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BACKGROUND: To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. METHODS: Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. RESULTS: This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. CONCLUSION: The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.
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Fibras Nerviosas , Atrofia Óptica Hereditaria de Leber , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Atrofia Óptica Hereditaria de Leber/fisiopatología , Atrofia Óptica Hereditaria de Leber/diagnóstico , Masculino , Femenino , Fibras Nerviosas/patología , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Estudios de Seguimiento , Adulto , Agudeza Visual/fisiología , Adulto Joven , Disco Óptico/patología , Disco Óptico/diagnóstico por imagen , Adolescente , Persona de Mediana Edad , Estudios Retrospectivos , Campos Visuales/fisiologíaRESUMEN
Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy. The oncometabolites have been studied in OSCC, but the mechanism of metabolic reprogramming remains unclear. To identify the potential metabolic markers to distinguish malignant oral squamous cell carcinoma (OSCC) tissue from adjacent healthy tissue and study the mechanism of metabolic reprogramming in OSCC. We compared the metabolites between cancerous and paracancerous tissues of OSCC patients by 1HNMR analysis. We established OSCC derived cell lines and analyzed their difference of RNA expression by RNA sequencing. We investigated the metabolism of γ-aminobutyrate in OSCC derived cells by real time PCR and western blotting. Our data revealed that much more γ-aminobutyrate was produced in cancerous tissues of OSCC patients. The investigation based on OSCC derived cells showed that the increase of γ-aminobutyrate was promoted by the synthesis of glutamate beyond the mitochondria. In OSCC cancerous tissue derived cells, the glutamate was catalyzed to glutamine by glutamine synthetase (GLUL), and then the generated glutamine was metabolized to glutamate by glutaminase (GLS). Finally, the glutamate produced by glutamate-glutamine-glutamate cycle was converted to γ-aminobutyrate by glutamate decarboxylase 2 (GAD2). Our study is not only benefit for understanding the pathological mechanisms of OSCC, but also has application prospects for the diagnosis of OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de la Boca/patología , Glutamina/genética , Glutamina/metabolismo , Reprogramación Metabólica , Glutamatos/genética , Glutamatos/metabolismo , Línea Celular TumoralRESUMEN
BACKGROUND: Quinoa is a highly nutritious and novel crop that is resistant to various abiotic stresses. However, its growth and development is restricted due to its limited utilization of soil phosphorus. Studies on the levels of phosphorus in quinoa seedlings are limited; therefore, we analyzed transcriptome data from quinoa seedlings treated with different concentrations of phosphorus. RESULTS: To identify core genes involved in responding to various phosphorus levels, the weighted gene co-expression network analysis method was applied. From the 12,085 expressed genes, an analysis of the gene co-expression network was done. dividing the expressed genes into a total of twenty-five different modules out of which two modules were strongly correlated with phosphorus levels. Subsequently we identified five core genes that correlated strongly either positively or negatively with the phosphorus levels. Gene ontology and assessments of the Kyoto Encyclopedia of Genes and Genomes have uncovered important biological processes and metabolic pathways that are involved in the phosphorus level response. CONCLUSIONS: We discovered crucial new core genes that encode proteins from various transcription factor families, such as MYB, WRKY, and ERF, which are crucial for abiotic stress resistance. This new library of candidate genes associated with the phosphorus level responses in quinoa seedlings will help in breeding varieties that are tolerant to phosphorus levels.
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Chenopodium quinoa , Plantones , Plantones/genética , Plantones/metabolismo , Chenopodium quinoa/genética , Chenopodium quinoa/metabolismo , Fósforo/metabolismo , Fitomejoramiento , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las PlantasRESUMEN
Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 â¶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 â¶32 and 1 â¶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 â¶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.
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Anemia Hemolítica Autoinmune , Anemia Hemolítica , Síndromes de Ojo Seco , Síndrome de Sjögren , Masculino , Humanos , Anciano , Anemia Hemolítica Autoinmune/complicaciones , Anemia Hemolítica Autoinmune/diagnóstico , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Anemia Hemolítica/complicaciones , Síndromes de Ojo Seco/complicaciones , AutoanticuerposRESUMEN
In Arabidopsis, the initiation and proliferation of stomatal lineage cells is controlled by SPEECHLESS (SPCH). Phosphorylation of SPCH at the post-translational level has been reported to regulate stomatal development. Here we report that IDD16 acts as a negative regulator for stomatal initiation by directly regulating SPCH transcription. In Arabidopsis, IDD16 overexpression decreased abaxial stomatal density in a dose-dependent manner. Time course analysis revealed that the initiation of stomatal precursor cells in the IDD16-OE plants was severely inhibited. Consistent with these findings, the transcription of SPCH was greatly repressed in the IDD16-OE plants. In contrast, IDD16-RNAi transgenic line resulted in enhanced stomatal density, suggesting that IDD16 is an intrinsic regulator of stomatal development. ChIP analysis indicated that IDD16 could directly bind to the SPCH promoter. Furthermore, Arabidopsis plants overexpressing IDD16 exhibited significantly increased drought tolerance and higher integrated water use efficiency (WUE) due to reduction in leaf transpiration. Collectively, our results established that IDD16 negatively regulates stomatal initiation via trans-repression of SPCH, and thus provide a practical tool for increasing plant WUE through the manipulation of IDD16 expression.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Regulación de la Expresión Génica de las Plantas , Estomas de Plantas/fisiología , Arabidopsis/fisiología , SequíasRESUMEN
To cope with environmental stresses, plants often adopt a memory response upon primary stress exposure to facilitate a quicker and stronger reaction to recurring stresses. However, it remains unknown whether light is involved in the manifestation of stress memory. Proline accumulation is a striking metabolic adaptation of higher plants during various environmental stresses. Here we show that salinity-induced proline accumulation is memorable and HY5-dependent light signaling is required for such a memory response. Primary salt stress induced the expression of Δ1-pyrroline-5-carboxylate synthetase 1 (P5CS1), encoding a proline biosynthetic enzyme and proline accumulation, which were reduced to basal level during the recovery stage. Reoccurring salt stress-induced stronger P5CS1 expression and proline accumulation were dependent upon light exposure during the recovery stage. Further studies demonstrated that salt-induced transcriptional memory of P5CS1 is associated with the retention of increased H3K4me3 level at P5CS1 during the recovery stage. HY5 binds directly to light-responsive element, C/A-box, in the P5CS1 promoter. Deletion of the C/A-box or hy5 hyh mutations caused rapid reduction of H3K4me3 level at P5CS1 during the recovery stage, resulting in impairment of the stress memory response. These results unveil a previously unrecognized mechanism whereby light regulates salt-induced transcriptional memory via the function of HY5 in maintaining H3K4me3 level at the memory gene.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/efectos de la radiación , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Glutamato-5-Semialdehído Deshidrogenasa/metabolismo , Luz , Complejos Multienzimáticos/metabolismo , Proteínas Nucleares/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Sales (Química)/química , Estrés Fisiológico , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Regulación de la Expresión Génica de las Plantas , Glutamato-5-Semialdehído Deshidrogenasa/genética , Histonas/metabolismo , Complejos Multienzimáticos/genética , Mutación , Proteínas Nucleares/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/efectos de la radiación , Pirroles , Semillas/metabolismo , Transducción de Señal , Transcripción Genética , Técnicas del Sistema de Dos HíbridosRESUMEN
A small private online course (SPOC) supports blended learning on a small scale, enabling students to have a more comprehensive and deeper learning experience. It also provides instructors with a flexible and feasible model to better understand the students' learning needs and to supervise students' learning behaviors. In this study, we adopted SPOC flipped classroom blended teaching in the physiology course for clinical undergraduate students of Kunming Medical University. Compared with the control group [lecture-based learning (LBL)], the SPOC flipped classroom method significantly increased the scores of students in the preclass test (65.13 ± 12.45 vs. 53.46 ± 8.09, SPOC vs. LBL) and postclass test (80.43 ± 14.29 vs. 69.01 ± 12.81, SPOC vs. LBL), which is induced by students' increased interest in self-learning. More importantly, the significant difference between the preclass scores of the two groups suggested that the video lecture-based preview is more effective than the textbook-based preview. The study indicated that the SPOC flipped classroom was effective in enhancing the examination scores of students, reflecting an improved learning efficiency and a deeper understanding of the knowledge. In summary, the flipped classroom based on SPOC improves learning outcomes compared with LBL and has a wide application in the learning of basic medical courses.
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Curriculum , Educación a Distancia/métodos , Fisiología/educación , Aprendizaje Basado en Problemas/métodos , Estudiantes de Medicina/psicología , Evaluación Educacional/métodos , Humanos , Programas de Autoevaluación/métodosRESUMEN
Microsporidiosis is an important zoonotic disease, even leading to severe diarrhea. However, no information about prevalence and genotypes of Enterocytozoon bieneusi infection in Asiatic black bears in southwestern China is available. The objectives of the present study were to investigate the prevalence of E. bieneusi and to characterize their genotypes using the nested PCR amplification of the internal transcribed spacer region of the ribosomal RNA gene cluster and multilocus sequence typing (MLST). The overall prevalence of E. bieneusi was 19.75% (80/405) and the rate of E. bieneusi in Xishuangbanna (33.33%) was significantly higher than that in any other regions (Honghe, 17.65%; Dehong, 13.04%; Kunming, 0; P = 0.01). Sequence analysis revealed that 4 known genotypes (D, n = 2; SC02, n = 10; SC01, n = 5; and CHB1, n = 4) and 13 novel genotypes (designed MJ1-MJ13) were identified. When 17, 5, 14, and 34 sequences at loci MS1, MS3, MS4, and MS7 via MLST analyses, representing 4, 4, 5, and 10 genotypes, respectively, were completed, one multilocus genotype (MLG novel-ABB1) was identified. This is the first report of E. bieneusi in Asiatic black bear in Yunnan province, Southwestern China. The results indicated the potential zoonotic risk of this parasite through the Asiatic black bear in this region and provided foundation data for preventing and controlling E. bieneusi infection of many other animals and humans in these regions.
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Enterocytozoon/genética , Microsporidiosis/epidemiología , Ursidae/parasitología , Zoonosis/epidemiología , Animales , China/epidemiología , ADN Espaciador Ribosómico/genética , Enterocytozoon/clasificación , Enterocytozoon/aislamiento & purificación , Genotipo , Microsporidiosis/parasitología , Tipificación de Secuencias Multilocus , Filogenia , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de Riesgo , Zoonosis/parasitologíaRESUMEN
BACKGROUND This study analyzed the risk factors of cognitive impairment (CI) in elderly patients with chronic diseases. MATERIAL AND METHODS In total of 385 elderly patients with chronic diseases were selected and assigned into CI and normal groups. The activities of daily living (ADL), global deterioration scale (GDS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), patient-generated subjective global assessment (PG-SGA), and mini nutritional assessment (MNA) were performed to analyze the differences between the 2 groups. Logistic regression analysis was conducted for risk factors of CI in elderly patients with chronic diseases. RESULTS There were differences in age, education level, type 2 diabetes mellitus, multifocal cerebral infarction, hearing, and eyesight between CI and normal groups. Patients in the CI group showed more CD4+ cells, more admission times, and higher GDS scores than the normal group. Also, MMSE and MoCA scores revealed differences in total score, directive force, attention and calculating ability, language, delayed memory, reading comprehension, writing, and visual-spatial ability between the 2 groups. The number of B and CD8+ cells, ADL, and MNA scores were protective factors, while cerebral infarction history, number of CD4+ cells, admission times, GDS score, and age were risk factors of CI in elderly patients with chronic diseases. CONCLUSIONS Our study provides evidence that cerebral infarction history, number of CD4+ cells, admission times, GDS score, and age are risk factors of CI in elderly patients with chronic diseases.
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Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/psicología , Actividades Cotidianas , Factores de Edad , Anciano , Anciano de 80 o más Años , China , Enfermedad Crónica , Cognición , Trastornos del Conocimiento/complicaciones , Disfunción Cognitiva/etiología , Análisis Factorial , Femenino , Humanos , Modelos Logísticos , Masculino , Pruebas Neuropsicológicas , Factores de RiesgoRESUMEN
AIMS: We conducted a meta-analysis of eligible studies to compare the surgical outcomes between diabetic patients and non-diabetic patients who have undergone cervical spondylotic myelopathy (CSM). METHODS: A systematic literature search of PubMed, Embase, and Web of Science (up to February 10, 2016) was conducted. Eligible studies were case-control or cohort studies that compared the outcomes of cervical surgery between diabetic patients and non-diabetic patients. Weighted mean differences, risk ratios, and 95% CIs were calculated and heterogeneity was assessed with Cochrane Q chi-square test and I2 statistic. RESULTS: Six studies with a total of 38,680 patients were included in this meta-analysis. Pooled estimates showed that diabetic patients had significantly lower Japanese Orthopaedic Association (JOA) score change between pre- and post operation, and recovery rate than patients without diabetes. Moreover, diabetic patients had significantly increased risk of operative wound, epidural/wound hematoma, chronic lung disease, and cardiac complication. Other postoperative complications, including cerebrospinal fluid leakage and C5 radiculopathy, were not significantly different between the 2 groups. CONCLUSION: Diabetes mellitus decreased the JOA score change and recovery rate, as well as increased the risk of postoperative complications in patients undergoing CSM. Controlling diabetes mellitus before cervical spine surgery may lead to better outcomes.
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Diabetes Mellitus , Enfermedades de la Médula Espinal/cirugía , Espondilosis/cirugía , Vértebras Cervicales , Estudios de Cohortes , Humanos , Complicaciones Posoperatorias/epidemiología , Enfermedades de la Médula Espinal/complicaciones , Espondilosis/complicaciones , Resultado del TratamientoRESUMEN
Cell plasma membrane proteins, playing a crucial role in cell malignant transformation and development, were the main targets of tumor detection and therapy. In this study, CyDye/biotin double-labeling proteomic approach was adopted to profile the membrane proteome of gastric cancer cell line BGC-823 and paired immortalized gastric epithelial cell GES-1. Real-time PCR, Western blotting, and immunohistochemical staining were used to validate the differential expression of a novel identified cell surface marker R-cadherin in gastric cancer cells and tissues. Clinicopathological study and survival analysis were performed to estimate its roles in tumor progression and outcome prediction. Real-time PCR and Western blotting showed that the expression level of R-cadherin in gastric cancer were significantly lower than non-cancerous epithelial cell and tissues. Clinicopathological study indicated that R-cadherin was dominantly expressed on cell surface of normal gastric epithelium, and its expression deletion in gastric cancer tissues was associated with tumor site, differentiation, lymph node metastasis, and pTNM (chi-square test, P < 0.05). Those patients with R-cadherin positive expression displayed better overall survivals than negative expression group (log-rank test, P = 0.000). Cox multivariate survival analysis revealed lacking the expression of R-cadherin was a main independent predictor for poor clinical outcome in gastric cancer (RR = 5.680, 95 % CI 2.250-14.341, P < 0.01). We have established a fundamental membrane proteome database for gastric cancer and identified R-cadherin as a tumor differentiation and progression-related cell surface marker of gastric cancer. Lacking the expression of R-cadherin indicates poor prognosis in patients with gastric cancer.
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Biomarcadores de Tumor/metabolismo , Cadherinas/metabolismo , Proteínas de la Membrana/metabolismo , Proteoma/metabolismo , Proteómica/métodos , Neoplasias Gástricas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Western Blotting , Cadherinas/genética , Diferenciación Celular , Línea Celular , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/aislamiento & purificación , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Proteoma/genética , Proteoma/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVES: Paclitaxel (PTX) is frequently used in the clinical treatment of solid tumors. But the PTX-resistance is a great obstacle in cancer treatment. Exploration of the mechanisms of drug resistance suggests that tumor suppressor genes (TSGs) play a key role in the response of chemotherapeutic drugs. TSGs, a set of genes that are often inactivated in cancers, can regulate various biological processes. In this study, an overview of the contribution of TSGs to PTX resistance and their underlying relationship in cancers are reported by using GeneMANIA, a web-based tool for gene/protein function prediction. METHODS: Using PubMed online database and Google web site, the terms "paclitaxel resistance" or "taxol resistance" or "drug resistance" or "chemotherapy resistance", and "cancer" or "carcinoma", and "tumor suppressor genes" or "TSGs" or "negative regulated protein" or "antioncogenes" were searched and analyzed. GeneMANIA data base was used to predict gene/protein interactions and functions. RESULTS: We identified 22 TSGs involved in PTX resistance, including BRCA1, TP53, PTEN, APC, CDKN1A, CDKN2A, HIN-1, RASSF1, YAP, ING4, PLK2, FBW7, BLU, LZTS1, REST, FADD, PDCD4, TGFBI, ING1, Bax, PinX1 and hEx. The TSGs were found to have direct and indirect relationships with each other, and thus they could contribute to PTX resistance as a group. The varied expression status and regulation function of the TSGs on cell cycle in different cancers might play an important role in PTX resistance. CONCLUSION: A further understanding of the roles of tumor suppressor genes in drug resistance is an important step to overcome chemotherapy tolerance. Tumor suppressor gene therapy targets the altered genes and signaling pathways and can be a new strategy to reverse chemotherapy resistance.
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Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride synthesis, the conversion of diacylglycerol (DAG) to triglyceride. Dgat1(-/-) mice exhibit a number of beneficial metabolic effects including reduced obesity and improved insulin sensitivity and no known cardiac dysfunction. In contrast, failing human hearts have severely reduced DGAT1 expression associated with accumulation of DAGs and ceramides. To test whether DGAT1 loss alone affects heart function, we created cardiomyocyte-specific DGAT1 knock-out (hDgat1(-/-)) mice. hDgat1(-/-) mouse hearts had 95% increased DAG and 85% increased ceramides compared with floxed controls. 50% of these mice died by 9 months of age. The heart failure marker brain natriuretic peptide increased 5-fold in hDgat1(-/-) hearts, and fractional shortening (FS) was reduced. This was associated with increased expression of peroxisome proliferator-activated receptor α and cluster of differentiation 36. We crossed hDgat1(-/-) mice with previously described enterocyte-specific Dgat1 knock-out mice (hiDgat1(-/-)). This corrected the early mortality, improved FS, and reduced cardiac ceramide and DAG content. Treatment of hDgat1(-/-) mice with the glucagon-like peptide 1 receptor agonist exenatide also improved FS and reduced heart DAG and ceramide content. Increased fatty acid uptake into hDgat1(-/-) hearts was normalized by exenatide. Reduced activation of protein kinase Cα (PKCα), which is increased by DAG and ceramides, paralleled the reductions in these lipids. Our mouse studies show that loss of DGAT1 reproduces the lipid abnormalities seen in severe human heart failure.
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Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/enzimología , Lípidos/sangre , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Envejecimiento/patología , Animales , Glucemia/metabolismo , Colesterol/sangre , Diacilglicerol O-Acetiltransferasa/antagonistas & inhibidores , Diacilglicerol O-Acetiltransferasa/metabolismo , Inhibidores Enzimáticos/farmacología , Exenatida , Ácidos Grasos/sangre , Eliminación de Gen , Regulación de la Expresión Génica/efectos de los fármacos , Insuficiencia Cardíaca/genética , Humanos , Intestinos/efectos de los fármacos , Intestinos/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Especificidad de Órganos , Péptidos/farmacología , Fenotipo , Proteína Quinasa C/metabolismo , Triglicéridos/sangre , Ponzoñas/farmacologíaRESUMEN
It has been reported that galanin and its receptors might be involved in the modulation and transmission of nociception in the central nervous system. Our previous research has also demonstrated that galanin induces antinociception in the nucleus accumbens (NAc) of intact rats. However, the interaction between galanin and its receptors in the NAc and the underlying mechanism of suppressing pain transmission remain unclear. The present study seeks to determine the antinociception induced by galanin receptor (GalR)-1 stimulation in the NAc of rats with neuropathic pain. The left sciatic nerve of rats was ligated to mimic a neuropathic pain model. Western blots showed that the expression of GalR1 was significantly upregulated in the NAc of rats with neuropathic pain. Intra-NAc injection of GalR1 agonist M617 induced a dose-dependent increase in hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulations in rats with neuropathic pain. Also, the effect of M617 was attenuated by M35, a GalR1/2 antagonist; at the same time, M35 reduced the galanin-induced antinociception, suggesting that GalR1 mediates antinociception induced by galanin in the NAc of rats with neuropathic pain. Furthermore, we found that M617-induced antinociception in rats with neuropathic pain was stronger than the antinociception in intact rats. We also found that injections of M617 and galanin each induced significant increases in HWL, but the galanin-induced antinociception was stronger than that of M617. All these results suggest that GalR1 plays an important role in antinociception and that other GalRs also are involved in pain modulation induced by galanin in the NAc of rats with neuropathic pain.
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Analgésicos/uso terapéutico , Núcleo Accumbens/metabolismo , Receptor de Galanina Tipo 1/metabolismo , Ciática/patología , Analgésicos/farmacología , Análisis de Varianza , Animales , Bradiquinina/análogos & derivados , Bradiquinina/farmacología , Bradiquinina/uso terapéutico , Modelos Animales de Enfermedad , Lateralidad Funcional , Galanina/farmacología , Galanina/uso terapéutico , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Masculino , Núcleo Accumbens/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Fragmentos de Péptidos/farmacología , Fragmentos de Péptidos/uso terapéutico , Ratas , Ratas Sprague-Dawley , Receptor de Galanina Tipo 1/genética , Ciática/tratamiento farmacológicoRESUMEN
In the research of xenon sampling and xenon measurements, the xenon breakthrough curve plays a significant role in the xenon concentrating dynamics. In order to improve the theoretical comprehension of the xenon concentrating procedure from the atmosphere, the method of the breakthrough curve combination for sampling techniques should be developed and investigated under pulse injection conditions. In this paper, we describe a xenon breakthrough curve in a carbon molecular sieve column, the combination curve method for five conditions is shown and debated in detail; the fitting curves and the prediction equations are derived in theory and verified by the designed experiments. As a consequence, the curves of the derived equations are in good agreement with the fitting curves by tested. The retention times of the xenon in the column are 61.2, 42.2 and 23.5 at the flow rate of 1200, 1600 and 2000 mL min(-1), respectively, but the breakthrough times are 51.4, 38.6 and 35.1 min.
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BACKGROUND: While a dietary pattern is often believed to be stable in a population, there is limited research assessing its stability over time. The objective of this study is to explore and compare major dietary patterns derived for the Canadian subpopulation residing in Newfoundland and Labrador (NL), through two time-separated studies using an identical method. METHODS: In this study, we derived and compared the major dietary patterns derived from two independent studies in the NL adult population. The first study was based on the healthy controls from a large population-based case-control study (CCS) in 2005. The second was from a food-frequency questionnaire validation project (FFQVP) conducted in 2012. In both studies, participants were recruited in the same manner and dietary information was collected by an identical self-administered food-frequency questionnaire (FFQ). Exploratory common factor analysis was conducted to identify major dietary patterns. A comparison was conducted between the two study populations. RESULTS: Four major dietary patterns were identified: Meat, Vegetables/fruits, Fish, and Grains explaining 22%, 20%, 12% and 9% variance respectively, with a total variance of 63%. Three major dietary patterns were derived for the controls of the CCS: Meat, Plant-based diet, and Fish explaining 24%, 20%, and 10% variance respectively, with a total variance of 54%. As the Plant-based diet pattern derived for the CCS was a combination of the Vegetables/fruits and Grains patterns derived for the FFQVP, no considerable difference in dietary patterns was found between the two studies. CONCLUSION: A comparison between two time-separated studies suggests that dietary patterns of the NL adult population have remained reasonably stable over almost a decade.
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Dieta , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Frutas , Humanos , Masculino , Carne , Persona de Mediana Edad , Terranova y Labrador , Evaluación Nutricional , Reproducibilidad de los Resultados , Factores Socioeconómicos , Encuestas y Cuestionarios , Verduras , Adulto JovenRESUMEN
OBJECTIVE: To explore the function and mechanism of CCL19 in the pathogenesis of rheumatoid arthritis. METHODS: Synovial fibroblasts were collected from 5 cases of rheumatoid arthritis. Peripheral blood mononuclear cells (PBMCs) were obtained from 5 healthy people by Ficoll-Hypaque density gradien centrifugation. The cells were stimulated with IL-1beta, TNF-alpha, IL-17 and other cytokines, and then the expression of CCL19 was detected by RT-PCR. The cells also were treated with different concentration of CCL19, then the expressions of IL-1beta, TNF-alpha were detected by RT-PCR, the expressions of p-ERK, p-p38 were detected by western blot. RESULTS: IL-1beta promoted the CCL19/CCR7 expression in both synovial fibroblasts and PBMCs. CCL19 upregulated the expression of IL-10 in both synovial fibroblasts and PBMCs. The stimulation of CCL19 also increased its receptor CCR7 expression. CCL19 activated p-ERK and p-p38 in PBMCs. CONCLUSION: The positive feedback loop between CCL19 and IL-1 participate in the development of rheumatoid arthritis.
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Artritis Reumatoide/fisiopatología , Quimiocina CCL19/metabolismo , Inflamación/fisiopatología , Interleucina-1beta/farmacología , Células Cultivadas , Fibroblastos/metabolismo , Humanos , Interleucina-10/metabolismo , Interleucina-17/farmacología , Leucocitos Mononucleares/metabolismo , Sistema de Señalización de MAP Quinasas , Membrana Sinovial/citología , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
GC is usually used for xenon concentration and radon removal in the International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty. In a gas chromatograph, the injection volume is defined to calculate the column capacity. In this paper, the injection volume was investigated and a fitting formula for the injection volume was derived and discussed subsequently. As a consequence, the xenon injection volume exponentially decreased with the column temperature increased, but exponentially increased as the flow rate increased.
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PURPOSE: To determine the overall success rate and potential influencing factors within the current evidence for percutaneous first annular pulley release. METHODS: We searched PubMed, EMBASE, and the Cochrane Library for all clinical studies of percutaneous release. The rates of successful procedure and complication were extracted and analyzed. We charted the overall success rate on a forest plot with 95% confidence intervals. Data of success rates were analyzed in 5- and 10-year intervals to determine whether the rate of success had increased chronologically. We then performed 3 subgroup analyses according to instrument type (needles vs knife blades), cortisone use (cortisone vs noncortisone), and sonography guidance (sonography vs non-sonography guidance). Pooled success rates were calculated in the subgroups and compared using chi-square test. RESULTS: A total of 34 studies involving 2,114 percutaneous procedures were included in this systematic review and meta-analysis. The total success rate was 94%. There was a trend toward increasing number of publications in the past 20 years. We found a statistically significant trend showing that overall success rates had increased over time. Chi-square test revealed that percutaneous release with sonography guidance had a significantly higher success rate than non-sonography guidance. There were no significant differences in other subgroup analyses including instrument type and cortisone use. CONCLUSIONS: Percutaneous release is an effective and safe procedure for the treatment of trigger digit. It has become progressively popular in recent years, with a trend toward increased overall success. Sonography might be a helpful tool for maximizing success. The success rates were not affected by instruments and cortisone use. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
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Trastorno del Dedo en Gatillo/cirugía , Humanos , Procedimientos Ortopédicos/métodos , Ultrasonografía IntervencionalRESUMEN
Pericytes are located in the stromal membrane of the capillary outer wall and contain endothelial cells (ECs). They are pivotal in regulating blood flow, enhancing vascular stability, and maintaining the integrity of the blood-retina barrier (BRB)/blood-brain barrier (BBB). The pluripotency of pericytes allows them to differentiate into various cell types, highlighting their significance in vascular disease pathogenesis, as demonstrated by previous studies. This potential enables pericytes to be a potential biomarker for the diagnosis and a target for treatment of vascular disorders. The retina, an essential part of the eyeball, is an extension of cerebral tissue with a transparent refractive medium. It offers a unique window for assessing systemic microvascular lesions. Routine fundus examination is necessary for patients with diabetes and hypertension. Manifestations, such as retinal artery tortuosity, dilation, stenosis, and abnormal arteriovenous anastomosis, serve as typical hallmarks of retinal vasculopathy. Therefore, studies of ocular vascular diseases significantly facilitate the exploration of systemic vascular diseases.