| 1. |
- Hyysalo, Jenni, et al.
(författare)
-
A population-based study on the prevalence of NASH using scores validated against liver histology.
- 2014
-
Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278. ; 60:4, s. 839-846
-
Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology.
|
|
| 2. |
- Kärjä, Vesa, et al.
(författare)
-
Does protein expression predict recurrence of benign World Health Organization grade I meningioma?
- 2010
-
Ingår i: Human Pathology. - : Elsevier BV. - 0046-8177 .- 1532-8392. ; 41:2, s. 199-207
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the predictive value of recurrence of protein expression in surgical samples of meningiomas. Thus, the expression of proteins that have been reported to be associated with prognosis of meningiomas was assessed in a sample of 59 World Health Organization grade I tumors obtained after Simpson grade I to III surgical resection (complete excision) and that were followed for 6 to 16 years. The expression was investigated applying immunohistochemical and tissue microarray techniques. One protein, the hepatocytic growth factor receptor, of 22 investigated proteins, showed significantly differing expression when comparing the 38 nonrecurrent with the 21 recurrent World Health Organization grade I meningiomas. It is noteworthy however that by means of logistic regression analyses, the independent predictive value of this protein expression was not significantly associated with the recurrence. Furthermore, it is noteworthy that the proliferation rate estimated by means of Ki67 expression did not show a significant difference, being 3.3 +/- 0.4 for the nonrecurrent meningioma and 3.9 +/- 0.5 for the recurrent and ranging from 0% to 10%. A significant and differing Spearman rank order of correlation was noted between 19 pairs of the investigated proteins when comparing nonrecurrent with recurrent World Health Organization grade I meningiomas. None of these correlations, however, showed a significant association by means of logistic regression analyses. Our results indicate that the Simpson grade significantly alters the outcome of a World Health Organization I grade meningioma and a longer follow-up period significantly increases the risk of recurrence. The expression of none of the proteins or correlation between protein expressions previously reported to be of significance regarding recurrence can be recommended as a diagnostic tool while assessing the risk of recurrence of World Health Organization grade I meningiomas.
|
|
| 3. |
- Libard, Sylwia, et al.
(författare)
-
Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:9, s. e108861-
-
Tidskriftsartikel (refereegranskat)abstract
- Human cytomegalovirus (HCMV) has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC) methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.
|
|
| 4. |
- Mancina, Rosellina Margherita, et al.
(författare)
-
PSD3 downregulation confers protection against fatty liver disease.
- 2022
-
Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:1, s. 60-75
-
Tidskriftsartikel (refereegranskat)abstract
- Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cells. Consistent with this, Psd3 downregulation by antisense oligonucleotides in vivo protects against FLD in mice fed a non-alcoholic steatohepatitis-inducing diet. Thus, translating these results to humans, PSD3 downregulation might be a future therapeutic option for treating FLD.
|
|
| 5. |
- Mancina, Rosellina Margherita, et al.
(författare)
-
The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent.
- 2016
-
Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 150:5, s. 1219-1230
-
Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage and is characterized by steatosis. Genetic factors increase risk for progressive NAFLD. A genome-wide association study showed that the rs641738 C>T variant in the locus that contains the membrane bound O-acyltransferase domain-containing 7 gene (MBOAT7, also called LPIAT1) and transmembrane channel-like 4 gene (TMC4) increased the risk for cirrhosis in alcohol abusers. We investigated whether the MBOAT7-TMC4 is a susceptibility locus for the development and progression of NAFLD.
|
|
| 6. |
- Pipitone, Rosaria M., et al.
(författare)
-
Programmed cell death 1 genetic variant and liver damage in nonalcoholic fatty liver disease
- 2023
-
Ingår i: Liver International. - 1478-3223 .- 1478-3231. ; 43:8, s. 1761-71
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Programmed cell death 1/programmed cell death-ligand 1 (PD-1/PDL-1) axis has been reported to modulate liver inflammation and progression to hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Here, we examined whether the PDCD1 variation is associated with NAFLD severity in individuals with liver biopsy. Methods: We examined the impact of PDCD1 gene variants on HCC, as robust severe liver disease phenotype in UK Biobank participants. The strongest genetic association with the rs13023138 G>C variation was subsequently tested for association with liver damage in 2889 individuals who underwent liver biopsy for suspected nonalcoholic steatohepatitis (NASH). Hepatic transcriptome was examined by RNA-Seq in a subset of NAFLD individuals (n = 121). Transcriptomic and deconvolution analyses were performed to identify biological pathways modulated by the risk allele. Results: The rs13023138 C>G showed the most robust association with HCC in UK Biobank (p = 5.28E-4, OR = 1.32, 95% CI [1.1, 1.5]). In the liver biopsy cohort, rs13023138 G allele was independently associated with severe steatosis (OR 1.17, 95% CI 1.02-1.34; p =.01), NASH (OR 1.22, 95% CI 1.09-1.37; p <.001) and advanced fibrosis (OR 1.26, 95% CI 1.06-1.50; p =.007). At deconvolution analysis, rs13023138 G>C allele was linked to higher hepatic representation of M1 macrophages, paralleled by upregulation of pathways related to inflammation and higher expression of CXCR6. Conclusions: The PDCD1 rs13023138 G allele was associated with HCC development in the general population and with liver disease severity in patients at high risk of NASH.
|
|
| 7. |
- Sasidharan, Kavitha, et al.
(författare)
-
IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids.
- 2024
-
Ingår i: Cell reports. Medicine. - 2666-3791. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- Steatotic liver disease (SLD) prevails as the most common chronic liver disease yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, the mechanistic link between IL-32 and intracellular triglyceride metabolism remains to be elucidated. We demonstrate invitro that incubation with IL-32β protein leads to an increase in intracellular triglyceride synthesis, while downregulation of IL32 by small interfering RNA leads to lower triglyceride synthesis and secretion in organoids from human primary hepatocytes. This reduction requires the upregulation of Phospholipase A2 group IIA (PLA2G2A). Furthermore, downregulation of IL32 results in lower intracellular type I collagen levels in di-lineage human primary hepatic organoids. Finally, we identify a genetic variant of IL32 (rs76580947) associated with lower circulating IL-32 and protection against SLD measured by non-invasive tests. These data suggest that IL32 downregulation may be beneficial against SLD.
|
|
