BACKGROUND Hepatic steatosis is a major cause of chronic liver disease.Two-dimensional(2D)ultrasound is the most widely used non-invasive tool for screening and monitoring,but associated diagnoses are highly subjectiv...BACKGROUND Hepatic steatosis is a major cause of chronic liver disease.Two-dimensional(2D)ultrasound is the most widely used non-invasive tool for screening and monitoring,but associated diagnoses are highly subjective.AIM To develop a scalable deep learning(DL)algorithm for quantitative scoring of liver steatosis from 2D ultrasound images.METHODS Using multi-view ultrasound data from 3310 patients,19513 studies,and 228075 images from a retrospective cohort of patients received elastography,we trained a DL algorithm to diagnose steatosis stages(healthy,mild,moderate,or severe)from clinical ultrasound diagnoses.Performance was validated on two multiscanner unblinded and blinded(initially to DL developer)histology-proven cohorts(147 and 112 patients)with histopathology fatty cell percentage diagnoses and a subset with FibroScan diagnoses.We also quantified reliability across scanners and viewpoints.Results were evaluated using Bland-Altman and receiver operating characteristic(ROC)analysis.RESULTS The DL algorithm demonstrated repeatable measurements with a moderate number of images(three for each viewpoint)and high agreement across three premium ultrasound scanners.High diagnostic performance was observed across all viewpoints:Areas under the curve of the ROC to classify mild,moderate,and severe steatosis grades were 0.85,0.91,and 0.93,respectively.The DL algorithm outperformed or performed at least comparably to FibroScan control attenuation parameter(CAP)with statistically significant improvements for all levels on the unblinded histology-proven cohort and for“=severe”steatosis on the blinded histology-proven cohort.CONCLUSION The DL algorithm provides a reliable quantitative steatosis assessment across view and scanners on two multi-scanner cohorts.Diagnostic performance was high with comparable or better performance than the CAP.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures.AIM To explore the molecular mechanism of NAFLD.METHODS Whole genome sequencing(WGS)analysis was performed on liver tissues from patients with NAFLD(n=6)and patients with normal metabolic conditions(n=6)to identify the target genes.A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2(FBXO2)overexpression mouse model were used for in vivo studies.Plasmid transfection,co-immunoprecipitation-based mass spectrometry assays,and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies.RESULTS A total of 30982 genes were detected in WGS analysis,with 649 up-regulated and 178 down-regulated.Expression of FBXO2,an E3 ligase,was upregulated in the liver tissues of patients with NAFLD.Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice.Overexpression of FBXO2 aggravated odium oleate(OA)-induced lipid accumulation in HepG2 cells,resulting in an abnormal expression of genes related to lipid metabolism,such as fatty acid synthase,peroxisome proliferator-activated receptor alpha,and so on.In contrast,knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes.The hydroxyl CoA dehydrogenase alpha subunit(HADHA),a protein involved in oxidative stress,was a target of FBXO2-mediated ubiquitination.FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells.Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells.CONCLUSION FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD。展开更多
BACKGROUND With increasing rates of liver transplantation and a stagnant donor pool,the annual wait list removals have remained high.Living donor liver transplantation(LDLT)is an established modality in expanding the ...BACKGROUND With increasing rates of liver transplantation and a stagnant donor pool,the annual wait list removals have remained high.Living donor liver transplantation(LDLT)is an established modality in expanding the donor pool and is the primary method of liver donation in large parts of the world.Marginal living donors,including those with hepatic steatosis,have been used to expand the donor pool.However,due to negative effects of steatosis on graft and recipient outcomes,current practice excludes overweight or obese donors with more than 10%macro vesicular steatosis.This has limited a potentially important source to help expand the donor pool.Weight loss is known to improve or resolve steatosis and rapid weight loss with short-term interventions have been used to convert marginal donors to low-risk donors in a small series of studies.There is,however,a lack of a consensus driven standardized approach to such interventions.AIM To assess the available data on using weight loss interventions in potential living liver donors with steatotic livers and investigated the feasibility,efficacy,and safety of using such donors on the donor,graft and recipient outcomes.The principal objective was to assess if using such treated donor livers,could help expand the donor pool.METHODS We performed a comprehensive literature review and meta-analysis on studies examining the role of short-term weight loss interventions in potential living liver donors with hepatic steatosis with the aim of increasing liver donation rates and improving donor,graft,and recipient outcomes.RESULTS A total of 6 studies with 102 potential donors were included.Most subjects were males(71).All studies showed a significant reduction in body mass index postintervention with a mean difference of-2.08(-3.06,1.10,I2=78%).A significant reduction or resolution of hepatic steatosis was seen in 93 of the 102(91.2%).Comparison of pre-and post-intervention liver biopsies showed a significant reduction in steatosis with a mean difference of-21.22(-27.02,-15.43,I2=56%).The liver donation rates post-intervention was 88.5(74.5,95.3,I2=42%).All donors who did not undergo LDLT had either recipient reasons or had fibrosis/steatohepatitis on post intervention biopsies.Post-operative biliary complications in the intervention group were not significantly different compared to controls with an odds ratio of 0.96[(0.14,6.69),I2=0].The overall post-operative donor,graft,and recipient outcomes in treated donors were not significantly different compared to donors with no steatosis.CONCLUSION Use of appropriate short term weight loss interventions in living liver donors is an effective tool in turning marginal donors to low-risk donors and therefore in expanding the donor pool.It is feasible and safe,with comparable donor,graft,and recipient outcomes,to non-obese donors.Larger future prospective studies are needed.展开更多
AIM:To establish a quantitative method to measure the amount of lipids.METHODS:The livers of 53 male Wistar rats(225 g) with different degrees of hepatic steatosis were studied.This model of hepatic steatosis was base...AIM:To establish a quantitative method to measure the amount of lipids.METHODS:The livers of 53 male Wistar rats(225 g) with different degrees of hepatic steatosis were studied.This model of hepatic steatosis was based on a high carbohydrate,fat-free modified diet.Biopsies were classified into four grades depending on fat accumulation,using the Kleiner and Brunt classification.Total fat was studied by the Soxtec method(SoxtecTM 2050 Auto Fat Extraction System),and agreement between both assays was assessed by calculating theκ coefficient.RESULTS:According to the histological classification,38% of rats presented grade 0,21% grade 1,22% grade 2 and 20% grade 3.The amount of fat per 100 g tissue was 2.60±0.64 g for grade 0,3.87±1.59 g for grade 1,5.82±1.37 g for grade 2 and 8.68± 2.30 g for grade 3.Statistically significant differences were found between the mean values for each of the histological grades(P<0.05).The correlation for the quantification of fat in the liver between both assays was moderate(κ=0.60).CONCLUSION:The biochemical quantification of fat in liver tissue by the Soxtec method was correlated with the histological classification,although the agreement between the two tests was only moderate.展开更多
Objective: To compare the effects of high-monounsaturated(MUFA) and polyunsaturated fatty acids(PUFA) against the metabolic disorders elicited by a high-cholesterol diet(HC) in rats. Methods: Using in vivo dietary man...Objective: To compare the effects of high-monounsaturated(MUFA) and polyunsaturated fatty acids(PUFA) against the metabolic disorders elicited by a high-cholesterol diet(HC) in rats. Methods: Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil(cholesterol free diet) and 1% HC containing 12% olive oil(HC+OO) enriched with MUFA and 12% sunflower oil(HC+SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period. Results: Comparatively, rats treated with HC+OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC+SO diet(P<0.05). Otherwise, HC+OO provoked significant microvesicular steatosis situated in the hepatic acinar zone 1. Conclusions: HC+OO diet has high absorption velocity in the acinar zone 1 of liver compared to the HC+SO diet. Based on this, the reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC+OO diet can be caused by the delay in the FA release to the blood.展开更多
Liver disease accounts for approximately 2 million deaths per year worldwide.All chronic liver diseases(CLDs),whether of toxic,genetic,autoimmune,or infectious origin,undergo typical histological changes in the struct...Liver disease accounts for approximately 2 million deaths per year worldwide.All chronic liver diseases(CLDs),whether of toxic,genetic,autoimmune,or infectious origin,undergo typical histological changes in the structure of the tissue.These changes may include the accumulation of extracellular matrix material,fats,triglycerides,or tissue scarring.Noninvasive methods for diagnosing CLD,such as conventional B-mode ultrasound(US),play a significant role in diagnosis.Doppler US,when coupled with B-mode US,can be helpful in evaluating the hemodynamics of hepatic vessels and detecting US findings associated with hepatic decompensation.US elastography can assess liver stiffness,serving as a surrogate marker for liver fibrosis.It is important to note that interpreting these values should not rely solely on a histological classification.Contrast-enhanced US(CEUS)provides valuable information on tissue perfusion and enables excellent differentiation between benign and malignant focal liver lesions.Clinical evaluation,the etiology of liver disease,and the patient current comorbidities all influence the interpretation of liver stiffness measurements.These measurements are most clinically relevant when interpreted as a probability of compensated advanced CLD.B-mode US offers a subjective estimation of fatty infiltration and has limited sensitivity for mild steatosis.The controlled attenuation parameter requires a dedicated device,and cutoff values are not clearly defined.Quan-titative US parameters for liver fat estimation include the attenuation coefficient,backscatter coefficient,and speed of sound.These parameters offer the advantage of providing fat quantification alongside B-mode evaluation and other US parameters.Multiparametric US(MPUS)of the liver introduces a new concept for complete noninvasive diagnosis.It encourages examiners to utilize the latest features of an US machine,including conventional B-mode,liver stiffness evaluation,fat quantification,dispersion imaging,Doppler US,and CEUS for focal liver lesion characterization.This comprehensive approach allows for diagnosis in a single examination,providing clinicians worldwide with a broader perspective and becoming a cornerstone in their diagnostic arsenal.MPUS,in the hands of skilled clinicians,becomes an invaluable predictive tool for diagnosing,staging,and monitoring CLD.展开更多
The tight junction (TJ) is a critical cellular component for maintenance of tissue integrity, cellular interactions and cell-cell communications, and physiologically functions as the "great wall" against ext...The tight junction (TJ) is a critical cellular component for maintenance of tissue integrity, cellular interactions and cell-cell communications, and physiologically functions as the "great wall" against external agents and the surrounding hostile environment. During the host-pathogen evolution, viruses somehow found the key to unlock the gate for their entry into cells and to exploit and exhaust the host cells. In the liver, an array of TJ molecules is localized along the bile canaliculi forming the blood-biliary barrier, where they play pivotal roles in paracellular permeability, bile secretion, and cell polarity. In pathology, certain hepatic TJ molecules mediate virus entry causing hepatitis infection; deregulation and functional abnormality of the TJ have also been implicated in triggering liver cancer development and metastasis. All these findings shed new insights on the understanding of hepatic TJs in the development of liver disease and provide new clues for potential intervention.展开更多
Lysosomal acid lipase(LAL) deficiency is an underrecognized lysosomal disease caused by deficient enzymatic activity of LAL.In this report we describe two affected female Mexican siblings with early hepatic complicati...Lysosomal acid lipase(LAL) deficiency is an underrecognized lysosomal disease caused by deficient enzymatic activity of LAL.In this report we describe two affected female Mexican siblings with early hepatic complications.At two months of age,the first sibling presented with alternating episodes of diarrhea and constipation,and later with hepatomegaly,elevated transaminases,high levels of total and low-density lipoprotein cholesterol,and low levels of highdensity lipoprotein.Portal hypertension and grade 2 esophageal varices were detected at four years of age.The second sibling presented with hepatomegaly,elevated transaminases and mildly elevated lowdensity lipoprotein and low high-density lipoprotein at six months of age.LAL activity was deficient in both patients.Sequencing of LIPA revealed two previously unreported heterozygous mutations in exon 4:c.253C>A and c.294C>G.These cases highlight the clinical continuum between the so-called Wolman disease and cholesteryl ester storage disease,and underscore that LAL deficiency represents a single disease with a degree of clinical heterogeneity.展开更多
Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunb...Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunbergii and appraised their LMPST on palmitic acid(PA)induced lipid accretion in Hep G2,and 3T3-L1 cells.LMPST treatment lessened lipid deposition and intracellular free fatty acid and triglyceride intensities in PA-treated above mentioned cells.The mechanistic study publicized that LMPST2 significantly suppressed adipogenesis and stimulated the PA-treated 3T3-L1 cells occupied in the lipolysis pathway.Furthermore,in PA-treated Hep G2 cells,the free fatty acid oxidation was significantly increased by LMPST2.Given these constructive properties of LMPST2 from S.thunbergii,is a potential candidate for diminishing the intracellular lipids,and for a therapeutic agent in those conditions.展开更多
Coiled-coil domain containing 3(CCDC3,also called Favine)is a highly conserved protein initially identified as a protein secreted from adipocytes and endothelial cells in the vascular system with endocrine-like functi...Coiled-coil domain containing 3(CCDC3,also called Favine)is a highly conserved protein initially identified as a protein secreted from adipocytes and endothelial cells in the vascular system with endocrine-like functions.Recently,CCDC3 was also found to function as a nuclear tumor suppressor in breast cancers.Although it is still understudied,CCDC3,since its discovery,has been shown to play multiple roles in lipid metabolism,fatty liver,abdominal obesity,anti-inflammation,atherosclerosis,and cancer.This essay is thus composed to offer an overview of these extracellular endocrine-like and intracellular(nuclear)functions of CCDC3.We also discuss the possible underlying cellular and molecular mechanisms of CCDC3,the implications for clinical translation,and the remaining puzzles about this special molecule.展开更多
基金Supported by the Maintenance Project of the Center for Artificial Intelligence,No.CLRPG3H0012 and No.SMRPG3I0011.
文摘BACKGROUND Hepatic steatosis is a major cause of chronic liver disease.Two-dimensional(2D)ultrasound is the most widely used non-invasive tool for screening and monitoring,but associated diagnoses are highly subjective.AIM To develop a scalable deep learning(DL)algorithm for quantitative scoring of liver steatosis from 2D ultrasound images.METHODS Using multi-view ultrasound data from 3310 patients,19513 studies,and 228075 images from a retrospective cohort of patients received elastography,we trained a DL algorithm to diagnose steatosis stages(healthy,mild,moderate,or severe)from clinical ultrasound diagnoses.Performance was validated on two multiscanner unblinded and blinded(initially to DL developer)histology-proven cohorts(147 and 112 patients)with histopathology fatty cell percentage diagnoses and a subset with FibroScan diagnoses.We also quantified reliability across scanners and viewpoints.Results were evaluated using Bland-Altman and receiver operating characteristic(ROC)analysis.RESULTS The DL algorithm demonstrated repeatable measurements with a moderate number of images(three for each viewpoint)and high agreement across three premium ultrasound scanners.High diagnostic performance was observed across all viewpoints:Areas under the curve of the ROC to classify mild,moderate,and severe steatosis grades were 0.85,0.91,and 0.93,respectively.The DL algorithm outperformed or performed at least comparably to FibroScan control attenuation parameter(CAP)with statistically significant improvements for all levels on the unblinded histology-proven cohort and for“=severe”steatosis on the blinded histology-proven cohort.CONCLUSION The DL algorithm provides a reliable quantitative steatosis assessment across view and scanners on two multi-scanner cohorts.Diagnostic performance was high with comparable or better performance than the CAP.
基金the National Natural Science Foundation of China,No.82070869 and 82270914.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures.AIM To explore the molecular mechanism of NAFLD.METHODS Whole genome sequencing(WGS)analysis was performed on liver tissues from patients with NAFLD(n=6)and patients with normal metabolic conditions(n=6)to identify the target genes.A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2(FBXO2)overexpression mouse model were used for in vivo studies.Plasmid transfection,co-immunoprecipitation-based mass spectrometry assays,and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies.RESULTS A total of 30982 genes were detected in WGS analysis,with 649 up-regulated and 178 down-regulated.Expression of FBXO2,an E3 ligase,was upregulated in the liver tissues of patients with NAFLD.Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice.Overexpression of FBXO2 aggravated odium oleate(OA)-induced lipid accumulation in HepG2 cells,resulting in an abnormal expression of genes related to lipid metabolism,such as fatty acid synthase,peroxisome proliferator-activated receptor alpha,and so on.In contrast,knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes.The hydroxyl CoA dehydrogenase alpha subunit(HADHA),a protein involved in oxidative stress,was a target of FBXO2-mediated ubiquitination.FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells.Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells.CONCLUSION FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD。
文摘BACKGROUND With increasing rates of liver transplantation and a stagnant donor pool,the annual wait list removals have remained high.Living donor liver transplantation(LDLT)is an established modality in expanding the donor pool and is the primary method of liver donation in large parts of the world.Marginal living donors,including those with hepatic steatosis,have been used to expand the donor pool.However,due to negative effects of steatosis on graft and recipient outcomes,current practice excludes overweight or obese donors with more than 10%macro vesicular steatosis.This has limited a potentially important source to help expand the donor pool.Weight loss is known to improve or resolve steatosis and rapid weight loss with short-term interventions have been used to convert marginal donors to low-risk donors in a small series of studies.There is,however,a lack of a consensus driven standardized approach to such interventions.AIM To assess the available data on using weight loss interventions in potential living liver donors with steatotic livers and investigated the feasibility,efficacy,and safety of using such donors on the donor,graft and recipient outcomes.The principal objective was to assess if using such treated donor livers,could help expand the donor pool.METHODS We performed a comprehensive literature review and meta-analysis on studies examining the role of short-term weight loss interventions in potential living liver donors with hepatic steatosis with the aim of increasing liver donation rates and improving donor,graft,and recipient outcomes.RESULTS A total of 6 studies with 102 potential donors were included.Most subjects were males(71).All studies showed a significant reduction in body mass index postintervention with a mean difference of-2.08(-3.06,1.10,I2=78%).A significant reduction or resolution of hepatic steatosis was seen in 93 of the 102(91.2%).Comparison of pre-and post-intervention liver biopsies showed a significant reduction in steatosis with a mean difference of-21.22(-27.02,-15.43,I2=56%).The liver donation rates post-intervention was 88.5(74.5,95.3,I2=42%).All donors who did not undergo LDLT had either recipient reasons or had fibrosis/steatohepatitis on post intervention biopsies.Post-operative biliary complications in the intervention group were not significantly different compared to controls with an odds ratio of 0.96[(0.14,6.69),I2=0].The overall post-operative donor,graft,and recipient outcomes in treated donors were not significantly different compared to donors with no steatosis.CONCLUSION Use of appropriate short term weight loss interventions in living liver donors is an effective tool in turning marginal donors to low-risk donors and therefore in expanding the donor pool.It is feasible and safe,with comparable donor,graft,and recipient outcomes,to non-obese donors.Larger future prospective studies are needed.
基金Supported by CIBERehd and Donostia Hospital,CIBER is funded by the Instituto de Salud Carlos Ⅲ
文摘AIM:To establish a quantitative method to measure the amount of lipids.METHODS:The livers of 53 male Wistar rats(225 g) with different degrees of hepatic steatosis were studied.This model of hepatic steatosis was based on a high carbohydrate,fat-free modified diet.Biopsies were classified into four grades depending on fat accumulation,using the Kleiner and Brunt classification.Total fat was studied by the Soxtec method(SoxtecTM 2050 Auto Fat Extraction System),and agreement between both assays was assessed by calculating theκ coefficient.RESULTS:According to the histological classification,38% of rats presented grade 0,21% grade 1,22% grade 2 and 20% grade 3.The amount of fat per 100 g tissue was 2.60±0.64 g for grade 0,3.87±1.59 g for grade 1,5.82±1.37 g for grade 2 and 8.68± 2.30 g for grade 3.Statistically significant differences were found between the mean values for each of the histological grades(P<0.05).The correlation for the quantification of fat in the liver between both assays was moderate(κ=0.60).CONCLUSION:The biochemical quantification of fat in liver tissue by the Soxtec method was correlated with the histological classification,although the agreement between the two tests was only moderate.
文摘Objective: To compare the effects of high-monounsaturated(MUFA) and polyunsaturated fatty acids(PUFA) against the metabolic disorders elicited by a high-cholesterol diet(HC) in rats. Methods: Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil(cholesterol free diet) and 1% HC containing 12% olive oil(HC+OO) enriched with MUFA and 12% sunflower oil(HC+SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period. Results: Comparatively, rats treated with HC+OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC+SO diet(P<0.05). Otherwise, HC+OO provoked significant microvesicular steatosis situated in the hepatic acinar zone 1. Conclusions: HC+OO diet has high absorption velocity in the acinar zone 1 of liver compared to the HC+SO diet. Based on this, the reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC+OO diet can be caused by the delay in the FA release to the blood.
文摘Liver disease accounts for approximately 2 million deaths per year worldwide.All chronic liver diseases(CLDs),whether of toxic,genetic,autoimmune,or infectious origin,undergo typical histological changes in the structure of the tissue.These changes may include the accumulation of extracellular matrix material,fats,triglycerides,or tissue scarring.Noninvasive methods for diagnosing CLD,such as conventional B-mode ultrasound(US),play a significant role in diagnosis.Doppler US,when coupled with B-mode US,can be helpful in evaluating the hemodynamics of hepatic vessels and detecting US findings associated with hepatic decompensation.US elastography can assess liver stiffness,serving as a surrogate marker for liver fibrosis.It is important to note that interpreting these values should not rely solely on a histological classification.Contrast-enhanced US(CEUS)provides valuable information on tissue perfusion and enables excellent differentiation between benign and malignant focal liver lesions.Clinical evaluation,the etiology of liver disease,and the patient current comorbidities all influence the interpretation of liver stiffness measurements.These measurements are most clinically relevant when interpreted as a probability of compensated advanced CLD.B-mode US offers a subjective estimation of fatty infiltration and has limited sensitivity for mild steatosis.The controlled attenuation parameter requires a dedicated device,and cutoff values are not clearly defined.Quan-titative US parameters for liver fat estimation include the attenuation coefficient,backscatter coefficient,and speed of sound.These parameters offer the advantage of providing fat quantification alongside B-mode evaluation and other US parameters.Multiparametric US(MPUS)of the liver introduces a new concept for complete noninvasive diagnosis.It encourages examiners to utilize the latest features of an US machine,including conventional B-mode,liver stiffness evaluation,fat quantification,dispersion imaging,Doppler US,and CEUS for focal liver lesion characterization.This comprehensive approach allows for diagnosis in a single examination,providing clinicians worldwide with a broader perspective and becoming a cornerstone in their diagnostic arsenal.MPUS,in the hands of skilled clinicians,becomes an invaluable predictive tool for diagnosing,staging,and monitoring CLD.
基金Supported by A GRF Grant from the Research Grants Council of Hong Kong to Luk JM,No.771607M
文摘The tight junction (TJ) is a critical cellular component for maintenance of tissue integrity, cellular interactions and cell-cell communications, and physiologically functions as the "great wall" against external agents and the surrounding hostile environment. During the host-pathogen evolution, viruses somehow found the key to unlock the gate for their entry into cells and to exploit and exhaust the host cells. In the liver, an array of TJ molecules is localized along the bile canaliculi forming the blood-biliary barrier, where they play pivotal roles in paracellular permeability, bile secretion, and cell polarity. In pathology, certain hepatic TJ molecules mediate virus entry causing hepatitis infection; deregulation and functional abnormality of the TJ have also been implicated in triggering liver cancer development and metastasis. All these findings shed new insights on the understanding of hepatic TJs in the development of liver disease and provide new clues for potential intervention.
文摘Lysosomal acid lipase(LAL) deficiency is an underrecognized lysosomal disease caused by deficient enzymatic activity of LAL.In this report we describe two affected female Mexican siblings with early hepatic complications.At two months of age,the first sibling presented with alternating episodes of diarrhea and constipation,and later with hepatomegaly,elevated transaminases,high levels of total and low-density lipoprotein cholesterol,and low levels of highdensity lipoprotein.Portal hypertension and grade 2 esophageal varices were detected at four years of age.The second sibling presented with hepatomegaly,elevated transaminases and mildly elevated lowdensity lipoprotein and low high-density lipoprotein at six months of age.LAL activity was deficient in both patients.Sequencing of LIPA revealed two previously unreported heterozygous mutations in exon 4:c.253C>A and c.294C>G.These cases highlight the clinical continuum between the so-called Wolman disease and cholesteryl ester storage disease,and underscore that LAL deficiency represents a single disease with a degree of clinical heterogeneity.
基金supported by Korea Institute of Marine Science&Technology Promotion(KIMST)funded by the Ministry of Oceans and Fisheries,Korea(20220488)。
文摘Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunbergii and appraised their LMPST on palmitic acid(PA)induced lipid accretion in Hep G2,and 3T3-L1 cells.LMPST treatment lessened lipid deposition and intracellular free fatty acid and triglyceride intensities in PA-treated above mentioned cells.The mechanistic study publicized that LMPST2 significantly suppressed adipogenesis and stimulated the PA-treated 3T3-L1 cells occupied in the lipolysis pathway.Furthermore,in PA-treated Hep G2 cells,the free fatty acid oxidation was significantly increased by LMPST2.Given these constructive properties of LMPST2 from S.thunbergii,is a potential candidate for diminishing the intracellular lipids,and for a therapeutic agent in those conditions.
基金H.L.and S.X.Z.were supported in part by NIH-NCI grants R01CA095441,R01CA234605,R01CA127724,as well as R21CA272890H.L.was also in part supported by the Reynolds and Ryan Families Endowed Chair fund and the NIH-NCI grant U01CA252965.
文摘Coiled-coil domain containing 3(CCDC3,also called Favine)is a highly conserved protein initially identified as a protein secreted from adipocytes and endothelial cells in the vascular system with endocrine-like functions.Recently,CCDC3 was also found to function as a nuclear tumor suppressor in breast cancers.Although it is still understudied,CCDC3,since its discovery,has been shown to play multiple roles in lipid metabolism,fatty liver,abdominal obesity,anti-inflammation,atherosclerosis,and cancer.This essay is thus composed to offer an overview of these extracellular endocrine-like and intracellular(nuclear)functions of CCDC3.We also discuss the possible underlying cellular and molecular mechanisms of CCDC3,the implications for clinical translation,and the remaining puzzles about this special molecule.
