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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 207-215, 2021 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33829693

RESUMEN

Objective: To investigate whether long-term exposure to inhaled sevoflurane, a volatile anesthetic, causes abnormal activities and memory impairment related to attention-deficit/hyperactivity disorder (ADHD) in neonatal rats. Methods: On postnatal day 5 (P5), Sprague-Dawley rats were randomly assigned to two sevoflurane subgroups and two control subgroups and underwent experimental intervention. The two sevoflurane (SEVO) subgroups were exposed to 3% sevoflurane for 2 h and 4 h respectively, while the two control subgroups were given pure oxygen for the same amount and duration. Behavioral tests, including open-field test (OFT), five-choice serial reaction time task (5-CSRTT), fear-conditioning (FC) and Morris water maze (MWM), were applied to evaluate changes in cognition, memory, anxiety and ADHD-related behavioral changes in the rats in adolescence (-P25) and in adulthood (-P65). Results: In OFT, the SEVO 2 h and SEVO 4 h subgroups displayed activity level and exploratory behaviors similar to those of the control subgroups on P21 and P61, with no statistically significant difference identified in the data. 5-CSRTT results on P25 and P65 indicated no statistically significant difference between the SEVO subgroups and the control subgroups in regard to ADHD-related abnormal behaviors, including number of immature reaction, rate of correct response and omission rate. In the FC experiment, SEVO 4 h group had a shorter freezing period and longer period of freezing latency ( P=0.029) in comparison to the control groups. The results of the MWM test showed that the escape latency period of rats in the SEVO 4 h group was significantly prolonged on the second day and the third day, compared to the control groups ( P<0.05). The average swimming speed of SEVO groups did no exhibit any statistically significant difference on P69 or P76. The time the SEVO 4 h group spent in the target quadrant was significantly shorter than that of the control group ( P=0.039) and percentage of distance traveled in the target quadrant was significantly reduced compared to that the control group ( P=0.048). Conclusion: The findings suggest that four hours of inhaled sevoflurane exposure in neonate rats may cause memory impairment, but does no increase risks for ADHD-related abnormal activities.


Asunto(s)
Anestésicos por Inhalación , Trastorno por Déficit de Atención con Hiperactividad , Anestésicos por Inhalación/toxicidad , Animales , Animales Recién Nacidos , Trastorno por Déficit de Atención con Hiperactividad/inducido químicamente , Aprendizaje por Laberinto , Ratas , Ratas Sprague-Dawley , Sevoflurano
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(4): 402-409, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33840414

RESUMEN

OBJECTIVE: To study the effect of astragaloside IV (AS-IV) on NOD-like receptor protein 3 (NLRP3) inflammasome in neonatal rats with hypoxic-ischemic brain damage (HIBD). METHODS: A total of 24 Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group, an HIBD group, and an AS-IV treatment group, with 8 rats in each group. After 24 hours of modeling, brain tissue was collected for hematoxylin-eosin staining, yo-PRO-1 staining, and EthD-2 immunofluorescent staining in order to observe the cerebral protection effect of AS-IV in vivo. HT22 cells were used to prepare a model of oxygen-glycogen deprivation (OGD), and a concentration gradient (50-400 µmol/L) was established for AS-IV. CCK-8 assay was used to measure the viability of HT22 cells. RT-PCR and Western blot were used to observe the effect of different concentrations of AS-IV on the mRNA and protein expression of NLRP3, gasdermin D (GSDMD), caspase-1, and interleukin-1ß (IL-1ß). RESULTS: Yo-Pro-1 and EthD-2 staining showed that compared with the sham-operation group, the HIBD group had an increase in pyroptotic cells with a small number of necrotic cells, and the AS-IV group had reductions in both pyroptotic and necrotic cells. Compared with the sham-operation group, the HIBD group had significantly higher protein expression levels of NLRP3, IL-1ß, caspase-1, and GSDMD (P < 0.05). Compared with the HIBD group, the AS-IV group had significant reductions in the protein expression levels of NLRP3, caspase-1, and GSDMD (P < 0.05). HT22 cell experiment showed that compared with the OGD group, the AS-IV group had inhibited mRNA and protein expression of NLRP3, GSDMD, caspase-1, and IL-1ß, with the best therapeutic effect at the concentration of 200 µmol/L (P < 0.05). CONCLUSIONS: AS-IV may alleviate HIBD in neonatal rats by inhibiting the expression of NLRP3, GSDMD, caspase-1, and IL-1ß.


Asunto(s)
Hipoxia-Isquemia Encefálica , Inflamasomas , Animales , Animales Recién Nacidos , Encéfalo , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Proteínas NLR , Ratas , Ratas Sprague-Dawley , Saponinas , Triterpenos
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(4): 410-415, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33840415

RESUMEN

OBJECTIVE: To study the effect of human oligodendrocyte precursor cell (hOPC) transplantation in the treatment of white matter injury (WMI). METHODS: Neonatal rats were randomly divided into a sham-operation group, a model group, and a transplantation group (n=10 each). At the age of 3 days, the rats in the model group and the transplantation group were treated with right common carotid artery ligation, followed by hypoxia for 2 hours, to prepare a rat model of WMI. hOPCs were isolated from a spontaneously aborted human fetal brain at week 11 of gestation, and then hOPCs were cultured and transplanted into the rats with WMI. At 3 months after transplantation, the water maze test was performed to evaluate neurological function, and an electron microscope was used to observe myelin sheath thickness and proliferation. RESULTS: The place navigation test using the Morris water maze showed that the model group had a significantly longer escape latency than the sham-operation group, and compared with the model group, the transplantation group had a significant reduction in escape latency (P < 0.05). To a certain degree, hOPC transplantation alleviated cognitive impairment in rats with WMI at the age of 90 days. The electron microscope images showed that hOPC transplantation promoted remyelination in the brain of WMI rats. Compared with the sham-operation group, the model group had a significant increase in the g-ratio (total axon diameter/total fiber diameter). Compared with the model group, the transplantation group had a significant reduction in the g-ratio (P < 0.05). CONCLUSIONS: Intrathecal hOPC transplantation may alleviate neurological injury and promote remyelination in a rat model of WMI.


Asunto(s)
Células Precursoras de Oligodendrocitos , Sustancia Blanca , Animales , Animales Recién Nacidos , Humanos , Vaina de Mielina , Oligodendroglía , Ratas
4.
Nat Commun ; 12(1): 1910, 2021 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-33771995

RESUMEN

Cardiac arrhythmias are a primary contributor to sudden cardiac death, a major unmet medical need. Because right ventricular (RV) dysfunction increases the risk for sudden cardiac death, we examined responses to RV stress in mice. Among immune cells accumulated in the RV after pressure overload-induced by pulmonary artery banding, interfering with macrophages caused sudden death from severe arrhythmias. We show that cardiac macrophages crucially maintain cardiac impulse conduction by facilitating myocardial intercellular communication through gap junctions. Amphiregulin (AREG) produced by cardiac macrophages is a key mediator that controls connexin 43 phosphorylation and translocation in cardiomyocytes. Deletion of Areg from macrophages led to disorganization of gap junctions and, in turn, lethal arrhythmias during acute stresses, including RV pressure overload and ß-adrenergic receptor stimulation. These results suggest that AREG from cardiac resident macrophages is a critical regulator of cardiac impulse conduction and may be a useful therapeutic target for the prevention of sudden death.


Asunto(s)
Anfirregulina/fisiología , Arritmias Cardíacas/complicaciones , Muerte Súbita Cardíaca/prevención & control , Macrófagos/fisiología , Miocardio/metabolismo , Anfirregulina/metabolismo , Animales , Animales Recién Nacidos , Células Cultivadas , Muerte Súbita Cardíaca/etiología , Femenino , Uniones Comunicantes/fisiología , Células HeLa , Humanos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Miocardio/citología , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología , Receptores Adrenérgicos beta/metabolismo
5.
Int J Nanomedicine ; 16: 1423-1434, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33654394

RESUMEN

Background: Interleukin-1ß (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown. Methods: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation. Results: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice. Conclusion: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.


Asunto(s)
Astrocitos/patología , Exosomas/metabolismo , Hipocampo/patología , Inflamación/terapia , Interleucina-1beta/farmacología , Células Madre Mesenquimatosas/citología , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal , Animales , Animales Recién Nacidos , Antiinflamatorios/farmacología , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Conducta Animal/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Exosomas/efectos de los fármacos , Exosomas/ultraestructura , Humanos , Inflamación/patología , Lipopolisacáridos , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Transducción de Señal/efectos de los fármacos , Estado Epiléptico/patología
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(3): 300-305, 2021 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33691926

RESUMEN

OBJECTIVE: To study the effect of different melatonin treatment regimens on long-term behavior and white matter damage in neonatal rats with hypoxic-ischemic brain damage (HIBD), and to seek an optimal melatonin treatment regimen. METHODS: Healthy Sprague-Dawley rats, aged 7 days, were randomly divided into four groups: sham-operation, HIBD, single-dose immediate treatment (SDIT), and 7-day continuous treatment (7DCT), with 8 rats in each group. A neonatal rat model of HIBD was prepared according to the classical Rice-Vannucci method. On day 21 after HIBD, the Morris water maze test was used to evaluate spatial learning and memory abilities. On day 70 after HIBD, immunofluorescence assay was used to measure the expression of neuronal nuclear antigen (NeuN) in the cerebral cortex and the hippocampal CA1 region of neonatal rats, and double-label immunofluorescence was used to measure the expression of myelin basic protein (MBP) and neurofilament 200 (NF200) in the corpus striatum and the corpus callosum. RESULTS: The results of the Morris water maze test showed that the SDIT and 7DCT groups had a significantly shorter mean escape latency than the HIBD group, and the 7DCT group had a significantly shorter mean escape latency than the SDIT group (P < 0.05). The results of immunofluorescence assay for NeuN showed that the SDIT and 7DCT groups had a significantly higher number of NeuN+ cells in the cerebral cortex and the hippocampal CA1 region than the HIBD group, and the 7DCT group had a significantly higher number than the SDIT group (P < 0.05). MBP/NF200 double-label immunofluorescence showed that compared with the HIBD group, the SDIT group and the 7DCT group had significantly higher fluorescence intensities of MBP and NF200 in the corpus striatum, and the 7DCT group had significantly higher fluorescence intensities than the SDIT group (P < 0.05); the 7DCT group had significantly higher fluorescence intensities of MBP and NF200 in the corpus callosum than the SDIT and HIBD groups (P < 0.05). CONCLUSIONS: Both SDIT and 7DCT can improve long-term behavior and reduce white matter damage in neonatal rats with HIBD, and 7DCT is more effective than SDIT.


Asunto(s)
Hipoxia-Isquemia Encefálica , Melatonina , Sustancia Blanca , Animales , Animales Recién Nacidos , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Melatonina/farmacología , Ratas , Ratas Sprague-Dawley
7.
Methods Mol Biol ; 2291: 365-379, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33704764

RESUMEN

Animal models represent part of the arsenal available to researchers studying the pathophysiology of potentially deadly human pathogens such as Shiga toxin-producing Escherichia coli (STEC). The optimal model may differ depending on what aspects of pathogen biology, disease progression, or host response are under study. Here, we provide detailed protocols for the infant rabbit model of STEC, which largely reproduces the intestinal disease seen following natural oral infection, and share insights from studies examining O157 and non-O157 serotypes.


Asunto(s)
Infecciones por Escherichia coli , Escherichia coli O157 , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Infecciones por Escherichia coli/metabolismo , Infecciones por Escherichia coli/patología , Escherichia coli O157/metabolismo , Escherichia coli O157/patogenicidad , Humanos , Conejos
8.
Animal ; 15(2): 100078, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33712217

RESUMEN

Inflammation and loss of tail integrity can be reasons for serious impairment of animal welfare and one of the major challenges facing modern pig farming. Evidence from practice increasingly suggests that tail lesions might be caused not only by tail biting but also by inflammation and necrosis, which can occur without any action from other pigs. Such changes are not limited to the tail but can also be observed in the ears, heels and soles, claw coronary bands, teats, navel, vulva and face. To describe inflammatory and necrotic manifestations in newborn piglets, all 146 piglets from 11 sows were clinically examined not later than 2 h after birth. In addition, the tail base of 30 randomly selected piglets out of the 146 was histo-pathologically examined as one of the most conspicuously affected body parts. Over 80% of the newborns showed affections in the tail base, claw wall and heels. In 65-87% of the animals, the coronary bands, teats, the face and the ears were affected. None of the 146 piglets was completely free from pathological manifestations. On average, the piglets were affected in six out of nine body parts simultaneously. Histological examinations showed that clear alterations in the skin were already manifested around the time of birth in all examined piglets. Alterations were characterised by the occurrence of numerous lymphocytes and granulocytes throughout the entire subepithelial connective tissue, predominantly in perivascular and perifollicular localisation but also within directly subepithelial glandular ducts and diffusely within the subepithelial connective tissue. In the majority of individuals, the epithelial structure was intact. This concurrence of symptoms in the newborns indicates a primarily endogenous aetiology of an inflammation and necrosis syndrome. Further studies in diverse herd contexts are necessary to establish the conditions for the emergence of such a syndrome and develop welfare indicators.


Asunto(s)
Bienestar del Animal , Enfermedades de los Porcinos , Animales , Animales Recién Nacidos , Femenino , Inflamación/veterinaria , Necrosis/veterinaria , Porcinos , Enfermedades de los Porcinos/diagnóstico , Cola (estructura animal)
9.
Methods Mol Biol ; 2244: 365-401, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33555596

RESUMEN

Human cytomegalovirus (HCMV) is a leading viral cause of congenital infections in the central nervous system (CNS) and may result in severe long-term sequelae. High rates of sequelae following congenital HCMV infection and insufficient antiviral therapy in the perinatal period makes the development of an HCMV-specific vaccine a high priority of modern medicine. Due to the species specificity of HCMV, animal models are frequently used to study CMV pathogenesis. Studies of murine cytomegalovirus (MCMV) infections of adult mice have played a significant role as a model of CMV biology and pathogenesis, while MCMV infection of newborn mice has been successfully used as a model of perinatal CMV infection. Newborn mice infected with MCMV have high levels of viremia during which the virus establishes a productive infection in most organs, coupled with a robust inflammatory response. Productive infection in the brain parenchyma during early postnatal period leads to an extensive nonnecrotizing multifocal widespread encephalitis characterized by infiltration of components of both innate and adaptive immunity. As a result, impairment in postnatal development of mouse cerebellum leads to long-term motor and sensor disabilities. This chapter summarizes current findings of rodent models of perinatal CMV infection and describes methods for analysis of perinatal MCMV infection in newborn mice.


Asunto(s)
Citomegalovirus/inmunología , Modelos Animales de Enfermedad , Animales , Animales Recién Nacidos , Encéfalo/inmunología , Sistema Nervioso Central/virología , Citomegalovirus/metabolismo , Citomegalovirus/patogenicidad , Infecciones por Citomegalovirus/inmunología , Encefalitis , Enfermedades Fetales , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Muromegalovirus/inmunología , Cultivo Primario de Células
10.
PLoS One ; 16(2): e0247510, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33626084

RESUMEN

Angiotensin converting enzyme 2 (ACE2) is the putative functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current literature on the abundance and distribution of ACE2 protein in the human respiratory tract is controversial. We examined the effect of age and lung injury on ACE2 protein expression in rodent and non-human primate (NHP) models. We also examined ACE2 expression in human tissues with and without coronavirus disease 19 (COVID-19). ACE2 expression was detected at very low levels in preterm, but was absent in full-term and adult NHP lung homogenates. This pattern of ACE2 expression contrasted with that of transmembrane protease serine type 2 (TMPRSS2), which was significantly increased in full-term newborn and adult NHP lungs compared to preterm NHP lungs. ACE2 expression was not detected in NHP lungs with cigarette smoke-induced airway disease or bronchopulmonary dysplasia. Murine lungs lacked basal ACE2 immunoreactivity, but responded to hyperoxia, bacterial infection, and allergen exposure with new ACE2 expression in bronchial epithelial cells. In human specimens, robust ACE2 immunoreactivity was detected in ciliated epithelial cells in paranasal sinus specimens, while ACE2 expression was detected only in rare type 2 alveolar epithelial cells in control lungs. In autopsy specimens from patients with COVID-19 pneumonia, ACE2 was detected in rare ciliated epithelial and endothelial cells in the trachea, but not in the lung. There was robust expression of ACE2 expression in F344/N rat nasal mucosa and lung specimens, which authentically recapitulated the ACE2 expression pattern in human paranasal sinus specimens. Thus, ACE2 protein expression demonstrates a significant gradient between upper and lower respiratory tract in humans and is scarce in the lung. This pattern of ACE2 expression supports the notion of sinonasal epithelium being the main entry site for SARS-CoV-2 but raises further questions on the pathogenesis and cellular targets of SARS-CoV-2 in COVID-19 pneumonia.


Asunto(s)
/biosíntesis , Lesión Pulmonar/enzimología , Factores de Edad , Células Epiteliales Alveolares/metabolismo , Animales , Animales Recién Nacidos , /metabolismo , Femenino , Expresión Génica , Humanos , Lesión Pulmonar/metabolismo , Lesión Pulmonar/patología , Macaca fascicularis , Masculino , Ratones , Ratones Endogámicos C57BL , Papio papio , Mucosa Respiratoria/enzimología , Mucosa Respiratoria/metabolismo , Sistema Respiratorio/metabolismo , Sistema Respiratorio/virología , Transcriptoma
11.
Animal ; 15(2): 100130, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33573954

RESUMEN

Temporary crating may be a more acceptable housing system for lactating sows than permanent crating from an animal welfare point of view. It remains unclear whether opening the crate leads to changes in sow lying down behaviour and piglet activity that may pose an increased risk of injury to piglets. This study aimed to assess whether the lying down behaviour of lactating sows housed in temporary crating changed shortly after removal of confinement, whether it was influenced by piglets' behaviour and age and whether sows preferentially used some support during lying down after crate opening. Sows (n = 13) were crated from 5 days pre partum to 3 days post partum. Their behaviours were recorded on video over a 24-h period both preceding and following crate opening, as well as over a 24-h period on day 25. The following behaviours were analysed: position and activity of the piglets when the sow lie down, duration of the lying down events, use of pen walls or crate bars as support when lying down; and position of the sow in the pen when lying down. Piglet mortality was assessed every day. Data were analysed in SAS using GLM. The duration of lying down events did not differ between the 24-h periods before and after opening the crate but increased on day 25 (P < 0.01). Similarly, the percentage of piglets in the danger zone did not differ between the 24-h periods before and after opening the crate, but increased on day 25 (P < 0.0001). The percentage of piglets in the creep area increased temporarily the day after the crate opening (P < 0.0001). Sows frequently utilised support when lying down, but less over the 24-h period after the crate opening compared to the two other periods (P < 0.001). A higher percentage of piglets in the creep area resulted in longer lying down events where the sow's snout was in contact with piglets located in the creep area (P < 0.05). The present study shows that opening the crate does have an immediate impact on lying down behaviour and piglet behaviour, but it does not pose an increased risk to piglets. Our results also indicate that piglet behaviour changed with age and influenced sow lying down behaviour. Finally, our findings further suggest that some available lying down support may be a very important feature of the pen during the whole lactation period.


Asunto(s)
Vivienda para Animales , Lactancia , Bienestar del Animal , Animales , Animales Recién Nacidos , Conducta Animal , Femenino , Porcinos
12.
Yonsei Med J ; 62(3): 215-223, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33635011

RESUMEN

PURPOSE: This study aimed to elucidate whether lncRNA ZFAS1 is involved in neuronal apoptosis and inflammation in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Ninety-six TLE patients were recruited, and their peripheral venous blood was gathered to determine Zfas1 expression with polymerase chain reaction. Neurons were separated from hippocampal tissue of newborn SD rats, and si-Zfas1 or pcDNA3.1-Zfas1 was transfected into the neurons. Inflammatory cytokines released by neurons were determined, and neuronal activities were evaluated through MTT assay, colony formation assay, and flow cytometry. RESULTS: Serum levels of Zfas1 were higher in TLE patients than in healthy controls (p<0.05). Furthermore, Zfas1 expression in neurons was raised by pcDNA3.1-Zfas1 and declined after silencing of Zfas1 (p<0.05). Transfection of pcDNA-Zfas1 weakened the viability and proliferation of neurons and increased neuronal apoptosis (p<0.05). Meanwhile, pcDNA3.1-Zfas1 transfection promoted lipopolysaccharide-induced release of cytokines, including tumor necrosis factor-α, interleukin (IL)-1, IL-6, and intercellular adhesion molecule-1 (p<0.05), and boosted NF-κB activation by elevating the expression of NF-κB p65, pIκBα, and IKKß in neurons (p<0.05). CONCLUSION: Our results indicated that lncRNA ZFAS1 exacerbates epilepsy development by promoting neuronal apoptosis and inflammation, implying ZFAS1 as a promising treatment target for epilepsy.


Asunto(s)
Apoptosis/genética , Epilepsia del Lóbulo Temporal/genética , Inflamación/patología , Neuronas/patología , ARN Largo no Codificante/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Animales Recién Nacidos , Biomarcadores/metabolismo , Estudios de Casos y Controles , Supervivencia Celular/genética , Niño , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica , Hipocampo/patología , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , FN-kappa B/metabolismo , ARN Largo no Codificante/genética , Ratas Sprague-Dawley , Transducción de Señal/genética , Adulto Joven
13.
Int J Nanomedicine ; 16: 741-752, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33564233

RESUMEN

Background: Quercetin has potential value in treating cardiovascular diseases, but it is not suitable for clinical application due to its own water solubility. The limitation of quercetin can be distinctly ameliorated by delivering it with nanocarriers. Objective: To determine the effect of quercetin-loaded mesoporous silica nanoparticles (Q-MSNs) on myocardial ischemia-reperfusion injury in rats and its mechanism. Methods: Q-MSNs were synthesized, and the morphology of Q-MSNs and MSNs was characterized by transmission electron microscopy and dynamic light scattering technique, respectively. Healthy rats were enrolled and randomly divided into a sham operation control group, an ischemia-reperfusion (IR) group, an IR+Q group, an IR+Q-MSNs group, and an MSNs group (each n = 10). Rats in the sham operation group were not treated with ischemia reperfusion, but given normal perfusion meantime. Rats in the sham operation control group, IR group, and MSNs group were given normal saline for 10 days before ischemia reperfusion, and rats in the IR+Q group and IR+Q-MSNs group were given drugs by gavage for 10 days before ischemia reperfusion. Primary myocardial cells were sampled from SD neonatal rats to construct hypoxia/reoxygenation myocardial cell models. The myocardial cells were assigned to a control group, IR group, quercetin (Q) group, Q-MSNs group, and MSNs group. Except for the control group, all the other groups were treated with hypoxia/reoxygenation. Cells in the Q group were treated with quercetin (10 µM, 20 µM, 40 µM) for 24 h in advance and then treated with measures to cause hypoxia-reoxygenation injury. Cells in the Q-MSNs group were treated with the same concentration of loaded quercetin and the same method used for the Q group. The myocardial apoptosis, myocardial infarction, ventricular remodeling, hemodynamic indexes, physiological and biochemical indexes, and JAK2/STAT3 pathway expression of each group were detected, and the apoptosis, viability, oxidative stress, and JAK2/STAT3 pathway expression of primary myocardial cells in each group were also detected. Results: Quercetin significantly activated the JAK2/STAT3 pathway in vivo and in vitro, and MSNs intensified the activation. Compared with quercetin, Q-MSNs were more effective in inhibiting cell apoptosis and oxidative stress, reducing myocardial infarction size, improving ventricular remodeling and cardiac function-related biochemical indexes, and promoting the recovery of cardiac blood flow. Conclusion: Q-MSNs can significantly enhance the activation effect of quercetin on JAK2/STAT3 pathway, thus enhancing its protection on the heart of MIRI rats.


Asunto(s)
Daño por Reperfusión Miocárdica/tratamiento farmacológico , Nanopartículas/química , Quercetina/uso terapéutico , Dióxido de Silicio/química , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Liberación de Fármacos , Hemodinámica/efectos de los fármacos , Quinasas Janus/metabolismo , Cinética , Masculino , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Nanopartículas/ultraestructura , Estrés Oxidativo/efectos de los fármacos , Porosidad , Quercetina/farmacología , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos
14.
Br J Anaesth ; 126(4): 845-853, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33549320

RESUMEN

BACKGROUND: Non-human primates are commonly used in neuroimaging research for which general anaesthesia or sedation is typically required for data acquisition. In this analysis, the cumulative effects of exposure to ketamine, Telazol® (tiletamine and zolazepam), and the inhaled anaesthetic isoflurane on early brain development were evaluated in two independent cohorts of typically developing rhesus macaques. METHODS: Diffusion MRI scans were analysed from 43 rhesus macaques (20 females and 23 males) at either 12 or 18 months of age from two separate primate colonies. RESULTS: Significant, widespread reductions in fractional anisotropy with corresponding increased axial, mean, and radial diffusivity were observed across the brain as a result of repeated anaesthesia exposures. These effects were dose dependent and remained after accounting for age and sex at time of exposure in a generalised linear model. Decreases of up to 40% in fractional anisotropy were detected in some brain regions. CONCLUSIONS: Multiple exposures to commonly used anaesthetics were associated with marked changes in white matter microstructure. This study is amongst the first to examine clinically relevant anaesthesia exposures on the developing primate brain. It will be important to examine if, or to what degree, the maturing brain can recover from these white matter changes.


Asunto(s)
Anestesia General/efectos adversos , Encéfalo/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/diagnóstico por imagen , Animales , Animales Recién Nacidos , Encéfalo/metabolismo , Imagen de Difusión Tensora/tendencias , Femenino , Macaca mulatta , Masculino
15.
J Vis Exp ; (167)2021 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-33554974

RESUMEN

The understanding of the mechanisms underlying adipocyte differentiation and function has greatly benefited from the use of immortalized white preadipocyte cell lines. These cultured cell lines, however, have limitations. They do not fully capture the diverse functional spectrum of the heterogenous adipocyte populations that are now known to exist within white adipose depots. To provide a more physiologically relevant model to study the complexity of white adipose tissue, a protocol has been developed and optimized to enable simultaneous isolation of primary white and brown adipocyte progenitors from newborn mice, their rapid expansion in culture, and their differentiation in vitro into mature, fully functional adipocytes. The primary advantage of isolating primary cells from newborn, rather than adult mice, is that the adipose depots are actively developing and are, therefore, a rich source of proliferating preadipocytes. Primary preadipocytes isolated using this protocol differentiate rapidly upon reaching confluence and become fully mature in 4-5 days, a temporal window that accurately reflects the appearance of developed fat pads in newborn mice. Primary cultures prepared using this strategy can be expanded and studied with high reproducibility, making them suitable for genetic and phenotypic screens and enabling the study of the cell-autonomous adipocyte phenotypes of genetic mouse models. This protocol offers a simple, rapid, and inexpensive approach to study the complexity of adipose tissue in vitro.


Asunto(s)
Adipocitos Marrones/citología , Adipocitos Blancos/citología , Diferenciación Celular , Separación Celular/métodos , Animales , Animales Recién Nacidos , Células Cultivadas , Metabolismo Energético , Ratones , Reproducibilidad de los Resultados
16.
Biol Res ; 54(1): 4, 2021 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-33557947

RESUMEN

BACKGROUND: Early-life stress in the form of maternal separation can be associated with alterations in offspring neurodevelopment and brain functioning. Here, we aimed to investigate the potential impact of prolonged maternal separation on proteomic profiling of prefrontal cortex, hippocampus and cerebellum of juvenile and young adult rats. A special attention was devoted to proteins involved in the process of cell death and redox state maintenance. METHODS: Long-Evans pups were separated from their mothers for 3 h daily over the first 3 weeks of life (during days 2-21 of age). Brain tissue samples collected from juvenile (22-day-old) and young adult (90-day-old) rats were used for label-free quantitative (LFQ) proteomic analysis. In parallel, selected oxidative stress markers and apoptosis-related proteins were assessed biochemically and by Western blot, respectively. RESULTS: In total, 5526 proteins were detected in our proteomic analysis of rat brain tissue. Approximately one tenth of them (586 proteins) represented those involved in cell death processes or regulation of oxidative stress balance. Prolonged maternal separation caused changes in less than half of these proteins (271). The observed alterations in protein expression levels were age-, sex- and brain region-dependent. Interestingly, the proteins detected by mass spectrometry that are known to be involved in the maintenance of redox state were not markedly altered. Accordingly, we did not observe any significant differences between selected oxidative stress markers, such as the levels of hydrogen peroxide, reduced glutathione, protein carbonylation and lipid peroxidation in brain samples from rats that underwent maternal separation and from the corresponding controls. On the other hand, a number of changes were found in cell death-associated proteins, mainly in those involved in the apoptotic and autophagic pathways. However, there were no detectable alterations in the levels of cleaved products of caspases or Bcl-2 family members. Taken together, these data indicate that the apoptotic and autophagic cell death pathways were not activated by maternal separation either in adolescent or young adult rats. CONCLUSION: Prolonged maternal separation can distinctly modulate expression profiles of proteins associated with cell death pathways in prefrontal cortex, hippocampus and cerebellum of juvenile rats and the consequences of early-life stress may last into adulthood and likely participate in variations in stress reactivity.


Asunto(s)
Encéfalo/fisiopatología , Muerte Celular , Privación Materna , Proteoma , Animales , Animales Recién Nacidos , Femenino , Masculino , Proteómica , Ratas , Ratas Long-Evans
17.
Nat Commun ; 12(1): 1042, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33589625

RESUMEN

Necrotizing enterocolitis (NEC) is a disease of premature infants characterized by acute intestinal necrosis. Current dogma suggests that NEC develops in response to post-natal dietary and bacterial factors, and so a potential role for in utero factors in NEC remains unexplored. We now show that during pregnancy, administration of a diet rich in the aryl hydrocarbon receptor (AHR) ligand indole-3-carbinole (I3C), or of breast milk, activates AHR and prevents NEC in newborn mice by reducing Toll-like receptor 4 (TLR4) signaling in the newborn gut. Protection from NEC requires activation of AHR in the intestinal epithelium which is reduced in mouse and human NEC, and is independent of leukocyte activation. Finally, we identify an AHR ligand ("A18") that limits TLR4 signaling in mouse and human intestine, and prevents NEC in mice when administered during pregnancy. In summary, AHR signaling is critical in NEC development, and maternally-delivered, AHR-based therapies may alleviate NEC.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Enterocolitis Necrotizante/genética , Indoles/administración & dosificación , Leche Humana/fisiología , Receptores de Hidrocarburo de Aril/genética , Receptor Toll-Like 4/genética , Animales , Animales Recién Nacidos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/agonistas , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/inmunología , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/inmunología , Dieta/métodos , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/inmunología , Enterocolitis Necrotizante/patología , Enterocolitis Necrotizante/prevención & control , Femenino , Regulación de la Expresión Génica , Humanos , Recién Nacido , Recien Nacido Prematuro , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Ligandos , Exposición Materna , Ratones , Embarazo , Receptores de Hidrocarburo de Aril/agonistas , Receptores de Hidrocarburo de Aril/inmunología , Transducción de Señal , Porcinos , Receptor Toll-Like 4/inmunología
18.
Nat Commun ; 12(1): 1064, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594056

RESUMEN

Polycystic ovary syndrome (PCOS) is characterized by an oligo-anovulation, hyperandrogenism and polycystic ovarian morphology combined with major metabolic disturbances. However, despite the high prevalence and the human and economic consequences of this syndrome, its etiology remains unknown. In this study, we show that female Goto-Kakizaki (GK) rats, a type 2 diabetes mellitus model, encapsulate naturally all the reproductive and metabolic hallmarks of lean women with PCOS at puberty and in adulthood. The analysis of their gestation and of their fetuses demonstrates that this PCOS-like phenotype is developmentally programmed. GK rats also develop features of ovarian hyperstimulation syndrome. Lastly, a comparison between GK rats and a cohort of women with PCOS reveals a similar reproductive signature. Thus, this spontaneous rodent model of PCOS represents an original tool for the identification of the mechanisms involved in its pathogenesis and for the development of novel strategies for its treatment.


Asunto(s)
Síndrome del Ovario Poliquístico/patología , Adiposidad , Animales , Animales Recién Nacidos , Peso Corporal , Análisis Discriminante , Modelos Animales de Enfermedad , Dislipidemias/patología , Sistema Endocrino/patología , Ciclo Estral , Femenino , Prueba de Tolerancia a la Glucosa , Gonadotropinas/farmacología , Hormonas/sangre , Humanos , Secreción de Insulina , Análisis de los Mínimos Cuadrados , Lípidos/química , Masculino , Intercambio Materno-Fetal , Análisis Multivariante , Ovario/patología , Ovario/fisiopatología , Fenotipo , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/fisiopatología , Embarazo , Ratas Wistar , Reproducción , Maduración Sexual
19.
Ecotoxicol Environ Saf ; 212: 112000, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33550075

RESUMEN

Perinatal exposure to polybrominated diphenyl ethers (PBDEs) may be a potential risk factor for autism spectrum disorders (ASD). BDE-47 is one of the most common PBDEs and poses serious health hazards on the central nervous system (CNS). However, effects of perinatal exposure to BDE-47 on social behaviors and the potential mechanisms are largely unexplored. Thus, we aimed to investigate whether BDE-47 exposure during gestation and lactation led to autistic-like behaviors in offspring rats in the present study. Valproic acid (VPA), which is widely used to establish animal model of ASD, was also adopted to induce autistic-like behaviors. A battery of tests was conducted to evaluate social and repetitive behaviors in offspring rats. We found that perinatal exposure to BDE-47 caused mild autistic-like behaviors in offspring, which were similar but less severe to those observed in pups maternally exposed to VPA. Moreover, perinatal exposure to BDE-47 aggravated the autistic-like behaviors in pups maternally exposed to VPA. Abnormal dendritic development is known to be deeply associated with autistic-like behaviors. Golgi-Cox staining was used to observe the morphological characteristics of dendrites in the prefrontal cortex of pups. We found perinatal exposure to BDE-47 reduced dendritic length and complexity of branching pattern, and spine density in the offspring prefrontal cortex, which may contribute to autistic-like behaviors observed in the present study. Perinatal exposure to BDE-47 also exacerbated the impairments of dendritic development in pups maternally exposed to VPA. Besides, our study also provided the evidence that the inhibition of BDNF-CREB signaling, a key regulator of dendritic development, may be involved in the dendritic impairments induced by perinatal exposure to BDE-47 and/or VPA, and the consequent autistic-like behaviors.


Asunto(s)
Trastorno del Espectro Autista/inducido químicamente , Dendritas/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Éteres Difenilos Halogenados/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ácido Valproico/toxicidad , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Femenino , Edad Gestacional , Lactancia , Masculino , Corteza Prefrontal/efectos de los fármacos , Embarazo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Conducta Social
20.
Animal ; 15(2): 100124, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33573946

RESUMEN

Enterotoxigenic Escherichia coli (ETEC) K99 is one of the major pathogens associated with calf diarrhea. The induction of passive immunity in animals by immunoglobulin Y and using probiotics are inexpensive alternatives to antibiotics for the prevention and treatment of a number of bacterial infections, including diarrhea. Hence, the aim of this research was to evaluate the impact of dietary probiotics and ETEC K99-specific egg yolk antibody supplements, alone and in combination with each other, on health and growth parameters, diarrhea incidence and immune stimulation in newborn Holstein calves. One hundred and twenty neonatal calves were allocated randomly into 4 dietary groups (n = 30 per group) received colostrum/milk without any additives (control group), or supplemented with egg yolk powder contained E. coli K99-specific antibody (Ab group; 1 g/day), a commercial probiotic, Hypro-calves (Pro group; 3 g/day), and their combination (Ab+Pro group), from day (d) 1 to d28 of age. Analyses of the growth parameters, feed efficiency, fecal score, and microbiota and immune function were carried out on d0, 14, 21, and 28 of the experiment. Calves in Ab or Ab+Pro group had higher (P < 0.05) average daily gain compared to control and Pro groups during 0-14d. Feed efficiency of calves in Ab and Ab+Pro groups was significantly higher than that in control group during the period of 0-14d; however, no significant differences were observed in 0-28d period. Diarrhea prevalence and fecal score in Ab+Pro group were lower than control group (P < 0.05). Calves in Ab+Pro group had the lowest number of fecal E. coli in comparison to other groups on d28 (P < 0.05). Feeding Ab+Pro supplement increased (P < 0.05) concentrations of blood IgA and serum CD4 compared to the control group. Likewise, calves in Pro group had higher CD4 levels as compared to the control calves (P < 0.05). Serum concentration of interferon-gamma in control group was lower than other groups (P < 0.05). Overall, these data suggest that feeding a combination of probiotic and specific antibody against ETEC to neonate Holstein calves enhances feed efficiency, boosts immunity, and reduces diarrhea prevalence.


Asunto(s)
Enfermedades de los Bovinos , Probióticos , Animales , Animales Recién Nacidos , Bovinos , Diarrea/prevención & control , Diarrea/veterinaria , Femenino , Sistema Inmunológico , Inmunoglobulinas , Incidencia , Óvulo , Embarazo
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