Pemafibrate Ameliorates Steatotic Liver Disease Regardless of Endothelial Dysfunction in Mice.

Endothelial dysfunction contributes to the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD). Pemafibrate has been shown to ameliorate MASLD in basic and clinical studies, but it is unclear whether it is also effective in the status of endothelial dysfunction. An MASLD animal model was induced in male wild-type (WT) and endothelial nitric oxide synthase (eNOS)-deficient (eNOSKO) mice by feeding them a high-fat/cholesterol/cholate diet, and they were administered either a vehicle or pemafibrate at 0.

Critical Role of Cholic Acid in the Development of iHFC Diet-induced MASH in TSNO Mice.

A high-fat/cholesterol/cholate-based (iHFC) diet induces pathological changes in Tsumura-Suzuki non-obese (TSNO) mice, resembling human metabolic dysfunction associated steatohepatitis (MASH), along with advanced liver fibrosis. In this study, we investigated the role of cholic acid (CA) in the development of iHFC diet-induced MASH development. In mice receiving an iHFC diet without CA (CA(-) iHFC diet), both lobular inflammation and fibrosis progression in the liver were attenuated compared to those on the standard iHFC diet.

Analysis of 69 Hepatocellular Carcinoma Cases from the National Center for Pathology in Mongolia : A Comprehensive Study of Samples Collected Nationwide.

The high rate of chronic hepatitis, including hepatitis B, C and D, in Mongolia creates a large health burden of advanced liver disease. This includes liver failure and the highest incidence rate of hepatocellular carcinoma (HCC) worldwide. In the present study, we histopathologically examined 69 recent cases of HCC from the Mongolian National Center for Pathology, which collects specimens from across the country.

Mechanistic Study of the Deuterium Effect in Chromatographic Separation for Chemical-Tagging Metabolomics and Its Application to Biomarker Discovery in Metabolic Dysfunction-Associated Steatohepatitis.

Over the past decade, numerous metabolomics techniques have been developed using liquid chromatography-mass spectrometry (LC-MS). These methodologies have yielded significant findings and facilitated the identification of biomarkers. Among these, chemical-tagging methodologies combined with isotope surrogate tags have garnered considerable attention as a leading approach.

Histopathological Features of Hepatocellular Carcinoma in Patients with Hepatitis B and D Virus Infection: A Single-Institution Study in Mongolia.

: Viral hepatitis, particularly hepatitis B (HBV) and hepatitis C (HCV), is highly prevalent in Mongolia. Moreover, Mongolia has the highest prevalence of hepatitis delta virus (HDV) globally, with over 60% of HBV-infected individuals also co-infected with HDV. Since HBV/HDV infections accelerate liver disease progression more compared to HBV infection alone, urgent national health measures are required.

Indigo Leaves-Induced Pulmonary Arterial Remodeling without Right Ventricular Hypertrophy in Rats.

Indigo naturalis (IN), derived from the leaves of the indigo plant, is a traditional Chinese medicine that has historically been used for its anti-inflammatory properties in the treatment of various diseases, including ulcerative colitis (UC). However, long-term use of IN in UC patients is incontrovertibly associated with the onset of pulmonary arterial hypertension (PAH). To investigate the mechanisms by which IN induces PAH, we focused on the raw material of IN, indigo leaves (IL).

Antibiotic effects on gut microbiota modulate diet-induced metabolic dysfunction-associated steatohepatitis development in C57BL/6 mice.

The potential involvement of the gut microbiota in metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis has garnered increasing attention. In this study, we elucidated the link between high-fat/cholesterol/cholate-based (iHFC)#2 diet-induced MASH progression and gut microbiota in C57BL/6 mice using antibiotic treatments. Treatment with vancomycin (VCM), which targets gram-positive bacteria, exacerbated the progression of liver damage, steatosis, and fibrosis in iHFC#2-fed C57BL/6 mice.

Emerging Insights into the Role of BDNF on Health and Disease in Periphery.

Brain-derived neurotrophic factor (BDNF) is a growth factor that promotes the survival and growth of developing neurons. It also enhances circuit formation to synaptic transmission for mature neurons in the brain. However, reduced BDNF expression and single nucleotide polymorphisms (SNP) are reported to be associated with functional deficit and disease development in the brain, suggesting that BDNF is a crucial molecule for brain health.

Impacts of liver macrophages, gut microbiota, and bile acid metabolism on the differences in iHFC diet-induced MASH progression between TSNO and TSOD mice.

Background: Tsumura-Suzuki non-obese (TSNO) mice exhibit a severe form of metabolic dysfunction-associated steatohepatitis (MASH) with advanced liver fibrosis upon feeding a high-fat/cholesterol/cholate-based (iHFC) diet. Another ddY strain, Tsumura-Suzuki diabetes obese (TSOD) mice, are impaired in the progression of iHFC diet-induced MASH.

Aim: To elucidate the underlying mechanisms contributing to the differences in MASH progression between TSNO and TSOD mice.

The Effects of Overnight Fasting Duration on Glucose and Lipid Metabolism in a Sprague-Dawley Rat Model of Nonalcoholic Steatohepatitis with Advanced Fibrosis.

Nonalcoholic steatohepatitis (NASH) can progress to hepatic fibrosis, and is associated with cardiovascular and liver-related mortality. To understand the pathogenesis of NASH, reliable animal models of the disease are useful. In animal studies, the animals are usually fasted overnight before biospecimens are taken, but little is known about the effects of fasting.

Brain-derived neurotrophic factor knock-out mice develop non-alcoholic steatohepatitis.

While brain-derived neurotrophic factor (BDNF), which is a growth factor associated with cognitive improvement and the alleviation of depression symptoms, is known to regulate food intake and body weight, the role of BDNF in peripheral disease is not fully understood. Here, we show that reduced BDNF expression is associated with weight gain and the chronic liver disease non-alcoholic steatohepatitis (NASH). At 10 months of age, BDNF-heterozygous (BDNF ) mice developed symptoms of NASH: centrilobular/perivenular steatosis, lobular inflammation with infiltration of neutrophils, ballooning hepatocytes, and fibrosis of the liver.

Establishment of repeated liver biopsy technique in experimental mice.

Biopsy is a commonly used method for determining pathological diagnoses by directly using human tissues and cells. Biopsies are widely used to determine disease progression and treatment efficacy. Although organs and tissues are usually obtained by sacrifice during animal experiments, it is theoretically possible to use the same biopsy techniques in humans.

Definitive Confirmation of Erythropoietic Protoporphyria via Re-biopsy Three Years After Initial Liver Biopsy at Age 15.

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of porphyrin metabolism that can cause liver damage and cholestatic hepatocellular failure. We report a case of EPP in a teenaged male who underwent liver biopsy for investigation of liver dysfunction of unknown cause. The diagnosis was not made until a re-biopsy approximately three years later, when the patient presented with recurrent skin lesions and elevated blood and urinary protoporphyrin levels.

Accumulation of α-synuclein in hepatocytes in nonalcoholic steatohepatitis and its usefulness in pathological diagnosis.

Backgrounds: Nonalcoholic steatohepatitis (NASH) is characterized by fat deposition, inflammation, and hepatocellular damage. The diagnosis of NASH is confirmed pathologically, and hepatocyte ballooning is an important finding for definite diagnosis. Recently, α-synuclein deposition in multiple organs was reported in Parkinson's disease.

Histological and immunohistochemical analysis of epithelial cells in epidermoid cysts in intrapancreatic accessory spleen.

Background: Epidermoid cysts in intrapancreatic accessory spleen (ECIPAS) are a rare lesion. Its pathogenesis, including the origin of cystic epithelium, is not well established. We aimed to elucidate new aspects of the pathological features of ECIPAS to clarify its pathogenesis.

The innate immune receptor RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function.

Radioprotective 105 (RP105) plays a key role in the development of high-fat diet (HFD)-induced metabolic disorders; however, the underlying mechanisms remain to be understood. Here, we aimed to uncover whether RP105 affects metabolic syndrome through the modification of gut microbiota. We confirmed that body weight gain and fat accumulation by HFD feeding were suppressed in Rp105 mice.

Breach of tolerance versus burden of bile acids: Resolving the conundrum in the immunopathogenesis and natural history of primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a classic autoimmune disease due to the loss of tolerance to self-antigens. Bile acids (BA) reportedly play a major role in biliary inflammation and/or in the modulation of dysregulated immune responses in PBC. Several murine models have indicated that molecular mimicry plays a role in autoimmune cholangitis; however, they have all been limited by the relative failure to develop hepatic fibrosis.

AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma.

Despite the clear distinction between cortical (cTECs) and medullary thymic epithelial cells (mTECs) in physiology, the cell of origin of thymic carcinomas (TCs) and other thymic epithelial tumors remained enigmatic. We addressed this issue by focusing on AIRE, an mTEC-specific transcriptional regulator that is required for immunological self-tolerance. We found that a large proportion of TCs expressed AIRE with typical nuclear dot morphology by immunohistochemistry.

Impact of Vancomycin Treatment and Gut Microbiota on Bile Acid Metabolism and the Development of Non-Alcoholic Steatohepatitis in Mice.

The potential roles of the gut microbiota in the pathogenesis of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH), have attracted increased interest. We have investigated the links between gut microbiota and NASH development in Tsumura-Suzuki non-obese mice fed a high-fat/cholesterol/cholate-based (iHFC) diet that exhibit advanced liver fibrosis using antibiotic treatments. The administration of vancomycin, which targets Gram-positive organisms, exacerbated the progression of liver damage, steatohepatitis, and fibrosis in iHFC-fed mice, but not in mice fed a normal diet.

Roles of Macrophages in Advanced Liver Fibrosis, Identified Using a Newly Established Mouse Model of Diet-Induced Non-Alcoholic Steatohepatitis.

Macrophages play critical roles in the pathogenesis of non-alcoholic steatohepatitis (NASH). However, it is unclear which macrophage subsets are critically involved in the development of inflammation and fibrosis in NASH. In TSNO mice fed a high-fat/cholesterol/cholate-based diet, which exhibit advanced liver fibrosis that mimics human NASH, we found that Kupffer cells (KCs) were less abundant and recruited macrophages were more abundant, forming hepatic crown-like structures (hCLS) in the liver.

Influence of Fasting Time on Serum and Hepatic Lipid Profiles in a Sprague-Dawley Rat Model of Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is associated with several cardiovascular risk factors, including atherogenic dyslipidemia. Recently, fasting prior to lipid profile evaluation has been thought to be unnecessary for most individuals. We investigated the impact of fasting for up to 9 h on the serum and hepatic lipid profiles in Sprague-Dawley (SD) rats of dietary-induced NASH model in comparison to SD rats fed a normal diet.