Interpersonal Violence in Five Regions in Asia: Ecological Risk Factors Associated with Perceptions of Justifiability of Violence.

In Asia, rates of interpersonal violence are increasing, with significant regional disparities. However, long-term, continental-scale research considering regional differences across the Asia regions is limited. Guided by the ecological model, we examined five ecological risk factors (low life satisfaction/happiness, economic hardship, neighborhood disadvantage, patriarchal values, and religiosity) associated with perceptions of justification of interpersonal violence (i.

An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD 'human proximity score' to define their metabolic relevance and ability to induce MASH-fibrosis.

Regulatory T-cell deficiency leads to features of autoimmune liver disease overlap syndrome in scurfy mice.

Introduction: Scurfy mice have a complete deficiency of functional regulatory T cells (Treg) due to a frameshift mutation in the gene. The impaired immune homeostasis results in a lethal lymphoproliferative disorder affecting multiple organs, including the liver. The autoimmune pathology in scurfy mice is in part accompanied by autoantibodies such as antinuclear antibodies (ANA).

Fibroblast Activation Protein Activates Macrophages and Promotes Parenchymal Liver Inflammation and Fibrosis.

Background & Aims: Fibroblast activation protein (FAP) is expressed on activated fibroblast. Its role in fibrosis and desmoplasia is controversial, and data on pharmacological FAP inhibition are lacking. We aimed to better define the role of FAP in liver fibrosis in vivo and in vitro.

Dual roles of B lymphocytes in mouse models of diet-induced nonalcoholic fatty liver disease.

Background And Aims: Growing evidence suggests an important role of B cells in the development of NAFLD. However, a detailed functional analysis of B cell subsets in NAFLD pathogenesis is lacking.

Approach And Results: In wild-type mice, 21 weeks of high fat diet (HFD) feeding resulted in NAFLD with massive macrovesicular steatosis, modest hepatic and adipose tissue inflammation, insulin resistance, and incipient fibrosis.

A structurally engineered fatty acid, icosabutate, suppresses liver inflammation and fibrosis in NASH.

Background & Aims: Although long-chain omega-3 fatty acids (LCn-3FAs) regulate inflammatory pathways of relevance to non-alcoholic steatohepatitis (NASH), their susceptibility to peroxidation may limit their therapeutic potential. We compared the metabolism of eicosapentaenoic acid (EPA) with an engineered EPA derivative (icosabutate) in human hepatocytes in vitro and their effects on hepatic glutathione metabolism, oxidised lipids, inflammation, and fibrosis in a dietary mouse model of NASH, and in patients prone to fatty liver disease.

Methods: Oxidation rates and cellular partitioning of EPA and icosabutate were compared in primary human hepatocytes.

Effects of urbanization on vulnerability to heat-related mortality in urban and rural areas in South Korea: a nationwide district-level time-series study.

Background: Although urbanization is often an important topic in climate change studies, the complex effect of urbanization on heat vulnerability in urban and rural areas has rarely been studied. We investigated the disparate effects of urbanization on heat vulnerability in urban and rural areas, using nationwide data.

Methods: We collected daily weather data for all 229 administrative districts in South Korea (2011-17).

Functional inhibition of Oct leads to HNF4α upregulation.

Organic cation transporters (human, OCT; mouse, Oct) are responsible for the intracellular uptake and detoxification of a broad spectrum of endogenous and exogenous substrates. The OCT1 gene SLC22A1 (human; mouse, Scl22a1) is transactivated by hepatocyte nuclear factor 4α (human, HNF4α; mouse, Hnf4α). HNF4α is a master regulator of hepatocyte differentiation and is frequently associated with hepatocellular carcinoma (HCC).

3D analysis of microvasculature in murine liver fibrosis models using synchrotron radiation-based microtomography.

Cirrhosis describes the development of excess fibrous tissue around regenerative nodules in response to chronic liver injury and usually leads to irreversible organ damage and end-stage liver disease. During the development of cirrhosis, the formation of collagenous scar tissue is paralleled by a reorganization and remodeling of the hepatic vascular system. To date, macrovascular remodeling in various cirrhosis models has been examined using three-dimensional (3D) imaging modalities, while microvascular changes have been studied mainly by two-dimensional (2D) light microscopic and electron microscopic imaging.

Social isolation and vulnerability to heatwave-related mortality in the urban elderly population: A time-series multi-community study in Korea.

Although several studies have reported that social isolation is one of the important health risk factors in the elderly population living in urban areas, its effects on vulnerability to heatwaves have been studied relatively less than climatic and other socio-economic factors. Thus, we investigated the association between social isolation levels and heatwave-related mortality risk in the elderly population in 119 urban administrative districts in Korea, using a time-series multi-city dataset (2008-2017). We used a two-stage analysis.

Huge Anterior Skull Base Defect Reconstruction on Communicating Between Cranium and Nasal Cavity: Combination Flap of Galeal Flap and Reverse Temporalis Flap.

Introduction: Traditionally, galeal flap or cranialization was often used to reconstruct the skull base defect caused by trauma or tumor removal. However, in the case of huge skull base defect, galeal flap is not enough to block the communication between nasal cavity and intracranial space. In this study, authors suggest combination flap of galea and reverse temporalis muscle as a method for reconstruction of huge skull base defect.

Dietary wheat amylase trypsin inhibitors promote features of murine non-alcoholic fatty liver disease.

We previously demonstrated that a common dietary protein component, wheat amylase trypsin inhibitors (ATI), stimulate intestinal macrophages and dendritic cells via toll like receptor 4. Activation of these intestinal myeloid cells elicits an inflammatory signal that is propagated to mesenteric lymph nodes, and that can facilitate extraintestinal inflammation. Mice were fed a well-defined high fat diet, with (HFD/ATI) or without (HFD) nutritionally irrelevant amounts of ATI.

Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices.

Fibrosis is the hallmark of pathologic tissue remodelling in most chronic diseases. Despite advances in our understanding of the mechanisms of fibrosis, it remains uncured. Fibrogenic processes share conserved core cellular and molecular pathways across organs.

PI3K inhibition reduces murine and human liver fibrogenesis in precision-cut liver slices.

Background: Liver fibrosis results from continuous inflammation and injury. Despite its high prevalence worldwide, no approved antifibrotic therapies exist. Omipalisib is a selective inhibitor of the PI3K/mTOR pathway that controls nutrient metabolism, growth and proliferation.

Deletion of organic cation transporter Oct3 promotes hepatic fibrosis via upregulation of TGFβ.

Organic cation transporters (OCT) are responsible for the intracellular uptake and detoxification of a broad spectrum of endogenous and exogenous substrates. OCTs are downregulated in cholestasis, fibrosis, and hepatocellular carcinoma, but the underlying molecular mechanisms and downstream effects of OCT deletion are unknown. Oct3-knockout (; ) and wild-type (WT; ) mice were subject to escalating doses of carbon tetrachloride (CCl) or thioacetamide (TAA) for 6 wk to induce advanced parenchymal liver fibrosis.

Liver fibrosis: Direct antifibrotic agents and targeted therapies.

Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C.

Niemann-Pick type C2 protein supplementation in experimental non-alcoholic fatty liver disease.

Background And Aims: Hepatic cholesterol deposition drives inflammation and fibrosis in non-alcoholic steatohepatitis (NASH). The Niemann-Pick type C2 (NPC2) protein plays an important role in regulating intracellular cholesterol trafficking and homeostasis. We hypothesized that intravenous NPC2 supplementation reduces cholesterol accumulation, hepatic inflammation and fibrogenesis in a nutritional NASH rat model.

IL-4 Receptor Alpha Signaling through Macrophages Differentially Regulates Liver Fibrosis Progression and Reversal.

Unlabelled: Chronic hepatitis leads to liver fibrosis and cirrhosis. Cirrhosis is a major cause of worldwide morbidity and mortality. Macrophages play a key role in fibrosis progression and reversal.

Loss of organic cation transporter 3 (Oct3) leads to enhanced proliferation and hepatocarcinogenesis.

Background: Organic cation transporters (OCT) are responsible for the uptake of a broad spectrum of endogenous and exogenous substrates. Downregulation of OCT is frequently observed in human hepatocellular carcinoma (HCC) and is associated with a poor outcome. The aim of our current study was to elucidate the impact of OCT3 on hepatocarcinogenesis.

Gliptins Suppress Inflammatory Macrophage Activation to Mitigate Inflammation, Fibrosis, Oxidative Stress, and Vascular Dysfunction in Models of Nonalcoholic Steatohepatitis and Liver Fibrosis.

Aims: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis, and increased cardiovascular mortality. Dipeptidyl peptidase-4 inhibitors (gliptins) are indirect glucagon-like peptide 1 agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored.

Effects of nintedanib on the microvascular architecture in a lung fibrosis model.

Nintedanib, a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis, has anti-fibrotic, anti-inflammatory, and anti-angiogenic activity. We explored the impact of nintedanib on microvascular architecture in a pulmonary fibrosis model. Lung fibrosis was induced in C57Bl/6 mice by intratracheal bleomycin (0.

Optimized Mouse Models for Liver Fibrosis.

Fibrosis is the excessive accumulation of extracellular matrix components due to chronic injury, with collagens as predominant structural components. Liver fibrosis can progress to cirrhosis, which is characterized by a severe distortion of the delicate hepatic vascular architecture, the shunting of the blood supply away from hepatocytes and the resultant functional liver failure. Cirrhosis is associated with a highly increased morbidity and mortality and represents the major hard endpoint in clinical studies of chronic liver diseases.

Hepatic B cell leukemia-3 promotes hepatic steatosis and inflammation through insulin-sensitive metabolic transcription factors.

Background & Aims: The pathomechanisms underlying non-alcoholic fatty liver disease (NAFLD) and the involved molecular regulators are incompletely explored. The nuclear factor-kappa B (NF-κB)-cofactor gene B cell leukemia-3 (Bcl-3) plays a critical role in altering the transcriptional capacity of NF-κB - a key inducer of inflammation - but also of genes involved in cellular energy metabolism.

Methods: To define the role of Bcl-3 in non-alcoholic steatohepatitis (NASH), we developed a novel transgenic mouse model with hepatocyte-specific overexpression of Bcl-3 (Bcl-3) and employed a high-fat, high-carbohydrate dietary feeding model.