RESUMEN
Dysfunction of the circadian rhythm is one of most common nonmotor symptoms in Parkinson's disease (PD), but the molecular role of the circadian rhythm in PD is unclear. We here showed that inactivation of brain and muscle ARNT-like 1 (BMAL1) in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-treated mice resulted in obvious motor functional deficit, loss of dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNpc), decrease of dopamine (DA) transmitter, and increased activation of microglia and astrocytes in the striatum. Time on the rotarod or calorie consumption, and food and water intake were reduced in the Bmal1-/- mice after MPTP treatment, suggesting that absence of Bmal1 may exacerbate circadian and PD motor function. We observed a significant reduction of DANs (~35%) in the SNpc, the tyrosine hydroxylase protein level in the striatum (~60%), the DA (~22%), and 3,4-dihydroxyphenylacetic acid content (~29%), respectively, in MPTP-treated Bmal1-/- mice. Loss of Bmal1 aggravated the inflammatory reaction both in vivo and in vitro. These findings suggest that BMAL1 may play an essential role in the survival of DANs and maintain normal function of the DA signaling pathway via regulating microglia-mediated neuroinflammation in the brain.
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1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/efectos adversos , Factores de Transcripción ARNTL/fisiología , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/inmunología , Inflamación/patología , Microglía/patología , Enfermedad de Parkinson/patología , Animales , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patología , Inflamación/etiología , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/efectos de los fármacos , Microglía/metabolismo , Neurotoxinas/toxicidad , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/metabolismoRESUMEN
BACKGROUND: Acromial anatomy has been found to be correlated with degenerative full-thickness rotator cuff tears in current studies. However, research on the relationship between acromial anatomy and articular-sided partial thickness of rotator cuff tears (PTRCTs) is still lacking. The purpose of this study was to evaluate whether these imaging graphic parameters exhibit any association between acromial anatomy and degenerative articular-sided PTRCTs. METHODS: Between January 2016 and December 2018, a total of 91 patients without a history of trauma underwent arthroscopy as an articular-sided PTRCT group. In the control group, with age- and sex-matched patients, we selected 91 consecutive outpatient patients who underwent shoulder magnetic resonance imaging (MRI) because of shoulder pain and an MRI diagnosis of only synovial hyperplasia and effusion. MRI was used to measure the acromial type, acromiohumeral distance (AHD), lateral acromial angle (LAA), acromion index (AI), and critical shoulder angle (CSA) by 2 independent observers. RESULTS: The acromion type, AHD and LAA showed no difference between degenerative articular-sided PTRCTs and controls (P = 0.532, 0.277, and 0.108, respectively). AI and CSA were significantly higher in degenerative articular-sided PTRCTs (P = 0.002 and 0.003, respectively). A good correlation was found between AI and CSA to measurement(Pearson correlation coefficient = 0.631). CONCLUSIONS: Our study revealed that higher AI and CSA were found in degenerative articular-sided PTRCTs. Acromial anatomy with a large acromial extension was associated with the occurrence of degenerative articular-sided PTRCTs.
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Lesiones del Manguito de los Rotadores , Articulación del Hombro , Acromion/diagnóstico por imagen , Artroscopía , Humanos , Imagen por Resonancia Magnética , Manguito de los Rotadores/diagnóstico por imagen , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Lesiones del Manguito de los Rotadores/cirugía , Articulación del Hombro/diagnóstico por imagenRESUMEN
OBJECTIVES: Sleep-disordered breathing adversely impacts stroke outcomes. We investigated whether sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep differentially influenced stroke outcomes. MATERIALS AND METHODS: Acute ischemic stroke patients who finished polysomnography within 14 days of stroke onset from April 2010 to August 2018 were reviewed. Patients were divided into four groups according to apnea-hypopnea index during rapid eye movement sleep and non-rapid eye movement sleep. The modified Rankin Scale was used to evaluate short-term outcome. During January and April 2019, another follow-up was performed for long-term outcomes, including stroke-specific quality-of-life scale, modified Rankin Scale, stroke recurrence and death. RESULTS: Of 140 patients reviewed, 109 were finally recruited. Although patients with sleep-disordered breathing during non-rapid eye movement sleep only and with sleep-disordered breathing during both rapid eye movement sleep and non-rapid eye movement sleep had higher apnea-hypopnea indices and more disrupted sleep structures, short-term and long-term outcomes did not significantly different between four groups. In Logistic regression analysis, apnea-hypopnea index (p = 0.013, OR 1.023, 95%CI 1.005-1.042) was found independently associated with short-term outcome. Rapid eye movement sleep latency (p = 0.045, OR 0.994, 95%CI 0.987-1.000) was found independently associated with quality of life. Apnea-hypopnea indices during rapid eye movement sleep or non-rapid eye movement sleep were not significantly associated with short-term or long-term outcomes. CONCLUSIONS: Apnea-hypopnea index is an independent risk factor of short-term outcome of acute ischemic stroke while sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep do not affect stroke outcomes differently.
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Accidente Cerebrovascular Isquémico/complicaciones , Pulmón/fisiopatología , Respiración , Síndromes de la Apnea del Sueño/complicaciones , Sueño REM , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/rehabilitación , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Síndromes de la Apnea del Sueño/diagnóstico , Síndromes de la Apnea del Sueño/fisiopatología , Rehabilitación de Accidente Cerebrovascular , Factores de Tiempo , Resultado del TratamientoRESUMEN
MicroRNAs (miRNAs) are potent post-transcriptional regulators of gene expression and play roles in DNA damage response (DDR). PLK1 is identified as a modulator of DNA damage checkpoint. Although down-regulation of PLK1 by certain microRNAs has been reported, little is known about the interplay between PLK1 and miR-509-3-5p in DDR. Here we have demonstrated that miR-509-3-5p repressed PLK1 expression by targeting PLK1 3'-UTR, thereby causing mitotic aberration and growth arrest of human lung cancer A549 cells. Repression of PLK1 by miR-509-3-5p was further evidenced by over-expression of miR-509-3-5p in A549, HepG2 and HCT116p53(-/-) cancer cells, in which PLK1 protein was suppressed. Consistently, miR-509-3-5p was stimulated, while PLK1 protein was down-regulated in A549 cells exposed to CIS and ADR, suggesting that suppression of PLK1 by miR-509-3-5p is a component of CIS/ADR-induced DDR pathway. Flow cytometry and immunofluorescence labeling showed that over-expression of miR-509-3-5p in A549 induced G2/M arrest and aberrant mitosis characterized by abnormal bipolar mitotic spindles, condensed chromosomes, lagging DNA and chromosome bridges. In addition, over-expression of miR-509-3-5p markedly blocked A549 cell proliferation and sensitized the cells to CIS and ADR treatment. Taken together, miR-509-3-5p is a feasible suppressor for cancer by targeting PLK1. Our data may provide aid in potential design of combined chemotherapy and in our better understanding of the roles of microRNAs in response to DNA damage.
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Proteínas de Ciclo Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Regiones no Traducidas 3' , Células A549 , Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Secuencia de Bases , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Doxorrubicina/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Células HCT116 , Células Hep G2 , Humanos , MicroARNs/metabolismo , Mitosis/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/metabolismo , Transducción de Señal , Quinasa Tipo Polo 1RESUMEN
Microglia-mediated neuroinflammation is implicated in the pathogenesis of several neurodegenerative disorders. Microglia can be activated and polarized to exert pro- or anti-inflammatory roles in response to specific stimulus. Rotenone is an environmental toxin that has been shown to activate microglia and neuroinflammation. However, the effects and mechanisms of rotenone on microglia polarization are poorly studied. In the present study, we demonstrated that rotenone enhanced the levels of M1 phenotypic genes including TNF-α, iNOS and COX-2/PGE2 but reduced that of M2 markers such as Ym1/2 and IL-10 in mouse primary and immortalized microglia. Moreover, the transcription and protein expression of cystathionine-ß-synthase (CBS), as well as hydrogen sulfide (H2S) production were decreased in rotenone-treated primary microglia. Elevating endogenous H2S via CBS over-expression in immortalized microglia not only reduced the expression of pro-inflammatory M1 genes, but also enhanced the anti-inflammatory M2 marker IL-10 production in response to rotenone stimulation as compared to vector-transfected cells. Similarly, pretreatment with H2S donor NaHS (50, 100 and 500µmol/L) attenuated the increases of M1 gene expression triggered by rotenone treatment, and enhanced the M2 gene Ym1/2 expression in mouse primary microglia. In addition, we observed reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine reversed the down-regulation of CBS and H2S generation caused by rotenone in microglia. NaHS pretreatment also decreased the ROS formation in rotenone-stimulated microglia. Taken together, these results reveal that probably via triggering ROS formation, rotenone suppressed the CBS-H2S pathway and thus promoted microglia polarization toward M1 pro-inflammatory phenotype.
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Cistationina betasintasa/genética , Cistationina betasintasa/metabolismo , Sulfuro de Hidrógeno/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Rotenona/toxicidad , Animales , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Interleucina-10/biosíntesis , Ratones , Microglía/clasificación , Fármacos Neuroprotectores/metabolismo , Neurotoxinas/toxicidad , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Hypophosphatemia was reported to frequently occur in patients with nontraumatic intracranial hemorrhage (ICH); however, the correlation between hypophosphatemia and outcomes of ICH remains unclear. This study aimed to examine the association between admission serum phosphate and all-cause mortality among patients with mild-moderate spontaneous ICH (sICH). METHODS: A total of 851 patients with sICH were enrolled. Serum phosphate was acquired within 24 hours on admission, and participants were divided according to phosphate quartiles. The primary outcome was all-cause mortality within 90 days, and univariate and multivariate models were employed to estimate the mortality risk. RESULTS: There were significant differences among sICH patients with different phosphate quartiles in terms of age, diastolic blood pressure (DBP), activated partial thromboplastin time (APTT), platelet count, and incidence of respiratory failure events on admission (P < 0.05). Log rank test showed a significant difference in the mortality risk among sICH patients with each phosphate quartile. Univariate Cox regression analysis revealed that age, smoking, DBP, APTT, NIH stroke scale (NIHSS) score, hematoma volume and serum phosphate might be associated with the 90-day all-cause mortality in patients with sICH (P < 0.05). Multivariable Cox regression analysis showed that the crude mortality was 4.3-fold greater in sICH patients with serum phosphate Q1 than those with Q4 (P < 0.001), and remained 3.18-fold higher after adjusting for age, smoking, DBP, APTT, NIHSS score, hematoma volume and early withdrawal of life-sustaining therapy (P = 0.011). Representative operating curve (ROC) analysis showed that admission serum phosphate was predictable for all-cause mortality within 90 days in patients with sICH (area under the ROC = 0.628, P < 0.001). CONCLUSION: Low admission serum phosphate is strongly associated with a high risk of mortality in patients with mild-moderate sICH, and hypophosphatemia may be a prognostic marker for all-cause mortality in patients with mild-moderate sICH.
RESUMEN
BACKGROUND: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. METHODS: A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student's t-test was used for continuous variables, and Pearson's chi-squared test or Fisher's exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. RESULTS: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428-0.814, P = 0.001; and OR = 0.654, 95% CI 0.457-0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179-4.608, P = 0.015; OR = 2.033, 95% CI 1.242-3.322, P = 0.005; OR = 3.040, 95% CI 1.522-6.061, P = 0.002; and OR = 2.890, 95% CI 1.199-6.993, P = 0.018, respectively). CONCLUSIONS: This is the first study to explore the association of mtDNA variants with individual's risk of developing severe COVID-19. Based on the case-control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual's resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual's risk of developing severe COVID-19.
Asunto(s)
COVID-19 , ADN Mitocondrial , COVID-19/genética , Estudios de Casos y Controles , China , ADN Mitocondrial/genética , Humanos , Mitocondrias/genética , Filogenia , Factores de RiesgoRESUMEN
Continuous jumping behavior, a kind of endurance locomotion, plays important roles in insect ecological adaption and survival. However, the methods used for the efficient evaluation of insect jumping behavior remain largely lacking. Here, we developed a locomotion detection system named JumpDetector with automatic trajectory tracking and data analysis to evaluate the jumping of insects. This automated system exhibits more accurate, efficient, and adjustable performance than manual methods. By using this automatic system, we characterized a gradually declining pattern of continuous jumping behavior in 4th-instar nymphs of the migratory locust. We found that locusts in their gregarious phase outperformed locusts in their solitary phase in the endurance jumping locomotion. Therefore, the JumpDetector could be widely used in jumping behavior and endurance locomotion measurement.
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Monitoreo Biológico/métodos , Insectos/fisiología , Locomoción/fisiología , Animales , Conducta Animal , Equipos y Suministros , Locusta migratoria , NinfaRESUMEN
Epigenetic gene control is maintained by chromatin-associated Polycomb group (PcG) and Trithorax group (TrxG) genes, which act antagonistically via the interplay between PcG and TrxG regulation to generate silenced or permissive transcriptional states. In this study, we searched for PcG/TrxG genes in 180 arthropod genomes, covering all the sequenced arthropod genomes at the time of conducting this study, to perform a global investigation of PcG/TrxG genes in a phylogenetic frame. Results of ancestral state reconstruction analysis revealed that the ancestor of arthropod species has an almost complete repertoire of PcG/TrxG genes, and most of these genes were seldom lost above order level. The domain diversity analysis indicated that the PcG/TrxG genes show variable extent of domain structure changes; some of these changes could be associated with lineage-specific events. The likelihood ratio tests for selection pressure detected a number of PcG/TrxG genes which underwent episodic positive selection on the branch leading to the insects with holometabolous development. These results suggest that, despite their high conservation across arthropod species, different members of PcG/TrxG genes showed considerable differences in domain structure and sequence divergence in arthropod evolution. Our cross species comparisons using large-scale genomic data provide insights into divergent evolutionary pattern on highly conserved genes in arthropods.
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Artrópodos/genética , Evolución Molecular , Proteínas del Grupo Polycomb/genética , Animales , Proteínas Cromosómicas no Histona/genética , Proteínas de Drosophila/genética , Genoma , Anotación de Secuencia Molecular , Filogenia , Dominios Proteicos , Selección GenéticaRESUMEN
PURPOSE: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine (131I) metuximab injection (Licartin), a novel 131I-labeled HAb18G/CD147-specific monoclonal antibody Fab'2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. METHODS AND MATERIALS: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. RESULTS: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p = 0.0019). CONCLUSION: Iodine (131I) metuximab injection is safe and active for HCC patients.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Basigina/inmunología , Carcinoma Hepatocelular/radioterapia , Radioisótopos de Yodo/uso terapéutico , Neoplasias Hepáticas/radioterapia , Radioinmunoterapia/métodos , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Combinación de Medicamentos , Femenino , Humanos , Radioisótopos de Yodo/efectos adversos , Radioisótopos de Yodo/farmacocinética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Masculino , Dosis Máxima Tolerada , Persona de Mediana EdadRESUMEN
Hydrogen sulfide (H2S) is a novel gaseous transmitter, regulating a multitude of biological processes in the cardiovascular and other systems. However, it remains unclear whether it exerts any effect on arterial thrombosis. In this study, we examined the effect of H2S on ferric chloride (FeCl3)-induced thrombosis in the rat common carotid artery (CCA). The results revealed a decrease of the H2S-producing enzyme cystathionine γ-lyase (CSE) expression and H2S production that persisted until 48 h after FeCl3 application. Intriguingly, administration with NaHS at appropriate regimen reduced the thrombus formation and enhanced the blood flow, accompanied with the alleviation of CSE and CD31 downregulation, and endothelial cell apoptosis in the rat CCA following FeCl3 application. Moreover, the antithrombotic effect of H2S was also observed in Rose Bengal photochemical model in which the development of thrombosis is contributed by oxidative injury to the endothelium. The in vitro study demonstrated that the mRNA and protein expression of CSE, as well as H2S production, was decreased in hydrogen peroxide (H2O2)-treated endothelial cells. Exogenous supplement of NaHS and CSE overexpression consistently alleviated the increase of cleaved caspase-3 and endothelial cell damage caused by H2O2. Taken together, our findings suggest that endogenous H2S generation in the endothelium may be impaired during arterial thrombosis and that modulation of H2S, either exogenous supplement or boost of endogenous production, may become a potential venue for arterial thrombosis therapy.
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Cloruros/química , Compuestos Férricos/química , Sulfuro de Hidrógeno/química , Trombosis/etiología , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratas , Transducción de SeñalRESUMEN
Cryptochromes (CRYs) are blue and UV light photoreceptors, known to play key roles in circadian rhythms and in the light-dependent magnetosensitivity of insects. Two novel cryptochrome genes were cloned from the brown planthopper, and were given the designations of Nlcry1 and Nlcry2, with the accession numbers KM108578 and KM108579 in GenBank. The complementary DNA sequences of Nlcry1 and Nlcry2 are 1935 bp and 2463 bp in length, and they contain an open reading frame of 1629 bp and 1872 bp, encoding amino acids of 542 and 623, with a predicted molecular weight of 62.53 kDa and 70.60 kDa, respectively. Well-conserved motifs such as DNA-photolyase and FAD-binding-7 domains were observed in Nlcry1 and Nlcry2. Phylogenetic analysis demonstrated the proteins of Nlcry1 and Nlcry2 to be clustered into the insect's cryptochrome 1 and cryptochrome 2, respectively. Quantitative polymerase chain reaction showed that the daily oscillations of messenger RNA (mRNA) expression in the head of the brown planthopper were mild for Nlcry1, and modest for Nlcry2. Throughout all developmental stages, Nlcry1 and Nlcry2 exhibited extreme fluctuations and distinctive expression profiles. Cryptochrome mRNA expression peaked immediately after adult emergence and then decreased subsequently. The tissue expression profiles of newly emerged brown planthopper adults showed higher expression levels of CRYs in the head than in the thorax or abdomen, as well as significantly higher levels of CRYs in the heads of the macropterous strain than in the heads of the brachypterous strain. Taken together, the results of our study suggest that the two cryptochrome genes characterized in the brown planthopper might be associated with developmental physiology and migration.
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Criptocromos/genética , Hemípteros/genética , Proteínas de Insectos/genética , Secuencia de Aminoácidos , Migración Animal , Animales , Ritmo Circadiano , Criptocromos/metabolismo , Femenino , Regulación del Desarrollo de la Expresión Génica , Genes de Insecto , Hemípteros/crecimiento & desarrollo , Hemípteros/metabolismo , Proteínas de Insectos/metabolismo , Masculino , Filogenia , Alas de Animales/crecimiento & desarrolloRESUMEN
The migratory locust Locusta migratoria L., which is widely distributed throughout the world, exhibits within- and between-population variation in cold tolerance. To understand physiological adaptation in populations, we studied the genetic basis of thermotolerance in Hainan (tropical) and Liaoning (temperate) populations and measured expression of Hsp70 and Hsp90 mRNA in both populations at low (0 degrees C) and high temperatures (40 degrees C). Phenotypic variation of thermotolerance is heritable. Heritable characteristics differed among different stages of locust egg development, as well as among different measures of thermotolerance. Nuclear genetic factors, rather than cytoplasmic factors, contribute to differences in cold tolerance between the tropical and temperate populations of the migratory locust; for heat tolerance, maternal effects were involved in three stages of egg development. Expression of Hsp90 mRNA was induced in temperate population after heat shock (40 degrees C x 12h), whereas expression of Hsp70 and 90 was induced in tropical population after cold shock (0 degrees C x 12h). We suggest that thermotolerance of locust eggs has a complex genetic basis and heat shock proteins may be involved in differences of thermotolerance between locust populations.
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Frío , Calor , Locusta migratoria/fisiología , Cigoto/fisiología , Aclimatación , Animales , Femenino , Expresión Génica , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP90 de Choque Térmico/genética , Locusta migratoria/embriología , Locusta migratoria/genética , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
This paper describes a rapid cold hardening process for first instar hoppers of the migratory locust Locusta migratoria L. First instar hoppers of this species are often subjected to subzero temperatures or frosts in early April or May after their emergence from the soil. The mean supercooling point of hoppers is -13.0 +/- 1.4 degrees C; the fact that none could survive this temperature suggests they are freezing intolerant. When young hoppers were transferred directly from 30 degrees C to -7 degrees C for 2 h, there was only 35.8% survival. However, exposure to 0 degrees C for 2 h prior to transfer to -7 degrees C increased the apparent survival to 75%. A similar rapid cold hardening response can also be induced by gradual cooling at rates of between 0.05 and 0.1 degreess C min(-1). Rapid cold hardening also elevates the Ltime50 of first instar hoppers at -7 degrees C by approximately 3 fold, and reduces the lethal temperature from -10 degrees C to -12 degrees C. However, the protection from cold shock gained through rapid cold hardening was transient and easily lost within 2 h of hoppers being returned to 30 degrees C. The rapid cold hardening response is possibly advantageous to first instar hoppers that are often exposed to large temperature fluctuations in spring or early summer.
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Frío , Ortópteros/fisiología , Adaptación Fisiológica , Animales , Factores de TiempoRESUMEN
OBJECTIVE: To screen out the HAb18G/CD147 binding peptides and find out an antagonist against hepatoma invasion. METHODS: HAb18G/CD147 was purified by affinity chromatographic method and the antigen binding peptides acquired by bio-panning a phage-displayed 12-peptide library. After obtaining the sequence of the selected phage-displayed peptides, all the 9 peptides were synthesized by solid-phase method and identified by mass spectrograph. The peptides' anti-metastatic function was tested by Boyden Chamber assay. RESULTS: The purified HAb18G/CD147, identified by Western blot (molecular weight about 65 kd) could be used to bio-pan the phage-displayed peptide library. After 3 rounds of bio-panning, 9 positive phage clones were selected and sequenced. The synthesized peptides had uneven inhibitory activities and three of them were able to markedly inhibit the hepatoma cell invasion (P < 0.01). The most effective peptide decreased by 90.1% of hepatoma cells migrating through the Boyden Chamber membrane as compared with the control. CONCLUSION: Bio-panning the phage-displayed peptide library can be used successfully to screen out the antigen binding peptides. Hepatoma metastatic potential can be inhibited by peptide antagonist which could be a good foundation of developing peptide therapeutic agent against hepatoma metastasis.
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Anticuerpos Monoclonales/uso terapéutico , Basigina/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Péptidos/uso terapéutico , Animales , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , Ratones , Invasividad Neoplásica , Biblioteca de PéptidosRESUMEN
To determine the role of vagi in heart rate variability, conscious rabbits were employed and electrocardiogram was recorded under conditions of bilateral vagi intact, unilateral vagotomy, and bilateral vagotomy. The variability of RR intervals (RRI) was analyzed using power spectrum and approximate entropy (ApEn). The results showed that the values of high frequency power (HF) component, low frequency power (LF) component and ApEn in animals with bilateral vagi intact were the highest, but the LF/HF ratio was the lowest; unilateral vagotomy decreased ApEn, right vagotomy increased LF/HF ratio but left vagotomy did not; the LF/HF ratio increased while ApEn decreased significantly in animals with bilateral vagotomy. It is suggested that the variability of RRI is mainly regulated by the vagi and the role of right vagi is more important than that of the left. When measuring heart rate variability, the results obtained with conventional method are consistent with those with nonlinear method.
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Frecuencia Cardíaca/fisiología , Nervio Vago/fisiología , Animales , Entropía , Masculino , ConejosRESUMEN
OBJECTIVES: To observe the cavernosal nerve dysfunction of diabetic Sprague Dawley rats. METHODS: Thirty-five Sprague-Dawley rats were divided randomly into diabetes model group(n = 25) and normal group(n = 10). Diabetes model was established by administration of streptozotocin (63 mg/kg) in single intraperitoneal dosing. Giving single wave stimulus, corpus cavernosal nerve was measured for its latent period of reaction and myopotential. RESULTS: Compared with other groups, diabetic rats had longer reflection latent period(P < 0.01) and higher corpus cavernosum smooth muscle myopotential (P < 0.01). CONCLUSIONS: The results indicate that corpus cavernosal nerve dysfunction may play an important role in the erectile dysfunction of diabetic rats.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Pene/inervación , Animales , Diabetes Mellitus Experimental/complicaciones , Disfunción Eréctil/etiología , Potenciales Evocados , Masculino , Óxido Nítrico/fisiología , Ratas , Ratas Sprague-Dawley , EstreptozocinaRESUMEN
Hydrogen sulfide (H2S), mainly produced by cystathionine γ-lyase (CSE) in vascular system, emerges as a novel gasotransmitter exerting anti-inflammatory and anti-atherosclerotic effects. Alterations of CSE/H2S pathway may thus be involved in atherosclerosis pathogenesis. However, the underlying mechanisms are poorly understood. The present study showed that the levels of CSE mRNA and protein expression, as well as H2S production were decreased in ox-LDL-treated macrophage. CSE overexpression reduced the ox-LDL-stimulated tumor necrosis factor-α (TNF-α) generation in Raw264.7 and primary macrophage while CSE knockdown enhanced it. Exogenous supplementation of H2S with NaHS and Na2S also decreased the production of TNF-α and intercellular adhesion molecule-1 (ICAM-1) in ox-LDL-stimulated macrophage, and alleviated the adhesion of macrophage to endothelial monolayer. Cysteine, a CSE preferential substrate for H2S biosynthesis, produced similar effects on the pro-inflammatory cytokine generation, which were reversed by CSE inhibitors PAG and BCA, respectively. Moreover, NaHS and Na2S attenuated the phosphorylation and degradation of IκBα and p65 nuclear translocation, as well as JNK activation caused by ox-LDL. The JNK inhibitor suppressed the NF-κB transcription activity in ox-LDL-treated cells. Furthermore, inhibitors of NF-κB (PDTC), ERK (U0126 and PD98059) and JNK (SP600125) partially blocked the suppression by ox-LDL on the CSE mRNA levels. Taken together, the findings demonstrate that ox-LDL may down-regulate the CSE/H2S pathway, which plays an anti-inflammatory role in ox-LDL-stimulated macrophage by suppressing JNK/NF-κB signaling. The study reveals new therapeutic strategies for atherosclerosis, based on modulating CSE/H2S pathway.
Asunto(s)
Cistationina gamma-Liasa/genética , Sulfuro de Hidrógeno/metabolismo , Lipoproteínas LDL/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Adhesión Celular/efectos de los fármacos , Línea Celular , Cistationina gamma-Liasa/antagonistas & inhibidores , Cistationina gamma-Liasa/metabolismo , Cisteína/metabolismo , Cisteína/farmacología , Regulación de la Expresión Génica , Guanidinas/farmacología , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Morfolinas/farmacología , Inhibidor NF-kappaB alfa , FN-kappa B/genética , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Cultivo Primario de Células , Piridoxal/farmacología , Compuestos de Sulfhidrilo/farmacología , Sulfuros/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Aeromonas hydrophila is a ubiquitous Gram-negative bacterium which can cause motile aeromonad septicemia in both fish and humans. A. hydrophila secretes many extracellular proteins associated with pathogenicity and environmental adaptability. In this study, an extracellular proteome map of A. hydrophila AH-1 was constructed. The major extracellular virulence factors were characterized by comparing the proteomes of various deletion mutants with that of the wild type. The results suggested that serine protease was involved in the processing of a toxin and secreted enzymes such as hemolysin, glycerophospholipid-cholesterol acyltransferase and metalloprotease. We also showed that expressions of polar and lateral flagellins were under the control of temperature, FlhA, LafK, and RpoN. In addition, three novel proteins (potential effector proteins including one ExoT-like protein) were revealed to be secreted via the type III secretion system (TTSS) of A. hydrophila AH-1. Another novel finding was the demonstration of a crosstalk between the lateral flagellar system and the TTSS in A. hydrophila. These results showed that proteomics is a powerful tool for characterizing virulence factors. The construction of proteome maps will provide a valuable means of finding potential candidates for developing suitable diagnostics and therapeutics for this emerging pathogen.