Reduced lysosomal acid lipase activity in blood and platelets is associated with nonalcoholic fatty liver disease

OBJECTIVES: To investigate whether blood total lysosomal acid lipase activity (BT-LAL) levels are uniquely associated with the noncirrhotic and cirrhotic stages of nonalcoholic fatty liver disease (NAFLD) and with protection from NAFLD in metabolically/genetically predisposed subjects and a normal liver. To clarify which enzyme-carrying circulating cells are involved in reduced BT-LAL of NAFLD.METHODS: In a cross-sectional study, BT-LAL was measured by a fluorigenic method in patients with NAFLD (n = 118), alcoholic (n = 116), and hepatitis C virus-related disease (n = 49), in 103 controls with normal liver and in 58 liver transplant recipients. Intracellular platelet and leukocyte LAL was measured in 14 controls and 28 patients with NAFLD.RESULTS: Compared with controls, (i) BT-LAL and LAL in platelets, but not in leukocytes, were progressively reduced in noncirrhotic NAFLD and in nonalcoholic steatohepatitis-related cirrhosis; (ii) platelet and leukocyte counts did not differ in patients with noncirrhotic NAFLD; and (iii) BT-LAL did not differ in alcoholic and hepatitis C virus noncirrhotic patients. BT-LAL progressively increased in controls with metabolic syndrome features according to their PNPLA3 rs738409 steatosis-associated variant status (II vs IM vs MM), and their BT-LAL was higher than that of noncirrhotic NAFLD, only when carriers of the PNPLA3 unfavorable alleles were considered. Liver transplant recipients with de novo NAFLD compared with those without de novo NAFLD had lower BT-LAL.DISCUSSION: LAL in blood and platelets is progressively and uniquely reduced in NAFLD according to disease severity. High BT-LAL is associated with protection from NAFLD occurrence in subjects with metabolic and genetic predisposition. Low LAL in platelets and blood could play a pathogenetic role in NAFLD

Focus on Anti-Tumour Necrosis Factor (TNF)-α-Related Autoimmune Diseases

Anti-tumour necrosis factor (TNF)-α agents have been increasingly used to treat patients affected by inflammatory bowel disease and dermatological and rheumatologic inflammatory disorders. However, the widening use of biologics is related to a new class of adverse events called paradoxical reactions. Its pathogenesis remains unclear, but it is suggested that cytokine remodulation in predisposed individuals can lead to the inflammatory process. Here, we dissect the clinical aspects and overall outcomes of autoimmune diseases caused by anti-TNF-α therapies

Predicting Treatment Response in Inflammatory Bowel Diseases: Cross-Sectional Imaging Markers

Therapeutic options for inflammatory bowel diseases (IBD) have largely expanded in the last decades, both in Crohn’s disease and ulcerative colitis, including multiple biological drugs targeting different inflammation pathways. However, choosing the best treatment and timing for each patient is still an undeniable challenge for IBD physicians due to the marked heterogeneity among patients and disease behavior. Therefore, early prediction of the response to biological drugs becomes of utmost importance, allowing prompt optimization of therapeutic strategies and thus paving the way towards precision medicine. In such a context, researchers have recently focused on cross-sectional imaging techniques (intestinal ultrasound, computed tomography, and magnetic resonance enterography) in order to identify predictive markers of response or non-response to biologic therapies. In this review, we aim to summarize data about imaging factors that may early predict disease behavior during biological treatment, potentially helping to define more precise and patient-tailored strategies

Ultrasound Evaluation of Sarcopenia in Patients with Hepatocellular Carcinoma: A Faster and Easier Way to Detect Patients at Risk

The condition of sarcopenia, defined as a progressive loss of musculoskeletal mass and muscular strength, is very common in patients with hepatocellular carcinoma (HCC) and presents a remarkable association with its prognosis. Thus, the early identification of sarcopenic patients represents one of the potential new approaches in the global assessment of HCC, and there is increasing interest regarding the potential therapeutic implications of this condition. The gold standard for the quantification of muscle mass is magnetic resonance imaging (MRI) or computed tomography (CT), but these techniques are not always feasible because of the high-cost equipment needed. A new possibility in sarcopenia identification could be muscle ultrasound examination. The measurement of specific parameters such as the muscle thickness, muscular fascicles length or pennation angle has shown a good correlation with CT or MRI values and a good diagnostic accuracy in the detection of sarcopenia. Recently, these results were also confirmed specifically in patients with chronic liver disease. This review summarizes the role of imaging for the diagnosis of sarcopenia in patients with HCC, focusing on the advantages and disadvantages of the diagnostic techniques currently validated for this aim and the future perspectives for the identification of this condition

Exploring the Role of Bempedoic Acid in Metabolic Dysfunction Associated Steatotic Liver Disease: Actual Evidence and Future Perspectives

Metabolic dysfunction-associated steatotic liver disease (MASLD) involves excessive lipid accumulation in hepatocytes, impacting global healthcare due to its high prevalence and risk of progression to severe liver conditions. Its pathogenesis involves genetic, metabolic, and inflammatory factors, with cardiovascular events as the leading cause of mortality. This review examines the role of lipid-lowering therapies in MASLD, with a particular focus on bempedoic acid, a recently approved cholesterol-lowering agent for hypercholesterolemia and high cardiovascular-risk patients. It explores its potential in liver disease by modulating lipid metabolism and inflammatory pathways based on the most recent studies available. Bempedoic acid inhibits ATP-citrate lyase, reducing cholesterol and fatty acid synthesis while activating AMP-activated protein kinase to suppress gluconeogenesis and lipogenesis. Animal studies indicate its efficacy in reducing hepatic steatosis, inflammation, and fibrosis. Bempedoic acid holds promise as a therapeutic for MASLD, offering dual benefits in lipid metabolism and inflammation. Further clinical trials are required to confirm its efficacy and safety in MASLD patients, potentially addressing the multifaceted nature of this disease

Inflammatory Response in the Pathogenesis and Treatment of Hepatocellular Carcinoma: A Double-Edged Weapon

Hepatocellular carcinoma (HCC) is the most frequent among primary liver tumors (90%) and one of the main causes of cancer-related death. It develops usually in a chronically inflamed environment, ranging from compensatory parenchymal regeneration to fibrosis and cirrhosis: carcinogenesis can potentially happen in each of these stages. Inflammation determined by chronic viral infection (hepatitis B, hepatitis C, and hepatitis delta viruses) represents an important risk factor for HCC etiology through both viral direct damage and immune-related mechanisms. The deregulation of the physiological liver immunological network determined by viral infection can lead to carcinogenesis. The recent introduction of immunotherapy as the gold-standard first-line treatment for HCC highlights the role of the immune system and inflammation as a double-edged weapon in both HCC carcinogenesis and treatment. In this review we highlight how the inflammation is the key for the hepatocarcinogenesis in viral, alcohol and metabolic liver diseases

Georeferenced Spectral Maps an Improved Instrument for Action Planning on Environmental Noise Mitigation

Exposure-response relationships have been widely studied using A weighted equivalent sound pressure level (Leq,A) measured outside building environments in contrast with field surveys. On one hand low frequencies are minimized by A-weighted filter network. On the other hand low frequencies are predominant even inside buildings for some of the most salient sources in many cities (i.e. road traffic). These relationships do not consider that people spend a large part of their time inside building environments. The spread of the exposure-response relationships can, presumably, be reduced by relating people response to the noise spectrum levels inside building environments instead of the outdoors Leq,A. Outdoors spectral maps can be georeferenced using geographical information systems. Then the indoors spectrum for each building can be estimated if the georeferenced data of façades and interiors properties were available. Furthermore city planners can use the outdoors spectral maps to estimate the adequate sound insulation of façades for new projects. In this article a georeferenced spectral map of a part of the city of Rosario, Argentina is developed using inexpensive resources and some interesting tools for this purpose are presented using technical computing software. Different forms of presenting the data are analyzed in relation to the requirements of different agents, public, city planners, Geographical Information Systems users, etc.Fil: Accolti Mostazo, Ernesto Enrique. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miyara, Federico. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; ArgentinaFil: Marengo Rodriguez, Fernando Alberto. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miechi, Pablo José. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; ArgentinaFil: Mignini, Ezequiel. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; ArgentinaFil: Pasch, Vivian Irene. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; ArgentinaFil: Cabanellas, Susana. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; ArgentinaFil: Yanitelli, Marta Susana. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; Argentin

Gut and Reproductive Tract Microbiota Adaptation during Pregnancy: New Insights for Pregnancy-Related Complications and Therapy

Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future

Georeferenced Spectral Maps an Improved Instrument for Action Planning on Environmental Noise Mitigation

Exposure-response relationships have been widely studied using A weighted equivalent sound pressure level (Leq,A) measured outside building environments in contrast with field surveys. On one hand low frequencies are minimized by A-weighted filter network. On the other hand low frequencies are predominant even inside buildings for some of the most salient sources in many cities (i.e. road traffic). These relationships do not consider that people spend a large part of their time inside building environments. The spread of the exposure-response relationships can, presumably, be reduced by relating people response to the noise spectrum levels inside building environments instead of the outdoors Leq,A. Outdoors spectral maps can be georeferenced using geographical information systems. Then the indoors spectrum for each building can be estimated if the georeferenced data of façades and interiors properties were available. Furthermore city planners can use the outdoors spectral maps to estimate the adequate sound insulation of façades for new projects. In this article a georeferenced spectral map of a part of the city of Rosario, Argentina is developed using inexpensive resources and some interesting tools for this purpose are presented using technical computing software. Different forms of presenting the data are analyzed in relation to the requirements of different agents, public, city planners, Geographical Information Systems users, etc.Fil: Accolti Mostazo, Ernesto Enrique. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miyara, Federico. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; ArgentinaFil: Marengo Rodriguez, Fernando Alberto. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miechi, Pablo José. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; ArgentinaFil: Mignini, Ezequiel. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; ArgentinaFil: Pasch, Vivian Irene. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; ArgentinaFil: Cabanellas, Susana. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; ArgentinaFil: Yanitelli, Marta Susana. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Ingeniería Electrónica. Laboratorio de Acústica y Electroacústica; Argentin