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A novel moderately thermophilic heterotrophic bacterium, designated strain 143-21T, was isolated from a deep-sea hydrothermal chimney sample collected from the Central Indian Ridge at a depth of 2â440 m. Phylogenetic analysis indicated that strain 143-21T belongs to the genus Crassaminicella. It was most closely related to Crassaminicella thermophila SY095T (96.79â% 16S rRNA gene sequence similarity) and Crassaminicella profunda Ra1766HT (96.52â%). Genomic analysis showed that strain 143-21T shares 79.79-84.45â% average nucleotide identity and 23.50-29.20â% digital DNA-DNA hybridization with the species of the genus Crassaminicella, respectively. Cells were rod-shaped, non-motile, Gram-positive-staining. Terminal endospores were observed in stationary-phase cells when strain 143-21T was grown on Thermococcales rich medium. Strain 143-21T was able to grow at 30-60 °C (optimum, 50 °C), pH 6.5-8.5 (optimum, pH 7.0) and in 1.0-7.0â% NaCl (w/v; optimum 2.0â%, w/v). Strain 143-21T utilized fructose, glucose, maltose, mannose, ribose, N-acetyl-d-(+)-glucosamine and casamino acids, as well as amino acids including glutamate, lysine, histidine and cysteine. The main fermentation products from glucose were acetate (2.07 mM), H2 and CO2. It did not reduce elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and Fe (III). The predominant cellular fatty acids were C14â:â0 (48.8â%), C16â:â0 (12.9â%), and summed feature 3 (C16â:â1 ω7c and/or C16â:â1 ω6c; 10.2â%). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol, as well as two unidentified phospholipids and four unidentified aminolipids. No respiratory quinones were detected. Based on its phylogenetic analysis and physiological characteristics, strain 143-21T is considered to represent a novel species of the genus Crassaminicella, for which the name Crassaminicella indica sp. nov. is proposed. The type strain is strain 143-21T (=DSM 114408T= MCCC 1K06400T).
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Ácidos Grasos , Respiraderos Hidrotermales , Ácidos Grasos/química , Filogenia , ARN Ribosómico 16S/genética , Composición de Base , Respiraderos Hidrotermales/microbiología , Anaerobiosis , Análisis de Secuencia de ADN , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Fosfolípidos/química , Bacterias AnaerobiasRESUMEN
A practical and efficient electrochemical intramolecular amino- or oxysulfonylation of internal alkenes equipped with pendant nitrogen or oxygen-centered nucleophiles with sodium sulfinate was developed. Under undivided electrolytic cell conditions, a variety of sulfonylated N-heterocycles and O-heterocycles, such as tetrahydrofurans, tetrahydropyrans, oxepanes, tetrahydropyrroles, piperidines, δ-valerolactones, etc., were efficiently prepared from easily accessible unsaturated alcohols, carboxylic acids, and N-tosyl amines without the need for additional metal or exogenous oxidant. The robust electrochemical transformation features excellent redox economy, high diastereoselectivity, and broad substrate specificity, which provide a general and practical access to sulfone-containing heterocycles and would facilitate the related synthetic and biological studies based on this electrosynthesis.
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Background: The systemic immune-inflammation index (SII) is used as an indicator of prognosis for a wide range of diseases. Thyroid function has been found to be strongly associated with inflammation. The purpose of this investigation was to analyze the correlation between SII and various thyroid functions. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. The association between SII and thyroid function was analyzed using weighted univariate and multivariate linear regression analyses. Subgroup analyses, interaction tests, and weighted restricted cubic spline (RCS) regression analyses were also employed to test this correlation. Results: Of the 6,875 participants (age ≥ 20 years), the mean age was 46.87 ± 0.40 years. The adjusted model showed that lnSII was negatively correlated with FT3 (ß = -0.0559, 95% CI -0.1060 to -0.0059,) and FT3/FT4 (ß = -0.0920, 95% CI -0.1667 to -0.0173,). There was a positive correlation between lnSII and TT4 (ß = 0.1499, 95% CI 0.0722-0.2276,). In subgroup analyses, lnSII still independently affected a wide range of thyroid functions. Weighted RCS analysis showed a nonlinear relationship between FT3 and lnSII. Conclusion: Close relationships exist between SII and a variety of thyroid functions. SII can be used as an indicator to predict thyroid dysfunction. Control of inflammatory activity may be a protective measure against thyroid dysfunction. More large-scale prospective studies are necessary to further explore the correlation between SII and thyroid function and the role of obesity in this.
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Inflamación , Glándula Tiroides , Humanos , Adulto , Persona de Mediana Edad , Adulto Joven , Encuestas Nutricionales , Estudios Prospectivos , Modelos LinealesRESUMEN
Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder, and there is an association between it and the development of cardiovascular disease. The aim of this study was to explore whether there is a glutamatergic pathway connecting the medial habenula (MHb) with the rostral ventrolateral medulla (RVLM) that is involved in the regulation of cardiovascular function in a rat model of PTSD. Vesicular glutamate transporter 2 (VGLUT2)-positive neurons in the MHb region were retrogradely labeled with FluoroGold (FG) by the double-labeling technique of VGLUT2 immunofluorescence and FG retrograde tracing. Rats belonging to the PTSD model group were microinjected with artificial cerebrospinal fluid (ACSF) or kynurenic acid (KYN; a nonselective glutamate receptor blocker) into their RVLM. Subsequently, with electrical stimulation of MHb, the discharge frequency of the RVLM neurons, heart rate, and blood pressure were found to be significantly increased after microinjection of ACSF using an in vivo multichannel synchronous recording technology; however, this effect was inhibited by injection of KYN. The expression of N-methyl-D-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits was significantly increased in RVLM of PTSD model rats analyzed by the Western blotting technique. These findings suggest that there may be a glutamatergic pathway connection between MHb and RVLM and that this pathway may be involved in the regulation of cardiovascular function in the PTSD model rats, by acting on NMDA and AMPA receptors in the RVLM.
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Habénula , Trastornos por Estrés Postraumático , Humanos , Ratas , Animales , Trastornos por Estrés Postraumático/metabolismo , N-Metilaspartato/metabolismo , N-Metilaspartato/farmacología , Habénula/metabolismo , Bulbo Raquídeo/metabolismo , Presión Sanguínea , Ácido Glutámico/metabolismo , Ácido Glutámico/farmacologíaRESUMEN
Post-traumatic stress disorder (PTSD) has been reported to be associated with a higher risk of cardiovascular disease. The amygdala may have an important role in regulating cardiovascular function. This study aims to explore the effect of amygdala glutamate receptors (GluRs) on cardiovascular activity in a rat model of PTSD. A compound stress method combining electrical stimulation and single prolonged stress was used to prepare the PTSD model, and the difference of weight gain before and after modeling and the elevated plus maze were used to assess the PTSD model. In addition, the distribution of retrogradely labeled neurons was observed using the FluoroGold (FG) retrograde tracking technique. Western blot was used to analyze the changes of amygdala GluRs content. To further investigate the effects, artificial cerebrospinal fluid (ACSF), non-selective GluR blocker kynurenic acid (KYN) and AMPA receptor blocker CNQX were microinjected into the central nucleus of the amygdala (CeA) in the PTSD rats, respectively. The changes in various indices following the injection were observed using in vivo multi-channel synchronous recording technology. The results indicated that, compared with the control group, the PTSD group exhibited significantly lower weight gain (P < 0.01) and significantly decreased ratio of open arm time (OT%) (P < 0.05). Retrograde labeling of neurons was observed in the CeA after microinjection of 0.5 µL FG in the rostral ventrolateral medulla (RVLM). The content of AMPA receptor in the PTSD group was lower than that in the control group (P < 0.05), while there was no significant differences in RVLM neuron firing frequency and heart rate (P > 0.05) following ACSF injection. However, increases in RVLM neuron firing frequency and heart rate were observed after the injection of KYN or CNQX into the CeA (P < 0.05) in the PTSD group. These findings suggest that AMPA receptors in the amygdala are engaged in the regulation of cardiovascular activity in PTSD rats, possibly by acting on inhibitory pathways.
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Trastornos por Estrés Postraumático , Ratas , Animales , Ratas Sprague-Dawley , Receptores AMPA , 6-Ciano 7-nitroquinoxalina 2,3-diona/metabolismo , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Receptores de Glutamato/metabolismo , Amígdala del Cerebelo , Aumento de Peso , Bulbo Raquídeo/fisiología , Presión SanguíneaRESUMEN
OBJECTIVE: To investigate the value of contrast-enhanced computed tomography (CECT) radiomics features in predicting the efficacy of epirubicin combined with ifosfamide in patients with pulmonary metastases from soft tissue sarcoma. METHODS: A retrospective analysis of 51 patients with pulmonary metastases from soft tissue sarcoma who received the chemotherapy regimen of epirubicin combined with ifosfamide was performed, and efficacy was evaluated by Recist1.1. ROIs (1 or 2) were selected for each patient. Lung metastases were used as target lesions (86 target lesions total), and the patients were divided into a progression group (n = 29) and a non-progressive group (n = 57); the latter included a stable group (n = 34) and a partial response group (n = 23). Information on lung metastases was extracted from CECT images before chemotherapy, and all lesions were delineated by ITK-SNAP software manually or semiautomatically. The decision tree classifier had a better performance in all radiomics models. A receiver operating characteristic curve was plotted to evaluate the predictive performance of the radiomics model. RESULTS: In total, 851 CECT radiomics features were extracted for each target lesion and finally reduced to 2 radiomics features, which were then used to construct a radiomics model. Areas under the curves of the model for predicting lesion progression were 0.917 and 0.856 in training and testing groups, respectively. CONCLUSION: The model established based on the radiomics features of CECT before treatment has certain predictive value for assessing the efficacy of chemotherapy for patients with soft tissue sarcoma lung metastases.
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Neoplasias Pulmonares , Sarcoma , Neoplasias de los Tejidos Blandos , Epirrubicina , Humanos , Ifosfamida , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Sarcoma/diagnóstico por imagen , Sarcoma/tratamiento farmacológico , Tomografía Computarizada por Rayos X/métodosRESUMEN
Cicadae Periostracum (CP) is a traditional Chinese medicinal herb derived from the slough that is molted from the nymph of the insect Cryptotympana pustulata Fabricius. Washing with water to remove residual silt is a primary processing method of CP that is recommended by the Chinese Pharmacopoeia, but how washing methods affect the quality and bioactivity of CP is unknown. In this study, the quality and bioactivity of non-washed CP (CP-NW), post-molting-washed CP (CP-WAT), and pre-molting-washed CP (CP-WBT) were comparatively investigated. The quality of these CP samples was evaluated in terms of the UPLC-QTOF-MS/MS-based chemical profiling and semi-quantification of 39 N-acetyldopamine oligomers (belonging to six chemical types), the HPLC-UV-based quantification of 17 amino acids, the ICP-MS-based quantification of four heavy metals, and the contents of ash; the bioactivities of the samples were compared regarding their anti-oxidant and anti-inflammatory activities. It was found that, compared with CP-NW, both CP-WBT and CP-WAT had significantly lower contents of ash and heavy metals. Moreover, compared with CP-WAT, CP-WBT contained lower levels of total ash, acid-insoluble ash, and heavy metals and higher contents of N-acetyldopamine oligomers and amino acids. It also had enhanced anti-oxidant and anti-inflammatory activities. A Spearman's correlation analysis found that the contents of N-acetyldopamine oligomers and free amino acids were positively correlated with the anti-oxidant/-inflammatory activities of CP. All these results suggest that pre-molting washing can not only remove the residual silt but can also avoid the loss of the bioactive components and assure higher bioactivities. It is concluded that pre-molting washing could enhance the quality and bioactivity of CP and should be a superior alternative method for the primary processing of qualified CP.
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Antioxidantes , Metales Pesados , Antioxidantes/farmacología , Oxidantes , Espectrometría de Masas en Tándem , Muda , Antiinflamatorios/farmacología , Metales Pesados/análisis , AminoácidosRESUMEN
This study was aimed to investigate the cardiovascular function in rats with post-traumatic stress disorder (PTSD) and the potential association with the activities of the rostral ventrolateral medulla (RVLM) and the medial habenular nucleus (MHb). Multi-channel in vivo recordings were used to simultaneously acquire spontaneous neuronal firing and peripheral physiological indices, and FluoroGold (FG) retrograde tracing technique was used to observe the projections of labeled neurons in the MHb. The results showed that the discharge frequency of RVLM and MHb neurons, the systolic blood pressure (SBP), and the mean arterial pressure (MAP) in the PTSD group were all increased significantly compared with those in control group (P < 0.05). MHb neurons were retrogradely labeled by FG through microinjection (4% FG, 0.5 µL) into the RVLM. In the control group, electrical stimulation in the MHb increased heart rate (HR) at 100-300 µA (P < 0.05), elevated SBP and MAP at 200-300 µA (P < 0.05), and remarkably increased the RVLM neuronal discharge frequency at 100-500 µA (P < 0.05 or P < 0.01). In the PTSD group, however, only the discharge frequency of RVLM neurons was increased by the electrical stimulation at 100-300 µA (P < 0.05). These results suggest that cardiovascular activities of the PTSD model rat are enhanced, and this change may be related to the activity changes of RVLM and MHb and the potential connection between the two nuclei.
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Trastornos por Estrés Postraumático , Animales , Presión Sanguínea , Bulbo Raquídeo , Neuronas , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro. METHODS: Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD. RESULTS: It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the ß-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered. CONCLUSION: Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the ß-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.
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Traumatismos de los Nervios Periféricos , Degeneración Walleriana , Animales , Claudinas , Regeneración Nerviosa , Ratas , Células de Schwann/patología , Nervio Ciático , Degeneración Walleriana/patologíaRESUMEN
It was reported that α7 nicotinic acetylcholine receptor (α7-nAChR) knockout (α7 KO) mice showed few functional phenotypes. The purpose of this study was to investigate the effect of α7 KO on the electrophysiological characteristics of hippocampus in mice. The effect of α7 KO on hippocampal CA3-CA1 synaptic transmission in mice was evaluated by standard extracellular field potential recordings. The electrophysiological phenotype of γ-aminobutyrate A receptors (GABAA-Rs) of single hippocampal neuron was detected by perforated patch-clamp recordings. The results showed that, the slope of field excitatory postsynaptic potential (fEPSP) and carbachol-induced theta oscillation were significantly decreased in the hippocampal CA1 neurons of α7 KO mice, compared with those of wild type mice. Under the treatment of GABAA-R agonist muscimol, the I-V curves of both the hippocampal CA1 and CA3 neurons of α7 KO mice shifted towards depolarizing direction obviously, compared with those of wild type mice. These results suggest that the hippocampal CA3-CA1 synaptic transmission in α7 KO mice was significantly impaired and GABAA-R maturation was significantly delayed, indicating that the deletion of α7-nAChR gene could significantly change the electrophysiological function of the hippocampus. The results may provide a new understanding of the role of α7-nAChR in hippocampal function and associated diseases.
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Hipocampo/citología , Neuronas/fisiología , Transmisión Sináptica , Receptor Nicotínico de Acetilcolina alfa 7/fisiología , Animales , Ratones , Ratones Noqueados , FenotipoRESUMEN
OBJECTIVE: This study aims to evaluate combined effects of MESSAGE communication strategy and group reminiscence therapy (GRT) on elders with mild cognitive impairment (MCI) in long-term care facilities in Changchun, China. METHODS: This study is a nonrandomized controlled trial. Subjects included 60 elders with MCI. Participants were divided into intervention (MESSAGE communication strategy combined with GRT) and control groups (without any intervention). Primary outcomes comprised cognitive function and quality of life of elderly people, as measured by the Beijing version of the Montreal Cognitive Assessment and the Chinese (mainland) version of Short-Form 36 Health Survey assessment. RESULTS: We observed significant changes in cognitive function with mean difference of 1.962 after 12 weeks (P = .000; 95% confidence interval [CI] = 1.341, 2.582), delayed memory dimension of 1.115 (P = .003; 95% CI = 0.417, 1.813). The intervention group exhibited the following improvements: general health of 14.731 (P = .000; 95% CI = 8.511, 20.951), mental health of 21.038 (P = .000; 95% CI = 17.301, 24.776), role-emotional of 26.925 (P = .003; 95% CI = 10.317, 45.533), and vitality of 14.231 (P = .000; 95% CI = 10.084, 18.377). CONCLUSIONS: Using a sample of Chinese elderly people with MCI and residing in long-term care facilities, we concluded that application of MESSAGE communication strategy combined with GRT resulted in improved cognitive function and quality of life.
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Cognición/fisiología , Disfunción Cognitiva/terapia , Cuidados a Largo Plazo/estadística & datos numéricos , Memoria , Psicoterapia de Grupo/métodos , Anciano , Anciano de 80 o más Años , China , Disfunción Cognitiva/psicología , Comunicación , Femenino , Humanos , Masculino , Calidad de VidaRESUMEN
Apelin is a novel endogenous active peptide. The aim of this study is to investigate whether apelin in the paraventricular nucleus (PVN) can improve the cardiac function in rats subjected to thoracic surgery trauma, and whether it is involved in the protective effect of electro-acupuncture (EA). Sprague-Dawley rats were randomly divided into non-stressed group (control), thoracic surgical trauma stressed group (trauma) and bilateral Neiguan EA applied on thoracic surgical trauma stressed group (trauma + EA-PC 6). The mRNA expressions of apelin receptor (APJR) and apelin in the PVN were detected by real time-PCR. The exogenous apelin-13 (6 mmol/L, 0.1 µL) was microinjected into the rat PVN in the thoracic trauma group, and the effects of apelin-13 on the blood pressure (BP), heart rate (HR) and the discharge of rostral ventrolateral medulla (RVLM) neurons were observed through the simultaneous recording technology by polygraph. The results showed that the APJR mRNA expression was significantly decreased in the rats of trauma group as compared with that in the control group (P < 0.05), and a decline trend of apelin mRNA expression was also observed. EA application at bilateral Neiguan acupoints partially recovered the decline of APJR and apelin mRNA expression by the treatment of thoracic trauma. Both mean arterial pressure and HR in the thoracic surgical trauma group were significantly increased by the microinjection of exogenous apelin-13 into the PVN (P < 0.05), and the single-unit discharge rate of RVLM neurons also had an increasing trend. These results suggest that apelin in the PVN can improve the cardiac function of thoracic surgical trauma rats, and may be involved in the protective effects of EA.
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Apelina/fisiología , Electroacupuntura , Núcleo Hipotalámico Paraventricular/fisiología , Procedimientos Quirúrgicos Torácicos , Animales , Receptores de Apelina/fisiología , Presión Sanguínea , Frecuencia Cardíaca , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Bulbo Raquídeo/fisiología , Neuronas , Ratas , Ratas Sprague-DawleyRESUMEN
AIM: To explore the situation of older nurses approaching retirement with regard to their retirement planning, and the relationship of their retirement planning behaviour with the job environment and job satisfaction under their current employment arrangements and other work-related variables. BACKGROUND: Nurse shortage has become a global phenomenon that can be alleviated by retaining older nurses in service. The Chinese government proposed the "Incremental Delay Retirement Age Policy." However, older nurses face delayed retirement but lack retirement plans. METHOD: A cross-sectional questionnaire survey was conducted among a convenience sample of older retiring nurses (n = 152; 84.92% response rate) recruited from every department of four large general hospitals in Changchun, Jilin Province from June to August 2016. RESULT: The majority of the respondents presented poor retirement planning (n = 122, 80.3%). The independent variables of information exchange with patients, teamwork and personal growth and development explained approximately 16.6% of the variance in retirement planning. Nurse-patient communication and personal growth and development can promote retirement planning, but teamwork is negatively related to retirement planning. CONCLUSION: Retirement planning by Chinese older nurses is related to certain work-related variables. However, many other work-related variables were not associated with retirement planning and require further research. Overall, Chinese older retiring nurses must improve their retirement planning practices.
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Empleo/normas , Enfermeras y Enfermeros/psicología , Jubilación/normas , Adulto , China , Estudios Transversales , Femenino , Humanos , Satisfacción en el Trabajo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Jubilación/psicología , Encuestas y CuestionariosRESUMEN
Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro. Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1ß, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis.
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Antineoplásicos Fitogénicos/toxicidad , Antioxidantes/uso terapéutico , Células Endoteliales/efectos de los fármacos , Flavanonas/uso terapéutico , Flebitis/tratamiento farmacológico , Vinblastina/análogos & derivados , Animales , Antioxidantes/farmacología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Células Endoteliales/metabolismo , Flavanonas/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Masculino , Flebitis/metabolismo , Conejos , Distribución Aleatoria , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Vinblastina/toxicidad , VinorelbinaRESUMEN
Our previous study has reported that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) regulates the growth and survival of hepatocellular carcinoma (HCC) cells. This study was undertaken to explore the roles of MAP4K4 in the epithelial-mesenchymal transition (EMT) and metastasis in HCC. Effects of overexpression and knockdown of MAP4K4 on the migration, invasion, and EMT of HCC cells were examined. The in vivo role of MAP4K4 in lung metastasis of HCC was determined in nude mice. The relationship between MAP4K4 expression and EMT in human HCC specimens was determined by immunohistochemistry. MAP4K4 overexpression significantly enhanced the migration and invasion of MHCC-97L HCC cells, whereas MAP4K4 silencing hindered the migration and invasion of MHCC-97H HCC cells. MAP4K4-overexpressing cells undergo EMT, which was accompanied by downregulation of E-cadherin and upregulation of vimentin. In contrast, MAP4K4 silencing caused a reversion from a spindle morphology to cobblestone-like morphology and induction of E-cadherin and reduction of vimentin. Pretreatment with chemical inhibitors of JNK and NF-κB abolished MAP4K4-mediated migration, invasion, and regulation of EMT markers in MHCC-97L cells. Ectopic expression of MAP4K4 promoted and knockdown of MAP4K4 inhibited lung metastasis of HCC, which was associated with regulation of JNK and NF-κB signaling and EMT markers. High MAP4K4 immunoreactivity was inversely correlated with E-cadherin and was positively correlated with vimentin, phospho-JNK, and phospho-NF-κB in HCC specimens. Taken together, MAP4K4 promotes the EMT and invasiveness of HCC cells largely via activation of JNK and NF-κB signaling.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundario , Transición Epitelial-Mesenquimal/fisiología , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Neoplasias Hepáticas/patología , Proteínas Serina-Treonina Quinasas/biosíntesis , Animales , Western Blotting , Carcinoma Hepatocelular/genética , Femenino , Técnica del Anticuerpo Fluorescente , Técnicas de Silenciamiento del Gen , Xenoinjertos , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , FN-kappa B/metabolismo , Invasividad Neoplásica/genética , Reacción en Cadena de la Polimerasa , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
The present study was designed to investigate the inhibitory effects of intravenous general anesthetic propofol (0.1-3.0 mmol/L) on excitatory synaptic transmission in supraoptic nucleus (SON) neurons of rats, and to explore the underlying mechanisms by using intracellular recording technique and hypothalamic slice preparation. It was observed that stimulation of the dorsolateral region of SON could elicit the postsynaptic potentials (PSPs) in SON neurons. Of the 8 tested SON neurons, the PSPs of 7 (88%, 7/8) neurons were decreased by propofol in a concentration-dependent manner, in terms of the PSPs' amplitude (P < 0.01), area under curve, duration, half-width and 10%-90% decay time (P < 0.05). The PSPs were completely and reversibly abolished by 1.0 mmol/L propofol at 2 out of 7 tested cells. The depolarization responses induced by pressure ejection of exogenous glutamate were reversibly and concentration-dependently decreased by bath application of propofol. The PSPs and glutamate-induced responses recorded simultaneously were reversibly and concentration-dependently decreased by propofol, but 0.3 mmol/L propofol only abolished PSPs. The excitatory postsynaptic potentials (EPSPs) of 7 cells increased in the condition of picrotoxin (30 µmol/L, a GABA(A) receptor antagonist) pretreatment. On this basis, the inhibitory effects of propofol on EPSPs were decreased. These data indicate that the presynaptic and postsynaptic mechanisms may be both involved in the inhibitory effects of propofol on excitatory synaptic transmission in SON neurons. The inhibitory effects of propofol on excitatory synaptic transmission of SON neurons may be related to the activation of GABA(A) receptors, but at a high concentration, propofol may also act directly on glutamate receptors.
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Potenciales Postsinápticos Excitadores/efectos de los fármacos , Neuronas/efectos de los fármacos , Propofol/farmacología , Núcleo Supraóptico/citología , Anestésicos Intravenosos/farmacología , Animales , Antagonistas de Receptores de GABA-A/farmacología , Ácido Glutámico/farmacología , Técnicas In Vitro , Ratas , Receptores de Glutamato/metabolismoRESUMEN
OBJECTIVE: To systematically screen and identify long noncoding RNA (lncRNA) associated with bone marrow adiposity changes in aplastic anemia (AA). METHODS: The PPARγ and C/EBPα ChIP-Seq data in ChIPBase was analyzed by bioinformatics and the potential lncRNA co-transcriptionally regulated by PPARγ and C/EBPα was screened. The expression of candidate lncRNA was verified by qRT-PCR in the in vitro adipogenic differentiation model of BM-MSC, BM-MSC infected with lenti-shPPARγ and lenti-shC/EBPα as well as clinical BM-MSC samples derived from AA and controls. RESULTS: PPARγ and C/EBPα were significantly highly expressed in AA BM-MSC, and knock-down of PPARγ and C/EBPα impaired the adipogenic capacity of AA BM-MSC. PPARγ and C/EBPα cotranscriptionally activate LINC01230 promoter activity in binding sites dependant manner. The LINC01230 was also aberrantly highly expressed in AA BM-MSC compared with controls. CONCLUSION: PPARγ and C/EBPα are aberrantly expressed in AA BM-MSC and may promote the adipogenic differentiation of AA BM-MSC, and to a certain extent mediate the bone marrow adiposity alteration by transcriptionally activating LINC01230 expression.
Asunto(s)
Anemia Aplásica , Médula Ósea , PPAR gamma , ARN Largo no Codificante , ARN Largo no Codificante/genética , Humanos , Anemia Aplásica/genética , PPAR gamma/genética , PPAR gamma/metabolismo , Médula Ósea/metabolismo , Proteína alfa Potenciadora de Unión a CCAAT/genética , Diferenciación Celular , Células Madre Mesenquimatosas/metabolismo , Adipogénesis , Adiposidad , Células de la Médula ÓseaRESUMEN
OBJECTIVES: To investigate the mechanism of the effect of acupuncture and moxibustion on improving liver injury in cisplatin (DDP) induced liver injury model mice by observing the changes of inositol-requiring enzyme (IRE) -1 signaling pathway. METHODS: Forty KM mice were randomly divided into control, model, acupuncture and moxibustion groups, with 10 mice in each group. The liver injury model was replicated by intraperitoneal injection of DDP (10 mg/kg). In the acupuncture group and the moxibustion group, acupuncture and moxibustion were performed at "Dazhui"(GV14), and bilateral "Ganshu"(BL18), "Shenshu" (BL23), and "Zusanli"(ST36), respectively for 6 min, once per day for 7 d. The apoptosis of hepatocytes was detected by TUNEL staining. The expression of phosphorylation(p)-IRE-1α, glucose-regulated protein (Grp) 78 and cysteine aspartic protease (Caspase) -12 in liver tissue were detected by immunohistochemistry and Western blot, respectively. The expression levels of Grp78 and Caspase-12 mRNA in liver tissue were detected by quantitative real-time PCR. RESULTS: Compared with the control group, the apoptosis rate of hepatocytes was increased (P<0.05), the positive expression and protein expression of p-IRE-1α, Grp78, and Caspase-12 were increased (P<0.05), the expression levels of Grp78 and Caspase-12 mRNA were increased (P<0.05) in the model group. Compared with the model group, all these indicators showed opposite trends (P<0.05) in the acupuncture and moxibustion groups. CONCLUSIONS: Acupuncture and moxibustion can reduce liver injury due to DDP chemotherapy by modulating IRE-1 signaling pathway, inhibiting the excessive activation of endoplasmic reticulum stress, and reducing liver cell apoptosis.
Asunto(s)
Terapia por Acupuntura , Apoptosis , Cisplatino , Chaperón BiP del Retículo Endoplásmico , Hígado , Moxibustión , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Animales , Ratones , Masculino , Humanos , Hígado/metabolismo , Hígado/lesiones , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Endorribonucleasas/metabolismo , Endorribonucleasas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Puntos de Acupuntura , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Caspasa 12/metabolismo , Caspasa 12/genética , Hepatocitos/metabolismoRESUMEN
Environmental heterogeneity partly drives microbial succession in arthropods, while the microbial assembly mechanisms during environmental changes remain largely unknown. Here, we explored the temporal dynamics and assembly mechanisms within both bacterial and fungal communities in Liriomyza huidobrensis (Blanchard) during the transition from field to laboratory conditions. We observed a decrease in bacterial diversity and complexity of bacterial-fungal co-occurrence networks in leaf miners transitioning from wild to captive environments. Both neutral and null models revealed that stochastic processes, particularly drift (contributing over 70%), play a crucial role in governing bacterial and fungal community assembly. The relative contribution of ecological processes such as dispersal, drift, and selection varied among leaf miners transitioning from wild to captive states. Furthermore, we propose a hypothetical scenario for the assembly and succession of microbial communities in the leaf miner during the short- and long-term transition from the wild to captivity. Our findings suggest that environmental heterogeneity determines the ecological processes governing bacterial and fungal community assembly in leaf miners, offering new insights into microbiome and mycobiome assembly mechanisms in invasive pests amidst environmental change.
RESUMEN
ABSTRACT: Objectives: Puerarin, the principal active constituent extracted from Pueraria, is believed to confer protection against sepsis-induced lung injury. The study aimed to elucidate the role and mechanism of Mst1/ERS in puerarin-mediated protection against acute lung injury (ALI). Methods: Monolayer vascular endothelial cell permeability was assessed by gauging the paracellular flow of FITC-dextran 40,000 (FD40). ELISA was employed for the quantification of inflammatory cytokines. Identification of target proteins was conducted through western blotting. Histological alterations and apoptosis were scrutinized using hematoxylin-eosin staining and TUNEL staining, respectively. The ultrastructure of the endoplasmic reticulum was observed via transmission electron microscopy. Results: Puerarin significantly protected mice from LPS-induced ALI, reducing lung interstitial width, neutrophil and lymphocyte infiltration, pulmonary interstitial and alveolar edema, and lung apoptosis. Puerarin treatment also markedly attenuated levels of TNF-α and IL-1ß in both alveolar lavage fluid and serum. Furthermore, puerarin significantly attenuated LPS-induced increases in Mst1, GRP78, CHOP, and Caspase12 protein expression and blunted LPS-induced decrease in ZO-1 protein expression in lung tissues. Puerarin obviously reduced endoplasmic reticulum expansion and vesiculation. Similarly, puerarin significantly mitigated the LPS-induced reduction in HUVEC cell viability and ZO-1 expression. Puerarin also attenuated LPS-induced increase in apoptosis, TNF-α and IL-1ß, FD40 flux, and Mst1, GRP78, CHOP, and Caspase12 expression in HUVEC cells. Nevertheless, the inhibitory impact of puerarin on vascular endothelial cell injury, lung injury, and endoplasmic reticulum stress (ERS) was diminished by Mst1 overexpression. Conclusion: These findings demonstrated that the Mst1/ERS signaling pathway played a pivotal role in the development of LPS-induced vascular endothelial cell dysfunction and ALI. Puerarin exhibited the ability to attenuate LPS-induced vascular endothelial cell dysfunction and ALI by inhibiting the Mst1/ERS signaling pathway.