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The Kurume Medical Journal May 2024Ultrasonography is a noninvasive and widely accessible modality in clinical practice. Recently, ultrasonography has been used to evaluate tissue stiffness; the two...
Ultrasonography is a noninvasive and widely accessible modality in clinical practice. Recently, ultrasonography has been used to evaluate tissue stiffness; the two representative techniques are transient elastography (FibroScan) and shear wave elastography. These modalities are now generally used for the assessment of liver fibrosis, the prediction of hepatocarcinogenesis, and determining prognosis. In addition, shear wave elastography is available, not only for the liver but also for various other organs, including the breast and brain. In the breast and brain, shear wave elastography distinguishes malignant lesions from benign ones. Moreover, shear wave elastography can be useful for differentiating between ischemic and hemorrhagic strokes. This review summarizes the recent progress in transient elastography and shear wave elastography of the liver and introduces the advantages of ultrasonographic assessment of tissue stiffness in various organs, including the breast, brain, kidney, heart, thyroid, pancreas, muscle, and bone.
PubMed: 38763738
DOI: 10.2739/kurumemedj.MS7012010 -
Scientific Reports May 2024Non-alcoholic steatohepatitis (NASH), caused by fat buildup, can lead to liver inflammation and damage. Elucidation of the spatial distribution of fibrotic tissue in the...
Non-alcoholic steatohepatitis (NASH), caused by fat buildup, can lead to liver inflammation and damage. Elucidation of the spatial distribution of fibrotic tissue in the fatty liver in NASH can be immensely useful to understand its pathogenesis. Thus, we developed a novel serial section-3D (SS3D) technique that combines high-resolution image acquisition with 3D construction software, which enabled highly detailed analysis of the mouse liver and extraction and quantification of stained tissues. Moreover, we studied the underexplored mechanism of fibrosis progression in the fatty liver in NASH by subjecting the mice to a high-fat diet (HFD), followed by lipopolysaccharide (LPS) administration. The HFD/LPS (+) group showed extensive fibrosis compared with control; additionally, the area of these fibrotic regions in the HFD/LPS (+) group was almost double that of control using our SS3D technique. LPS administration led to an increase in Tnfα and Il1β mRNA expression and the number of macrophages in the liver. On the other hand, transforming growth factor-β1 (Tgfβ1) mRNA increased in HFD group compared to that of control group without LPS-administration. In addition, COL1A1 levels increased in hepatic stellate cell (HSC)-like XL-2 cells when treated with recombinant TGF-β1, which attenuated with recombinant latency-associated protein (rLAP). This attenuation was rescued with LPS-activated macrophages. Therefore, we demonstrated that fatty liver produced "latent-form" of TGF-β1, which activated by macrophages via inflammatory cytokines such as TNFα and IL1β, resulting in activation of HSCs leading to the production of COL1A1. Moreover, we established the effectiveness of our SS3D technique in creating 3D images of fibrotic tissue, which can be used to study other diseases as well.
Topics: Animals; Lipopolysaccharides; Transforming Growth Factor beta1; Mice; Macrophages; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Diet, High-Fat; Male; Liver; Mice, Inbred C57BL; Macrophage Activation; Imaging, Three-Dimensional; Disease Models, Animal; Hepatic Stellate Cells; Interleukin-1beta
PubMed: 38762616
DOI: 10.1038/s41598-024-60845-6 -
Ultrasound in Medicine & Biology May 2024The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the... (Review)
Review
The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.
PubMed: 38762390
DOI: 10.1016/j.ultrasmedbio.2024.03.013 -
The Journal of Biological Chemistry May 2024Liver fibrosis/cirrhosis is a pathological state caused by excessive extracellular matrix deposition. Sustained activation of hepatic stellate cells (HSC) is the...
Liver fibrosis/cirrhosis is a pathological state caused by excessive extracellular matrix deposition. Sustained activation of hepatic stellate cells (HSC) is the predominant cause of liver fibrosis, but the detailed mechanism is far from clear. In this study, we found that long noncoding RNA Fendrr is exclusively increased in hepatocytes in the murine model of CCl- and bile duct ligation-induced liver fibrosis, as well as in the biopsies of liver cirrhosis patients. In vivo, ectopic expression of Fendrr aggravated the severity of CCl-induced liver fibrosis in mice. In contrast, inhibiting Fendrr blockaded the activation of HSC and ameliorated CCl-induced liver fibrosis. Our mechanistic study showed that Fendrr binds to STAT2 and enhances its enrichment in the nucleus, which then promote the expression of IL-6, and, ultimately, activates HSC in a paracrine manner. Accordingly, disrupting the interaction between Fendrr and STAT2 by ectopic expression of a STAT2 mutant attenuated the pro-fibrotic response inspired by Fendrr in the CCl-induced liver fibrosis. Notably, the increase of Fendrr in patient fibrotic liver is positively correlated with the severity of fibrosis and the expression of IL-6. Meanwhile, hepatic IL-6 positively correlates with the extent of liver fibrosis and HSC activation as well, thus suggesting a causative role of Fendrr in HSC activation and liver fibrosis. In conclusion, these observations identify an important regulatory crosstalk between hepatocyte Fendrr and HSC activation in the progression of liver fibrosis, which might represent a potential strategy for therapeutic intervention.
PubMed: 38762176
DOI: 10.1016/j.jbc.2024.107376 -
Journal of Lipid Research May 2024Metabolic programming underpins inflammatory processes of immune cells. In the context of chronic liver disease, liver macrophage activation and response to...
Metabolic programming underpins inflammatory processes of immune cells. In the context of chronic liver disease, liver macrophage activation and response to hepatocellular damage is dependent on profound metabolic changes. Here, we sought to identify the role of an important metabolic regulator, AMP-activated protein kinase (AMPK), specifically within myeloid cells during the progression of non-alcoholic steatohepatitis (NASH) and whether treatment with metformin, a first line therapy for diabetes and activator of AMPK could stem disease progression. Male and female Prkaa1/Prkaa2 (Flox) control and Flox-LysM-Cre (MacKO) mice were fed a low-fat control or a choline-deficient, amino acid defined 45% Kcal high fat diet (CDAHFD) for 8 weeks, where metformin was introduced in the drinking water (50 or 250 mg/kg/day) for the last 4 weeks. Hepatic steatosis and fibrosis were dramatically increased in response to CDAHFD-feeding compared to low-fat control. While myeloid AMPK signaling had no effect on markers of hepatic steatosis or circulating markers, fibrosis as measured by total liver collagen was significantly elevated in livers from MacKO mice, independent of sex. Although treatment with 50 mg/kg/day metformin had no effect on any parameter, intervention with 250 mg/kg/day metformin completely ameliorated hepatic steatosis and fibrosis in both male and female mice. While the protective effect of metformin was associated with lower final body weight, decrease expression of lipogenic and Col1a1 transcripts, it was independent of myeloid AMPK signaling. These results suggest that endogenous AMPK signaling in myeloid cells, both liver-resident and infiltrating, acts to restrict fibrogenesis during CDAHFD-induced NASH progression but is not the mechanism by which metformin improves markers of NASH.
PubMed: 38762124
DOI: 10.1016/j.jlr.2024.100564 -
Environment International May 2024Microplastic (MP) pollution has become a global environmental issue, and increasing concern has been raised about its impact on human health. Current studies on the... (Review)
Review
Microplastic (MP) pollution has become a global environmental issue, and increasing concern has been raised about its impact on human health. Current studies on the toxic effects and mechanisms of MPs have mostly been conducted in animal models or in vitro cell cultures, which have limitations regarding inter-species differences or stimulation of cellular functions. Organoid technology derived from human pluripotent or adult stem cells has broader prospects for predicting the potential health risks of MPs to humans. Herein, we reviewed the current application advancements and opportunities for different organoids, including brain, retinal, intestinal, liver, and lung organoids, to assess the human health risks of MPs. Organoid techniques accurately simulate the complex processes of MPs and reflect phenotypes related to diseases caused by MPs such as liver fibrosis, neurodegeneration, impaired intestinal barrier and cardiac hypertrophy. Future perspectives were also proposed for technological innovation in human risk assessment of MPs using organoids, including extending the lifespan of organoids to assess the chronic toxicity of MPs, and reconstructing multi-organ interactions to explore their potential in studying the microbiome-gut-brainaxis effect of MPs.
PubMed: 38761429
DOI: 10.1016/j.envint.2024.108744 -
Biomedicine & Pharmacotherapy =... May 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent liver diseases worldwide, and its occurrence is strongly associated... (Review)
Review
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent liver diseases worldwide, and its occurrence is strongly associated with obesity, insulin resistance (IR), genetics, and metabolic stress. Ranging from simple fatty liver to metabolic dysfunction-associated steatohepatitis (MASH), even to severe complications such as liver fibrosis and advanced cirrhosis or hepatocellular carcinoma, the underlying mechanisms of MASLD progression are complex and involve multiple cellular mediators and related signaling pathways. Pattern recognition receptors (PRRs) from the innate immune system, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs), and DNA receptors, have been demonstrated to potentially contribute to the pathogenesis for MASLD. Their signaling pathways can induce inflammation, mediate oxidative stress, and affect the gut microbiota balance, ultimately resulting in hepatic steatosis, inflammatory injury and fibrosis. Here we review the available literature regarding the involvement of PRR-associated signals in the pathogenic and clinical features of MASLD, in vitro and in animal models of MASLD. We also discuss the emerging targets from PRRs for drug developments that involved agent therapies intended to arrest or reverse disease progression, thus enabling the refinement of therapeutic targets that can accelerate drug development.
PubMed: 38761424
DOI: 10.1016/j.biopha.2024.116724 -
Clinical Gastroenterology and... May 2024The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide...
BACKGROUND AND AIMS
The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs.
METHODS
This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at seven medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality.
RESULTS
A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% versus 13.6%, P=0.005) and OHE (31.0% versus 39.4%, P=0.02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% versus 9.7%, P=0.42). In patients with GOV2 and IGV1, TIPS+E reduced both rebleeding (GOV2: 7.8% versus 25.1%, P=0.01; IGV1: 5.6% versus 30.8%, P=0.03) and OHE (GOV2: 31.8% versus 51.5%, P=0.008; IGV1: 11.6% versus 38.5%, P=0.04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% versus 8.7%, P=0.37) or OHE (33.1% versus 35.3%, P=0.60).
CONCLUSIONS
Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.
PubMed: 38759828
DOI: 10.1016/j.cgh.2024.04.037 -
Alternative Therapies in Health and... May 2024Cirrhotic portal hypertension and associated opening of collateral circulation, improper feeding or sudden increase of abdominal pressure are the causes of esophageal...
BACKGROUND
Cirrhotic portal hypertension and associated opening of collateral circulation, improper feeding or sudden increase of abdominal pressure are the causes of esophageal and gastric variceal bleeding. Esophageal and gastric variceal bleeding is one of the most common and serious complications during decompensation of cirrhosis. Endoscopic surgery is an effective method for treating esophageal and gastric variceal hemorrhage. Still, postoperative health management is required to reduce the occurrence of rebleeding and improve the quality of life of patients with esophageal and gastric variceal hemorrhage.
OBJECTIVE
Our study aims to assess the impact of a health management program on the clinical efficacy, rebleeding rate, varicose vein disappearance, self-management ability, and quality of life of patients who have undergone endoscopic surgery for esophageal and gastric variceal hemorrhage.
DESIGN
This was a retrospective study.
SETTING
This study was performed in the Department of Gastroenterology, Taihe County People's Hospital, due that all the author came to take up positions in the hospital.
PARTICIPANTS
A total of 80 esophageal and gastric variceal hemorrhage patients who received endoscopic surgery in our hospital from January 2020 to January 2022 were selected as the research subjects and were divided into a study group and control group based on the random number table method, with 40 patients in each group. There were 59 males and 11 females, aged from 29 to 81 years old. For Child-Pugh classification of liver function, there were 27 cases in grade A, 34 cases in grade B and 19 cases in grade C.
INTERVENTIONS
Patients in both groups received endoscopic treatment. Postoperative health management procedures were implemented in the observation group, including establishing a health management team, health management including self-psychological counseling, daily diet management, rest management, medication management, and complications prevention and management and procedure implementation including pre-discharge guidance and follow up after discharge. Routine health management was implemented in the control group, including understanding the lifestyle and disease control status of patients after treatment, giving health education and guidance, including diet, daily exercise, intervention drugs, psychological state, and other aspects, and reminding patients to return to the hospital outpatient clinic once a time after discharge.
PRIMARY OUTCOME MEASURES
(1) clinical efficacy (2) rebleeding rate (3) varicose vein disappearance (4) self-management ability, and (5) quality of life.
RESULTS
The total clinical effective rate was 92.5% in the observation group and 82.5% in the control group (P < .05). The rebleeding rate and varicose vein disappearance rate were 2.5% and 70.0% in the observation group, presented better relative to those of 12.5% and 55% in the control group, respectively (P < .05). After intervention, the scores of self-management ability [(18.27±3.11) points, (17.84±3.64) points, (17.17±3.10) points and (18.34±3.32) points vs (16.08±2.86) points, (15.10±2.86) points, (15.48±2.54) points and (16.18±2.84) points] and quality of life [(78.23±8.10) points, (79.06±6.62) points, (78.12±3.10) points and (80.15±7.12) points vs (64.11±6.46) points, (65.15±2.36) points, (65.48±2.57) points and (72.16±2.97) points] in the observation group were higher than the control group (P < .05).
CONCLUSION
The implementation of a health management program in esophageal and gastric variceal hemorrhage patients after endoscopic treatment is helpful to improve the clinical effect of endoscopic treatment, reduce the rebleeding rate and varicose veins, and improve the self-management ability and quality of life of patients, which has important clinical significance.
PubMed: 38758139
DOI: No ID Found -
Zoological Research May 2024Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and...
Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.
Topics: Animals; Non-alcoholic Fatty Liver Disease; Carcinoma, Hepatocellular; Mice; Liver Neoplasms; Proto-Oncogene Proteins p21(ras); Disease Models, Animal; Mice, Transgenic; Mice, Inbred C57BL; Humans
PubMed: 38757223
DOI: 10.24272/j.issn.2095-8137.2024.002