60 research outputs found
A Mixed Methods Approach Towards Mapping and Economic Valuation of the Divici-Pojejena Wetland Ecosystem Services in Romania
Mapping and valuating ecosystem services has gained increasing attention over the last years and remains high in the research agenda. In this paper, a mixed methods approach is used to valuate ecosystem services provided by the Divici-Pojejena wetland in Romania. A qualitative part relied on focus group discussions and interviews to identify key stakeholders and the ecosystem services provided by the wetland site. The benefit transfer (BT) method was used for the monetary valuation of the identified ecosystem services that the wetland provides. Bird watching opportunities, water quality, and flood prevention services are among the highest valued services, while the amenity services are the least valued among all wetland services
Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis
<p>Abstract</p> <p>Background</p> <p>Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of collagens by proteases produces small fragments, so-called neoepitopes, which are released systemically. Technologies investigating MMP-generated fragments of collagens may provide more useful information than traditional serological assays that crudely measure total protein. In the present study, we developed an ELISA for the quantification of a neoepitope generated by MMP degradation of type IV collagen and evaluated the association of this neoepitope with liver fibrosis in two animal models.</p> <p>Methods</p> <p>Type IV collagen was degraded <it>in vitro </it>by a variety of proteases. Mass spectrometric analysis revealed more than 200 different degradation fragments. A specific peptide sequence, 1438'GTPSVDHGFL'1447 (CO4-MMP), in the Îą1 chain of type IV collagen generated by MMP-9 was selected for ELISA development. ELISA was used to determine serum levels of the CO4-MMP neoepitope in two rat models of liver fibrosis: inhalation of carbon tetrachloride (CCl<sub>4</sub>) and bile duct ligation (BDL). The levels were correlated to histological findings using Sirius red staining.</p> <p>Results</p> <p>A technically robust assay was produced that is specific to the type IV degradation fragment, GTPSVDHGFL. CO4-MMP serum levels increased significantly in all BDL groups compared to baseline, with a maximum increase of 248% seen two weeks after BDL. There were no changes in CO4-MMP levels in sham-operated rats. In the CCl<sub>4 </sub>model, levels of CO4-MMP were significantly elevated at weeks 12, 16 and 20 compared to baseline levels, with a maximum increase of 88% after 20 weeks. CO4-MMP levels correlated to Sirius red staining results.</p> <p>Conclusion</p> <p>This ELISA is the first assay developed for assessment of proteolytic degraded type IV collagen, which, by enabling quantification of basement membrane degradation, could be relevant in investigating various fibrogenic pathologies. The CO4-MMP degradation fragment was highly associated with liver fibrosis in the two animal models studied.</p
Disease Progression and Pharmacological Intervention in a Nutrient-Deficient Rat Model of Nonalcoholic Steatohepatitis
Hepatoprotective effects of semaglutide, lanifibranor and dietary intervention in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH
Nonâalcoholic steatohepatitis (NASH) has emerged as a major challenge for public health because of high global prevalence and lack of evidenceâbased therapies. Most animal models of NASH lack sufficient validation regarding disease progression and pharmacological treatment. The GubraâAmylin NASH (GAN) dietâinduced obese (DIO) mouse demonstrate clinical translatability with respect to disease etiology and hallmarks of NASH. This study aimed to evaluate disease progression and responsiveness to clinically effective interventions in GAN DIOâNASH mice. Disease phenotyping was performed in male C57BL/6J mice fed the GAN diet high in fat, fructose, and cholesterol for 28â88Â weeks. GAN DIOâNASH mice with biopsyâconfirmed NASH and fibrosis received lowâcaloric dietary intervention, semaglutide (30Â nmol/kg/day, s.c.) or lanifibranor (30Â mg/kg/day, p.o.) for 8 and 12Â weeks, respectively. Withinâsubject change in nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) and fibrosis stage was evaluated using automated deep learningâbased image analysis. GAN DIOâNASH mice showed clear and reproducible progression in NASH, fibrosis stage, and tumor burden with high incidence of hepatocellular carcinoma. Consistent with clinical trial outcomes, semaglutide and lanifibranor improved NAS, whereas only lanifibranor induced regression in the fibrosis stage. Dietary intervention also demonstrated substantial benefits on metabolic outcomes and liver histology. Differential therapeutic efficacy of semaglutide, lanifibranor, and dietary intervention was supported by quantitative histology, RNA sequencing, and blood/liver biochemistry. In conclusion, the GAN DIOâNASH mouse model recapitulates various histological stages of NASH and faithfully reproduces histological efficacy profiles of compounds in advanced clinical development for NASH. Collectively, these features highlight the utility of GAN DIOâNASH mice in preclinical drug development
Human translatability of the GAN diet-induced obese mouse model of non-alcoholic steatohepatitis
Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats
A novel marker for assessment of liver matrix remodeling: An enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)
Measurement of matrix metalloproteinase 9-mediated Collagen type III degradation fragment as a marker of skin fibrosis
Extracellular matrix specific protein fingerprints measured in serum can separate pancreatic cancer patients from healthy controls
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