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OBJECTIVE: The purpose of this preliminary investigation into the pathogenesis of pre-eclampsia was to screen the differential proteins in the serum of pregnant women with normal pregnancy and early-onset pre-eclampsia using isobaric tags for relative and absolute quantitation (iTRAQ), so as to identify serum biomarkers for the early diagnosis of pre-eclampsia. METHODS: We examined the peripheral serum of 58 normal pregnant women and 42 pregnant women with early-onset pre-eclampsia using iTRAQ; the differentially expressed proteins were screened for bioinformatics analysis; and the expression of candidate proteins human leukocyte antigen-1 (HLA-1) and ß2-microglobulin (ß2M) in placental tissues was detected using western blot. RESULTS: We identified a total of 63 differential proteins in the serum of patients from the normal control group and the pre-eclampsia group, and this included 24 up-regulated proteins and 39 down-regulated proteins. The western blot results of placental tissue showed reduced HLA-1 expression (1.12 ± 0.23) in the placenta in the pre-eclampsia group as compared with the normal control group (1.34 ± 0.22). Consistent with the results observed in the serum, ß2M in the placenta in the pre-eclampsia group was significantly elevated (1.05 ± 0.47) in comparison with the normal group (0.75 ± 0.33) (P < 0.05). CONCLUSION: In this study, we found that iTRAQ technology was useful for identifying differentially expressed proteins in the peripheral serum of pregnant women with pre-eclampsia, and that HLA-1 and ß2M, which may be involved in the occurrence of pre-eclampsia, show promise as predictive markers of pre-eclampsia.
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Biomarcadores , Antígenos HLA , Placenta , Preeclampsia , Microglobulina beta-2 , Adulto , Femenino , Humanos , Embarazo , Microglobulina beta-2/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Placenta/metabolismo , Preeclampsia/sangre , Preeclampsia/diagnóstico , Proteómica/métodos , Antígenos HLA/sangreRESUMEN
Objective: To study the effect of congenital dyskeratosis 1 (DKC1) on neuroblastoma and its regulation mechanism. Methods: The expression of DKC1 in neuroblastoma was analyzed by TCGA database and molecular assay. NB cells were transfected with siDKC1 to observe the effects of DKC1 on proliferation, cloning, metastasis, and invasion, and apoptosis and apoptosis-related proteins. The tumor-bearing mouse model was constructed, shDKC1 was transfected to observe the tumor growth and tumor tissue changes, and the expression of DKC1 and Ki-67 was detected. Screening and identification of miRNA326-5p targeting DKC1. NB cells were treated with miRNA326-5p mimic or inhibitors to detect the expression of DKC1. NB cells were transfected with miRNA326-5p and DKC1 mimics to detect cell proliferation, apoptosis, and apoptotic protein expression. Results: DKC1 was highly expressed in NB cells and tissues. The activity, proliferation, invasion, and migration of NB cells were significantly decreased by DKC1 gene knockout, while apoptosis was significantly increased. The expression level of B-cell lymphoma-2 in shDKC1 group was significantly lower than that of the control group, while the expression level of BAK, BAX, and caspase-3 was significantly higher than that of the control group. The results of experiments on tumor-bearing mice were consistent with the above results. The results of miRNA assay showed that miRNA326-5p could bind DKC1 mRNA to inhibit the protein expression, thereby inhibiting the proliferation of NB cells, promoting their apoptosis, and regulating the expression of apoptotic proteins. Conclusion: miRNA326-5p targeting DKC1 mRNA regulates apoptosis-related proteins to inhibit neuroblastoma proliferation and promote the apoptotic process.
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MicroARNs , Neuroblastoma , Animales , Ratones , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patologíaRESUMEN
PURPOSE: To investigate the expression and significance of NEK2 and EMT-related molecules in oral squamous cell carcinoma (OSCC). METHODS: The expression levels of NEK2 and EMT-related molecules (E-Cadherin, N-Cadherin, Vimentin) in 60 cases of primary OSCC tissues and normal oral mucosa tissues were detected by immunohistochemistry(IHC). NEK2 mRNA expression in 25 OSCC tissues and 10 normal oral mucosa tissues was detected by qRT-PCR. Statistical analysis was performed using SPSS 26.0 software package. RESULTS: The expression of NEK2, N-Cadherin, and Vimentin increased in OSCC tissues, while the expression of E-Cadherin decreased(Pï¼0.05). The worse the differentiation, the higher the expression of NEK2 and the lower the expression of E-Cadherin(Pï¼0.05). CONCLUSIONS: NEK2 can be used as a prognostic marker for OSCC. The up-regulation of NEK2 and the changes in the expression levels of EMT related molecules can promote the occurrence and development of OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de la Boca/metabolismo , Vimentina/genética , Vimentina/metabolismo , Relevancia Clínica , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Quinasas Relacionadas con NIMA/genéticaRESUMEN
BACKGROUND: This study aimed to investigate the effects of LINC00240/miR-155/Nrf2 axis on trophoblast function and macrophage polarization in the pathogenesis of preeclampsia. METHODS: Bindings between LINC00240, miR-155 and Nrf2 were validated by dual luciferase reporter assay or RNA-immunoprecipitation. Cell proliferation, migration, invasion, and pyroptosis were detected by CCK-8, clone formation, wound healing, Transwell system, and flow cytometry, respectively. Macrophage polarization was tested by flow cytometry. The expression levels of LINC00240, miR-155, Nrf2, and oxidative stress and pyroptosis-related markers in in vitro and in vivo preeclampsia models were analyzed by qPCR, western blot, or ELISA assays. Blood pressure, urine protein levels, liver and kidney damages, and trophoblast markers in placenta tissues were further studied in vivo. RESULTS: Placenta tissues from preeclampsia patients and animals showed decreased LINC00240 and Nrf2 and increased miR-155 expression levels, and the decreased M2 macrophage polarization. LINC00240 directly bound and inhibited expression of miR-155, which then inhibited oxidative stress-induced pyroptosis, promoting proliferation, migration and invasion abilities of trophoblasts, and M2 macrophage polarization. Inhibition of miR-155 led to increased Nrf2 expression and similar changes as LINC00240 overexpression in trophoblast function and macrophage polarization. Overexpression of LINC00240 in in vivo preeclampsia model decreased blood pressure, urine protein, liver and kidney damages, increased fetal weight and length, and induced trophoblast function and M2 macrophage polarization. CONCLUSION: LINC00240 inhibited symptoms of preeclampsia through regulation on miR-155/Nrf2 axis, which suppressed oxidative stress-induced pyroptosis to improve trophoblast function and M2 macrophage polarization. LINC00240 could be a potential therapeutic target for preeclampsia.
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MicroARNs , Preeclampsia , ARN Largo no Codificante , Animales , Apoptosis , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Macrófagos/metabolismo , MicroARNs/genética , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Preeclampsia/genética , Embarazo , Piroptosis , ARN Largo no Codificante/genética , Sincalida/metabolismo , Trofoblastos/metabolismoRESUMEN
This study aimed to investigate the roles of the lysine (K)-specific demethylase 5C (KDM5C)-bone morphogenetic protein-7 (BMP-7) signaling pathway in the pathogenesis of severe preeclampsia (sPE). A total of 180 pregnant patients were enrolled in the study and classified into three groups: an early-onset sPE group (EOsPE) (n = 60), a late-onset sPE group (LOsPE) (n = 60), and a control group (normal pregnancy; n = 60). The messenger RNA (mRNA) and protein expression levels of bone morphogenetic protein receptor II (BMPRII), BMP-7, and KDM5C were detected in placenta samples from the two sPE groups, and their sites were evaluated using immunohistochemistry (IHC). The sPE groups showed an increased KDM5C mRNA expression, and the EOsPE group showed a decreased BMP-7 and BMPRII mRNA expression compared with the LOsPE group. However, contradictory results were discovered in terms of protein expression. Immunostaining of KDM5C, BMP-7, and BMPRII was observed in villous trophoblast and extravillous trophoblast cells. Compared with the control group, the staining intensity of KDM5C in the placental tissue trophoblast cell nucleus and vascular endothelial cells of the sPE groups was weaker, while that of BMP-7 and BMPRII was stronger, and the staining intensity was more subjective in the LOsPE group. Consistent findings were obtained by IHC and Western blot analysis. KDM5C nuclear-cytoplasmic translocation may regulate sPE through BMP-7 and its receptors. The KDM5C-BMP-7 signaling pathway may also lead to less invasion and increased apoptosis of the trophoblast cells, which is involved in the pathogenesis of sPE.
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Proteína Morfogenética Ósea 7 , Receptores de Proteínas Morfogenéticas Óseas de Tipo II , Histona Demetilasas , Preeclampsia , Proteína Morfogenética Ósea 7/genética , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética , Células Endoteliales/metabolismo , Femenino , Histona Demetilasas/genética , Humanos , Incidencia , Lisina , Placenta/metabolismo , Preeclampsia/genética , Embarazo , ARN Mensajero/genéticaRESUMEN
SOX17 has been shown to be involved in the transcriptional regulation of CXCR4, and CXCL12 functions by binding to its receptor CXCR4. Here, we explored the expression of SOX17 in neuroblastoma (NB), its mutual regulation with CXCL12, and its effects on cancer cell proliferation, migration and invasion. Five human NB cell lines and 15 pairs of NB and adjacent tissue specimens were used, to conduct RT-qPCR, immunohistochemistry, western blot, ELISA, CCK-8, colony formation, Edu, transwell, chromatin immunoprecipitation (ChIP), and dual-luciferase assays, to study the role of SOX17 in NB. SOX17 levels were reduced in both NB tissues and cell lines. SOX17 inhibited NB tumor growth, migration and invasion in vivo and suppressed NB cell proliferation, migration, and invasion in vitro. SOX17 knockdown or overexpression revealed a negative correlation between SOX17 and CXCL12/CXCR4 pathway activation. ChIP and dual-luciferase assays in NB cells demonstrated that SOX17 significantly inhibited CXCL12 gene and protein levels by binding to CXCL12 promoter regions. In vivo and in vitro experiments using the CXCR4 antagonist, AMD3100, demonstrated that cell proliferation, migration and invasion were significantly abrogated by AMD3100 in NB cells with SOX17 knocked down. Further, AMD3100 impaired growth of NB tumors with SOX17 knocked down in mice. Importantly, SOX17 bound to the CXCL12 promoter, which then activated downstream targets to regulate cell viability, proliferation, and migration. In conclusion, our data demonstrate that SOX17 expression is repressed in NB tissues and cells, and that SOX17 suppresses NB tumor formation and proliferation through inhibition of CXCL12/CXCR4 signaling.
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Quimiocina CXCL12 , Neuroblastoma , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Supervivencia Celular , Quimiocina CXCL12/metabolismo , Proteínas HMGB/metabolismo , Proteínas HMGB/farmacología , Ratones , Neuroblastoma/genética , Receptores CXCR4/metabolismo , Factores de Transcripción SOXF/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: To analyze the causes of renal artery stenosis (RAS) and compare the clinical characteristics in accordance with the primary disease among patients aged from 30 to 50. METHODS: Patients were grouped by etiologies of RAS. Groups were retrospectively examined and compared regarding demographic data, clinical manifestations, laboratory findings, and imaging findings. RESULTS: A total of 152 patients (74 females, 78 males; mean age: 40.70 ± 6.01 years) were enrolled, including 84 patients (55.3%) with atherosclerosis (AS), 46 patients (30.3%) with Takayasu arteritis (TA), 18 patients (11.8%) with fibromuscular dysplasia (FMD), and four patients (2.6%) with other etiologies. Patients in AS group had greater body mass index, higher prevalence of comorbidities and higher rate of smoking and drinking history. TA patients showed more constitutional symptoms and vascular findings, and higher erythrocyte sedimentation rate. RAS in both AS group and TA group mainly located on ostia and proximal segments, but RAS in FMD group mainly involved middle to distal segment of renal artery. The AS group had significantly lesser stenosis than the other groups. Although renal function evaluated by the estimated glomerular filtration rate did not significantly differ among the groups, the incidence of kidney shrinkage was significantly higher in the TA and FMD groups (39.1% and 50%, respectively) than in the AS group (8.3%). The FMD group had milder cardiac damage than other groups. CONCLUSIONS: AS was the most common cause of RAS in patients aged from 30 to 50, followed by TA and FMD. The etiology of RAS should be carefully distinguished based on clinical manifestations, laboratory findings, and imaging to ensure that proper treatment is provided.
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Background: Rare cases of concurrent primary aldosteronism (PA) and renal artery stenosis (RAS) have been reported. Methods: In this retrospective case-control study, we selected a cohort of 10 PA with RAS patients and a control group of 20 PA without RAS patients from January 1, 2006, to January 1, 2016. Results: All patients presented with refractory hypertension, and a nonstatistically significant trend toward lower mean serum potassium was seen in the PA with RAS group (p =.07). PA with RAS patients had lower mean orthostatic aldosterone-to-renin ratios (38.4 ± 41.4 ng dL-1/ng mL-1 h-1 vs. 87.4.4 ± 38.4 ng dL-1/ng mL-1 h-1, respectively; p < .01) and a higher false-negative rate (50% vs. 15%, respectively; p < .05) compared with controls. All misdiagnosed patients had the diagnosis of PA confirmed when we revaluated the repeated screening and confirmative tests because of residual hypertension or hypokalemia after successful revascularization of renal artery stenosis. Conclusions: PA is easily missed in patients with RAS because of the high false-negative rate for screening tests. RAS patients with residual hypertension after successful renal angioplasty should be monitored for coexisting PA. Reevaluation of screening and confirmatory tests is helpful in establishing the correct diagnoses.
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Hiperaldosteronismo/fisiopatología , Hipertensión/fisiopatología , Hipopotasemia/sangre , Obstrucción de la Arteria Renal/fisiopatología , Adulto , Aldosterona/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Errores Diagnósticos , Femenino , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hipertensión/etiología , Hipopotasemia/etiología , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Obstrucción de la Arteria Renal/sangre , Obstrucción de la Arteria Renal/complicaciones , Obstrucción de la Arteria Renal/diagnóstico , Renina/sangre , Estudios RetrospectivosRESUMEN
BACKGROUND: Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare. CASE PRESENTATION: Two cases of MMA with homocysteinemia in children are reported. Proteinuria were a primary presenting symptom, followed by anemia and neurologic symptoms (frequent convulsions and unstable walking, respectively). Screening of amino acids and acyl carnitine in serum showed that the propionyl carnitine:acetylcarnitine ratio increased. Profiling of urinary organic acids by gas chromatography-mass spectrometry revealed high levels of methylmalonic acid. Homocysteine content in blood was increased. Comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC) and amnionless (AMN) genes in our two patients, respectively. After active treatment, the clinical manifestations in Case 1 were relieved and urinary protein ceased to be observed; Case 2 had persistent proteinuria and was lost to follow-up. CONCLUSIONS: Analyses of the organic acids in blood and urine suggested MMA combined with homocysteinemia. In such diseases, reports of renal damage are uncommon and proteinuria as the initial presentation is rare. Molecular analysis indicated two different genetic causes. Although the pathologic mechanisms were related to vitamin B12, the severity and prognosis of renal lesions were different. Therefore, gene detection provides new insights into inherited metabolic diseases.
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Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Hiperhomocisteinemia/complicaciones , Proteinuria/diagnóstico , Adolescente , Errores Innatos del Metabolismo de los Aminoácidos/genética , Aminoácidos/sangre , Secuencia de Bases , Carnitina/análogos & derivados , Carnitina/sangre , Preescolar , ADN/sangre , ADN/genética , Cromatografía de Gases y Espectrometría de Masas , Homocisteína/sangre , Humanos , Hiperhomocisteinemia/genética , Masculino , Ácido Metilmalónico/orina , Proteinuria/etiologíaRESUMEN
Emodin is an effective component in rhubarb to cure intestinal dysfunction, but the specific mechanism remains unknown. This study aimed to evaluate the protective effects of emodin on intestinal dysfunction caused by acute severe pancreatitis and reveal the functional mechanism of emodin in the treatment of this condition. An acute severe pancreatitis model was prepared using taurocholate. In the treatment group, 50 mg/kg emodin was injected intravenously 2 h before the induction of acute severe pancreatitis at an interval of 8 h. After 24 h, the gene expression and protein levels of miR-218a-5p, RhoA, ROCK1, Akt, Notch1, Bax, Bcl-2, Fas, FasL, caspase-3, and caspase-9 were determined through reverse transcription polymerase chain reaction and Western blot analysis. The protein levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract were also determined through Western blot analysis. The effects of miR-218a-5p on the apoptosis of rat intestinal epithelial cell-18 were observed through flow cytometry. The effects of emodin on intestinal cell apoptosis induced by acute severe pancreatitis were observed via TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Pathological changes in the pancreas and intestine of rats in each group were observed through hematoxylin and eosin staining. After 24 h of acute severe pancreatitis induced by taurocholate, emodin reduced the expression of miR-218a-5p in the intestinal tract; increased the expression of Notch1 and Bcl-2; decreased the expression levels of RhoA, ROCK1, Akt, Bax, Fas, FasL, caspase-3, and caspase-9; inhibited the intestinal cell apoptosis caused by acute severe pancreatitis; increased the protein expression levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract; and alleviated intestinal dysfunction caused by acute severe pancreatitis. Emodin could regulate Notch1 and RhoA/ROCK pathways by regulating the miR-218a-5p expression in the intestine. It could also inhibit intestinal cell apoptosis induced by acute severe pancreatitis and improve the intestinal dysfunction caused by severe acute pancreatitis.
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Apoptosis/efectos de los fármacos , Emodina/farmacología , Enfermedades Intestinales/prevención & control , Mucosa Intestinal/efectos de los fármacos , MicroARNs/metabolismo , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Enfermedades Intestinales/etiología , Enfermedades Intestinales/metabolismo , Enfermedades Intestinales/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , MicroARNs/genética , Pancreatitis Aguda Necrotizante/inducido químicamente , Ratas Sprague-Dawley , Receptor Notch1/genética , Receptor Notch1/metabolismo , Transducción de Señal , Ácido Taurocólico , Regulación hacia Arriba , Proteínas de Unión al GTP rho/genética , Proteínas de Unión al GTP rho/metabolismo , Quinasas Asociadas a rho/genética , Quinasas Asociadas a rho/metabolismoRESUMEN
Preeclampsia (PE) is a pregnancy-specific syndrome that substantially leads to maternal and fetal mortality. Multiple factors contribute to the disease, but the exact pathogenesis still remains elusive. Here we explored the roles of lncRNA MALAT1 and miR-206 in PE. qRT-PCR was applied to measure mRNA levels of MALAT1 and miR-206 in the placenta of PE patients. Scratch wound healing assay and transwell invasion assay were conducted to test the effects of MALAT1 and miR-206 on migration and invasion of trophoblast cells. In addition, we validated MALAT1/miR-206 and miR-206/IGF-1 interactions with dual luciferase reporter assay. Western bot was used to detect protein expressions of IGF-1, p-PI3K, PI3K, p-Akt and Akt. We found that MALAT1 was decreased but miR-206 was increased in the placenta of patients with PE. Inhibition of MALAT1, knockdown IGF-1, or miR-206 mimics suppressed the trophoblast cells migration and invasion, while overexpression of MALAT1, IGF-1 or miR-206 inhibitors exhibited opposite effects. Further, miR-206 was confirmed as a direct target of MALAT1. Besides, miR-206 inhibited IGF-1 expression by directly binding to the 3'UTR. Mechanistically, our study demonstrated that MALAT1 regulates IGF-1/PI3K/Akt signaling via miR-206. Together, these results suggest that MALAT1 and miR-206 play important roles in PE. MALAT1 regulates miR-206/IGF-1 axis, thereby modulating trophoblast cells migration and invasion through PI3K/Akt signal pathway. These results show light on the underlying mechanisms of PE and provide potential targets for PE therapy.Abbreviations: PE: Preeclampsia; lncRNA: Long-non-coding RNA; MALAT1: Metastasis-associated lung adenocarcinoma transcript 1; IGF-1: Insulin-like growth factor 1; PI3k: Phosphatidylinositol-4, 5-bisphosphate 3-kinase; Akt: Protein kinase B; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; qRT-PCR: Quantitative Reverse Transcription polymerase chain reaction; shRNA: Short hairpin RNA; siRNA: Small interfering RNA; EMT: Epithelial-mesenchymal transition.
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Movimiento Celular/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Transducción de Señal , Trofoblastos/citología , Secuencia de Bases , Línea Celular , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , MicroARNs/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Placenta/metabolismo , Preeclampsia/genética , Preeclampsia/patología , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/genética , Transducción de Señal/genética , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: Hypertension and brachydactyly syndrome (HTNB), also called Bilginturan syndrome, is a rare autosomal dominant disorder characterized by severe salt-independent hypertension, a short stature, brachydactyly, and death from stroke before the age of 50 years when untreated. The purpose of the present study was to identify a PDE3A mutation leading to HTNB associated with vertebral artery malformation in a Chinese family. METHODS: Peripheral blood samples were collected from all subjects for DNA extraction. Next-generation sequencing and Sanger sequencing were performed to identify the PDE3A mutation. A comparative overview was performed in the probands with HTNB caused by PDE3A mutations. RESULTS: Genetic analysis identified a missense mutation in PDE3A, c.1346G>A, in the proband with HTNB. This mutation, resulting in p.Gly449Asp, was located in a highly conserved domain and predicted to be damaging by different bioinformatics tools. Cosegregation analyses showed that the proband inherited the identified mutation from her father. Antihypertensive therapy was effective for the proband. Comparative overview of HTNB probands with 9 different PDE3A mutations revealed phenotypic heterogeneity. CONCLUSIONS: Genetic screening can significantly improve the diagnosis of HTNB patients at an early age. Our study not only adds to the spectrum of PDE3A mutations in the Chinese population and extends the phenotype of HTNB patients to include vertebral malformation but also improves the awareness of pathogenesis in HTNB patients. We emphasize the importance of antihypertensive treatment and long-term follow-up to prevent stroke and adverse cardiovascular events.
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Presión Sanguínea/genética , Braquidactilia/genética , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3/genética , Hipertensión/congénito , Mutación Missense , Arteria Vertebral/anomalías , Braquidactilia/diagnóstico , Braquidactilia/fisiopatología , Braquidactilia/terapia , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Hipertensión/diagnóstico , Hipertensión/genética , Hipertensión/fisiopatología , Hipertensión/terapia , Masculino , Persona de Mediana Edad , Fenotipo , Pronóstico , Arteria Vertebral/diagnóstico por imagen , Adulto JovenRESUMEN
Primary aldosteronism (PA) is mainly treated by mineralocorticoid receptor antagonists or laparoscopic adrenalectomy (LA), but the effectiveness of surgical versus medical treatment in patients with adrenal venous sampling (AVS)-proven unilateral PA is unclear. Fifty-one consecutive patients with AVS-proven PA were enrolled. We compared the therapeutic effects between the surgery group (n = 21) and medication group (n = 30) by evaluating the complete control rate (CCR) of hypertension, blood pressure (BP), and number of antihypertensive drugs after a long-term follow-up (>12 months). The CCR of hypertension was assessed using a multivariate adjusted Cox proportional hazards regression model. After a mean follow-up of 21.18 ± 5.35 months, the CCR was significantly higher in the surgery than medication group (85.7% vs. 13.3%, respectively; p < 0.001). Before adjustment for covariates, the CCR of hypertension in patients who underwent LA was 7.75 times higher than that in patients who underwent medical treatment (95% CI, 2.33-25.78; p = 0.001); significant results were also shown in the adjusted models. Systolic and diastolic BP were also lower in the surgery than medication group (120.3 ± 12.99 vs. 133.54 ± 16.60 and 79.00 ± 7.62 vs. 87.35 ± 12.36 mmHg, respectively; p = 0.01 for both), as was the number of antihypertensive drugs (0.19 ± 0.51 vs. 2.33 ± 0.78, respectively; p < 0.001). The rate of hypokalemia was not significantly different between the two groups (0.0% vs. 13.3%, respectively; p = 0.13). In conclusion, AVS plays an essential role in the subtype diagnosis of PA, and surgical candidates with AVS-proven unilateral PA should be highly suggested to undergo LA.
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Glándulas Suprarrenales , Hiperaldosteronismo , Adrenalectomía , Aldosterona , Presión Sanguínea , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Anemia is a common comorbidity of patients with Takayasu arteritis (TA). This study evaluated the prevalence, clinical characteristics, and treatment in Chinese TA patients with anemia. METHODS: This retrospective study included 533 consecutive patients hospitalized for TA from January 2009 to April 2018. Anemia was diagnosed on the basis of hemoglobin level, according to World Health Organization criteria. RESULTS: A total of 194 patients (36.4%) were diagnosed with anemia. Most had mild anemia (177, 91.2%). Female patients were predominant (92.8% of anemic patients). Normocytic anemia (62.9%) was the most common pattern. Anemic patients were more likely than non-anemic patients to have dizziness (29.4% vs. 21.2%), low body mass index (22.0 ± 3.6 vs. 22.9 ± 3.4 kg/m2), and active disease stage (64.9% vs. 50.1%); pulmonary involvement (12.4% vs. 26.8%), pulmonary hypertension (12.9% vs. 20.1%) and pulmonary hypertensive-target drugs (2.8% vs. 11.6%) were less common among anemic than non-anemic patients (all P < 0.05). Larger left ventricular end-diastolic diameter and lower left ventricular ejection fraction were observed in anemic patients. Over a median follow-up of four months, the increase of hemoglobin in anemic patients was associated with the use of iron supplementation. CONCLUSIONS: Anemia is a very common concurrent condition in TA, especially in young, female patients. Patients with anemia are more likely to be in the active disease stage. Iron supplementation helps increase hemoglobin.
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BACKGROUND: Tuberculosis (TB) infection has been reported to have a possible relationship with the occurrence and clinical course of Takayasu arteritis (TA). We aimed to describe the characteristics of TB in a large population of TA patients. METHODS: We included a total of 1105 patients with TA, who were hospitalized between January 1992 and December 2017. Comparisons of clinical features were made according to the presence of TB. RESULTS: Among the 1105 patients, 109 (9.9%) had TB, including 53 patients (48.6%) diagnosed with TB before the onset of TA, 23 (21.1%) with a concurrent diagnosis of TB and TA, and 24 patients (22.0%) who developed TB after TA. Pulmonary TB was the most frequently identified (97 patients, 89.0%). Patients with TB had more frequent involvement of the pulmonary artery and experienced more chest discomfort and constitutional symptoms but had less interventional treatment. Demographic characteristics, comorbid diseases, and use of steroids were similar between patients with and without TB. CONCLUSIONS: The proportion of Chinese TA patients with TB was not low, and about half of the patients had TB before TA. Pulmonary TB was the most common. Pulmonary artery involvement and pulmonary hypertension was more frequent in TA patients with TB.
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BACKGROUND/AIMS: Liddle syndrome (LS) is a rare autosomal dominant disease caused by mutations in genes coding for epithelial sodium channel (ENaC) subunits. The aim of this study was to identify the mutation responsible for the LS in an extended Chinese family. METHODS: DNA samples from the proband with early-onset, treatment-resistant hypertension, and hypokalemia and 19 additional relatives were all sequenced for mutations in exon 13 of the ß-ENaC and γ-ENaC genes, using amplification by polymerase chain reaction and direct DNA sequencing. RESULTS: Genetic testing of exon 13 of SCNN1B revealed duplication of guanine into a string of 3 guanines located at codon 602. This frameshift mutation is predicted to generate a premature stop codon at position 607, resulting in truncated ß-ENaC lacking the remaining 34 amino acids, including the crucial PY motif. Among a total of 9 participants with the identical mutation, different phenotypes were identified. Tailored treatment with amiloride was safe and effective in alleviating disease symptoms in LS. No mutation of SCNN1G was identified in any of the examined participants. CONCLUSIONS: We report here a family affected by LS harboring a frameshift mutation (c.1806dupG) with a premature stop codon deleting the PY motif of ß-ENaC. Our study demonstrates that the earlier LS patients are diagnosed by genetic testing and treated with tailored medication, the greater the likelihood of preventing or minimizing complications in the vasculature and target organs.
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Canales Epiteliales de Sodio/genética , Mutación del Sistema de Lectura/genética , Pruebas Genéticas/métodos , Síndrome de Liddle/diagnóstico , Adolescente , Adulto , Anciano , Pueblo Asiatico , Niño , Preescolar , Femenino , Humanos , Síndrome de Liddle/patología , Masculino , Persona de Mediana Edad , Fenotipo , Adulto JovenRESUMEN
Tree shrews are most closely related to the primates and so possess a number of advantages in experimental studies; they have been used as an animal model in bacterial and virus infection, cancer, endocrine system disease, and certain nervous system diseases. Their olfactory ensheathing cells (OECs) are able to release several cytokines to promote neuronal survival, regeneration and remyelination. The present study used western blot analysis to identify antibody specificity in protein extracts from whole tree shrew brains to identify the specificity of p75 nerve growth factor receptor (NGFR) derived from rabbits (75 kDa). OECs were cultured and isolated, then stained and identified using the antibodies for p75NGFR. To investigate the capacity of OECs to express cytokines and growth factors, microarray technology was used, and the analysis revealed that OECs were able to express 9,821 genes. Of these genes, 44 genes were from the neurotrophic factor family, which may indicate their potential in transplantation in vivo. The present study considered the function of OECs as revealed by other studies, and may contribute to future research.
Asunto(s)
Neuronas/metabolismo , Bulbo Olfatorio/metabolismo , Receptor de Factor de Crecimiento Nervioso/genética , Tupaia/genética , Animales , Anticuerpos/inmunología , Citocinas/biosíntesis , Regulación de la Expresión Génica/genética , Humanos , Neuroglía/metabolismo , Bulbo Olfatorio/citología , Regeneración/genética , Remielinización/genética , Tupaia/crecimiento & desarrollo , Tupaia/metabolismoRESUMEN
BACKGROUND: Neuroblastoma (NB) displays the most heterogeneity in clinical manifestation. The insulin-like growth factor 1 receptor (IGF1R) has long been recognized for its role in tumourigenesis and growth. The IGF/IGF1R pathway is important in maintaining cell survival. It is reported that IGF1R participates in the occurrence of NB, but the mechanism is still unclear. METHODS: Human NB cell lines IMR-32 and SH-SY5Y were recruited in this study. IGF1R was knocked down by transfection with short hairpin RNA. Signal transducer and activator of transcription 3 (STAT3) expression was inhibited by Cryptotanshinone treatment. Cell proliferation, migration, and invasion were determined by MTT assay, wound healing assay, and cell invasion assay, respectively. The cancer stem cell properties were characterized by tumour sphere formation assay and colony formation assay. The mRNA and protein expression levels of related proteins were detected by RT-PCR and Western blot, respectively. RESULTS: The knockdown of IGF1R inhibits NB cell tumourigenesis and the epithelial-mesenchymal transition (EMT) of NB cells. Additionally, IGF1R was found to stimulate cancer stem cell-like properties in NPC cells. The knockdown of IGF1R significantly reduced the phosphorylation of AKT, and STAT3, indicating that the activation of the AKT and STAT3 pathways was inhibited by IGF1R knockdown. Furthermore, IGF1R was demonstrated to stimulate cancer stem cell-like properties in NB cells via the regulation of the STAT3/AKT axis. CONCLUSION: IGF1R promotes cancer stem cell properties to facilitate EMT in neuroblastoma via the STAT3/AKT axis.