Down-regulation of complement genes in lipopolysaccharide-challenged zebrafish (Danio rerio) larvae exposed to Indonesian propolis

Although propolis has been reported for having anti-inflammatory activities, its effects on complement system has not been much studied. This research was conducted to find out the effects of Indonesian propolis on the expression levels of C3, C1r/s, Bf, MBL, and C6 in zebrafish larvae which were induced by lipopolysaccharide (LPS). Counting of macrophages migrating to yolk sac and liver histology were carried out. Larvae were divided into four groups: CON (cultured in E3 medium only), LPS (cultured in a medium containing 0.5 μg/L LPS), LPSIBU (cultured in a medium containing LPS, and then treated with 100 μg/L ibuprofen for 24 hours), and LPSPRO (cultured in a medium containing LPS, and then immersed in 14,000 μg/L propolis for 24 hours) groups. The results showed that complement gene expression in larvae from the LPSIBU and LPSPRO groups were generally lower than in larvae from the LPS group. The number of macrophage migrations to the yolk in the LPSPRO group was also lower than in the LPS group. Histological structure of liver in all groups were considered normal. This study shows that Indonesian propolis has the potential to be used as an alternative to the substitution of NSAIDs.

The association between serum albumin and depression in chronic liver disease may differ by liver histology

Background There are conflicting results regarding the association between chronic liver disease (CLD) and depression and the underlying biological mechanisms are lack of investigation. To address the impact of depression and its effects on the management of CLD, its biological marker is critical to be identified. The present study explored the association between serum albumin and depression in CLD patients and whether the association varied in different liver histological stages. Methods Based on the United States National Health and Nutrition Examination Survey 2017–2018, the data of serum albumin and depressive symptoms from 627 participants with CLD were used. Depression symptoms were assessed with the nine-item Patient Health Questionnaire (PHQ-9). We used multivariate linear regression to evaluate the association between serum albumin and PHQ-9 scores. Stratified analysis was performed according to the liver histology examined by vibration controlled transient elastography. Results Serum albumin level was inversely associated with PHQ-9 scores in the multivariate regression model after adjusting for mainly potential confounders (β = − 1.113, 95% CI: − 2.065 to − 0.162, P = 0.0221). In the subgroup analysis stratified by gender, controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), the inverse association remained significant in female (β = − 2.002, 95% CI: − 3.515 to − 0.489, P = 0.0100), patients with CAP < 274 dB/m (β = − 2.215, 95% CI: − 3.621 to − 0.808, P = 0.0023) and patients with LSM ≥8.2 kPa (β = − 4.074, 95% CI: − 6.237 to − 1.911, P = 0.0003). Moreover, the association was much stronger when the serum albumin was higher than 3.4 g/dL among patients with LSM ≥8.2 kPa (β = − 4.835, 95% CI: − 7.137 to − 2.533, P < 0.0001). Conclusion Our study revealed an inverse association between serum albumin and depression in CLD patients and this association differed according to liver histological changes. Serum albumin could be a warning marker for depressive symptoms in CLD patients. It is essential for taking corresponding intervention strategies.

Liver Histology in Short Telomere Syndrome: A Case Report and Review of the Literature

Short telomere syndrome (STS) encompasses a broad family of genetically inherited conditions caused by various mutations in telomerase and other telomere maintenance genes, resulting in premature telomere shortening. STS involves a variety of clinical manifestations, including dyskeratosis congenita, premature achromotrichia, bone marrow failure, immunodeficiency, pulmonary fibrosis and liver disease. Liver histopathologic features in STS patients have not been well characterized. We report a 46-year-old male patient who presented for dyspnea. The patient had a complicated medical history significant for immune thrombocytopenic purpura and splenectomy, recurrent respiratory tract infections, pneumonia, primary immunodeficiency, and severe hepatopulmonary syndrome. He and his brother both developed gray hair by their late 20s. He had a long history of intermittently elevated liver enzymes starting at age 33. These clinical manifestations prompted an evaluation for a possible telomere biology disorder, which revealed the telomere length was critically short and fell at or below the first percentile for age, supporting the diagnosis. The liver biopsy showed marked portal inflammation with interface hepatitis, ductular reaction and frequent foci of lobular inflammation with focal hepatocyte dropout. Hepatocytes around the portal tracts demonstrated ballooning degeneration and occasional Mallory-Denk bodies. A trichrome stain highlighted bridging fibrosis. A literature review shows liver histology is available in only a small number of STS patients, demonstrating a variety of morphologic features. Our case and others suggest liver disease associated with STS exhibits a spectrum of histopathology. Being aware of these features is important for establishing the correct diagnosis of STS which is under recognized.

Correlation between HDL2, HDL3 and serum ferritin levels with fatty liver and NAFLD activity score (NAS) in liver histology of organ donors

Background Nonalcoholic fatty liver disease (NAFLD) is one of the most important liver diseases. High-density lipoprotein (HDL) has anti-atherogenic properties and its reduction can be associated with fatty liver. Serum ferritin levels are usually elevated in patients with NAFLD. This study aimed to evaluate the correlation between HDL subtypes and serum ferritin levels with evidence of NAFLD in liver histology of organ donors. Methods One hundred organ donor patients who were eligible for the study were included in the study and ferritin; HDL2 and HDL3 were measured in blood samples. Donated liver tissue biopsy specimens were evaluated for fatty liver and NAFLD activity score (NAS). In addition, AST and ALT were measured in recipients 24 h after transplant. All data abstracted and analyzed statistically. Results Serum HDL2 levels and HDL2/HDL3 ratio in patients with NAS > 1 were significantly lower (P < 0.05). Serum levels of HDL3 and ferritin were not significantly associated with NAS >1 (P > 0.05). In addition, serum ferritin > 1000 ng/ml in organ donors associated with increased AST and ALT levels 24 h after transplantation in the liver organ recipient. Conclusions Lower HDL2 values and HDL2/HDL3 ratio were associated with increased NAFLD activity score, but HDL3 and ferritin did not show such a relationship. In addition, higher levels of ferritin in organ donors may be associated with increased AST and ALT 24 h after liver transplantation in the organ recipient.

Indole-3-Propionic Acid, a Gut-Derived Tryptophan Metabolite, Associates with Hepatic Fibrosis

Background and Aims: Gut microbiota-derived metabolites play a vital role in maintenance of human health and progression of disorders, including obesity and type 2 diabetes (T2D). Indole-3-propionic acid (IPA), a gut-derived tryptophan metabolite, has been recently shown to be lower in individuals with obesity and T2D. IPA’s beneficial effect on liver health has been also explored in rodent and cell models. In this study, we investigated the association of IPA with human liver histology and transcriptomics, and the potential of IPA to reduce hepatic stellate cell activation in vitro. Methods: A total of 233 subjects (72% women; age 48.3 ± 9.3 years; BMI 43.1 ± 5.4 kg/m2) undergoing bariatric surgery with detailed liver histology were included. Circulating IPA levels were measured using LC-MS and liver transcriptomics with total RNA-sequencing. LX-2 cells were used to study hepatoprotective effect of IPA in cells activated by TGF-β1. Results: Circulating IPA levels were found to be lower in individuals with liver fibrosis compared to those without fibrosis (p = 0.039 for all participants; p = 0.013 for 153 individuals without T2D). Accordingly, levels of circulating IPA associated with expression of 278 liver transcripts (p < 0.01) that were enriched for the genes regulating hepatic stellate cells (HSCs) activation and hepatic fibrosis signaling. Our results suggest that IPA may have hepatoprotective potential because it is able to reduce cell adhesion, cell migration and mRNA gene expression of classical markers of HSCs activation in LX-2 cells (all p < 0.05). Conclusion: The association of circulating IPA with liver fibrosis and the ability of IPA to reduce activation of LX-2 cells suggests that IPA may have a therapeutic potential. Further molecular studies are needed to investigate the mechanisms how IPA can ameliorate hepatic fibrosis.

Liver histology in short telomere syndrome: A case report and review of the literature

Introduction/Objective Short telomere syndrome (STS) is a genetically inherited syndrome resulting in premature telomere shortening. STS encompasses a spectrum of clinical manifestations, including dyskeratosis congenita, premature hair graying, bone marrow failure, immunodeficiency, pulmonary fibrosis and liver disease. Liver histopathologic features in STS patients have not been well characterized. Methods/Case Report A 46-year-old man presented for dyspnea and cryptogenic cirrhosis. He had a complicated medical history significant for immune thrombocytopenic purpura and splenectomy, recurrent respiratory tract infections, pneumonia, sepsis, primary immunodeficiency, pulmonary mucosa-associated lymphoid tissue lymphoma, and severe hepatopulmonary syndrome. He and his brother had gray hair in their late 20s. He also had a long history of intermittently elevated liver enzymes starting at age 33. A liver biopsy performed 12 years before showed chronic portal inflammation with hepatocellular damage without significant fibrosis. These clinical manifestations prompted an evaluation for a possible telomere biology disorder, which revealed the telomere length was critically short and fell at or below the first percentile for age, supportive of the diagnosis. The most recent liver biopsy showed marked portal lymphocytic inflammation with interface hepatitis, bile ductular reaction and frequent foci of lobular inflammation with focal hepatocyte dropout. Some hepatocytes around the portal tracts were swollen with feathery degeneration and occasional Mallory-Denk bodies. A Rhodanine stain highlighted copper granules in the periportal hepatocytes, suggesting chronic cholestasis. Trichrome and reticulin stains demonstrated portal/periportal/pericellular/perisinusoidal fibrosis and focal bridging fibrosis. Results (if a Case Study enter NA) NA Conclusion Partly due to the rarity of STS and the risk of bleeding associated with biopsies, liver histology was described in only few limited studies with small samples of STS patients, including inflammation, nodular regenerative hyperplasia, steatohepatitis, hemosiderosis, cholestasis, cirrhosis, and large cell change of hepatocytes. Our case and others suggest liver disease associated with STS demonstrates a spectrum of histopathology. Being aware of these histomorphologic features in STS is important for establishing the correct diagnosis.

Effect of Streptozotocin on Liver Histology Damage in Rats Model of Gestational Diabetes Mellitus

Background: Gestational Diabetes Mellitus (GDM) is a disorder of carbohydrate metabolism that causes hyperglycemia, insulin resistance and failure of organs especially the liver. There is great interest in understanding the pathophysiology and treatment of GDM. Due to ethical issues involving human studies, it is necessary to use animal models to understand pathophysiology and potential treatment for GDM. Streptozotocin-induced diabetes mellitus in pregnant rats was commonly used by several author. Aims: The aim of this study is to investigate the effect of streptozotocin (STZ) on liver histology in pregnant rats. Methods: Pregnant rats were divided into two groups; 1) Negative control, 2) Positive control. Positive control were pregnant rats induced with a single intraperitoneal injection of streptozotocin 40 mg/Kg b.w. Fourteen days after induction, rats were sacrificed to evaluate the histopathological effect of STZ on the liver using hematoxylin Eosin staining and calculate the presentation of degraded cell and sinusoidal area with ImageJ 1.49v software, National Institute of Health, Bethesda, MD, USA. Data were processed statistically using SPSS with T-Test. Results: Microscopic examination of the liver of STZ-induced rats showed histologic changes in the form of an increase in the number of degenerated cells and a significant expansion of the sinusoidal area (p < 0.000). The percentage of degenerated cells in the healthy group was 9.3%, increased to 70% in the STZ-induced group. In addition, the percentage of the sinusoidal area, which was 19.98% in the healthy group, increased to 49.5%. Conclusions: Streptozotocin induces liver damage in the pregnant rats model. Keywords: Gestational Diabetes Mellitus, Streptozotocin, Liver, Histology