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Objective: To evaluate the value of cardiac troponin(cTn), myoglobin(Myo) combined with heart-type fatty acid-binding protein(H-FABP) detection in the diagnosis of early acute myocardial infarction(AMI). Methods: This study was a clinical comparative study. Eighty patients with AMI hospitalized in Tangshan Workers' Hospital were selected as study group, and another 80 individuals receiving normal physical examination were selected as control group from September 20, 2021 to September 20, 2022. The concentrations of cTn, Myo and H-FABPP, diagnostic indicators, the sensitivity and specificity of combined diagnosis, as well as the diagnostic efficacy for AMI were compared between the two groups. Results: The levels of cTn, Myo and H-FABPP in the study group were significantly higher than those in the control group(P= 0.00). Multivariate logistic regression analysis showed that cTn, Myo and H-FABP were all relevant indicators for AMI. H-FABP alone has better diagnostic efficacy for AMI. The area under the curve of their combined detection, the specificity, and the sensitivity were higher than those of cTn, Myo and H-FABP alone, indicating that their combined application has the best diagnostic efficiency. cTn, Myo and H-FABP levels were positively correlated with Glu, TC, LDL-C and hs-CRP levels(P< 0.01), while negatively correlated with HDL level(P< 0.01). Conclusions: The combined detection of cardiac markers such as cTn, Myo and H-FABP presents higher sensitivity and specificity in the diagnosis of AMI compared with any single detection, and can provide better data support for the definite diagnosis of AMI, with high clinical application value.
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[This corrects the article DOI: 10.3389/fneur.2023.1103026.].
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Objectives: We aimed to determine a method to identify normal cerebrospinal fluid (CSF) glucose levels by examining the correlation between blood and CSF glucose levels in patients with normal and abnormal glucose metabolism. Methods: One hundred ninety-five patients were divided into two groups according to their glucose metabolism. The glucose levels were obtained from CSF and fingertip blood at 6, 5, 4, 3, 2, 1, and 0 h before lumbar puncture. SPSS 22.0 software was used for the statistical analysis. Results: In both the normal and abnormal glucose metabolism groups, CSF glucose levels increased with blood glucose levels at 6, 5, 4, 3, 2, 1, and 0 h before lumbar puncture. In the normal glucose metabolism group, the CSF/blood glucose ratio range was 0.35-0.95 at 0-6 h before lumbar puncture, and the CSF/average blood glucose ratio range was 0.43-0.74. In the abnormal glucose metabolism group, the CSF/blood glucose ratio range was 0.25-1.2 at 0-6 h before lumbar puncture, and the CSF/average blood glucose ratio range was 0.33-0.78. Conclusion: The CSF glucose level is influenced by the blood glucose level 6 h before lumbar puncture. In patients with normal glucose metabolism, direct measurement of the CSF glucose level can be used to determine whether the CSF level is normal. However, in patients with abnormal or unclear glucose metabolism, the CSF/average blood glucose ratio should be used to determine whether the CSF glucose level is normal.
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Spermatogenesis is a complex process that includes spermatogonia self-renewal, spermatocyte meiosis and spermatozoa assembly. Recent studies have revealed that WD40-repeat domain-containing (WDR) proteins play important roles in spermatocyte division, spermatozoa flagella assembly and head shaping. In this study, we investigated the expression pattern of WDR87 and found that it was highly expressed in the testis of both humans and mice. Immunofluorescence staining revealed that mouse WDR87 was distributed in the perinuclear cytoplasm of primary spermatocytes, secondary spermatocytes and round spermatids. In the spermiogenesis stage, with extension of the nucleus, WDR87 migrated to the manchette and finally localized to the middle piece of the spermatozoa tail. Furthermore, we identified a cilia- and flagella-associated protein, CFAP47, which interacted with WDR87 in the flagellar midpiece of the spermatozoa, suggesting that WDR87 may be associated with multiple morphological abnormalities of the flagella (MMAF). Subsequently, we screened gene mutations in seven MMAF individuals and found two novel mutations in CFAP47 (c.706G>A, Val236Met; c.1337C>T, Thr446Met) in one case. Immunoblotting and immunofluorescence revealed that CFAP47 was dramatically reduced in spermatozoa from the CFAP47-mutated man. Meanwhile, the expression of WDR87 was also significantly decreased, and weak signals were detected adjacent to the spermatozoa nuclei, indicating that CFAP47 was necessary for WDR87 transportation during spermatozoa flagella biogenesis. These data indicate that WDR87 is located in the middle piece of the sperm tail and interacts with CFAP47 to form a complex which is involved in spermatozoa tail assembly.
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Infertilidad Masculina , Cola del Espermatozoide , Humanos , Masculino , Animales , Ratones , Infertilidad Masculina/genética , Semen , Espermatozoides , Flagelos/genética , Proteínas , Espermatogénesis/genéticaRESUMEN
Purpose: Cerebral aspergillosis (CA) is a rare but often fatal, difficult-to-diagnose, opportunistic infection. The utility of metagenomic next-generation sequencing (mNGS) for diagnosis of CA is unclear. We evaluated the usefulness of mNGS of the cerebrospinal fluid (CSF) for the diagnosis of CA. Methods: This prospective study involved seven consecutive patients with confirmed CA in whom CSF mNGS was performed. Serum (1â3)-ß-D-glucan and galactomannan levels were determined, and histopathological examination and mNGS of the CSF were conducted. CSF specimens from three non-infected patients were used as positive controls. Results: mNGS of the CSF was positive in six of the seven confirmed CA cases (85.71% sensitivity). In the cryptococcal meningitis group (control), mNGS of the CSF was positive for Aspergillus in two patients (84.62% specificity). The positive likelihood ratio, negative likelihood ratio, and Youden's index of mNGS for CA in the CSF were 5.565, 0.169, and 0.7, respectively. Among the six mNGS-positive cases, more than two Aspergillus species were found in four (4/6, 66.67%). In the positive controls, the addition of one A. fumigatus spore yielded a standardised species-specific read number (SDSSRN) of 25.45 by mNGS; the detection rate would be 0.98 if SDSSRN was 2. Conclusion: mNGS facilitates the diagnosis of CA and may reduce the need for cerebral biopsy in patients with suspected CA. Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR1800020442.
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Polycystic ovarian syndrome (PCOS) is a major severe ovary disorder affecting 5-10% of reproductive women around the world. PCOS can be considered a metabolic disease because it is often accompanied by obesity and diabetes. Brown adipose tissue (BAT) contains abundant mitochondria and adipokines and has been proven to be effective for treating various metabolic diseases. Recently, allotransplanted BAT successfully recovered the ovarian function of PCOS rat. However, BAT allotransplantation could not be applied to human PCOS; the most potent BAT is from infants, so voluntary donors are almost inaccessible. We recently reported that single BAT xenotransplantation significantly prolonged the fertility of aging mice and did not cause obvious immunorejection. However, PCOS individuals have distinct physiologies from aging mice; thus, it remains essential to study whether xenotransplanted rat BAT can be used for treating PCOS mice. In this study, rat-to-mouse BAT xenotransplantation, fortunately, did not cause severe rejection reaction, and significantly recovered ovarian functions, indicated by the recovery of fertility, oocyte quality, and the levels of multiple essential genes and kinases. Besides, the blood biochemical index, glucose resistance, and insulin resistance were improved. Moreover, transcriptome analysis showed that the recovered PCOS F0 mother following BAT xenotransplantation could also benefit the F1 generation. Finally, BAT xenotransplantation corrected characteristic gene expression abnormalities found in the ovaries of human PCOS patients. These findings suggest that BAT xenotransplantation could be a novel therapeutic strategy for treating PCOS patients.
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Tejido Adiposo Pardo/trasplante , Infertilidad Femenina/cirugía , Ovario/metabolismo , Síndrome del Ovario Poliquístico/cirugía , Animales , Femenino , Fertilidad , Humanos , Infertilidad Femenina/sangre , Ratones Endogámicos BALB C , Oocitos/citología , Síndrome del Ovario Poliquístico/sangre , Ratas Sprague-Dawley , Transcriptoma , Trasplante HeterólogoRESUMEN
OBJECTIVES: Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue. METHODS: We first examine KBTBD8 expression in EOC tissues and cells. Next, we performed RNA sequencing to reveal the overall mechanism. Then we investigated the roles of KBTBD8 in the proliferation, migration, and health status of cultured EOC cells. Finally, we employed tumor xenograft models to evaluate the role of KBTBD8 in vivo. RESULTS: First, KBTBD8 level was significantly higher in EOC tissues and cells. Next, comparative RNA sequencing identified more tumorigenesis-related genes that KBTBD8 might regulate. Then we found that KBTBD8 knockdown significantly decreased EOC cell proliferation, migration, and the activities of multiple tumorigenesis-related kinases. Finally, KBTBD8 knockdown significantly diminished ovarian tumor formation in vivo. CONCLUSION: Proper KBTBD8 level is essential for the healthy growth of ovarian somatic cells, such as ovarian epithelial cells. Excessive KBTBD8 might be a significant impetus for EOC progression. KBTBD8 reduction greatly inhibits EOC proliferation and migration.
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Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/patología , Regulación Neoplásica de la Expresión Génica , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Anciano , Animales , Biomarcadores de Tumor , Carcinoma Epitelial de Ovario/diagnóstico por imagen , Línea Celular Tumoral , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Técnicas de Silenciamiento del Gen , Xenoinjertos , Humanos , Inmunohistoquímica , Ratones , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Ováricas/diagnóstico por imagen , Análisis de Matrices TisularesRESUMEN
BACKGROUND: Sporadic Creutzfeldt-Jakob disease (sCJD) is an extremely rare fatal and infectious neurodegenerative brain disorder characterized by rapidly progressive dementia, cerebellar ataxia, and visual disturbances. This article summarizes the retrospective analysis of 104 sCJD patients in the First Medical Center of Chinese PLA General Hospital from 2003 to 2019. METHODS: A retrospective analysis of the medical records of the 104 patients diagnosed with sCJD was performed from the aspects of demographic data, clinical manifestations, laboratory examinations, cerebrospinal fluid analysis, electroencephalograms (EEGs), diffusion-weighted imaging (DWI) scans, positron emission tomography (PET) scans, and prion protein gene mutations. RESULTS: In the 104 sCJD patients, pathological evidence of a spongiform change was found in 11 patients, while the remaining 93 patients were probable sCJD. The 104 patients included 57 males and 47 females, with the age of onset ranging from 29 to 82 (mean: 58, median: 60) years. The time from disease onset to death ranged from 1 to 36 months. Most of the patients died 7-12 months after the onset of sCJD. In most patients, rapidly progressive dementia appeared as the initial symptom, followed by cerebellar ataxia, visual disturbances, and neurobehavioral disorders. Most patients' DWI images showed symmetric or asymmetric hyperintensity in the cortex. In terms of EEGs, 38.2% of the patients had periodic sharp wave complexes. The sensitivity of 14-3-3 protein detection was 34.1%. The brain PET scans of 50 patients with sCJD presented 96% sensitivity for the diagnosis of sCJD. CONCLUSIONS: This study indicated that sCJD occurred at an early age in patients in China. The sensitivity of 14-3-3 protein detection was significantly low, but brain PET was highly sensitive in the diagnosis of sCJD.
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Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/fisiopatología , Proteínas 14-3-3/líquido cefalorraquídeo , Adulto , Anciano , China , Imagen de Difusión por Resonancia Magnética , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroimagen/métodos , Tomografía de Emisión de Positrones , Estudios RetrospectivosRESUMEN
Purpose: We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis. Methods: This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningitis, bacterial meningitis, fungal meningitis, and non-central nervous system (CNS) infections were subjected to mNGS. Results: In total, 213 patients with infectious and non-infectious CNS diseases were finally enrolled from November 2016 to May 2019; the mNGS-positive detection rate of definite CNS infections was 57.0%. At a species-specific read number (SSRN) ≥2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] = 0.659, 95% confidence interval [CI] = 0.566-0.751); the positivity rate was 42.6%. At a genus-specific read number ≥1, mNGS performance in the diagnosis of tuberculous meningitis (definite or probable) was optimal (AUC=0.619, 95% CI=0.516-0.721); the positivity rate was 27.3%. At SSRNs ≥5 or 10, the diagnostic performance was optimal for definite bacterial meningitis (AUC=0.846, 95% CI = 0.711-0.981); the sensitivity was 73.3%. The sensitivities of mNGS (at SSRN ≥2) in the diagnosis of cryptococcal meningitis and cerebral aspergillosis were 76.92 and 80%, respectively. Conclusion: mNGS of cerebrospinal fluid effectively identifies pathogens causing infectious CNS diseases. mNGS should be used in conjunction with conventional microbiological testing. Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020442.
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Infecciones del Sistema Nervioso Central/diagnóstico , Encefalitis Viral/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento , Meningitis/diagnóstico , Metagenoma , Adolescente , Adulto , Infecciones del Sistema Nervioso Central/líquido cefalorraquídeo , Infecciones del Sistema Nervioso Central/microbiología , Infecciones del Sistema Nervioso Central/virología , Líquido Cefalorraquídeo/microbiología , Líquido Cefalorraquídeo/virología , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/virología , Femenino , Humanos , Masculino , Meningitis/líquido cefalorraquídeo , Meningitis/microbiología , Meningitis/virología , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/microbiología , Meningitis Fúngica/líquido cefalorraquídeo , Meningitis Fúngica/diagnóstico , Meningitis Fúngica/microbiología , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/diagnóstico , Meningitis Viral/virología , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Tuberculosis Meníngea/líquido cefalorraquídeo , Tuberculosis Meníngea/diagnóstico , Tuberculosis Meníngea/microbiología , Adulto JovenRESUMEN
Glutamate dehydrogenase (GDH) is a key enzyme in glutaminolysis and can regulate allosteric functions. Immunohistochemical study found that GDH expressed in gastric cancer cell cytoplasm and membrane, and a few located in the nucleus, ranging from light yellow to tan to sepia. According to the analysis by Kaplan Meier survival curve and the Log-Rank test, the median survival of GDH high expression in patients was 51.7 months with 95% confidence intervals (CI) was 41.138-55.262. The expression level of GDH was significantly reduced after silencing GDH gene in gastric cancer cells and tissues. Further, after silencing GDH gene, gastric cancer cell migration and invasion ability were decreased significantly. Protein expression of. In addition, tumor growth was significantly reduced after silencing GDH gene. In vivo and in vitro experiments suggest that GDH can decrease gastric cancer cell migration and invasion, thus inhibiting tumor growth.
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Biomarcadores de Tumor/metabolismo , Glutamato Deshidrogenasa/metabolismo , Receptores Notch/metabolismo , Neoplasias Gástricas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Movimiento Celular/genética , Estudios de Seguimiento , Gastrectomía , Silenciador del Gen , Glutamato Deshidrogenasa/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones , Persona de Mediana Edad , ARN Interferente Pequeño/metabolismo , Transducción de Señal/genética , Estómago/patología , Estómago/cirugía , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto JovenRESUMEN
INTRODUCTION: In recent years, metagenomic next-generation sequencing (mNGS) has become widely used in medical microbiology to detect pathogen infection. AIM: We aimed to assess the diagnostic performance of mNGS of cerebrospinal fluid (CSF) for prediction of cryptococcal meningitis (CM). METHODOLOGY: A comparative evaluation of mNGS (performed on CSF samples) and conventional methods, including India ink staining, culture for fungi and cryptococcal-antigen (CrAg) detection by enzyme immunoassay, was performed on 12 consecutive non-HIV-infected patients with chronic or subacute CM. RESULTS: India ink staining and culture of the CSF were positive for Cryptococcus in 83.33 % (10/12) of the samples; 100 % (11/11) were positive via CrAg EIA. The mNGS results of the CSF identified DNA sequences corresponding to Cryptococcus in 75 % of samples (9/12). However, the DNA of both C. neoformans s.l. and C. gattii s.l. was detected concurrently in 33.33 % (4/12). CONCLUSION: mNGS is helpful for identifying Cryptococcus species. The application of mNGS, together with India ink staining, culture methods, and CrAg, may significantly improve the diagnostic precision in CM, thereby informing choice of appropriate antifungal treatment courses.
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Cryptococcus gattii/genética , Cryptococcus neoformans/genética , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/microbiología , Metagenómica , Técnicas de Diagnóstico Molecular/métodos , Adolescente , Adulto , Anciano , Coinfección/diagnóstico , Cryptococcus gattii/aislamiento & purificación , Cryptococcus neoformans/aislamiento & purificación , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/normas , Humanos , Masculino , Meningitis Criptocócica/líquido cefalorraquídeo , Técnicas Microbiológicas , Persona de Mediana Edad , Sensibilidad y Especificidad , Análisis de Secuencia de ADNRESUMEN
Stress plays a crucial role in several psychiatric disorders, including anxiety. However, the underlying mechanisms remain poorly understood. Here, we used acute stress (AS) and chronic restraint stress (CRS) models to develop anxiety-like behavior and investigate the role of miR-150 in the hippocampi of mice. Corticosterone levels as well as glutamate receptors in the hippocampus were evaluated. We found that anxiety-like behavior was induced after either AS or CRS, as determined by the open-field test (OFT) and elevated plus-maze test (EPM). Increased corticosterone levels were observed in the blood of AS and CRS groups, while the expression of miR-150 mRNA in the hippocampus was significantly decreased. The expressions of GluN2A, GluR1, GluR2, and V-Glut2 in the hippocampus were decreased after either AS or CRS. Hippocampal GAD67 expression was increased by AS but not CRS, and GluN2B expression was decreased by CRS but not AS. Adult miR-150 knockout mice showed anxiety-like behavior, as assessed by the OFT and EPM. The expressions of GluN2A, GluN2B, GluR1, and GluR2 were also downregulated, but the expression of V-Glut2 was upregulated in the hippocampi of miR-150 knockout mice compared with wild-type mice. Interestingly, we found that the miR-150 knockout mice showed decreased dendrite lengths, dendrite branchings, and numbers of dendrite spines in the hippocampus compared with wild-type mice. These results suggest that miR-150 may influence the synaptic plasticity of the hippocampus and play a significant role in stress-induced anxiety-like behavior in adult mice.
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Ansiedad/etiología , Ansiedad/metabolismo , MicroARNs/metabolismo , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Sistema de Transporte de Aminoácidos X-AG/metabolismo , Animales , Ansiedad/patología , Corticosterona/metabolismo , Dendritas/metabolismo , Dendritas/patología , Regulación de la Expresión Génica , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , MicroARNs/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Receptores de Glutamato/metabolismo , Restricción Física , Estrés Psicológico/patologíaRESUMEN
BACKGROUND: There are sparse and limited studies on small sample size reporting the application of next-generation sequencing (NGS) in the detection of central nervous system (CNS) viral infections. We assessed the diagnostic performance of NGS of cerebrospinal fluid (CSF) for predicting viral infections of the CNS caused by the neurotropic herpes viruses in a pilot population. MATERIALS AND METHODS: We prospectively collected CSF samples from 24 patients with CNS viral infection from April 2017 to October 2018. Of the 24 patients, 19 patients were infected with herpes simplex virus 1 (HSV-1), 1 patient with HSV-2, and 4 patients with varicella-zoster virus (VZV). All CSF samples were screened for viral DNA using NGS technologies to detect viral CNS infections. RESULTS: Of the 24 patients with confirmed viral CNS infection caused by the neurotropic herpes viruses, 10 (10/24, 41.67%) patients exhibited positive NGS results. With the help of NGS, HSV-1 DNA was detected in the CSF of 6 patients (6/19; 31.58%). HSV-2 DNA was detected in 1 patient (1/1; 100%) and VZV DNA was detected in 3 patients (3/4; 75%). The positive rate of virus detected by NGS decreased with time. The positive rates of NGS of CSF in the first, second, and third weeks were 54.5% (6/11), 44.4% (4/9), and 0% (0/4), respectively. CONCLUSIONS: NGS method is a promising pathogen detection tool for identifying viral CNS infections. It should be recommended to sequence viral DNA of CSF in the early stage of CNS viral infections.
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Enfermedades Virales del Sistema Nervioso Central/diagnóstico , ADN Viral/análisis , Infecciones por Herpesviridae/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Adulto JovenRESUMEN
The ß1adrenergic receptor (AR) is the primary ßAR subtype in the heart and is the target of metoprolol (Met), which is commonly used to treat angina and hypertension. Previous studies have revealed a positive correlation between the methylation levels of the adrenoreceptor ß1 gene (Adrb1) promoter in the myocardium with the antihypertensive activity of Met in spontaneously hypertensive rats (SHR), which affects ß1AR expression in H9C2 cells. The aim of the present study was to investigate the effects of myocardial ß1AR downregulation using shorthairpin RNA (shRNA) against Adrb1 on the antihypertensive activity of Met in SHR. Recombinant adenoassociated virus type 9 (rAAV9) vectors carrying Adrb1 shRNA (rAAV9Adrb1) or a negative control sequence (rAAV9NC) were generated and used to infect rat hearts via the pericardial cavity. The results of reverse transcriptionquantitative polymerase chain reaction, immunohistochemistry and western blotting analyses demonstrated that cardiac ß1AR expression in the rAAV9Adrb1 group was significantly downregulated when compared with the rAAV9NC group (P<0.001, P<0.001 and P=0.032, respectively). In addition, a greater reduction in systolic blood pressure (SBP) was observed in the rAAV9NC group compared with the rAAV9Adrb1 group following Met treatment (P=0.035). Furthermore, downregulation of myocardial ß1AR was associated with a significant decrease in SBP (P<0.001). In conclusion, these data suggest that suppression of ß1AR expression in the myocardium reduces SBP and sensitivity to Met in SHR.
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Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Regulación hacia Abajo , Metoprolol/farmacología , Miocardio/metabolismo , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/metabolismo , Animales , Antihipertensivos/uso terapéutico , Línea Celular , Dependovirus/genética , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Células HEK293 , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Hipertensión/patología , Masculino , Metoprolol/uso terapéutico , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Endogámicas SHR , Receptores Adrenérgicos beta 1/químicaRESUMEN
In the past 10 years, several publications have highlighted the role of the regulator of G protein signalling (RGS) family in multiple diseases, including cardiovascular diseases. As one of the multifunctional family members, RGS14 is involved in various biological processes, such as synaptic plasticity, cell division, and phagocytosis. However, the role of RGS14 in cardiovascular diseases remains unclear. In the present study, we used a genetic approach to examine the role of RGS14 in pathological cardiac remodelling in vivo and in vitro. We observed that RGS14 was down-regulated in human failing hearts, murine hypertrophic hearts, and isolated hypertrophic cardiomyocytes. Moreover, the extent of aortic banding-induced cardiac hypertrophy and fibrosis was exacerbated in RGS14 knockout mice, whereas RGS14 transgenic mice exhibited a significantly alleviated response to pressure overload. Furthermore, research of the underlying mechanism revealed that the RGS14-dependent rescue of cardiac remodelling was attributed to the abrogation of mitogen-activated protein kinase (MEK)-extracellular signal-regulated protein kinase (ERK) 1/2 signalling. The results showed that constitutive activation of MEK1 nullified the cardiac protection in RGS14 transgenic mice, and inhibition of MEK-ERK1/2 by U0126 reversed RGS14 deletion-related hypertrophic aggravation. These results demonstrated that RGS14 attenuated the development of cardiac remodelling through MEK-ERK1/2 signalling. RGS14 exhibited great potential as a target for the treatment of pathological cardiac remodelling.
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Sistema de Señalización de MAP Quinasas/fisiología , Proteínas RGS/metabolismo , Remodelación Ventricular/fisiología , Animales , Western Blotting , Cardiomegalia/metabolismo , Técnica del Anticuerpo Fluorescente , Insuficiencia Cardíaca/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Autoimmune encephalitis associated with anti-voltage-gated potassium channel antibodies are most likely to be misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Our goal was to delineate patients who were initially suspected to have CJD but were later found to have AE. We performed a retrospective clinical review of cases of individuals and made a comparison between groups of patients diagnosed with sCJD and AE. Patients who had rapidly progressing dementia and focal neurological impairment, such as aphasia, gait disturbance, visual disturbance, and depression, at onset were diagnosed with sCJD, whereas epilepsy, hyponatremia and dysautonomia were strong hints for AE. Fluoroscope-positron emission tomography (PET) of patients with AE revealed variable metabolism and normative and long-term immunosuppression were less likely to relapse.
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Síndrome de Creutzfeldt-Jakob/fisiopatología , Poliendocrinopatías Autoinmunes/diagnóstico , Anciano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/inmunología , Diagnóstico Diferencial , Electroencefalografía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Proteínas del Tejido Nervioso/inmunología , Proteínas del Tejido Nervioso/metabolismo , Poliendocrinopatías Autoinmunes/fisiopatología , Tomografía de Emisión de Positrones , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To prepare a specific polyclonal antibody against full-length SUN5 for detecting the expression of SUN5 in human germ cells. METHODS: Bioinformatic methods were used to compare the full-length SUN5 and its variant SUN5ß, and a short peptide was designed based on the differential region to prepare SUN5 antibody. The prepared antibody was used to detect the expression of SUN5 in Ntera-2 cells and in human germ cells by Western blotting and immunofluorescence assay. RESULTS: The short peptide was correctly synthesized and SUN5 antibody was obtained and purified. Western blotting showed that the prepared antibody was capable of recognizing full-length SUN5 in Ntera-2 cells, and SUN5 expression was localized on the nuclear membrane and in the cytoplasm as shown by immunofluorescence assay. Using this antibody, we detected SUN5 expression in the spermatocytes, round spermatids and sperms in human germ cells. CONCLUSION: We successfully prepared SUN5-specific antibody. SUN5 is expressed in the spermatocytes, round spermatids and sperms in human germ cells, suggesting its important role in spermatogenesis.
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Anticuerpos/química , Proteínas/metabolismo , Espermátides/metabolismo , Espermatocitos/metabolismo , Espermatozoides/metabolismo , Western Blotting , Citoplasma/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Proteínas de la Membrana , Membrana Nuclear/metabolismo , Proteínas/inmunología , EspermatogénesisRESUMEN
BACKGROUND: Cryptococcal meningitis (CM) is a relatively common opportunistic infection in patients with human immunodeficiency virus (HIV) infection and can also occur in patients with no underlying disease. The aim of this study was to evaluate the clinical manifestations, laboratory findings, diagnosis and misdiagnosis, treatment, and prognosis of CM at a tertiary care hospital. METHODS: We performed a retrospective study of 55 patients at a tertiary care hospital from January 1, 1992 to December 31, 2013. All the patients had a definite diagnosis based on etiology. RESULTS: All 55 patients had a positive cerebrospinal fluid (CSF) India ink staining result. The predominant change observed on magnetic resonance imaging (MRI) was leptomeningeal liner enhancement, which is also called 'lumbriciform-enhancing.' Only 15 patients were first diagnosed with CM, indicating a misdiagnosis rate of 72.7%. At the follow-up end point, 8 patients were cured, 33 had improved, and 14 had died. The overall response rate was 74.5%. The voriconazole group had a response rate of 100%, which was significantly higher than the other two groups. CONCLUSIONS: Most CM patients in China were previously healthy without any potential risk factors. CM was easily misdiagnosed due to the lack of specificity of early clinical symptoms. Repeated CSF India ink staining should be performed to identify the pathogen. Voriconazole could be administered to the patients with CM, especially to patients who had a treatment failure with amphotericin B alone or accompanied by fluconazole.
Asunto(s)
Antifúngicos/uso terapéutico , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/tratamiento farmacológico , Voriconazol/uso terapéutico , Infecciones Oportunistas Relacionadas con el SIDA/líquido cefalorraquídeo , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/administración & dosificación , Carbono , China , Cryptococcus neoformans/aislamiento & purificación , Errores Diagnósticos , Quimioterapia Combinada , Femenino , Fluconazol/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Masculino , Meningitis Criptocócica/líquido cefalorraquídeo , Meningitis Criptocócica/microbiología , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria , Factores de Tiempo , Voriconazol/administración & dosificaciónRESUMEN
The objective of this study is to investigate the hyperintense lesions on diffusion-weighted magnetic resonance imaging (DWI) and its clinical correlation in sporadic Creutzfeldt-Jakob disease (sCJD). Patients who suffered from sCJD and followed up at the Department of Neurology at the General Hospital of the People's Liberation Army during the period of June 1, 2007 to July 1, 2014 were reviewed. The location of the hyperintense lesions on DWI, apparent diffusion coefficient (ADC) values of the hyperintense lesions were correlated with symptoms and clinical course. A total of 58 sCJD patients and ten healthy controls were included. Hyperintense lesions on DWI were observed in all the patients. The patients with basal ganglia (BG) hyperintense lesions on DWI had shorter disease duration and higher incidence of myoclonus (92 versus 44 %) than those without BG hyperintense lesions. The patients with occipital cortex hyperintense lesions on DWI had shorter disease duration between symptom onset and akinetic mutism than those without these lesions. The lower of the BG ADC value the faster presence of akinetic mutism and the shorter disease duration the patients will have. The presence of BG and occipital cortex hyperintense lesions on DWI and BG ADC values is correlated with the clinical course and clinical symptoms.
Asunto(s)
Ganglios Basales/patología , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/fisiopatología , Imagen de Difusión por Resonancia Magnética , Encefalopatía Espongiforme Bovina/diagnóstico , Encefalopatía Espongiforme Bovina/fisiopatología , Estadística como Asunto , Adulto , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Opioid addiction is a major social, economic, and medical problem worldwide. Long-term adverse consequences of chronic opiate exposure not only involve the individuals themselves but also their offspring. Adolescent maternal morphine exposure results in behavior and morphologic changes in the brain of their adult offspring. However, few studies investigate the effect of adult opiate exposure on their offspring. Furthermore, the underlying molecular signals regulating the intergenerational effects of morphine exposure are still elusive. We report here that morphine exposure of adult male and female rats resulted in anxiety-like behavior and dendritic retraction in the dentate gyrus (DG) region of the hippocampus in their adult offspring. The behavior and morphologic changes were concomitant with the downregulation of insulin-like growth factor (IGF)-2 signaling in the granular zone of DG. Overexpression of hippocampal IGF-2 by bilateral intra-DG injection of lentivirus encoding the IGF-2 gene prevented anxiety-like behaviors in the offspring. Furthermore, exposure to an enriched environment during adolescence corrected the reduction of hippocampal IGF-2 expression, normalized anxiety-like behavior and reversed dendritic retraction in the adult offspring. Thus, parental morphine exposure can lead to the downregulation of hippocampal IGF-2, which contributed to the anxiety and hippocampal dendritic retraction in their offspring. An adolescent-enriched environment experience prevented the behavior and morphologic changes in their offspring through hippocampal IGF-2 signaling. IGF-2 and an enriched environment may be a potential intervention to prevention of anxiety and brain atrophy in the offspring of parental opioid exposure.