Exploring the Th2 Response in Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Potential Modulator of the Renin-Angiotensin System (RAS) Pathway in Hypertension Development.

Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), is alarmingly increasing alongside the cases of obesity worldwide. MASLD is an underestimated metabolic abnormality closely linked with a higher risk of developing systemic arterial hypertension (SAH). However, the underlying mechanism of association between MASLD and SAH remains unknown. Inflammation may link these two entities by regulating the renin-angiotensin system (RAS). For this reason, in this study, we evaluated the hepatic expression of a cytokine profile and critical molecules in the RAS pathway in patients with morbid obesity and MASLD, both with SAH. We found a statistically significant correlation between ACE levels and the cytokines IL-4, IL-10, and IL-13 of Th2 response. Furthermore, according to a multiple linear regression analysis, the cytokines IL-4 and IL-13 were the best predictors of ACE levels. Moreover, we observed increased hepatic IL-13 expression in patients with morbid obesity, MASLD, and SAH compared to those without SAH. These results allow us to propose, for the first time, that the Th2 response, through regulating the RAS, could play a critical role in developing SAH in individuals with MASLD and obesity.

Decreased Hepatic and Serum Levels of IL-10 Concur with Increased Lobular Inflammation in Morbidly Obese Patients.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods: We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild (n = 7), moderate (n = 19), or severe (n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Results: The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group (p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.005 and p < 0.0001, respectively). Conclusions: In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.

Tuberculosis extrapulmonar en paciente embarazada. Reporte de caso / Extrapulmonary Tuberculosis in Pregnant Patient. Case Report

Introducción: La tuberculosis (TB) extrapulmonar es la afectación de cualquier órgano, sin compromiso pulmonar demostrado, como consecuencia de la diseminación hematógena/linfática del bacilo de Koch. Presentación de caso: Paciente en puerperio inmediato cursando cuadro clínico de gonalgia que se estudió con resonancia magnética que mostró lesión endomedular en región distal del fémur izquierdo. Se estudió con tomografía de tórax, abdomen y pelvis que evidenciaron otras lesiones a nivel esplénico, sin compromiso hepático ni pulmonar. Se realizó punción diagnóstica femoral con evidencia de granulomas con necrosis central. Se interpretó tuberculosis extrapulmonar y se inició tratamiento antifímico con mejora sintomática. Discusión: La TB extrapulmonar puede impactar a nivel de pleura, ganglios linfáticos, vías urinarias, sistema osteoarticular, sistema nervioso central y abdomen. En el embarazo, la prevalencia de TB extrapulmonar es baja. Conclusión: La TB femoral y esplénica concomitante en pacientes embarazadas es un hallazgo infrecuente por lo que su análisis resulta de gran importancia. Arribar al diagnóstico requiere un elevado índice de sospecha. El retraso diagnóstico conlleva a un aumento de la morbimortalidad

Introduction: Extrapulmonary tuberculosis (TB) is the involvement of any organ, without demonstrated pulmonary involvement, as a consequence of the hematogenous/lymphatic dissemination of the Koch bacillus. Case presentation: Patient in the immediate postpartum period with clinical symptoms of gonalgia that was studied with magnetic resonance imaging showing intramedullary lesion in the distal region of the left femur. A CT scan of the chest, abdomen and pelvis showed other lesions at the splenic level, without liver or lung involvement. A femoral diagnostic puncture was performed with evidence of granulomas with central necrosis. Extrapulmonary tuberculosis was interpreted and antifimic treatment was started with symptomatic improvement. Discussion: Extrapulmonary TB can impact the pleura, lymph nodes, urinary tract, osteoarticular system, central nervous system and abdomen. During pregnancy, the prevalence of extrapulmonary TB is low. Conclusion: Concomitant femoral and splenic TB in pregnant patients is a rare finding, which is why its analysis is of great importance. Arriving at a diagnosis requires a high index of suspicion. Delayed diagnosis leads to an increase in morbidity and mortalit

Exome Sequencing has a high diagnostic rate in sporadic congenital hypopituitarism and reveals novel candidate genes.

CONTEXT: The pituitary gland is key for childhood growth, puberty, and metabolism. Pituitary dysfunction is associated with a spectrum of phenotypes, from mild to severe. Congenital Hypopituitarism (CH) is the most commonly reported pediatric endocrine dysfunction with an incidence of 1:4000, yet low rates of genetic diagnosis have been reported. OBJECTIVE: We aimed to unveil the genetic etiology of CH in a large cohort of patients from Argentina. METHODS: We performed whole exome sequencing of 137 unrelated cases of CH, the largest cohort examined with this method to date. RESULTS: Of the 137 cases, 19.1% and 16% carried pathogenic or likely pathogenic variants in known and new genes, respectively, while 28.2% carried variants of uncertain significance. This high yield was achieved through the integration of broad gene panels (genes described in animal models and/or other disorders), an unbiased candidate gene screen with a new bioinformatics pipeline (including genes high loss of function intolerance), and analysis of copy number variants. Three novel findings emerged. First, the most prevalent affected gene encodes the cell adhesion factor ROBO1. Affected children had a spectrum of phenotypes, consistent with a role beyond pituitary stalk interruption syndrome. Second, we found that CHD7 mutations also produce a phenotypic spectrum, not always associated with full CHARGE syndrome. Third, we add new evidence of pathogenicity in the genes PIBF1 and TBC1D32, and report 13 novel candidate genes associated with CH (e.g. PTPN6, ARID5B). CONCLUSION: Overall, these results provide an unprecedented insight into the diverse genetic etiology of hypopituitarism.

Sucralose: From Sweet Success to Metabolic Controversies-Unraveling the Global Health Implications of a Pervasive Non-Caloric Artificial Sweetener.

Sucralose is a food additive initially used to mitigate glycemic peaks and calorie intake in patients with diabetes and obesity. Although sucralose has been considered safe for human consumption, the World Health Organization (WHO) issued a global alert in 2023 concerning the potential health implications of this artificial sweetener. This review aims to comprehensively explore the effects of sucralose intake on human health by understanding sucralose absorption, metabolism, and excretion. We also outline the role of the sweet taste 1 receptor 3 (T1R3) in mediating sucralose-dependent signaling pathways that regulate satiety, incretin release, and insulin response. Finally, we discuss the impact of sucralose on microbiome dysbiosis, inflammatory response origin, liver damage, and toxicity. Gaining a deeper understanding of the manifold effects of sucralose on human physiology will help promote further studies to ensure its consumption is deemed safe for a broader population, including children, adolescents, and pregnant women.

Using the model cestode Taenia crassiceps for the study of cysticercosis.

Taenia solium is the aetiological agent of taeniasis/cysticercosis, one of the most severe neglected tropical diseases (NTD) according to the World Health Organization (WHO). The life cycle of T. solium alternates between pigs (intermediate host) and humans (definitive host). In addition, humans can act as accidental intermediate hosts if they ingest infective eggs. In this case, the most severe condition of the disease occurs when parasites invade the central nervous system, causing neurocysticercosis (NCC). The complexity of the life cycle of T. solium imposes a barrier to study this pathogen thoroughly. Thus, related species, such as T. crassiceps are commonly used. Due to its capacity to multiply asexually, T. crassiceps can be maintained by serial passage in laboratory mice in standard biosecurity level facilities. In addition, an in vitro system to generate cysticerci in the presence of feeder cells has been recently developed. Despite model species display biological differences with their zoonotic counterparts, they have historically helped to understand the biology of the related pathogenic species and hence, generate improvements in NTD detection and control. In this chapter, we describe the procedures to carry out both in vivo and in vitro systems for T. crassiceps in the laboratory.

Metabolic Syndrome Components in Patients with Pituitary Adenoma.

Pituitary adenomas are benign tumors of the anterior portion of the pituitary gland (adenohypophysis), representing the 25% of all the tumor alterations. Pituitary adenomas are classified by the type of hormone secreted, cellularity, size, and structural alterations by the hormonal segregation. The diagnosis consists on the histopathological identification of cell types and the image-guided by magnetic resonance or tomography; the treatment can be both pharmacological and surgical. Metabolic Syndrome is the set of clinical conditions that increase the risk of cardiovascular diseases with an estimated prevalence of 25% worldwide. The alterations of metabolic syndrome are obesity, hypertension, dyslipidemia, insulin resistance, and diabetes mellitus type II. Pituitary adenomas and metabolic syndrome have an important relationship, hormone-secreting by pituitary adenomas affects a myriad of signaling pathways, which allows a favorable environment for the appearance of the metabolic syndrome. Moreover, patients with pituitary adenomas are shown to have an improvement in metabolic parameters after the medical/surgical treatment. The objective of this review is to explore the possible mechanisms through which PAs contributes to MetSx.

Endoscopic scoring system utilization for inflammatory bowel disease activity assessment: A multicenter real-world study from Argentina.

BACKGROUND: The frequency and patterns of use of scores for the assessment of endoscopic activity in inflammatory bowel disease patients are not known. AIM: To describe the prevalence of adequate use of endoscopic scores in IBD patients who underwent colonoscopy in a real-life setting. MATERIALS AND METHODS: A multicenter observational study comprising six community hospitals in Argentina was undertaken. Patients with a diagnosis of Crohn's disease or ulcerative colitis who underwent colonoscopy for endoscopic activity assessment between 2018 and 2022 were included. Colonoscopy reports of included subjects were manually reviewed to determine the proportion of colonoscopies that included an endoscopic score report. We determined the proportion of colonoscopy reports that included all of the IBD colonoscopy report quality elements proposed by BRIDGe group. Endoscopist's specialty, years of experience as well as expertise in IBD were assessed. RESULTS: A total of 1556 patients were included for analysis (31.94% patients with Crohn's disease). Mean age was 45.94±15.46. Endoscopic score reporting was found in 58.41% of colonoscopies. Most frequently used scores were Mayo endoscopic score (90.56%) and SES-CD (56.03%) for ulcerative colitis and Crohn's disease, respectively. In addition, 79.11% of endoscopic reports failed to comply with all recommendations on endoscopic reporting for inflammatory bowel disease. CONCLUSIONS: A significant proportion of endoscopic reports of inflammatory bowel disease patients do not include the description of an endoscopic score to assess mucosal inflammatory activity in a real-world setting. This is also associated with a lack of compliance in recommended criteria for proper endoscopic reporting.

Maternal Consumption of Non-Nutritive Sweeteners during Pregnancy Is Associated with Alterations in the Colostrum Microbiota.

Non-nutritive sweeteners (NNSs) provide a sweet taste to foods and beverages without significantly adding calories. Still, their consumption has been linked to modifications in adult's and children's gut microbiota and the disruption of blood glucose control. Human milk microbiota are paramount in establishing infants' gut microbiota, but very little is known about whether the consumption of sweeteners can alter it. To address this question, we sequenced DNA extracted colostrum samples from a group of mothers, who had different levels of NNS consumption, using the Ion Torrent Platform. Our results show that the "core" of colostrum microbiota, composed of the genera Bifidobacterium, Blautia, Cutibacteium, Staphylococcus, and Streptococcus, remains practically unchanged with the consumption of NNS during pregnancy, but specific genera display significant alterations, such as Staphylococcus and Streptococcus. A significant increase in the unclassified archaea Methanobrevibacter spp. was observed as the consumption frequency of NNS increased. The increase in the abundance of this archaea has been previously linked to obesity in Mexican children. NNS consumption during pregnancy could be related to changes in colostrum microbiota and may affect infants' gut microbiota seeding and their future health.

A Comparative Analysis of the Protein Cargo of Extracellular Vesicles from Helminth Parasites.

Helminth parasites cause debilitating-sometimes fatal-diseases in humans and animals. Despite their impact on global health, mechanisms underlying host-parasite interactions are still poorly understood. One such mechanism involves the exchange of extracellular vesicles (EVs), which are membrane-enclosed subcellular nanoparticles. To date, EV secretion has been studied in helminth parasites, including EV protein content. However, information is highly heterogeneous, since it was generated in multiple species, using varied protocols for EV isolation and data analysis. Here, we compared the protein cargo of helminth EVs to identify common markers for each taxon. For this, we integrated published proteomic data and performed a comparative analysis through an orthology approach. Overall, only three proteins were common in the EVs of the seven analyzed species. Additionally, varied repertoires of proteins with moonlighting activity, vaccine antigens, canonical and non-canonical proteins related to EV biogenesis, taxon-specific proteins of unknown function and RNA-binding proteins were observed in platyhelminth and nematode EVs. Despite the lack of consensus on EV isolation protocols and protein annotation, several proteins were shown to be consistently detected in EV preparations from organisms at different taxa levels, providing a starting point for a selective biochemical characterization.

The cardiovascular polypill as baseline treatment improves lipid profile and blood pressure regardless of body mass index in patients with cardiovascular disease. The Bacus study.

BACKGROUND: Pharmacological treatment with lipid-lowering and antihypertensive drugs has been proposed as a strategy to improve excess cardiovascular (CV) risk among obese individuals. The present study aimed to assess whether the CV polypill (Sincronium®) could be an effective strategy to help improve CV risk factor control in obese/overweight individuals requiring secondary prevention. METHODS: This was an observational, retrospective study reviewing the hospital medical records of 479 patients with established CV disease who initiated treatment with the CV polypill between 2013 and 2019 at a general hospital in Mexico. Patients were grouped as normal weight, overweight or obese according to their initial body mass index (BMI). We collected blood pressure (BP), lipid profile, and vascular age at the last visit recorded during the period following treatment. RESULTS: At the end of the study, all assessed lipid parameters improved compared to baseline regardless of the initial BMI category (all p<0.001). There was an increase from baseline regarding the proportion of patients with at target low-density lipoprotein cholesterol after treatment (2.3% vs. 30.1%; p<0.001), more than 80% of patients achieved triglyceride levels <200 mg/dL (p<0.001), and more than 80% achieved target BP levels in all BMI subgroups (p<0.001). The subanalyses in the elderly population yielded similar results, with a significant overall improvement in lipid and BP control after initiating the CV polypill strategy. CONCLUSIONS: The use of the CV polypill as baseline therapy for secondary prevention seems to be a reasonable strategy that enhances CV risk factor control regardless of the patient's BMI.

Assessing the RP-LC-MS-Based Metabolic Profile of Hass Avocados Marketed in Europe from Different Geographical Origins (Peru, Chile, and Spain) over the Whole Season.

Spain dominates avocado production in Europe, with the Hass variety being the most prominent. Despite this, Spanish production satisfies less than 10% of the overall avocado demand in Europe. Consequently, the European avocado market heavily relies on imports from overseas, primarily sourced from Peru and Chile. Herein, a comprehensive characterization of the metabolic profile of Hass avocado fruits from Spain, Peru, and Chile, available in the European market throughout the year, was carried out. The determination of relevant substances was performed using high- and low-resolution RP-LC-MS. Remarkable quantitative differences regarding phenolic compounds, amino acids, and nucleosides were observed. Principal component analysis revealed a natural clustering of avocados according to geographical origin. Moreover, a specific metabolic pattern was established for each avocado-producing country using supervised partial least squares discriminant analysis. Spanish fruits exhibited high levels of coumaric acid malonyl-hexose II, coumaric acid hexose II, and ferulic acid hexose II, together with considerably low levels of pantothenic acid and uridine. Chilean avocado fruits presented high concentrations of abscisic acid, uridine, ferulic acid, succinic acid, and tryptophan. Fruits from Peru showed high concentrations of dihydroxybenzoic acid hexose, alongside very low levels of p-coumaric acid, ferulic acid, coumaric acid malonyl-hexose I, and ferulic acid hexose II.

Common carp as an ecological indicator of environmental pollution in reservoirs of southern Spain: inferring the environmental risks of anthropogenic activities.

Extraction and mineral processing, as well as the waste generated by old abandoned mining sites, are the main sources of contamination of water bodies and lands by potentially toxic elements (PTEs). The common carp (Cyprinus carpio Linnaeus 1758) has been reported to be a good ecological indicator of environmental pollution in water bodies. Hence, we evaluated the concentration of eleven PTEs (As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn) in different tissues of common carp in two reservoirs of the province of Jaén, southern Spain: El Tranco de Beas (S1) and La Fernandina (S2). We also assessed the concentration of PTEs in water and sediment samples. We used inductively coupled plasma mass spectrometry for all the collected samples. We found high concentrations of As and Fe in water in the S2 reservoir, above the maximum limits allowed by the sanitary criteria in Spain; however, the analysis of sediments indicated low ecological risk in S1 and moderate ecological risk for As in S2. The concentration of PTEs in common carp was higher in the S2 reservoir, exceeding the permissible limits in the case of As, Cd, Pb, and Zn. As and Cd showed higher concentrations in the kidney; Cu, Fe, and Zn showed higher concentrations in the liver; and Pb and Mn presented higher concentrations in the gill and gill bone. There was a good correlation between the concentrations found in water/sediment samples and those in common carp, corroborating its usefulness as a good ecological indicator, allowing the detection of environmental pollution and inferring previous or current anthropogenic activities such as mining.

Neurological Diseases Define the Cytokine Profile in CFS during SARS-CoV-2 Infection in Highly Ill Patients.

Neuroinflammation is critical in developing and progressing neurological diseases. The underlying pro-inflammatory cytokine expression combined with additional mechanisms in the neuropathology, such as oxidative stress, brain-blood barrier damage, and endothelial dysfunction, could contribute to the susceptibility to developing severe COVID-19. The physiopathology of SARS-CoV-2 and other human coronaviruses (H-CoVs) has not been completely understood; however, they have all been linked to a disproportionated response of the immune system, particularly an exacerbated cytokine production and the dysregulation of total cell counts. In this article, based on the compilation of studies reported by our working group regarding COVID-19 and neurological diseases, we propose that the inflammation observed in the central nervous system, through a CSF analysis, could be conditioned by neurological disease(s) and enhanced by COVID-19. Therefore, it is necessary to determine the cytokine profile in different neurological disorders to propose adequate treatments and avoid severe forms of the disease in these patients.

Storage Stability of Arauco Virgin Olive Oil: Evolution of Its Quality Parameters and Phenolic and Triterpenic Compounds under Different Conservation Conditions.

The storage conditions are very critical to minimize hydrolytic and oxidative reactions of virgin olive oils (VOOs). These reactions are logically influenced by the composition of the VOO, so that each variety may have a specific behavior. The aim of this study was to evaluate changes in quality parameters and in the phenolic and triterpenic profile of Arauco VOOs, a unique local variety from Argentina, after storage under different conditions. The effects of exposure to light (darkness and light), temperature (24 and 40 °C), packaging material (polyethylene (PET) and dark glass), and headspace (air and N2 atmosphere) were investigated for 76 days. A reduction in total phenolic compounds was observed after storage treatments, but all samples still complied with the EFSA health claim after the different handlings. Overall, the results revealed that the preservation of the oils in PET appears adequate, with improved stability when N2 was used in the headspace, along with darkness and low temperature. The study of phenolic profiles showed that substances previously reported as possible markers of olive oil aging, such as hydroxytyrosol and an isomer of decarboxymethyl oleuropein aglycone, also have a similar behavior during the aging of Arauco variety oil. Interestingly, some evidence was found that another oleuropein-derived compound (oleuropein aglycone isomer 3) could also be used as an aging marker.

Newborns from Mothers Who Intensely Consumed Sucralose during Pregnancy Are Heavier and Exhibit Markers of Metabolic Alteration and Low-Grade Systemic Inflammation: A Cross-Sectional, Prospective Study.

Robust data in animals show that sucralose intake during gestation can predispose the offspring to weight gain, metabolic disturbances, and low-grade systemic inflammation; however, concluding information remains elusive in humans. In this cross-sectional, prospective study, we examined the birth weight, glucose and insulin cord blood levels, monocyte subsets, and inflammatory cytokine profile in 292 neonates at term from mothers with light sucralose ingestion (LSI) of less than 60 mg sucralose/week or heavy sucralose intake (HSI) of more than 36 mg sucralose/day during pregnancy. Mothers in the LSI (n = 205) or HSI (n = 87) groups showed no differences in age, pregestational body mass index, blood pressure, and glucose tolerance. Although there were no differences in glucose, infants from HSI mothers displayed significant increases in birth weight and insulin compared to newborns from LSI mothers. Newborns from HSI mothers showed a substantial increase in the percentage of inflammatory nonclassical monocytes compared to neonates from LSI mothers. Umbilical cord tissue of infants from HSI mothers exhibited higher IL-1 beta and TNF-alpha with lower IL-10 expression than that found in newborns from LSI mothers. Present results demonstrate that heavy sucralose ingestion during pregnancy affects neonates' anthropometric, metabolic, and inflammatory features.

A multiomics integrative analysis of color de-synchronization with softening of 'Hass' avocado fruit: A first insight into a complex physiological disorder.

Exocarp color de-synchronization with softening of 'Hass' avocado is a relevant recurrent problem for the avocado supply chain. This study aimed to unravel the mechanisms driving this de-synchronization integrating omics datasets from avocado exocarp of different storage conditions and color phenotypes. In addition, we propose potential biomarkers to predict color synchronized/de-synchronized fruit. Integration of transcriptomics, proteomics and metabolomics and network analysis revealed eight transcription factors associated with differentially regulated genes between regular air (RA) and controlled atmosphere (CA) and twelve transcription factors related to avocado fruit color de-synchronization control in ready-to-eat stage. CA was positively correlated to auxins, ethylene, cytokinins and brassinosteroids-related genes, while RA was characterized by enrichment of cell wall remodeling and abscisic acid content associated genes. At ready-to-eat higher contents of flavonoids, abscisic acid and brassinosteroids were associated with color-softening synchronized avocados. In contrast, de-synchronized fruit revealed increases of jasmonic acid, salicylic acid and auxin levels.

Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations.

SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for which numerous neurological symptoms have been reported, ranging from mild and non-life-threatening (e.g., headaches, anosmia, dysgeusia, and disorientation) to severe and life-threatening symptoms (e.g., meningitis, ischemic stroke, and cerebral thrombosis). The cellular receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), an enzyme that belongs to the renin-angiotensin system (RAS). RAS is an endocrine system that has been classically associated with regulating blood pressure and fluid and electrolyte balance; however, it is also involved in promoting inflammation, proliferation, fibrogenesis, and lipogenesis. Two pathways constitute the RAS with counter-balancing effects, which is the key to its regulation. The first axis (classical) is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and angiotensin type 1 receptor (AT1R) as the main effector, which -when activated- increases the production of aldosterone and antidiuretic hormone, sympathetic nervous system tone, blood pressure, vasoconstriction, fibrosis, inflammation, and reactive oxygen species (ROS) production. Both systemic and local classical RAS' within the brain are associated with cognitive impairment, cell death, and inflammation. The second axis (non-classical or alternative) includes ACE2, which converts Ang II to Ang-(1-7), a peptide molecule that activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions. Thus, the alternative RAS axis enhances cognition, synaptic remodeling, cell survival, cell signal transmission, and antioxidant/anti-inflammatory mechanisms in the brain. In a physiological state, both RAS axes remain balanced. However, some factors can dysregulate systemic and local RAS arms. The binding of SARS-CoV-2 to ACE2 causes the internalization and degradation of this enzyme, reducing its activity, and disrupting the balance of systemic and local RAS, which partially explain the appearance of some of the neurological symptoms associated with COVID-19. Therefore, this review aims to analyze the role of RAS in the development of the neurological effects due to SARS-CoV-2 infection. Moreover, we will discuss the RAS-molecular targets that could be used for therapeutic purposes to treat the short and long-term neurological COVID-19-related sequelae.