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Norberto C Chavez-Tapia,1,2 Sofía Murúa-Beltrán Gall,1 Ana Luisa Ordoñez-Vázquez,1 Natalia Nuño-Lambarri,2 Paulina Vidal-Cevallos,1 Misael Uribe1 1Gastroenterology Department, Medica Sur Clinic & Foundation, Mexico City, Mexico; 2Transational Research Department, Medica Sur Clinic & Foundation, Mexico City, MexicoCorrespondence: Norberto C Chavez-Tapia, Gastroenterology Department, Medica Sur Clinic & Foundation, Puente de Piedra 150. Col. Toriello Guerra, Tlalpan, Mexico City, CP 14050, Mexico, Email nchavezt@medicasur.org.mxAbstract: Hepatocellular carcinoma (HCC) and metabolic syndrome (MetS) have a rising prevalence worldwide. The relationship between these two entities has long been studied and understanding it has become a public health and clinical priority. This association follows, in most patients, the path through non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis and finally HCC. Nonetheless, increasing evidence has been found, that shows MetS as an independent risk factor for the development of HCC. This review brings together the clinical evidence of the relationship between these highly prevalent diseases, with a particular interest in the impact of each component of MetS on HCC; It aims to summarize the complex physiopathological pathways that explain this relationship, and to shed light on the different clinical scenarios of this association, the impact of treating the different components of MetS on the risk of HCC and what is known about screening for HCC in patients with MetS. By doing so, it hopes to improve awareness on this topic.Keywords: metabolic syndrome, hepatocellular carcinoma, excess body weight, diabetes mellitus, non-alcoholic fatty liver disease

Introduction: Obesity is one of the biggest modern health issues worldwide. Owing to the failure of both behavioral and pharmacological measures, the surgical approach has been established as the main conduct to follow, with bariatric surgery being one of the most effective and safe procedures. One of the bases for the optimal analgesic strategy is the use of adjuvants during the perioperative period. One of the main drugs in use is lidocaine., Aim: To evaluate postoperative pain after perioperative lidocaine infusion in patients undergoing bariatric surgery and describe the presence of nausea and vomiting during the first 24 h., Methods: This was a retrospective study of patients who underwent laparoscopic bariatric surgery at ABC Medical Center. Two study arms were established: a group of patients who received lidocaine infusion and a control group. The presence of pain, nausea, or vomiting was evaluated upon admission to the recovery area and 1 h and 24 h after the intervention. The normal distribution of the data was first verified via the Shapiro-Wilk test. The data are presented as medians for quantitative variables and as frequencies for qualitative variables., Results: A total of 50 surgeries were performed, with a significant correlation between lidocaine infusion and lower pain values at 1 h (p = 0.04). Similarly, there was a marked trend in the presence of nausea in control group 4 (18.6%) vs. 15 (53.5%)., Conclusions: Our data suggest that the use of intraoperative lidocaine infusion is limited in postoperative pain management; nonetheless, it significantly improves the incidence of postoperative nausea., (© 2024. The Author(s).)

One potential complication in bariatric surgery is rhabdomyolysis, which is a condition involving muscle tissue damage that can significantly impact a patient's health. The causes of rhabdomyolysis can be broadly classified into two major categories: traumatic and non-traumatic. Early investigations into the development of intraoperative rhabdomyolysis in bariatric surgery identified the main risk factors as tissue compression-primarily affecting the lower extremities, gluteal muscles, and lumbar region-as well as prolonged periods of immobilization. Clinically, rhabdomyolysis is typically suspected when a patient presents with muscle pain, weakness, and potentially dark urine or even anuria. However, the most reliable biomarker for rhabdomyolysis is elevated serum creatine kinase levels. The primary goal in managing hydration is to correct intravascular volume depletion, with solutions such as Lactated Ringer's or 0.9% saline being appropriate options for resuscitation. Perioperative diagnosis of rhabdomyolysis poses a significant challenge for anesthesiologists, requiring a high degree of clinical suspicion, particularly in bariatric patients. In this vulnerable population, prevention is crucial. The success of treatment depends on its early initiation; however, there are still significant limitations in the therapies available to prevent renal injury secondary to rhabdomyolysis.

Robotic surgery has emerged as a cornerstone in urological interventions, offering effectiveness and safety for patients. For anesthesiologists, this technological advancement presents a myriad of new challenges, spanning from patient selection and assessment to intraoperative dynamics and post-surgical pain management. This article aims to elucidate these challenges and provide guidance for anesthesiologists in navigating the complexities of anesthesia administration in robotic urological procedures. Through a detailed exploration of patient optimization, team coordination, intraoperative adjustments, and post-surgical care, this article serves as a valuable resource for ensuring the success of such interventions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a term that entails a broad spectrum of conditions that vary in severity. Its development is influenced by multiple factors such as environment, microbiome, comorbidities, and genetic factors. MASLD is closely related to metabolic syndrome as it is caused by an alteration in the metabolism of fatty acids due to the accumulation of lipids because of an imbalance between its absorption and elimination in the liver. Its progression to fibrosis is due to a constant flow of fatty acids through the mitochondria and the inability of the liver to slow down this metabolic load, which generates oxidative stress and lipid peroxidation, triggering cell death. The development and progression of MASLD are closely related to unhealthy lifestyle habits, and nutritional epigenetic and genetic mechanisms have also been implicated. Currently, lifestyle modification is the first-line treatment for MASLD and nonalcoholic steatohepatitis; weight loss of ≥10% produces resolution of steatohepatitis and fibrosis regression. In many patients, body weight reduction cannot be achieved; therefore, pharmacological treatment should be offered in particular populations.

Background: Pancreatic cancer is a lethal proliferative disease driven by multiple genetic and epigenetic alterations. Microarrays and omics-based sequencing techniques are potent tools that have facilitated a broader understanding of the complex biological processes that drive pancreatic ductal adenocarcinoma (PDAC). In turn, these tools have resulted in the identification of novel disease markers, prognostic factors, and therapeutic targets. Herein, we provide a review of the genetic and epigenetic drivers of PDAC relative to recent discoveries that impact patient management., Methods: A review of PubMed, Medline, Clinical Key, and Index Medicus was conducted to identify literature from January 1995 to July 2022 that is related to PDAC genetics and epigenetics. Articles in Spanish and English were considered during selection., Results: Molecular, genetic, and epigenetic diagnostic tools, novel biomarkers, and promising therapeutic targets have emerged in the treatment of pancreatic cancer. The implementation of microarray technology and application of large omics-based data repositories have facilitated recent discoveries in PDAC. Multiple molecular analyses based on RNA interference have been instrumental in the identification of novel therapeutic targets for patients with PDAC. Moreover, microarrays and next-generation omics-based discoveries have been instrumental in the characterization of subtypes of pancreatic cancer, thereby improving prognostication and refining patient selection for available targeted therapies., Conclusion: Advances in molecular biology, genetics, and epigenetics have ushered in a new era of discovery in the pathobiology of PDAC. Current efforts are underway to translate these findings into clinical tools and therapies to improve outcomes in patients with PDAC., (© 2023. The Society for Surgery of the Alimentary Tract.)

Metabolically associated fatty liver disease, formerly called nonalcoholic fatty liver disease, is the most common liver disease globally, representing the third cause of liver transplantation. Metabolically associated fatty liver disease is defined as having more than 5% lipid droplets in hepatocytes without other concomitant liver diseases. Various stimuli such as the secretion of inflammatory cytokines, mitochondrial and endoplasmic reticulum dysfunction due to oxidative stress, alteration of the intestine-liver axis, bacterial dysbiosis, as well as genetic and epigenetic factors can modify the progression of metabolically associated fatty liver disease to fibrosis, cirrhosis, and may reach hepatocellular carcinoma. Epigenetics is responsible for a highly sophisticated regulatory system that controls many cellular processes in response to multiple environmental factors as an adaptive mechanism unrelated to alterations in the primary deoxyribonucleic acid sequence, including gene expression, microRNAs, DNA methylation, modifications in histones, and DNA-protein interactions. Several studies have shown that epigenetic changes are associated with various diseases, including metabolically associated fatty liver disease. Nutri epigenomics is the interaction between nutrition and components at the transcriptional or post-transcriptional level. Methylation processes involve micronutrients that regulate epigenetic states in a physiological and pathological context. Micronutrients such as methionine, folate, and choline are the main components of one-carbon metabolism, functioning as methyl group donors, and their deficiency predisposes to various pathologies such as metabolically associated fatty liver disease. Understanding of epigenetic modifiers leads us to develop new therapeutic therapies for patients with metabolically associated fatty liver disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Metabolic (dysfunction) associated fatty liver disease (MAFLD) and cholelithiasis are highly prevalent and are associated with common risk factors such as obesity, hypertriglyceridemia, and fasting glucose levels; however, it is not clear whether cholelithiasis is associated with MAFLD or fibrosis., Objective: To determine MAFLD severity and associated risk factors in patients diagnosed with cholelithiasis., Materials and Methods: Observational, cross-sectional and prolective study (from October 2018 to March 2020) of patients undergoing elective laparoscopic cholecystectomy with liver biopsy, excluding other causes of hepatic disease or significant alcohol consumption. MAFLD detection was based on histology using the Kleiner score and one of the following criteria: overweight/obesity, T2DM, or evidence of metabolic dysregulation. The AST to Platelet Ratio Index, the NAFLD Fibrosis Score, the fibrosis-4 index and the hepatic steatosis index were performed to assess the relationship of non-invasive hepatic scores with histopathology., Results: 80 patients median age (interquartile range) was 42 (18) years, with a BMI of 27.9 (6.11) Kg/m 2 . Of all patients, 58.8% had MAFLD, 78.7% were women, and 13.8% had the severe form (formerly named NASH). No substantial correlation between biochemical parameters and histopathological analysis of MAFLD and fibrosis was observed., Conclusion: Because cholelithiasis and MAFLD are highly prevalent diseases, it is essential to conduct studies on the relationship between both pathologies. Currently, liver biopsy is the best diagnostic method since the predictive biochemical models did not show a substantial correlation to classify MAFLD. Its early detection is relevant since a considerable percentage of advanced fibrosis (8.7%) was found., Competing Interests: Conflicts of interest Itzayana Rodríguez-Antonio, Guillermo N. López-Sánchez, Víctor A. Reyes-Gómez, Ericka H. Contreras-Flores, Fernanda Farías-García, Mariana Espejel-Deloiza, Marco A. Durán-Padilla, Fredy Chablé-Montero, Misael Uribe, Norberto C. Chávez-Tapia, Eduardo E. Montalvo-Javé and Natalia Nuño-Lámbarri have no related conflicts of interest to declare., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Pyroptosis is a type of programmed cell death mediated by a multiprotein complex called the inflammasome through the pro-inflammatory activity of gasdermin D. This study aimed to recognize the final biological product that leads to pore formation in the cell membrane, lysis, pro-inflammatory cytokines release, and the establishment of an immune response. An exhaustive search engine investigation of an elevated immune response can induce a sustained inflammation that directly links this mechanism to non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis. Clinical studies and systematic reviews suggest that gasdermin D is a critical molecule between the immune response and the disease manifestation, which could be considered a therapeutic target for highly prevalent diseases characterized by presenting perpetuated inflammatory processes. Both basic and clinical research show evidence on the expression and regulation of the inflammasome-gasdermin D-pyroptosis trinomial for the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Non-alcoholic fatty liver disease is defined as hepatic fat accumulation in more than 5% of hepatocytes, without other liver steatosis causes. It comprises a broad spectrum that can range from benign steatosis and progress to non-alcoholic steatohepatitis, fibrosis, and ultimately hepatocellular carcinoma. Non-alcoholic fatty liver is considered a multisystemic disease since it is related to multiple disorders, such as type 2 diabetes mellitus, polycystic ovary syndrome, chronic kidney disease, psoriasis, osteoporosis, hypothyroidism, cardiovascular diseases, and obstructive sleep apnea syndrome; it is becoming increasingly clear that it is also a risk factor for developing certain respiratory diseases. This article aims to understand the liver and chronic obstructive pulmonary disease mechanisms, obstructive sleep apnea syndrome, asthma, and lung cancer. Given that non-alcoholic fatty liver disease has a considerable impact on the patient's well-being and life quality, as well as on the costs they generate for the country's health services, it is essential to continue research, especially in areas such as the respiratory tract, as there is much misinformation about it., (Copyright © 2021 AEDV. Published by Elsevier España, S.L.U. All rights reserved.)

The obesity pandemic that affects the global population generates one of the most unfavorable microenvironmental conditions in the hepatocyte, which triggers the metabolic hepatopathy known as non-alcoholic fatty liver; its annual rates increase in its prevalence and does not seem to improve in the future. The international consortia, LITMUS by the European Union and NIMBLE by the United States of America, have started a race for the development of hepatic steatosis and steatohepatitis reliable biomarkers to have an adequate diagnosis. MicroRNAs have been proposed as diagnostic and prognostic biomarkers involved in adaptation to changes in the liver microenvironment, which could improve clinical intervention strategies in patients with hepatic steatosis., (Copyright © 2020 AEDV. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Hepatic steatosis and gallstone disease are highly prevalent in the general population; the shared risk factors are age, ethnicity, obesity, insulin resistance, metabolic syndrome, atherosclerosis, risk of cardiovascular disease, and mortality. The presence of insulin resistance is the critical element in this association because it represents a crucial link between metabolic syndrome and non-alcoholic fatty liver disease, as well as a higher susceptibility to gallstone formation., Methods: An exhaustive search engine investigation of gallstone disease, cholecystectomy, and liver steatosis latest literature was made., Results: Clinical studies and systematic reviews suggest an association between gallstone disease, cholecystectomy, and hepatic steatosis., Conclusion: The bidirectional relationship between liver steatosis and gallstone disease and cholecystectomy is summarized in the role of insulin resistance, lipid metabolism, bile acids signaling pathways regulated by transcription factors expression, and to the gallbladder physiological role; however, more epidemiological and experimental studies should be complemented., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction and Objectives: The association between non-alcoholic fatty liver disease and cerebral hemodynamics arises from cardiovascular damage mechanisms such as endothelial dysfunction, arterial wall increased stiffness, high thickness of the intimate index of the internal carotid artery, left ventricular hypertrophy, left diastolic dysfunction, calcification coronary arteries and increased epicardial fat. The multidirectional relationship between systemic inflammation and lipid metabolism constitutes a common and simultaneous mechanism that causes vascular damage. This study aims to provide insight into the relationship between non-alcoholic fatty liver disease and the function of systemic circulation and cerebral circulation using Doppler ultrasound., Patients and Methods: Is an observational, cross-sectional, prospective, comparative study conducted at Medica Sur Hospital. Thirty-five patients were selected consecutively. The patients consulted neurological service for various symptoms without severity criteria, such as vertigo, primary headache and balance disturbances., Results: There is a difference in the variables mean of the right MCA PI (p = 0.023), left MCA PI" (p = 0.004), and left VA PI (p = 0.036) between the control and NAFLD groups. The correlation analysis between these variables and the CAP showed a positive correlation of the three variables with the CAP, "right MCA PI" (r = 0.384), left MCA PI "(r = 0.509) and" left VA PI " (r = 0.551)., Conclusions: This study demonstrates a subclinical process of the middle cerebral artery in subjects with NAFLD, which suggests it may be involved in the disease development and points the need to make decisions for this liver manifestation prevention and treatment., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: nonalcoholic fatty liver disease (NAFLD) comprises a broad spectrum of diseases, which can progress from benign steatosis to nonalcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma. NAFLD is the most common chronic liver disease in developed countries, affecting approximately 25% of the general population. Insulin resistance, adipose tissue dysfunction, mitochondrial and endoplasmic reticulum stress, chronic inflammation, genetic and epigenetic factors are NAFLD triggers that control the disease susceptibility and progression., Areas Covered: In recent years a large number of investigations have been carried out to elucidate genetic and epigenetic factors in the disease pathogenesis, as well as the search for diagnostic markers and therapeutic targets. This paper objective is to report the most studied genetic and epigenetic variants around NAFLD., Expert Opinion: NAFLD lead to various comorbidities, which have a considerable impact on the patient wellness and life quality, as well as on the costs they generate for the country's health services. It is essential to continue with molecular research, since it could be used as a clinical tool for prognosis and disease severity. Specifically, in the field of hepatology, plasma miRNAs could provide a novel tool in liver diseases diagnosis and monitoring, representing an alternative to invasive diagnostic procedures.

Disorders of vitamin D concentration (deficiency or insufficiency) are a global health problem, which are associated with various chronic diseases. In Latin America, alterations in vitamin D prevalence are different from those shown in previous studies and may be due to differences in geographic location, skin color, and diet type., Purpose: To know the prevalence of vitamin D insufficiency (21-29 ng/mL) and deficiency (< 20 ng/mL) in Mexican patients; although it is a risk factor for developing multiple complex diseases, its prevalence in the population is still unknown., Methods: Cross-sectional study carried out at the endocrinology service of the highly specialized national center November 20. Data on cardiovascular risk factors were obtained and 25-hydroxy vitamin D was measured by chemiluminescence. Prevalence was calculated, and the results were analyzed to categorize the patients according to 25-hydroxy vitamin D deficient or insufficient levels., Results: The mean value of the serum vitamin D concentration was 18.37 ng/mL. Of the 117 patients, 93.2% (n = 109) have decreased vitamin D values; 62.4% (n = 73) of the patients had vitamin D deficiency and 30.8% (n = 36) vitamin D insufficiency. The prevalence of vitamin D deficiency was 62.4% and 30.8% for vitamin D insufficiency. The total prevalence of alterations in vitamin D levels in this population was 93.2%., Conclusions: This study reports a prevalence of vitamin D deficiency and insufficiency much higher than those described by previous studies, which is of utmost importance for the population due to the morbidities associated with these alterations.

Introduction and Objectives: Polycystic ovary syndrome (PCOS) is the most common endocrinology disorder in women of reproductive age; these patients have a higher risk of suffering from non-alcoholic fatty liver disease (NAFLD). We determine the frequency of NAFLD in Mexican patients with PCOS and matched-controls., Patients and Methods: Cross-sectional study, with 98 women of 18-44 years old. Rotterdam 2003 criteria integrated PCOS diagnosis. Those with significant alcohol consumption, chronic liver disease, use of steatogenic drugs, and pharmacological PCOS treatment or fertility protocol were excluded. Controls were matched in a 1:1 ratio by age and body mass index (BMI). The presence of NAFLD was determined by transient elastography performed by a single experienced operator., Results: A total of 98 female volunteers at reproductive age were recruited. NAFLD denoted markedly higher in patients with than without PCOS at 69.3% vs. 34.6%, respectively. Compared to controls, PCOS patients had a significantly higher risk of NAFLD (OR=4.26, 95% CI 1.83-9.93). Severe steatosis was the most frequent NAFLD stage between women with PCOS and NAFLD. Patients with hyperandrogenism have a significantly higher mean CAP 277.83dB/m than controls without hyperandrogenism 191.57dB/m. NAFLD prevalence was 84.3% in PCOS patients with phenotype A, while in another phenotype, it was 41.1%., Conclusions: PCOS is an independent risk factor for NAFLD development. NAFLD screening needs to be considered in all PCOS patients independently of BMI, except in PCOS patients without hyperandrogenism and BMI<25., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Acute-on-chronic liver failure (ACLF) is a life-threatening condition characterized by a rapid deterioration of previously well-compensated chronic liver diseases. One of the main obstacles in ACLF is the lack of knowledge of the pathogenesis and specific broad-spectrum treatments. An excessive systemic inflammatory response has been proposed to explain the pathogenesis of ACLF; this hypothesis involves stellate cells, which are implicated in many liver homeostatic functions that include vitamin A storage, regulation of sinusoidal blood flow, local inflammation, maintenance of the hepatocyte phenotype and extracellular matrix remodeling. However, when there is damage to the liver, these cells are the main target of the inflammatory stimulus, as a result, the secretion of the extracellular matrix is altered. Activated hepatic stellate cells raise the survival of neutrophils by the stimulation of granulocytes colonies and macrophages, which exacerbates liver inflammation and promotes damage to hepatocytes. Elevation of pathogen-associated molecular patterns is related to liver damage by different pathophysiological mechanisms of decompensation, showing ballooning degeneration and cell death with a predominance of cholestatic infection. Moreover, patients with ACLF present a marked elevation of C-reactive protein together with an elevation of the leukocyte count. Chronic liver disease is a complex pathological state with a heterogeneous pathophysiology in which genetic factors of the host and external triggers interact and culminate in hepatic insufficiency. The better understanding of such interactions should lead to a better comprehension of the disease and to the discovery of new treatment targets that will make acute decompensations preventable and even decrease mortality.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women. Patients with non-alcoholic fatty liver disease (NAFLD) often suffer from metabolic syndrome, atherosclerosis, ischemic heart disease, and extrahepatic tumors, conferring a lower survival than the general population; therefore it is crucial to study the association between NAFLD and PCOS since it remains poorly understood. Insulin resistance (IR) plays a central role in the pathogenesis of NAFLD and PCOS; also, hyperandrogenism enhances IR in these patients. IR, present in the NAFLD-PCOS association could decrease the hepatic production of sex hormone-binding globulin through a possible regulation mediated by hepatocyte nuclear factor 4 alpha. On the other hand, apoptotic processes initiated by androgens actively contribute to the progression of NAFLD. Considering the association between the two conditions, the screening of women with PCOS for the presence of NAFLD appears reasonable. The pathophysiological mechanisms of PCOS-NAFLD association and the initial approach will be reviewed here., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) represents a broad spectrum of liver damage, ranging from simple steatosis to steatohepatitis and fibrosis; as well, there is a close association between NAFLD, obesity, metabolic syndrome and type 2 diabetes mellitus. There is a certain degree of uncertainty regarding the natural history and prognosis of NAFLD; however, several methods are currently used for its diagnostic approach. In the first instance, non-invasive tests could be used to identify patients at low risk of developing fibrosis and to establish more easily the need for a liver biopsy, whose accuracy in the evaluation of fibrosis has been questioned, mainly due to errors of intra and interobserver sampling, technical problems and cost, which limits its use. Therefore, it is essential to determine the diagnostic strategy for patients with NAFLD., Competing Interests: Nicolás Salva-Pastor, Norberto C. Chávez-Tapia, Misael Uribe and Natalia Nuño-Lámbarri certify that have no commercial associations (e.g., consultancies, stock ownership, equity interests, patent-licensing arrangements) that might pose a conflict of interest in connection with the submitted article., (©2019 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

Mitochondrial cholesterol accumulation is a hallmark of alcoholic and non-alcoholic fatty liver diseases and impairs the function of specific solute carriers through changes in membrane physical properties. However, its impact on mitochondrial respiration and organization of respiratory supercomplexes has not been determined so far. Here we fed mice a cholesterol-enriched diet (HC) supplemented with sodium cholate to examine the effect of cholesterol in mitochondrial function. HC feeding increased liver cholesterol content, which downregulated Srebp2 and Hmgcr expression, while sodium cholate administration decreased Cyp7a1 and Cyp8b1 mRNA levels, suggesting the downregulation of bile acid synthesis through the classical pathway. HC-fed mice exhibited increased expression of Stard1 and Mln64 and enhanced mitochondrial free cholesterol levels (2-3 fold), leading to decreased membrane fluidity. Mitochondria from HC-fed mice displayed increased cholesterol loading in both outer and inner mitochondrial membranes. Cholesterol loading decreased complex I and complex II-driven state 3 respiration and mitochondrial membrane potential. Decreased respiratory and uncoupling control ratio from complex I was also observed after in situ enrichment of mouse liver mitochondria with cholesterol or enantiomer cholesterol, the mirror image of natural cholesterol. Moreover, in vivo cholesterol loading decreased the level of complex III 2 and the assembly of respiratory supercomplexes I 1 +III 2 +IV and I 1 +III 2 . Moreover, HC feeding caused oxidative stress and mitochondrial GSH (mGSH) depletion, which translated in hepatic steatosis and liver injury, effects that were rescued by replenishing mGSH with GSH ethyl ester. Overall, mitochondrial cholesterol accumulation disrupts mitochondrial functional performance and the organization of respiratory supercomplexes assembly, which can contribute to oxidative stress and liver injury., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of histopathological changes ranging from non-inflammatory intracellular fat deposition to non-alcoholic steatohepatitis (NASH), which may progress into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. Recent data suggest that impaired hepatic cholesterol homeostasis and its accumulation are relevant to the pathogenesis of NAFLD/NASH. Despite a vital physiological function of cholesterol, mitochondrial dysfunction is an important consequence of dietary-induced hypercholesterolemia and was, subsequently, linked to many pathophysiological conditions. The aim in the current study was to evaluate the morphological and molecular changes of cholesterol overload in mouse liver and particularly, in mitochondria, induced by a high-cholesterol (HC) diet for one month. Histopathological studies revealed microvesicular hepatic steatosis and significantly elevated levels of liver cholesterol and triglycerides leading to impaired liver synthesis. Further, high levels of oxidative stress could be determined in liver tissue as well as primary hepatocyte culture. Transcriptomic changes induced by the HC diet involved disruption in key pathways related to cell death and oxidative stress as well as upregulation of genes related to glutathione homeostasis. Impaired liver function could be associated with a decrease in mitochondrial membrane potential and ATP content and significant alterations in mitochondrial dynamics. We demonstrate that cholesterol overload in the liver leads to mitochondrial changes which may render damaged hepatocytes proliferative and resistant to cell death whereby perpetuating liver damage., (© 2018 Wiley Periodicals, Inc.)

Several microorganisms belonging to the intestinal microbiota act in an ecosystem responsible for maintaining the homeostasis and vital functions of human beings. From birth to old age the diversity of the intestinal microbiota may change due to environmental factors such as nutrition, immunity, diseases or the use of antibiotics leading to dysbiosis. Improvement in microbiota diversity can be achieved by modifying related risk factors through changes in lifestyle and a healthy diet. Besides, the addition of probiotics, prebiotics or the combination of both (symbiotics), can result in the improvement of the intestinal permeability, inflammatory pathways and the immune system. Also, the use of probiotics prevents harmful bacteria and their derived products (e.g., bacteriocins, endotoxins, hydrogen sulfide, etc.) to leak through the intestinal wall to the circulation that results in the activation of signaling pathways that may be implicated in liver disease. The liver receives a constant flow of noxious entities that promote inflammation and oxidative stress. The use of probiotics with clinical evidence in liver disease, represent a novel therapeutic alternative, inducing positive changes in the balance of the intestinal microbiota which lead to improvement in liver function tests (AST and ALT), decreasing tumor necrosis factor-α (TNF-α), andblood cholesterol, among other risk factors. In this review, we discuss the main elements that play a leading role in the development of steatosis as well as the benefits of using probiotics and the impact in the quality of life of patients that develop cirrhosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction and Aim: Nonalcoholic fatty liver disease (NAFLD) is closely associated with overweight and obesity, becoming one of the most prevalent hepatic diseases nowadays. Circulating hemoglobin (Hb) concentration is significantly higher in people with NAFLD, compared to healthy patients. While liver biopsy remains the gold standard for NAFLD diagnosis, it is not the best technique due to adverse events that may occur. Therefore it is important to find less invasive and more sensitive markers. This study aimed to determine the association of serum Hb levels in patients with steatosis and fibrosis as a noninvasive marker., Material and Methods: A 1,186 patient cross-sectional study nested in a randomized clinical trial (NCT01874249) was conducted. Patients were diagnosed by ultrasound for hepatic steatosis and fibroscan for fibrosis; blood test and anthropometric measurements were also assessed., Results: Serum Hb increased proportionally related to the steatosis level, being significantly higher in patients with severe steatosis than in patients with moderate and mild steatosis., Conclusion: Patients with non-alcoholic fatty liver disease showed elevated levels of circulating Hb, evidence that suggests that Hb exerts a protective role, as it may act as an antioxidant and may counteract the adverse effects of this disease.

Mexico owns approximately 4500 medicinal plants species, a great diversity that position it at the second place after China. According to the Mexican health department, 90% of common population consumes them to treat various diseases. Additionally, herbal remedies in Latin America (LA) are considered a common practice, but the frequency of use and the liver damage related to its consumption is still unknown. Despite the high prevalence and indiscriminate herbal consumption, the exact mechanism of hepatotoxicity and adverse effects is not fully clarified and is still questioned. Some herb products associated with herb induced liver injury (HILI) are characterized by presenting a different chemical composition that may vary from batch to batch, also the biological activity of many medicinal plants and other natural products are directly related to their most active component and its concentration. There are two main biological components that are associated with liver damage, alkaloids, and flavonoids, which are frequent constituents of commonly used herbs. The interaction with the different cytochrome P-450 isoforms, inflammatory, and oxidative activities seem to be the main damage pathway involved in the liver. It is important to know the herbal adverse effects and mechanisms involved; therefore, this article is focused on the beneficial and deleterious effects as well as the possible toxicity mechanisms and interactions of the herbs that are frequently used in LA, since the herb-host interaction may not always be the expected or desired depending on the clinical context in which it is administered.

Cholestasis results from defective bile flow through the biliary ducts leading to the accumulation of bile acids (BAs) in hepatocytes and serum. It has been seen that cholestasis is associated with hypercholesterolemia, which is a prerequisite for gallstone formation and primary biliary cirrhosis, being some of the most common gastrointestinal disorders in Western societies. Cytotoxic BAs induce proinflammatory mediators, oxidative stress, and apoptosis in hepatocytes, whereas cytoprotective BAs prevent them; they can also modify the plasmatic membrane structure of cells or mitochondrial outer membrane properties as well as the distribution of cholesterol, altering various proteins involved in BAs homeostasis., (© 2016 Wiley Periodicals, Inc.)

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition that can progress to nonalcoholic steatohepatitis, cirrhosis and cancer. It is considered an emerging health problem due to malnourishment or a high-fat diet (HFD) intake, which is observed worldwide. It is well known that the hepatocytes' apoptosis phenomenon is one of the most important features of NAFLD. Thus, this review focuses on revealing, through a proteomics approach, the complex network of protein interactions that promote fibrosis, liver cell stress, and apoptosis. According to different types of in vitro and murine models, it has been found that oxidative/nitrative protein stress leads to mitochondrial dysfunction, which plays a major role in stimulating NAFLD damage. Human studies have revealed the importance of novel biomarkers, such as retinol-binding protein 4, lumican, transgelin 2 and hemoglobin, which have a significant role in the disease. The post-genome era has brought proteomics technology, which allows the determination of molecular pathogenesis in NAFLD. This has led to the search for biomarkers which improve early diagnosis and optimal treatment and which may effectively prevent fatal consequences such as cirrhosis or cancer.

Cholesterol overload in the liver has shown toxic effects by inducing the aggravation of nonalcoholic fatty liver disease to steatohepatitis and sensitizing to damage. Although the mechanism of damage is complex, it has been demonstrated that oxidative stress plays a prominent role in the process. In addition, we have proved that hepatocyte growth factor induces an antioxidant response in hepatic cells; in the present work we aimed to figure out the protective effect of this growth factor in hepatocytes overloaded with free cholesterol. Hepatocytes from mice fed with a high-cholesterol diet were treated or not with HGF, reactive oxygen species present in cholesterol overloaded hepatocytes significantly decreased, and this effect was particularly associated with the increase in glutathione and related enzymes, such as γ-gamma glutamyl cysteine synthetase, GSH peroxidase, and GSH-S-transferase. Our data clearly indicate that HGF displays an antioxidant response by inducing the glutathione-related protection system.

Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

The increment in the prevalence of obesity incidence in Mexico is leading to the increase in many chronic maladies, including liver diseases. It is well known that lipid-induced liver sensitization is related to the kind of lipid rather than the amount of them in the organ. Cholesterol overload in the liver aggravates the toxic effects of canonical liver insults. However, the status on the repair and survival response elicited by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the hepatocyte growth factor (HGF) is not completely understood. In the present, work we aimed to figure out the HGF/NADPH oxidase-induced cellular protection in the hepatocyte with a cholesterol overload. Our results show that a hypercholesterolemic diet induced liver damage and steatosis in mice. The hepatocytes isolated from these animals exhibited an increase in basal NADPH oxidase activity, although transcriptional levels of some of its components were decreased. No effect on the oxidase activity was observed in HGF treatments. The protective effect of HGF was abrogated as a result of cholesterol cellular overload, calculated by a survival assay. In conclusion, the cholesterol overload in hepatocytes impairs the HGF/NADPH oxidase-induced cellular protection.

Currently, fatty liver represents a serious public health problem in the Western world. In our country, a large amount of food rich in cholesterol is consumed. Cholesterol is an important component in lipid rafts, where many receptors for growth factors are localized, so its functionality could be altered in the presence of high cholesterol concentration. Hepatocyte growth factor (HGF) and its receptor c-Met are known to promote repair after an injury. The aim in the present work was to study the effect of a high cholesterol diet in the molecular repair process mediated by HGF in hepatocytes and liver tissue. Data show a delay in the activation of the HGF-mediated signaling cascade which results in a deficient repair process, that in the case of a continuous aggression could favor the progression of liver damage.

Background and Aim: Development of hepatic fibrosis is a complex process that involves oxidative stress (OS) and an altered balance between pro- and anti-apoptotic molecules. Since Bcl-2 overexpression preserves viability against OS, our objective was to address the effect of Bcl-2 overexpression in the hepatic stellate cells (HSC) cell-line CFSC-2G under acetaldehyde and H(2)O(2) challenge, and explore if it protects these cells against OS, induces replicative senescence and/or modify extracellular matrix (ECM) remodeling potential., Methods: To induce Bcl-2 overexpression, HSC cell line CFSC-2G was transfected by lipofection technique. Green fluorescent protein-only CFSC-2G cells were used as a control. Cell survival after H(2)O(2) treatment and total protein oxidation were assessed. To determine cell cycle arrest, proliferation-rate, DNA synthesis and senescence were assessed. Matrix metalloproteinases (MMP), tissue-inhibitor of MMP (TIMP), transglutaminases (TG) and smooth muscle a-actin (alpha-SMA) were evaluated by western blot in response to acetaldehyde treatment as markers of ECM remodeling capacity in addition to transforming growth factor-beta (TGF-beta) mRNA., Results: Cells overexpressing Bcl-2 survived approximately 20% more than control cells when exposed to H(2)O(2) and approximately 35% proteins were protected from oxidation, but Bcl-2 did not slow proliferation or induced senescence. Bcl-2 overexpression did not change alpha-SMA levels, but it increased TIMP-1 (55%), tissue transglutaminases (tTG) (25%) and TGF-beta mRNA (49%), when exposed to acetaldehyde, while MMP-13 content decreased (47%)., Conclusions: Bcl-2 overexpression protected HSC against oxidative stress but it did not induce replicative senescence. It increased TIMP-1, tTG and TGF-beta mRNA levels and decreased MMP-13 content, suggesting that Bcl-2 overexpression may play a key role in the progression of fibrosis in chronic liver diseases.