Browsing by Author "Cabrera, Daniel"
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- ItemA Mineralocorticoid Receptor Deficiency in Myeloid Cells Reduces Liver Steatosis by Impairing Activation of CD8+ T Cells in a Nonalcoholic Steatohepatitis Mouse Model(2020) Munoz-Durango, Natalia; Arrese, Marco; Hernandez, Alejandra; Jara, Evelyn; Kalergis, Alexis M.; Cabrera, DanielBackground and Aims
- ItemA Precision Medicine Guided Approach to the Utilization of Biomarkers in MASLD(2024) Thakral, Nimish; Desalegn, Hailemichael; Diaz Piga, Luis Antonio; Cabrera, Daniel; Loomba, Rohit; Arrese Jiménez, Marco Antonio; Arab Verdugo, Juan PabloThe new nomenclature of metabolic dysfunction-associated steatotic liver disease (MASLD) emphasizes a positive diagnosis based on cardiometabolic risk factors. This definition is not only less stigmatizing but also allows for subclassification and stratification, thereby addressing the heterogeneity of what was historically referred to as nonalcoholic fatty liver disease. The heterogeneity within this spectrum is influenced by several factors which include but are not limited to demographic/dietary factors, the amount of alcohol use and drinking patterns, metabolic status, gut microbiome, genetic predisposition together with epigenetic factors. The net effect of this dynamic and intricate system-level interaction is reflected in the phenotypic presentation of MASLD. Therefore, the application of precision medicine in this scenario aims at complex phenotyping with consequent individual risk prediction, development of individualized preventive strategies, and improvements in the clinical trial designs. In this review, we aim to highlight the importance of precision medicine approaches in MASLD, including the use of novel biomarkers of disease, and its subsequent utilization in future study designs.
- ItemAndrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis(2017) Cabrera, Daniel; Wree, Alexander; Povero, Davide; Solís, Nancy; Hernández, Alejandra; Pizarro Rojas, Margarita Alicia; Moshage, Han; Torres Montes, Paula Javiera; Feldstein, Ariel E.; Cabello Verrugio, Claudio Alejandro; Brandan, Enrique; Barrera Martínez, Francisco Javier; Arab Verdugo, Juan Pablo; Arrese Jiménez, Marco
- ItemAngiotensin-(1-7) improves skeletal muscle regeneration(2023) Valero-Breton, Mayalen; Tacchi, Franco; Abrigo, Johanna; Simon, Felipe; Cabrera, Daniel; Cabello-Verrugio, ClaudioSkeletal muscle possesses regenerative potential via satellite cells, compromised in muscular dystrophies leading to fibrosis and fat infiltration. Angiotensin II (Ang-II) is commonly associated with pathological states. In contrast, Angiotensin (1-7) [Ang-(1-7)] counters Ang-II, acting via the Mas receptor. While Ang-II affects skeletal muscle regeneration, the influence of Ang-(1-7) remains to be elucidated. Therefore, this study aims to investigate the role of Ang-(17) in skeletal muscle regeneration. C2C12 cells were differentiated in the absence or presence of 10 nM of Ang-(1-7). The diameter of myotubes and protein levels of myogenin and myosin heavy chain (MHC) were determined. C57BL/6 WT male mice 16-18 weeks old) were randomly assigned to injury-vehicle, injury-Ang-(1-7), and control groups. Ang-(1-7) was administered via osmotic pumps, and muscle injury was induced by injecting barium chloride to assess muscle regeneration through histological analyses. Moreover, embryonic myosin (eMHC) and myogenin protein levels were evaluated. C2C12 myotubes incubated with Ang-(1-7) showed larger diameters than the untreated group and increased myogenin and MHC protein levels during differentiation. Ang-(1-7) administration enhances regeneration by promoting a larger diameter of new muscle fibers. Furthermore, higher numbers of eMHC (+) fibers were observed in the injured-Ang-(1-7), which also had a larger diameter. Moreover, eMHC and myogenin protein levels were elevated, supporting enhanced regeneration due to Ang-(1-7) administration. Ang-(1-7) effectively promotes differentiation in vitro and improves muscle regeneration in the context of injuries, with potential implications for treating muscle-related disorders.
- ItemAssessment of hepatic fatty acids during non-alcoholic steatohepatitis progression using magnetic resonance spectroscopy(2021) Xavier, Aline; Zacconi, Flavia C. M.; Santana Romo, Fabián Mauricio; Eykyn, Thomas R.; Lavin, Begona; Phinikaridou, Alkystis; Botnar, Rene; Uribe, Sergio; Esteban Oyarzun, Juan; Cabrera, Daniel; Arrese, Marco; Andia, Marcelo E.Abstract: Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities including steatosis, steatohepatitis, fibrosis, and cirrhosis. Liver biopsy remains the gold standard method to determine the disease stage in NAFLD but is an invasive and risky procedure. Studies have previously reported that changes in intrahepatic fatty acids (FA) composition are related to the progression of NAFLD, mainly in its early stages. The aim of this study was to characterize the liver FA composition in mice fed a Choline-deficient L-amino-defined (CDAA) diet at different stages of NAFLD using magnetic resonance spectroscopy (MRS). Methods: We used in-vivo MRS to perform a longitudinal characterization of hepatic FA changes in NAFLD mice for 10 weeks. We validated our findings with ex-vivo MRS, gas chromatography-mass spectrometry and histology. Results: In-vivo and ex-vivo results showed that livers from CDAA-fed mice exhibit a significant increase in liver FA content as well as a change in FA composition compared with control mice. After 4 weeks of CDAA diet, a decrease in polyunsaturated and an increase in monounsaturated FA were observed. These changes were associated with the appearance of early stages of steatohepatitis, confirmed by histology (NAFLD Activity Score (NAS) = 4.5). After 10 weeks of CDAA-diet, the liver FA composition remained stable while the NAS increased further to 6 showing a combination of early and late stages of steatohepatitis. Conclusion: Our results suggest that monitoring lipid composition in addition to total water/fat with MRS may yield additional insights that can be translated for non-invasive stratification of high-risk NAFLD patients.
- ItemBile Acids Induce Alterations in Mitochondrial Function in Skeletal Muscle Fibers(2022) Abrigo, Johanna; Olguin, Hugo; Gutierrez, Danae; Tacchi, Franco; Arrese, Marco; Cabrera, Daniel; Valero-Breton, Mayalen; Elorza, Alvaro A.; Simon, Felipe; Cabello-Verrugio, ClaudioCholestatic chronic liver disease is characterized by developing sarcopenia and elevated serum levels of bile acids. Sarcopenia is a skeletal muscle disorder with the hallmarks of muscle weakness, muscle mass loss, and muscle strength decline. Our previous report demonstrated that deoxycholic acid (DCA) and cholic acid (CA), through the membrane receptor TGR5, induce a sarcopenia-like phenotype in myotubes and muscle fibers. The present study aimed to evaluate the impact of DCA and CA on mitochondrial mass and function in muscle fibers and the role of the TGR5 receptor. To this end, muscle fibers obtained from wild-type and TGR5(-/-) mice were incubated with DCA and CA. Our results indicated that DCA and CA decreased mitochondrial mass, DNA, and potential in a TGR5-dependent fashion. Furthermore, with TGR5 participation, DCA and CA also reduced the oxygen consumption rate and complexes I and II from the mitochondrial electron transport chain. In addition, DCA and CA generated more mitochondrial reactive oxygen species than the control, which were abolished in TGR5(-/-) mice muscle fibers. Our results indicate that DCA and CA induce mitochondrial dysfunction in muscle fibers through a TGR5-dependent mechanism.
- ItemCentral Role of Transforming Growth Factor Type Beta 1 in Skeletal Muscle Dysfunctions: An Update on Therapeutic Strategies(2018) Abrigo, Johanna; Simon, Felipe; Cabrera, Daniel; Cordova, Gonzalo; Trollet, Capucine; Cabello Verrugio, Claudio Alejandro
- ItemCombined Administration of Andrographolide and Angiotensin- (1-7) Synergically Increases the Muscle Function and Strength in Aged Mice(2022) Abrigo, Johanna; Simon, Felipe; Cabrera, Daniel; Vilos, Cristian; Cabello-Verrugio, ClaudioBackground: Sarcopenia is a progressive and generalized skeletal muscle disorder characterized by muscle weakness, loss of muscle mass, and decline in the capacity of force generation. Aging can cause sarcopenia. Several therapeutic strategies have been evaluated to prevent or alleviate this disorder. One of them is angiotensin 1-7 [Ang-(1-7)], an anti-atrophic peptide for skeletal muscles that regulates decreased muscle mass for several causes, including aging. Another regulator of muscle mass and function is andrographolide, a bicyclic diterpenoid lactone that decreases the nuclear factor kappa B (NF-kappa B) signaling and attenuates the severity of some muscle diseases. Objective: Evaluate the effect of combined administration of Ang-(1-7) with andrographolide on the physical performance, muscle strength, and fiber ' s diameter in a murine model of sarcopenia by aging. Methods: Aged male mice of the C57BL/6J strain were treated with Andrographolide, Ang-(1-7), or combined for three months. The physical performance, muscle strength, and fiber ' s diameter were measured. Results: The results showed that aged mice (24 months old) treated with Ang-(1-7) or Andrographolide improved their performance on a treadmill test, muscle strength, and their fiber ' s diameter compared to aged mice without treatment. The combined administration of Ang-(1-7) with andrographolide to aged mice has an enhanced synergically effect on physical performance, muscle strength, and fiber ' s diameter. Conclusion: Our results indicated that in aged mice, the effects of andrographolide and Ang-(1-7) on muscle function, strength, and fiber ' s diameter are potentiated.
- ItemExtracellular vesicles derived from fat-laden hepatocytes undergoing chemical hypoxia promote a pro-fibrotic phenotype in hepatic stellate cells(2020) Hernandez, Alejandra; Reyes, Daniela; Geng, Yana; Pablo Arab, Juan; Cabrera, Daniel; Sepulveda, Rolando; Solis, Nancy; Buist-Homan, Manon; Arrese, Marco; Moshage, HanBackground: The transition from steatosis to non-alcoholic steatohepatitis (NASH) is a key issue in non-alcoholic fatty liver disease (NAFLD). Observations in patients with obstructive sleep apnea syndrome (OSAS) suggest that hypoxia contributes to progression to NASH and liver fibrosis, and the release of extracellular vesicles (EVs) by injured hepatocytes has been implicated in NAFLD progression.
- ItemHepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12(2020) Arab, Juan P.; Cabrera, Daniel; Sehrawat, Tejasav S.; Jalan-Sakrikar, Nidhi; Verma, Vikas K.; Simonetto, Douglas; Cao, Sheng; Yaqoob, Usman; Leon, Jonathan; Freire, Mariela; Vargas, Jose, I; De Assuncao, Thiago M.; Kwon, Jung H.; Guo, Yi; Kostallari, Enis; Cai, Qing; Kisseleva, Tatiana; Oh, Youngman; Arrese, Marco; Huebert, Robert C.; Shah, Vijay H.Background & Aims: Steatohepatitis drives fibrogenesis in alcohol-related liver disease. Recent studies have suggested that hepatic stellate cells (HSCs) may regulate the parenchymal cell injury and inflammation that precedes liver fibrosis, although the mechanism remains incompletely defined. Neuropilin-1 (NRP-1) and synectin are membrane proteins implicated in HSC activation. In this study, we disrupted NRP-1 and synectin as models to evaluate the role of HSC activation on the development of steatohepatitis in response to alcohol feeding in mice.
- ItemHigh Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration : Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis(2016) Abrigo, Johanna; Rivera, Juan Carlos; Aravena, Javier; Cabrera, Daniel; Simon, Felipe; Ezquer, Fernando; Ezquer, Marcelo; Cabello Verrugio, Claudio Alejandro
- ItemIncrease in decorin and biglycan in Duchenne Muscular Dystrophy: role of fibroblasts as cell source of these proteoglycans in the disease(2006) Fadic, Ricardo; Mezzano, Valeria; Alvarez, Karin; Cabrera, Daniel; Holmgren, Jenny; Brandan, EnriqueFibrosis is a common pathological feature observed in muscles of patients with. Duchenne muscular dystrophy (DMD). Biglycan and decorin are small chondroitin/dermatan sulfate proteoglycans in the muscle extracellular matrix (ECM) that belong to the family of structurally related proteoglycans called small leucine-rich repeat proteins. Decorin is considered an anti-fibrotic agent, preventing the process by blocking TGF-beta activity. There is no information about their expression in DMD patients. We found an increased amount of both proteoglycans in the ECM of skeletal muscle biopsies obtained from DMD patients. Both biglycan and decorin were augmented in the perimysium of muscle tissue, but only decorin increased in the endomysium as seen by immunohistochemical analyses. Fibroblasts were isolated from explants obtained from muscle of DMD patients and the incorporation of radioactive sulfate showed an increased synthesis of both decorin and biglycan in cultured fibroblasts compared to controls. The size of decorin and biglycan synthesized by DMD and control fibroblasts seems to be similar in size and anion charge. These findings show that decorin and biglycan are increased in DMD skeletal muscle and suggest that fibroblasts would be, at least, one source for these proteoglycans likely playing a role in the muscle response to dystrophic cell damage.
- ItemLetter: Potential impact of Helicobacter pylori infection on oesophageal disorders in chronic liver disease—Authors' reply(2024) Idalsoaga Ferrer, Francisco Javier; Diaz Piga, Luis Antonio; Ayares Campos, Gustavo Ignacio; Cabrera, Daniel; Chahuan Abde, Javier Nicolas; Monrroy Bravo, Hugo Alfonso; Halawi, Houssam; Arrese Jiménez, Marco Antonio; Arab Verdugo, Juan Pablo
- ItemLong-Term, Fructose-Induced Metabolic Syndrome-Like Condition Is Associated with Higher Metabolism, Reduced Synaptic Plasticity and Cognitive Impairment in Octodon degus(2018) Rivera, Daniela S.; Lindsay, Carolina B.; Codocedo Henríquez, Juan Francisco; Carreño, Laura E.; Cabrera, Daniel; Arrese Jiménez, Marco; Vio Lagos, Carlos P.; Bozinovic Kuscevic, Francisco; Inestrosa Cantín, Nibaldo
- ItemMineralocorticoid receptor modulation by dietary sodium influences NAFLD development in mice(ELSEVIER ESPANA, 2021) Cabrera, Daniel; Rao, Isabel; Raasch, Fabiola; Solis, Nancy; Pizarro, Margarita; Freire, Mariela; De Urturi, Diego Saenz; Ramirez, Carolina A.; Triantafilo, Nicolas; Leon, Jonathan; Riquelme, Arnoldo; Barrera Martínez, Francisco; Baudrand, Rene; Aspichueta, Patricia; Arrese, Marco; Arab, Juan P.Introduction and Objectives: Nonalcoholic-fatty-liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Mineralocorticoid receptor (MR) activation is associated with increased risk of MetS but few studies have assessed the role of liver MR on NAFLD. We aimed to evaluate the effect of MR modulation by sodium intake in liver injury in experimental models of NAFLD.
- ItemNeurogastroenterology and motility disorders in patients with cirrhosis(Lippincott Williams and Wilkins, 2025) Idalsoaga Ferrer, Francisco Javier; Ayares Campos, Gustavo Ignacio; Blaney, Hanna; Cabrera, Daniel; Chahuan Abde, Javier Nicolas; Monrroy Bravo, Hugo Alfonso; Matar, Ayah; Halawi, Houssam; Arrese Jimenez Marco Antonio; Arab Verdugo, Juan Pablo; Díaz Piga, Luis AntonioNeurogastroenterology and motility disorders are complex gastrointestinal conditions that are prevalent worldwide, particularly affecting women and younger individuals. These conditions significantly impact the quality of life of people suffering from them. There is increasing evidence linking these disorders to cirrhosis, with a higher prevalence compared to the general population. However, the link between neurogastroenterology and motility disorders and cirrhosis remains unclear due to undefined mechanisms. In addition, managing these conditions in cirrhosis is often limited by the adverse effects of drugs commonly used for these disorders, presenting a significant clinical challenge in the routine management of patients with cirrhosis. This review delves into this connection, exploring potential pathophysiological links and clinical interventions between neurogastroenterology disorders and cirrhosis.
- ItemNew steatotic liver disease criteria diagnostic performance in an agricultural population in Chile(2025) Spencer Sandino, María de los Ángeles; Godoy, Franco; Huidobro, Laura; Alvares, Danilo; Cruz, Francisco; Marco, Claudia; Garrido, Macarena; Cabrera, Daniel; Arab, Juan Pablo; Arrese, Marco; Barrera Martínez, Francisco; Ferreccio Readi, CatterinaIntroduction and Objectives: This study aims to assess the performance of Steatotic Liver Disease (SLD) criteria in identifying liver steatosis compared to the NAFLD and MAFLD definitions in an agricultural population in Chile. Patients and Methods: We performed a cross-sectional analysis on the MAUCO cohort, composed of 9,013 individuals aged 38 to 74. Health conditions, socio-demographics, anthropometrics, hepatic ultrasonography, blood pressure, and biological samples were obtained. Participants were classified as NAFLD, MAFLD, or any of the five SLD categories: Metabolic dysfunction-associated steatosis liver disease (MASLD), Metabolic and Alcohol-Associated Liver Disease (MetALD), Alcohol-Associated Liver Disease (ALD), Specific aetiologies, and Cryptogenic. The Framingham cardiovascular risk score and BARD liver fibrosis score were used to assess clinical relevance. Results: Liver steatosis was present in 4,082 participants (45%); SLD criteria captured an additional 176 individuals not classified under NAFLD and 103 not included under MAFLD definition. The main SLD subgroups were MASLD (95%), MetALD (1.9%) and ALD (1.3%). Individuals classified in the MetALD and ALD subgroups exhibited more severe liver steatosis and a higher cardiovascular risk. Notably, participants categorized under specific etiologies and cryptogenic subgroups were younger and had a higher risk for liver fibrosis. Conclusions: The study reveals that SLD offers a more inclusive classification to identify high-risk individuals in the Chilean population, capturing cases that could be missed by NAFLD or MAFLD definitions by using the same resources.
- ItemPredictive value of history and physical examination for the diagnosis of community-acquired pneumonia in adults(2007) Saldias, Fernando; Cabrera, Daniel; de Solminihac, Ignacio; Hernandez, Pamela; Gederlini, Alessandra; Diaz, AlejandroBackground- Community-acquired pneumonia in adults is a serious health problem in the ambulatory care setting. Aim To define clinical variables associated with the presence of pneumonia in adult patients presenting with fever or respiratory symptoms to the emergency department. Material and methods: Prospective study carried out in the emergency department from the Catholic University Hospital in Santiago, Chile. Three hundred twenty-five patients (53 22 years) presenting fever or acute respiratory symptoms were included. After obtaining a clinical history and physical examination, the physician established a tentative diagnosis. Subsequently, a definitive diagnosis was made with the chest X rays. Results: Thirty-four percent of the patients had pneumonia. The clinical diagnosis of pneumonia before X-ray examination, was variable among emergency physicians (positive likelihood ratio 1.5-4.8) and showed only moderate sensitivity (79%) and specificity (66%). The clinical variables significantly associated with the presence of pneumonia were: advanced age (over 75 years), cardiovascular disease, fever, chills, sputum production, orthopnea, altered mental status, cyanosis, dullness on percussion, bronchial breath sounds, crackles, any abnormal vital sign (heart rate >= 100 beats/min, respiratory rate >= 20 breaths/min or temperature >= 38 degrees C) and oxygen. saturation below 90% breathing air Conclusions: Clinical judgment prior to observation. of chest X rays had moderate sensitivity and specificity for the diagnosis of pneumonia. There were no individual clinical findings, or combination of findings, that could confirm or exclude the diagnosis of pneumonia for a patient suspected of having this illness.
- ItemPrevention and control of risk factors in metabolic and alcohol-associated steatotic liver disease(2024) Desalegn, Hailemichael; Farias Siel, Renata Francisca; Hudson, David; Idalsoaga Ferrer, Francisco Javier; Cabrera, Daniel; Díaz Piga, Luis Antonio; Arab Verdugo, Juan PabloSteatotic liver disease (SLD), including metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), is the primary cause of illness and mortality. In particular, MASLD affects more than 30% of the global population, while ALD accounts for 5.1% of all diseases and injuries worldwide. The SLD spectrum includes a variety of clinical conditions, from mild fatty liver and inflammation to different stages of liver fibrosis. Additionally, both conditions (MASLD and ALD) can be complicated by hepatocellular carcinoma (HCC), while around one-third of ALD patients can also develop at least one alcohol associated hepatitis (AH) episode. Both of these diseases are also associated with multiple extrahepatic complications, such as cardiovascular disease, chronic kidney disease, and malignancies. In MASLD, the rapid rise in global obesity and type 2 diabetes mellitus (T2DM) prevalence due to Westernized lifestyles has led to an increase in the prevalence of MASLD. Thus, the prevention and control of cardiometabolic risk factors (CMRFs) are the cornerstone of its treatment. Hypertension and atherogenic dyslipidemia are also important CMRFs associated with MASLD. Susceptible individuals with MASLD are adversely affected by even a small amount of alcohol consumption (though there is no agreed definition of a small amount), increasing the risk of severe outcomes and a faster progression of liver disease. This review explores factors that play a role in the development of SLD, especially focusing on the management of CMRFs and levels of alcohol use to prevent liver disease progression.
- ItemReducing CTGF/CCN2 slows down mdx muscle dystrophy and improves cell therapy(2013) Morales France, María Gabriela; Gutiérrez Pérez, Jaime Agustín; Cabello Verrugio, Claudio Alejandro; Cabrera, Daniel; Lipson, Kenneth E.; Goldschmeding, Roel; Brandan, Enrique