ABSTRACT
This research investigated the impact of ohmic heating (OH) on the physicochemical properties and resistant starch formation in native corn starch. Electric field strengths (EFS) of 50, 75, and 100 V/cm were applied to native starch, at a starch-water ratio of 1:1 w/v. The conductivity of the medium is a crucial factor in ohmic heating. In this study, the conductivity values at 120 °C were measured at 1.5 mS/m. The study revealed two distinct outcomes resulting from the application of different EFS. Firstly, a thermal effect induced gelatinization, resulting in a reduction in the enthalpy of corn starch, an increase in the water absorption index (WAI) and the water solubility index (WSI), and a decrease in peak viscosity. Secondly, a non-thermal effect of OH was observed, leading to the electrolysis of certain starch compounds and water. This electrolysis process generated radicals (-OH) that interacted with starch components, augmenting the percentage of resistant starch. This increase was associated with elevated levels of carbonyl and carboxyl groups at 75 and 100 V/cm.
Subject(s)
Electricity , Solubility , Starch , Water , Zea mays , Zea mays/chemistry , Starch/chemistry , Viscosity , Water/chemistry , Heating , Chemical Phenomena , Hot Temperature , Electric ConductivityABSTRACT
Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The sympathetic nervous system is controlled within the central nervous system by neurons located in the hypothalamus, which in turn are regulated by hormones like leptin. Leptin action in the hypothalamus leads to increased sympathetic activity in the adipose tissue. In this short report, we propose that leptin action in the brain also controls the sympathetic innervation of other organs like the liver and the ovary. We performed two experiments: We performed an intracerebroventricular (ICV) injection of leptin and measured norepinephrine levels in several organs, and we used a validated model of overnutrition and obesity to evaluate whether an increase in leptin levels coexists with high levels of norepinephrine in the liver and ovaries. Norepinephrine was measured by ELISA in adipose tissue and by HPLC-EC in other tissues. Leptin was measured by ELISA. We found that the ICV injection of leptin increases norepinephrine levels in several organs, including the liver and ovaries. Also, we found that diet-induced obesity leads to an increase in leptin levels while inducing an increase in norepinephrine levels in the liver and ovaries. Finally, since hyperactivity of the sympathetic nervous system is observed both in non-alcoholic fatty liver disease and polycystic ovary syndrome, we think that an increase in norepinephrine levels induced by hyperleptinemia could be involved in the pathogenesis of both diseases.
Subject(s)
Leptin , Norepinephrine , Female , Adipose Tissue/metabolism , Diet , Leptin/metabolism , Norepinephrine/metabolism , Obesity/metabolism , Sympathetic Nervous System , Animals , RatsABSTRACT
Lead (Pb2+) exposure during early life induces cognitive impairment, which was recently associated with an increase in brain kynurenic acid (KYNA), an antagonist of NMDA and alpha-7 nicotinic receptors. It has been described that N-acetylcysteine (NAC) favors an antioxidant environment and inhibits kynurenine aminotransferase II activity (KAT II, the main enzyme of KYNA production), leading to brain KYNA levels decrease and cognitive improvement. This study aimed to investigate whether the NAC modulation of the brain KYNA levels in mice ameliorated Pb2+-induced cognitive impairment. The dams were divided into four groups: Control, Pb2+, NAC, and Pb2++NAC, which were given drinking water or 500 ppm lead acetate in the drinking water ad libitum, from 0 to 23 postnatal days (PNDs). The NAC and Pb2++NAC groups were simultaneously fed NAC (350 mg/day) in their chow from 0 to 23 PNDs. At PND 60, the effect of the treatment with Pb2+ and in combination with NAC on learning and memory performance was evaluated. Immediately after behavioral evaluation, brain tissues were collected to assess the redox environment; KYNA and glutamate levels; and KAT II activity. The NAC treatment prevented the long-term memory deficit exhibited in the Pb2+ group. As expected, Pb2+ group showed redox environment alterations, fluctuations in glutamate levels, and an increase in KYNA levels, which were partially avoided by NAC co-administration. These results confirmed that the excessive KYNA levels induced by Pb2+ were involved in the onset of cognitive impairment and could be successfully prevented by NAC treatment. NAC could be a tool for testing in scenarios in which KYNA levels are associated with the induction of cognitive impairment.
ABSTRACT
Many diseases and degenerative processes affecting the nervous system and peripheral organs trigger the activation of inflammatory cascades. Inflammation can be triggered by different environmental conditions or risk factors, including drug and food addiction, stress, and aging, among others. Several pieces of evidence show that the modern lifestyle and, more recently, the confinement associated with the COVID-19 pandemic have contributed to increasing the incidence of addictive and neuropsychiatric disorders, plus cardiometabolic diseases. Here, we gather evidence on how some of these risk factors are implicated in activating central and peripheral inflammation contributing to some neuropathologies and behaviors associated with poor health. We discuss the current understanding of the cellular and molecular mechanisms involved in the generation of inflammation and how these processes occur in different cells and tissues to promote ill health and diseases. Concomitantly, we discuss how some pathology-associated and addictive behaviors contribute to worsening these inflammation mechanisms, leading to a vicious cycle that promotes disease progression. Finally, we list some drugs targeting inflammation-related pathways that may have beneficial effects on the pathological processes associated with addictive, mental, and cardiometabolic illnesses.
Subject(s)
Behavior, Addictive , COVID-19 , Cardiovascular Diseases , Nervous System Diseases , Humans , Pandemics , COVID-19/complications , Aging/metabolism , Inflammation/complications , Nervous System Diseases/etiologyABSTRACT
White adipose tissue (AT) dysfunction plays an important role in the development of cardiometabolic alterations associated with obesity. AT dysfunction is characterized by the loss of the expansion capacity of the AT, an increment in adipocyte hypertrophy, and changes in the secretion profile of adipose cells, associated with accumulation of macrophages and inflammation. Since not all people with an excess of adiposity develop comorbidities, it is necessary to find simple tools that can evidence AT dysfunction and allow the detection of those people with the potential to develop metabolic alterations. This review focuses on the current pathophysiological mechanisms of white AT dysfunction and emerging measurements to assess its functionality.
Subject(s)
Adipose Tissue, White , Obesity , Humans , Obesity/metabolism , Adipose Tissue, White/metabolism , Adiposity , Adipocytes/metabolism , Inflammation/metabolism , Adipose Tissue/metabolismABSTRACT
Obesity is a pandemic caused by many factors, including a chronic excess in hypercaloric and high-palatable food intake. In addition, the global prevalence of obesity has increased in all age categories, such as children, adolescents, and adults. However, at the neurobiological level, how neural circuits regulate the hedonic consumption of food intake and how the reward circuit is modified under hypercaloric diet consumption are still being unraveled. We aimed to determine the molecular and functional changes of dopaminergic and glutamatergic modulation of nucleus accumbens (NAcc) in male rats exposed to chronic consumption of a high-fat diet (HFD). Male Sprague-Dawley rats were fed a chow diet or HFD from postnatal day (PND) 21 to 62, increasing obesity markers. In addition, in HFD rats, the frequency but not amplitude of the spontaneous excitatory postsynaptic current is increased in NAcc medium spiny neurons (MSNs). Moreover, only MSNs expressing dopamine (DA) receptor type 2 (D2) increase the amplitude and glutamate release in response to amphetamine, downregulating the indirect pathway. Furthermore, NAcc gene expression of inflammasome components is increased by chronic exposure to HFD. At the neurochemical level, DOPAC content and tonic dopamine (DA) release are reduced in NAcc, while phasic DA release is increased in HFD-fed rats. In conclusion, our model of childhood and adolescent obesity functionally affects the NAcc, a brain nucleus involved in the hedonic control of feeding, which might trigger addictive-like behaviors for obesogenic foods and, through positive feedback, maintain the obese phenotype.
Subject(s)
Dopamine , Pediatric Obesity , Rats , Male , Animals , Dopamine/metabolism , Nucleus Accumbens/metabolism , Diet, High-Fat , Rats, Sprague-Dawley , Pediatric Obesity/metabolism , Synaptic Transmission/physiology , Receptors, Dopamine/metabolismABSTRACT
Kynureninase (KYNU) is a kynurenine pathway (KP) enzyme that produces metabolites with immunomodulatory properties. In recent years, overactivation of KP has been associated with poor prognosis of several types of cancer, in particular by promoting the invasion, metastasis, and chemoresistance of cancer cells. However, the role of KYNU in gliomas remains to be explored. In this study, we used the available data from TCGA, CGGA and GTEx projects to analyze KYNU expression in gliomas and healthy tissue, as well as the potential contribution of KYNU in the tumor immune infiltrate. In addition, immune-related genes were screened with KYNU expression. KYNU expression correlated with the increased malignancy of astrocytic tumors. Survival analysis in primary astrocytomas showed that KYNU expression correlated with poor prognosis. Additionally, KYNU expression correlated positively with several genes related to an immunosuppressive microenvironment and with the characteristic immune tumor infiltrate. These findings indicate that KYNU could be a potential therapeutic target for modulating the tumor microenvironment and enhancing an effective antitumor immune response.
ABSTRACT
La proliferación miofibroblastica es una lesión localmente agresiva, benigna, de etiología desconocida, tiene una histopatología distintiva de células fusiformes mi fibroblásticas en proliferación con infiltración de células inflamatorias predominantes células plasmáticas y linfocitos. La incidencia de esta lesión en cabeza y cuello es muy rara. Su diagnóstico definitivo es histológico y el tratamiento de elección es la resección quirúrgica. Reportamos un caso raro en un joven de 13 años de edad. La proliferación miofibroblastica en la cavidad oral es una condición poco común, con poca información, en cuanto a su etiología y patogenia
Subject(s)
Neoplasms, Muscle TissueABSTRACT
Obesity-induced neuroinflammation is a chronic aseptic central nervous system inflammation that presents systemic characteristics associated with increased pro-inflammatory cytokines such as interleukin 1 beta (IL-1ß) and interleukin 18 (IL-18) and the presence of microglia and reactive astrogliosis as well as the activation of the NLRP3 inflammasome. The obesity pandemic is associated with lifestyle changes, including an excessive intake of obesogenic foods and decreased physical activity. Brain areas such as the lateral hypothalamus (LH), lateral septum (LS), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been implicated in the homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. In this context, a chronic lipid intake triggers neuroinflammation in several brain regions such as the hypothalamus, hippocampus, and amygdala. This review aims to present the background defining the significant impact of neuroinflammation and how this, when induced by an obesogenic diet, can affect feeding control, triggering metabolic and neurological alterations.
Subject(s)
Neuroinflammatory Diseases , Nucleus Accumbens , Humans , Nucleus Accumbens/metabolism , Diet/adverse effects , Obesity/etiology , Obesity/metabolism , Eating/physiologyABSTRACT
Actualmente varios biomateriales restauradores resinosos endurecen mediante una reacción de fotopolimerización, para lo cual es necesaria una unidad de polimerización (UP). El objetivo de este manuscrito es generar una guía basada en la evidencia científica actual para contribuir al correcto uso de las UP. Se realizó una búsqueda de artículos publicados desde el año 2002 hasta enero del 2022 a través de PubMed y Google Scholar. Se organizó la información en 10 tópicos de relevancia en forma de decálogo: longitud de onda, intensidad de la luz, diámetro de la punta, tiempo de curado, modo de curado, distancia de curado, uso de barreras, batería y carga, limpieza y desinfección, finalizando con los controles periódicos. Los profesionales de la salud deben conocer y recordar la importancia de realizar un adecuado uso y mantenimiento de las UP, ya que esto puede influir en el desempeño clínico de los biomateriales.
Atualmente, diversos biomateriais restauradores resinosos endurecem através de uma reação de fotopolimerização, para a qual é necessária uma unidade de polimerização (UP). O objetivo deste manuscrito é gerar um guia baseado em evidências científicas atuais para o uso correto de UPs. Foi feita uma busca por artigos publicados de 2002 a janeiro de 2022 por meio do PubMed e Google Scholar. As informações foram organizadas em 10 tópicos relevantes na forma de um decálogo: comprimento de onda, intensidade da luz, diâmetro da ponta, tempo de cura, modo de cura, distância de cura, uso de barreiras, bateria e carregamento, limpeza e desinfecção e verificações regulares. Os profissionais de saúde devem conhecer e lembrar a importância do uso e manutenção adequados das UPs, pois isso pode influenciar no desempenho clínico do biomaterial.
Subject(s)
Humans , Female , Middle Aged , Bile Ducts/pathology , Bile Ducts/diagnostic imaging , Anastomosis, Surgical/adverse effects , Cholestasis/diagnostic imaging , Constriction, Pathologic/diagnostic imaging , Cholangiography , Cholestasis/therapy , Constriction, Pathologic/therapy , Liver/blood supplyABSTRACT
Indoleamine dioxygenase (IDO), a rate limiting enzyme of the tryptophan catabolism through the kynurenine pathway (KP), has been related with a lower survival and a poor patient prognosis on several solid tumors, including gliomas. However, the use of IDO inhibitors as a therapeutic strategy for tumor treatment remains controversial in clinical trials and the role of other KP enzymes on tumor progression has remained poorly understood so far. Recently, different studies on different types of cancer have pointed out the importance of KP enzymes downstream IDO. Because of this, we conducted a bioinformatic analysis of the expression of different KP enzymes and their correlation with the gene expression of molecules related to the hallmarks of cancer in transcriptomic datasets from patients with different types of brain tumors including low grade gliomas, glioblastoma multiforme, neuroblastoma, and paraganglioma and pheochromocytoma. We found that KP enzymes that drive to NAD+ synthesis are overexpressed on different brain tumors compared to brain cortex data. Moreover, these enzymes presented positive correlations with the expression of genes related to immune response modulation, angiogenesis, Signal Transducer and Activator of Transcription (STAT) signaling, and Rho GTPase expression. These correlations suggest the relevance of the expression of the KP enzymes in brain tumor pathogenesis.
ABSTRACT
Gestational Diabetes Mellitus (GDM) and preeclampsia (PE) affects 6-25% of pregnancies and are characterized by an imbalance in natural prooxidant/antioxidant mechanisms. Due to their antioxidant and anti-inflammatory properties, polyphenols consumption during the pregnancy might exert positive effects by preventing GDM and PE development. However, this association remains inconclusive. This systematic review and metanalysis is aimed to analyze the association between polyphenol-rich food consumption during pregnancy and the risk of GDM and PE. A systematic search in MEDLINE, EMBASE, and Web of Science (Clarivate Analytics, London, United Kingdom) for articles dated between 1 January 1980 and July 2022 was undertaken to identify randomized controlled trials and observational studies evaluating polyphenol-rich food consumption and the risk of GDM and PE. The Newcastle-Ottawa Scale was used to evaluate the quality of these included studies. Twelve studies were included, of which eight articles evaluated GDM and four studied PE. A total of 3785 women presented with GDM (2.33%). No association between polyphenol consumption and GDM was found (ES = 0.85, 95% CI 0.71-1.01). When total polyphenol intake was considered, a lower likelihood to develop GDM was noted (ES = 0.78, 95% CI 0.69-0.89). Furthermore, polyphenol consumption was not associated with PE development (ES = 0.90, 95% CI 0.57-1.41). In conclusion, for both outcomes, pooled analyses showed no association with polyphenol-rich food consumption during pregnancy. Therefore, association of polyphenol intake with a decreased risk of GDM and PE remains inconclusive.
ABSTRACT
Computer vision syndrome causes vision problems and discomfort mainly due to dry eye. Several studies show that dry eye in computer users is caused by a reduction in the blink rate and an increase in the prevalence of incomplete blinks. In this context, this article introduces Eye-LRCN, a new eye blink detection method that also evaluates the completeness of the blink. The method is based on a long-term recurrent convolutional network (LRCN), which combines a convolutional neural network (CNN) for feature extraction with a bidirectional recurrent neural network that performs sequence learning and classifies the blinks. A Siamese architecture is used during CNN training to overcome the high-class imbalance present in blink detection and the limited amount of data available to train blink detection models. The method was evaluated on three different tasks: blink detection, blink completeness detection, and eye state detection. We report superior performance to the state-of-the-art methods in blink detection and blink completeness detection, and remarkable results in eye state detection.
ABSTRACT
Endurance and resistance exercises, alone or in combination, induce metabolic changes that affect tryptophan (Trp) catabolism. The kynurenine pathway (KP) is the main route of Trp degradation, and it is modulated by the inflammatory and redox environments. Previous studies have shown that KP metabolites work as myokines that mediate the positive systemic effects related to exercise. However, it is poorly understood how different exercise modalities and intensities impact the KP. The aim of this study was to characterize the effect of two different exercise modalities, military diving and swimming, on the KP and the redox environment. A total of 34 healthy men from the Mexican Navy were included in the study, 20 divers and 14 swimmers, who started and stayed in military training consistently during the six months of the study; 12 Mexican men without fitness training were used as the control group. Physical fitness was determined at the beginning and after 6 months of training; criteria included body composition; serum levels of Trp, kynurenine (KYN), kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK); the glutathione ratio (GSH/GSSG); and malondialdehyde (MDA).. Results showed a significant loss of body fat in both the diver and swimmer groups. Compared with the control group, divers showed a decrease in Trp and 3-HK levels, but no changes were observed in the KYN/Trp, KYNA/Trp or 3-HK/Trp ratios, while swimmers showed a decrease in KYN levels and an increase in the KYNA and 3-HK levels. Additionally, divers showed a decrease in the GSH/GSSG ratio and an increase in MDA levels, in contrast to the swimmers, who showed a decrease in MDA levels and an increase in GSH/GSSG levels. Our findings suggest a differential shift in the KP and redox environment induced by diving and swimming. Swimming promotes an antioxidant environment and a peripheral overactivation of the KP.
ABSTRACT
The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However, several clinical trials are investigating MOD as an alternative pharmacological treatment for attentional deficit and hyperactivity disorder (ADHD) in children and adolescents. On the other hand, the early use of psychostimulants and the misdiagnosis rates in ADHD make it crucial to investigate the brain effects of this type of drug in young healthy individuals. The aim of this work was to evaluate the effects of chronic MOD treatment on neurochemicals (γ-aminobutyric acid and glutamate), dopamine receptor 2 (D2) expression and behavior (non-selective attention "NSA") in the mesocorticolimbic system of young healthy Sprague-Dawley rats. Preadolescent male rats were injected with MOD (75 mg/kg, i.p.) or a vehicle for 14 days (from postnatal day 22 to 35). At postnatal day 36, we measured the GLU and GABA contents and their extracellular levels in the nucleus accumbens (NAc). In addition, the GLU and GABA contents were measured in the ventral tegmental area (VTA) and D2 protein levels in the prefrontal cortex (PFC). Chronic use of MOD during adolescence induces behavioral and neurochemical changes associated with the mesocorticolimbic system, such as a reduction in PFC D2 expression, VTA GABA levels and NSA. These results contribute to the understanding of the neurological effects of chronic MOD use on a young healthy brain.
Subject(s)
Central Nervous System Stimulants , Ventral Tegmental Area , Adolescent , Animals , Attention , Central Nervous System Stimulants/pharmacology , Glutamic Acid/metabolism , Humans , Male , Modafinil/metabolism , Modafinil/pharmacology , Nucleus Accumbens/metabolism , Prefrontal Cortex/metabolism , Rats , Rats, Sprague-Dawley , Ventral Tegmental Area/metabolism , gamma-Aminobutyric Acid/metabolismABSTRACT
BACKGROUND: Polycystic Ovary Syndrome (PCOS) is an endocrine disorder that affects women in reproductive age and represents an unfavourable risk factor for several pregnancy and perinatal outcomes. Despite, no guidelines or pharmaceutical strategies for treating PCOS during pregnancy are available. The aim of this study is to determine the association between polycystic ovary syndrome with or without metformin and the pregnancy, perinatal outcomes as well as the risk of obesity in children born to these mothers. METHODS: In this nationwide population-based cohort study based in Swedish population, all singleton births (n = 1,016,805) from 686,847 women since 2006 up to 2016 were included. Multivariable logistic and Cox regression modelling with odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals were used to study the association between the exposure of maternal PCOS, metformin during pregnancy (or the combination of both) and: 1) Pregnancy outcomes: preeclampsia, gestational diabetes, caesarean section, and acute caesarean section, 2) Perinatal outcomes: preterm birth, stillbirth, low birth weight, macrosomia, Apgar < 7 at 5 min, small for gestational age and large for gestational age, and 3) Childhood Obesity. RESULTS: PCOS in women without metformin use during pregnancy was associated with higher risks of preeclampsia (OR = 1.09, 1.02-1.17), gestational diabetes (OR = 1.71, 1.53-1.91) and caesarean section (OR = 1.08, 1.04-1.12), preterm birth (OR = 1.30, 1.23-1.38), low birth weight (OR = 1.29, 1.20-1.38), low Apgar scores (OR = 1.17, 1.05-1.31) and large for gestational age (OR = 1.11, 1.03-1.20). Metformin use during pregnancy (in women without PCOS) was associated with a 29% lower risks of preeclampsia (OR = 0.71, 0.51-0.97), macrosomia and large for gestational age. Obesity was more common among children born to mothers with PCOS without metformin (HR = 1.61, 1.44-1.81); and those with metformin without PCOS (HR = 1.67, 1.05-2.65). PCOS with metformin was not associated with any adverse outcome. CONCLUSION: PCOS was associated with increased risks of adverse pregnancy and perinatal outcomes and childhood obesity. Metformin appears to reduce these risks in mothers with polycystic ovary syndrome and their children; but may increase the risk of childhood-obesity in children form women without PCOS.
Subject(s)
Metformin/therapeutic use , Pediatric Obesity/epidemiology , Polycystic Ovary Syndrome , Pregnancy Outcome/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Adult , Child , Child, Preschool , Cohort Studies , Diabetes, Gestational/epidemiology , Female , Humans , Infant, Newborn , Pediatric Obesity/etiology , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/epidemiology , Pre-Eclampsia/epidemiology , Pregnancy , Pregnancy Complications/drug therapy , Pregnancy Complications/epidemiology , Prenatal Exposure Delayed Effects/etiology , Prognosis , Risk Factors , Sweden/epidemiology , Treatment Outcome , Young AdultABSTRACT
Los schwannomas son neoplasias predominantemente benignas y de crecimiento lento, encapsulado y generalmente solitario, que se originan a partir de las células de Schwann de la vaina del nervio periférico. En la cavidad oral su prevalencia es muy baja, siendo la localización más frecuente la lengua. El diagnóstico se basa en el estudio histopatológico. El tratamiento de elección es la exéresis quirúrgica. Reportamos un caso raro de schwannoma lingual en un joven de 12 años de edad que acude por consulta externa por aumento de volumen en región dorsal de lengua que abarca hasta región submentoniana, de 4 años de evolución, con dificultad en la deglución y pronunciación. Después de estudios histopatológicos y de imagen se confirma el diagnostico de Schwannoma lingual, es intervenido quirúrgicamente a exéresis de lesión confirmando el diagnostico. El schwannoma lingual es una neoplasia benigna poco frecuente cuyo pronóstico es excelente y con bajas tasas de recurrencia tras su exéresis quirúrgica.
Schwannomas are predominantly benign, slow-growing encapsulated and usually solitary neoplasms that arise from Schwann cells of the peripheral nerve sheath. In the oral cavity its prevalence is very low, the most common location being the tongue. Diagnosis is based on histopathological study. The treatment of choice is surgical removal. We report a rare case of lingual schwannoma in a 12-year-old boy who came to the outpatient clinic due to an increase in volume in the dorsal region of the tongue that reached the submental region of 4 years of evolution, with difficulty in swallowing and pronunciation. After histopathological and imaging studies confirmed the diagnosis of lingual Schwannoma, he underwent surgery to remove the lesion, confirming the diagnosis. Lingual schwannoma is a rare benign neoplasm whose prognosis is excellent and with low rates of recurrence after surgical removal.
Subject(s)
Humans , Male , Child , Schwann Cells , NeoplasmsABSTRACT
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. The enzyme indoleamine-2,3-dioxygenase (IDO), which participates in the rate-limiting step of tryptophan catabolism through the kynurenine pathway (KP), is associated with poor prognosis in patients with GBM. The metabolites produced after tryptophan oxidation have immunomodulatory properties that can support the immunosuppressor environment. In this study, mRNA expression, protein expression, and activity of the enzyme kynurenine monooxygenase (KMO) were analyzed in GBM cell lines (A172, LN-18, U87, U373) and patient-derived astrocytoma samples. KMO mRNA expression was assessed by real-time RT-qPCR, KMO protein expression was evaluated by flow cytometry and immunofluorescence, and KMO activity was determined by quantifying 3-hydroxykynurenine by HPLC. Heterogenous patterns of both KMO expression and activity were observed among the GBM cell lines, with the A172 cell line showing the highest KMO expression and activity. Higher KMO mRNA expression was observed in glioma samples than in patients diagnosed with only a neurological disease; high KMO mRNA expression was also observed when using samples from patients with GBM in the TCGA program. The KMO protein expression was localized in GFAP+ cells in tumor tissue. These results suggest that KMO is a relevant target to be explored in glioma since it might play a role in supporting tumor metabolism and immune suppression.
Subject(s)
Astrocytoma/genetics , Brain Neoplasms/genetics , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Kynurenine 3-Monooxygenase/genetics , Adult , Astrocytoma/enzymology , Brain Neoplasms/enzymology , Cell Line, Tumor , Female , Glioma/enzymology , Glioma/genetics , Humans , Kaplan-Meier Estimate , Kynurenine/analogs & derivatives , Kynurenine/metabolism , Kynurenine 3-Monooxygenase/metabolism , Male , Middle Aged , Mutation , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Young AdultABSTRACT
The gastrointestinal lumen is a rich source of eukaryotic and prokaryotic viruses which, together with bacteria, fungi and other microorganisms comprise the gut microbiota. Pathogenic viruses inhabiting this niche have the potential to induce local as well as systemic complications; among them, the viral ability to disrupt the mucosal barrier is one mechanism associated with the promotion of diarrhea and tissue invasion. This review gathers recent evidence showing the contributing effects of diet, gut microbiota and the enteric nervous system to either support or impair the mucosal barrier in the context of viral attack.