3K inhibitor activity by lymphocytes incubated with H. pylori LPS compared to that of E. coli [37]. The beginning of 2011 was marked by a promising publication in the field of H. pylori vaccine development made by Moss et al. [38]. They used a computational method to predict novel T-cell epitopes. The multi-epitope vaccine was administered intranasally or intramuscularly to H. pylori-infected

mice, followed by a boost with the peptides themselves formulated in liposomes with CpG oligonucleotides and heat-labile enterotoxin. The vaccine induced a broad immune response, as determined Ponatinib mw by IFN-γ production, and led to a sterilizing immunity 32 weeks after challenge in 5 of 19 mice. Another promising vector platform for the

expression of H. pylori antigens was published in the beginning of 2011 by Iankov, et al. [39]. They produced a measles virus (MV) vaccine strain encoding the H. pylori neutrophil-activating protein (NAP). Nine months post vaccination, all animals immunized with MV strains expressing the secretory NAP antigen developed a strong humoral immunity against NAP within 2-4 weeks. By using IFN-γ ELISpot assay, they also confirmed effective NAP-specific cell-mediated immunity. Their experiments importantly demonstrated that immunization with a live replication competent vaccine expressing H. pylori molecules (NAP or potentially CagA, VacA, etc.) induced not only robust antibody production but also distinctive cell-mediated response against H. pylori antigens. Improved efficacy of vaccines may be achieved in new trials of vaccine formulations that include multiple antigens and use methods to optimize cellular immunity. An approach made by Chen et al. [40] used a H. pylori oipA gene-encoded construct co-delivered by IL-2 gene-encoded construct and B subunit heat-labile toxin of Escherichia coli gene-encoded construct.

In another experiment performed in WD-fed hApoE2 KI/PPAR-α KO mice, the pure PPAR-γ agonist, rosiglitazone,

had no effect on inflammatory and fibrosis gene expression, whereas the pure PPAR-δ agonist, GW501516, showed a similar profile to GFT505 (Supporting Table 2). These results further suggest that, in hApoE2 KI/PPAR-α KO mice, GFT505 likely acts through activation of PPAR-δ in the liver. Olaparib To evaluate the effect of GFT505 on later stages of fatty liver disease, we next studied a model of advanced steatosis with strong inflammation induced by an MCD diet. In two independent experiments, insulin-resistant db/db mice were fed the MCD diet for 7 weeks and concomitantly treated with vehicle or 1, 3, 10 (experiment 1), or 30 mg/kg/day (experiment 2) of GFT505. The MCD diet provoked a significant increase of plasma ALT levels, associated with intrahepatic accumulation of cholesterol and TGs (Fig. 3A-C). Upon histological examination, a marked macrovesicular steatosis induced by MCD diet feeding was accompanied by increased buy Quizartinib inflammation and weak fibrosis (Fig. 4A-D). In mice concomitantly treated with GFT505, intrahepatic cholesterol and TG

content were significantly reduced in a dose-dependent manner to reach levels comparable to those in mice fed the control diet (Fig. 3B,C). Microscopic Immune system examination showed that GFT505 administration at 10 mg/kg/day completely prevented MCD diet-induced macrovesicular steatosis and inflammation (Fig. 4B,C). The weak hepatic fibrosis observed in

MCD diet-fed mice was not significantly reduced by GFT505 treatment (Fig. 4D). Consistent with liver protection by GFT505, plasma ALT activity was reduced to levels comparable to the control diet group (Fig. 3A), and liver weight was also significantly reduced (Fig. 3D). In a study performed at 30 mg/kg/day of GFT505 and giving similar results, transcriptomic analyses showed that the MCD diet-induced increased expression of hepatic inflammatory and profibrosis genes (IL-1β, TNF-α, TGF-β, and collagens) was blocked by GFT505 (Supporting Table 3). Moreover, hepatic expression of macrophage markers CD11b and F4/80 was significantly decreased by GFT505 treatment (Supporting Table 3). The effect of GFT505 on liver fibrosis was studied in a rat model induced by repeated IP injections of CCl4. Rats were injected with CCl4 or vehicle twice-weekly for 7 weeks, with parallel oral treatment with 30 mg/kg/day of GFT505 or vehicle. CCl4 administration induced a strong liver fibrosis with the formation of collagen bridges between veins (Fig. 5A), associated with an increased number of macrophages (KCs; Fig. 5B) and activated hepatic stellate cells (HSCs) expressing alpha smooth muscle actin (αSMA; Fig. 5C).

80 95% CI 4.31–405.1, P = 0.001). Among 14 patients who received operation initially, six (42%) patients had recurrence. One patient received radiofrequency

ablation; three (50%) patients received TAE combined with percutaneous ethanol injection (PEI) and one patient received chemotherapy due to lung metastasis and one patient received traditional herb therapy. Of the nine (75%) out of 12 patients who received percutaneous local ablation and had recurrence, six (66.6%) patients received TAE combined with PEI, one patient received TAE alone, one patient received PEI alone and one patient received BGB324 traditional herb therapy. Of the 34 (77%) out of 44 patients who received TAE and had recurrence, 20 patients received TAE, seven (20%) patients received TAE combined with PEI, five patients received percutaneous local ablation therapy and two patients received radiation therapy. In the current, large-scale study, a total of 61 318 adults aged 40 years or more were screened for HCC, and 97 cases were detected. This prevalence of HCC (158/105) is three to five times higher than the reported annual incidence in Taiwan, and may be associated with an earlier detection of more asymptomatic or subclinical HCC cases. More than half of the cases (n = 51, 52.6%) detected were in the very early or early stage of HCC, and thus

were detected early enough to have a chance of treatment being effective. As based on the practice guidelines of the American Association for the Study of Liver Disease (AASLD), cases of either very early or early stage HCC should receive

curative treatment, cases of intermediate stage click here be treated with transcatheter arterial chemoembolization, and cases beyond the intermediate stage should DNA Methyltransferas inhibitor undergo either experimental or conservative treatment.26 In the current study, 70 of the 88 treatable cases (79.5%) received heterogeneous treatment in one of nine hospitals with various facilities because a national consensus or practice guidelines do not exist, the selection of treatment modalities varied from doctor to doctor. In addition, 18 treatable cases resisted our suggestions and chose either alternative medicine or no active treatment, which suggests that post-screening education and consultation services should be augmented. In order to demonstrate the survival benefit in the screening cases, a randomized controlled study provided the best evidence. However, ethical problems are a major concern in carrying out this kind of study. According to the randomized controlled study of Zhang et al.,11 3-year and 4-year survival rates were 7.2% and 0% in the control group who did not receive the screening program. In the current study, 3-year and 4-year overall survival rate was 56.8% and 46.8%, respectively, in patients that received community screening, which was higher than the historical control.

In the secondary analysis

Kinase Inhibitor Library supplier increased levels of genera Parabacteroides and Collinsella were observed comparing PSC-UC with UC samples. Conclusions: This is the first study, to our knowledge, to characterise the intestinal microbiota of patients with UC with and without PSC. The genus level analysis revealed differences comparing PSC-UC and UC subjects which may reflect microbial representatives of PSC pathogenesis. Increased levels of genus Collinsella observed in primary and secondary analyses are of interest due to the role of these organisms in bile acid metabolism. Functional annotations of the genus level findings and replication in independent panels are presently ongoing. Disclosures: David Kevans – Speaking and Teaching: Abbvie The following people have nothing to disclose: Andrea D. Tyler, Kristian Holm, Kristin K. Jørgensen, Morten H. Vatn, Tom H. Karlsen, Dirk Gevers, Johannes R. Hov, Mark S. Silverberg Background/aims: Vascular adhesion protein (VAP)−1 is an adhesion molecule which possesses potent amine oxidase activity, and deaminates dietary amines resulting in the production of H2O2.Through this function, VAP-1 leads to activation of NFқB in hepatic sinusoidal endothelium (HSEC) resulting in expression of mucosal-vascular cell-adhesion

molecule-1 (MAdCAM-1); a mechanism proposed to contribute to the homing of gut-tropic lymphocytes expressing α4β7 to the liver. Given the putative role this pathway has in hepatic diseases complicating inflammatory bowel disease PLX3397 cost (IBD), we set out to quantify circulating/soluble (sVAP-1) and intrahepatic VAP-1 enzyme activity in primary sclerosing cholangitis (PSC), and evaluate the functional consequence of its inhibition on MAdCAM-1 dependent lymphocyte recruitment to HSEC. Methods: Total VAP-1 concentration was measured by ELISA. VAP-1 amine oxidase activity was

quantified in human serum and explanted liver tissue using the amplex red assay. Flow-based adhesion assays were performed using human HSEC isolated from almost liver explants, activated with TNFα and methylamine (VAP-1 substrate), and treated with VAP-1 antibody or semicarbazide (VAP-1 enzyme inhibitor). FAC-sorted peripheral blood leucocytes expressing α4β7 were perfused over HSEC under flow rates simulating physiological shear (0.05Pa) and adhesion and transmigration quantified. Results: Patients with PSC had significantly higher circulating median VAP-1 enzyme activity (114.5pmol H2〇 2 produced/min/ml serum, IQR 100.6-134.7) than patients with IBD (60.3, IQR 38.5-73.0; P=0.006), normal controls (84.0, IQR 77.7-105.7; P=0.020) and individuals with PBC (53.9, IQR 33.0-90.9; P=0.006), and trended higher than AIH (77.6, IQR 51.0-124.5; P=0.200) (Mann-Whitney). Total sVAP-1 concentration correlated well with sVAP-1 enzyme activity (R2=0.75). Intrahepatic median VAP-1 activity was also significantly higher in PSC (97.

It therefore behoves us to be aware of the range of conditions that click here can present with ‘Atypical’ or ‘Noncardiac’ chest pain, and the clinical features of these, so that we can make a more informed diagnosis. Treatment may be available and, even if treatment is not available, the cause is defined and the benign nature of the condition can be emphasized (provided adequate investigation has been carried out), even if the pain continues. “
“See article in J. Gastroenterol. Hepatol. 2010; 25: 1366–1373. In the mid-1970s a number of papers from South Africa indicated that a deficiency of dietary fiber was a factor in the development

of irritable bowel syndrome (IBS), and recommended supplementing its intake as a treatment for this condition.1 A number of poorly designed studies purported to support a role for the use of bran cereal in the treatment of IBS, although some recognized that it may be a harmless placebo. Recent systematic reviews have consistently shown that there is little if any benefit beyond a marginal improvement in stool consistency.2 In fact, a number of contrarian studies, which had been largely ignored, had suggested that favorite sources of dietary fiber such as

bran and other cereals, and vegetables and fruits, might actually aggravate symptoms in IBS. The symptoms that appeared to be aggravated were flatulence, bloating and abdominal pain. Based on the use of an exclusion ICG-001 diet, Nanda et al. from Oxford reported that dairy, grains, in particular wheat and rye, and onions were the major foods implicated by IBS patients, and that patients responding to dietary manipulation were likely to have presented with flatulence as an initial symptom.3 They had also observed that intolerance to either wheat or rye was specifically associated with abdominal distension. Whorwell and Prior from Manchester recorded that 55% of their patients felt worse and only 10% felt better on bran.4 John Hunter’s group from Cambridge used a whole-body calorimeter

to measure the 24-h excretion of hydrogen and methane in both the flatus and the breath.5,6 They compared the gas production of IBS patients and healthy controls old on a standard diet with regular fiber intake, an exclusion diet, and a fiber-free diet. They found that IBS patients had a significantly faster rate of gas production on a fiber-rich diet, which reduced significantly on the exclusion and the fiber-free diet, and this appeared to be associated with an improvement in symptoms. Others have also suggested that malabsorption of fructose and sorbitol, of which fruits are rich sources, may give rise to symptoms in IBS patients.7 The study presented by Ong et al.

The locations of the most serious lesions were involved in right upper quadrant (24 of 53), and right lower quadrant (14 of 53). Pleural changes (49 of 53) and solid abdominal viscera infiltration (43 of 53) were more common. According to the CT apperance, malignant peritoneal mesothelioma could be divided into diffuse malignant peritoneal mesothelioma and limited malignant peritoneal mesothelioma. Conclusion: Pleural changes combined with CT findings that

the most serious lesions mainly involving right peritoneum and right cardiophrenic nodes enlarged can suggest, but are not diagnostic of, mesothelioma, and may indicate that asbestos fiber may migrate Autophagy activator to the peritoneum through the diaphragm and/or its hiatus, leading to the peritoneal mesothelioma. Key Word(s): 1. Mesothelioma; 2. Peritoneum; 3. Computed tomography; Presenting Author: YANG BAI Additional Authors: YINGQIAO ZHU, QIANG ZHOU Corresponding Author: YANG BAI Affiliations: ultrasound department; internal medicine Objective: To investigate the value of preoperative ultrasound examination in appendix. Methods: From AZD4547 March 2011 to September 2012, there were 86 patients participated in the study because of abdominal pain with suspected appendicitis (45 men, 41

women, median age 36 years). All the patients accepted preoperative ultrasound exanimation and appendectomy, get pathological results. Siemens S2000 color Doppler ultrasonic diagnostic system, with convex array probe (2.5 MHz–5.0 MHz),

at the McBurney point or in local pain most obvious to find the appendix, to determine the location of the appendix, and measure the diameter of the appendix, wall hierarchy, inter echo and seep around. Results: we can not display the structure of the appendix in 6 patients because of the limitation of abdominal imaging conditions, accounting for 6.98% (6/86); 80 patients with preoperative ultrasound examination can show the structure of the appendix, accounting for 93.02% (80/86), all patients were confirmed by surgery and pathological findings. Ultrasound prompt location of the appendix: ileum anterior appendix 5 cases (5.81%)% ileum posterior appendix ioxilan 8 (9.30%)%, Pelvic appendix 32 cases (37.21%), cecum under appendix 9 cases of 10 (10.47), the Pericecal appendix 17 cases of (19.77 %), retrocecal appendix 9 cases (10.47%). Confirmed by surgery, 3 cases of discrepancies, 77 cases with surgical findings consistent in position. The ultrasound positioning accuracy rate is 89.53% (77/86). The ultrasonography prompt simple appendicitis 55 cases, 20 cases of suppurative appendicitis, perforated appendix 5 cases, around the appendix encapsulated effusion in 14 cases. preoperative ultrasonography with pathological consistent rate is 84.88% (73/86).

Ethanol-induced oxidative stress has been attributed to a decrease in the NAD+ : NADH ratio, acetaldehyde formation, CYP2E1 induction, hypoxia,

cytokine signaling, mitochondrial damage, LPS activation of Kupffer cells, reduction in antioxidants particularly mitochondrial and cytosolic GSH, one electron oxidation of ethanol to 1-hydroxy ethyl radical, and the conversion of xanthine dehydrogenase to xanthine oxidase. Fibrosis is a common response of the liver to a chronic inflammatory condition, where hepatic stellate cells (HSC) play a critical (though not exclusive) role.[19] HSCs exist in a quiescent state in the normal liver, but can be activated directly

or indirectly in response to apoptotic or necrotic cell death. Cytokines released in the tissue as a result of injury further contribute to HSC activation, resulting in the expression of a myofibroblast HM781-36B cost check details phenotype and stimulating the expression of extracellular matrix (ECM) proteins, in particular collagen type 1, which are not normally expressed in the liver. Under conditions of an acute tissue injury, the deposition of collagen fibers is a transient wound-healing response and is followed by fibrinolysis mediated by metalloproteases that are activated as damaged tissue is replaced by newly generated liver cells by the regenerative response. Continuous tissue damage and

repair after chronic inflammation, and an imbalance in the normal liver repair mechanisms results in excessive deposition of collagen fibers.[19] Chronic ethanol consumption can influence this process at multiple levels: Sclareol (i) enhancement of the pro-inflammatory environment in the liver by stimulating the release of pro-inflammatory cytokines from macrophages and decreasing the activity of protective cell types, including natural killer cells;[20] (ii) enhancement of hepatocyte apoptosis and necrosis in response to oxidative stress and shifting in stress defense signaling pathways; (iii) activation of HSCs and collagen formation (studies on isolated HSCs have demonstrated that ethanol alters their response to transforming growth factor (TGF-β) and IFN-γ through effects on intracellular signaling pathways); and (iv) suppression of the regenerative response to tissue damage that is an essential component of the liver’s repair mechanism and thereby facilitates the deposition of scar tissue, which is the hallmark of fibrosis. This is probably accompanied by a suppression of metalloproteases (e.g. by the activation of inhibitor proteins, such as plasminogen activator inhibitor-1 [PAI-1]), which normally would maintain the balance of ECM deposition and resolution to facilitate tissue repair.