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This study aimed to investigate the expression and significance of serum procalcitonin (PCT), leukotriene B4 (LTB4), Serum amyloid A (SAA), and C-reactive protein (CRP) in children with different types of pneumonia caused by different pathogenic infections. One hundred and one children with pneumonia admitted to The Fifth People Hospital of Zhuhai from July 2019 to June 2020 were enrolled and divided into 38 cases in the bacterial group, 30 cases in the mycoplasma group, and 33 cases in the virus group according to the different types of pathogens. The patients were divided into 42 cases in the noncritical group, 33 cases in the critical group, and 26 cases in the very critical group according to the pediatric clinical illness score (PCIS), and 30 healthy children were selected as the control group during the same period. Comparison of serum PCT, SAA: bacterial groupâ >â mycoplasma groupâ >â viral groupâ >â control group with significant differences (P < .05). Receiver operator characteristic (ROC) analysis showed that the area under the curves (AUCs) of serum PCT, LTB4, SAA, and CRP for the diagnosis of bacterial pneumonia were 1.000, 0.531, 0.969, and 0.833, respectively, and the AUCs for the diagnosis of mycoplasma pneumonia were 0.653, 0.609, 0.547, and 0.652, respectively, and the AUCs for the diagnosis of viral pneumonia were 0.888, 0.570, 0.955, and 1.000, respectively. Comparison of serum PCT, LTB4, SAA: very critical groupâ >â critical groupâ >â noncritical groupâ >â control group, with significant differences (P < .05). Serum PCT, LTB4, and SAA were negatively correlated with PCIS score by Pearson analysis (P < .05). Serum PCT and SAA showed diagnostic value for bacterial pneumonia, and serum SAA and CRP showed diagnostic value for viral pneumonia; serum PCT, LTB4, and SAA correlate with severity of disease and show higher expression with worsening of the condition.
Asunto(s)
Biomarcadores , Proteína C-Reactiva , Leucotrieno B4 , Neumonía Bacteriana , Polipéptido alfa Relacionado con Calcitonina , Proteína Amiloide A Sérica , Humanos , Proteína C-Reactiva/análisis , Proteína Amiloide A Sérica/análisis , Proteína Amiloide A Sérica/metabolismo , Masculino , Femenino , Polipéptido alfa Relacionado con Calcitonina/sangre , Preescolar , Neumonía Bacteriana/sangre , Neumonía Bacteriana/diagnóstico , Niño , Leucotrieno B4/sangre , Biomarcadores/sangre , Curva ROC , Neumonía por Mycoplasma/sangre , Neumonía por Mycoplasma/diagnóstico , Lactante , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía/sangre , Neumonía/diagnósticoRESUMEN
The acidity of Chinese dwarf cherry [Cerasus humilis (Bge.) Sok.] fruits is a key factor affecting the sensory quality of fruits, and it undergoes great changes during development. The molecular mechanisms of these changes are still unclear. In this study, fruits of high-acid 'Nongda4' and low-acid 'DS-1' varieties of Chinese dwarf cherry were used to determine the acid content at different developmental stages. We used transcriptome profiles to identify key genes related to organic acid metabolism and construct their co-expression networks, and we studied the expression patterns of key genes in 36 Chinese dwarf cherry accessions. The titratable acid content of both 'DS-1' and 'Nongda4' fruits first increased and then decreased during fruit development; however, the titratable acid content of 'DS-1' fruits changed to a minor extent. The organic acid content of 'Nongda4' was significantly higher than that of 'DS-1'. The organic acids in mature fruits were mainly malic acid and citric acid. Analysis of the differentially expressed genes related to organic acid metabolism revealed six key genes, including two MDH genes, one tDT gene, one ME gene, one PEPCK gene, and one VHA gene. Weighted gene co-expression network association analysis revealed four modules that were significantly correlated with organic acid content, and 10 key genes with high connectivity among these four modules were screened, including two PK genes, two MDH genes, two ME genes, one PEPCK gene, one VHA gene, one PEPC gene, and one tDT gene. According to the expression patterns of genes in different Chinese dwarf cherry accessions, seven genes were confirmed to represent key genes related to the regulation of organic acids during Chinese dwarf cherry fruit development. These results provide a foundation for further studies on the molecular mechanism of organic acid accumulation in Chinese dwarf cherry fruit.
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The inhibition of Type II angiotensin II receptor (AT2R) or BK2R (bradykinin type II receptor) stimulates basolateral Kir4.1/Kir5.1 in the distal convoluted tubule (DCT) and activates thiazide-sensitive NCC (Na-Cl cotransporter). The aim of the present study is to examine the role of AT2R and BK2R in mediating the effect of HK (high dietary K+) intake on the basolateral K+ channels, NCC, and renal K+ excretion. Feeding mice (male and female) with HK diet for overnight significantly decreased the basolateral K+ conductance, depolarized the DCT membrane, diminished the expression of pNCC (phosphorylated NCC) and tNCC (total NCC), and decreased thiazide-sensitive natriuresis. Overnight HK intake also increased the expression of cleaved ENaC-α and -γ subunits but had no effect on NKCC2 expression. Pretreatment of the mice (male and female) with PD123319 and HOE140 stimulated the expression of tNCC and pNCC, augmented hydrochlorothiazide-induced natriuresis, and increased the negativity of the DCT membrane. The deletion of Kir4.1 not only decreased the NCC activity but also abolished the stimulatory effect of PD123319 and HOE140 perfusion on NCC activity. Moreover, the effect of overnight HK loading on Kir4.1/Kir5.1 in the DCT and NCC expression/activity was compromised in the mice treated with AT2R/BK2R antagonists. Renal clearance study showed that inhibition of AT2R and BK2R impairs renal K+ excretion in response to overnight HK loading, and the mice pretreated with PD123319 and HOE140 were hyperkalemic during HK intake. We conclude that synergistic activation of AT2R and BK2R is required for the effect of overnight HK diet on Kir4.1/Kir5.1 in the DCT and NCC activity.
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Hiperpotasemia/metabolismo , Túbulos Renales Distales/metabolismo , Potasio/metabolismo , Receptor de Bradiquinina B2/metabolismo , Receptores de Angiotensina/metabolismo , Animales , Transporte Biológico , Modelos Animales de Enfermedad , Femenino , Hiperpotasemia/patología , Immunoblotting , Túbulos Renales Distales/patología , Masculino , Potenciales de la Membrana , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor de Bradiquinina B2/efectos de los fármacos , Receptores de Angiotensina/efectos de los fármacosRESUMEN
The present study aimed to investigate the effect of ß-asarone treatment in a rat model of depression induced by chronic unpredictable mild stress (CUMS) and to further explore the underlying molecular mechanisms. A rat model of depression was established by subjecting rat to CUMS and treated with various concentrations of ß-asarone (12.5, 25 and 50 mg/kg/day) and fluoxetine (20 mg/kg/day). Next, behavioral tests, including an open field, sucrose preference and forced swimming tests, were performed. In addition, the apoptosis of hippocampal neuronal cells was determined by flow cytometry, gene expression levels were detected by reverse transcription-quantitative polymerase chain reaction and protein levels were determined by western blot assay. The results revealed that ß-asarone significantly mitigated CUMS-induced depression-like behavior, evidenced by the increased sucrose intake, crossing and rearing numbers, and decreased immobility time in the forced swimming test. Furthermore, ß-asarone significantly decreased the apoptosis rate of hippocampal neuronal cells in rats subjected to CUMS. ß-asarone was also found to enhance CREB, BDNF, Trk-B and Bcl-2 levels, and reduce Bad level in the hippocampus of CUMS-treated rats. In addition, the activation of extracellular signal-regulated kinase pathway inhibited by CUMS was promoted by ß-asarone treatment. In conclusion, the present study findings indicated the antidepressant-like effects of ß-asarone on CUMS-induced depression in rats.
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Recent studies have identified certain non-coding RNAs (ncRNAs) as biomarkers of disease progression. Glioma is the most common primary intracranial cancer, with high mortality. Here, we developed a prognostic signature for prediction of overall survival (OS) of glioma patients by analyzing ncRNA expression profiles. We downloaded gene expression profiles of glioma patients along with their clinical information from the Gene Expression Omnibus and extracted ncRNA expression profiles via a microarray annotation file. Correlations between ncRNAs and glioma patients' OS were first evaluated through univariate Cox regression analysis and a permutation test, followed by random survival forest analysis for further screening of valuable ncRNA signatures. Prognostic signatures could be established as a risk score formula by including ncRNA signature expression values weighted by their estimated regression coefficients. Patients could be divided into high risk and low risk subgroups by using the median risk score as cutoff. As a result, glioma patients with a high risk score tended to have shorter OS than those with low risk scores, which was confirmed by analyzing another set of glioma patients in an independent dataset. Additionally, gene set enrichment analysis showed significant enrichment of cancer development-related biological processes and pathways. Our study may provide further insights into the evaluation of glioma patients' prognosis.
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Neoplasias Encefálicas/genética , Glioma/genética , ARN no Traducido/análisis , Transcriptoma/genética , Arildialquilfosfatasa/genética , Neoplasias Encefálicas/epidemiología , Endopeptidasas/genética , Glioma/epidemiología , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Análisis de SupervivenciaRESUMEN
Basolateral inwardly-rectifying K+ channels (Kir) play an important role in the control of resting membrane potential and transepithelial voltage, thereby modulating water and electrolyte transport in the distal part of nephron. Kir4.1 and Kir4.1/Kir5.1 heterotetramer are abundantly expressed in the basolateral membrane of late thick ascending limb (TAL), distal convoluted tubule (DCT), connecting tubule (CNT) and cortical collecting duct (CCD). Loss-of-function mutations in KCNJ10 cause EAST/SeSAME syndrome in humans associated with epilepsy, ataxia, sensorineural deafness and water-electrolyte metabolism imbalance, which is characterized by salt wasting, hypomagnesaemia, hypokalaemia and metabolic alkalosis. In contrast, mice lacking Kir5.1 have severe renal phenotype apart from hypokalaemia such as high chlorine metabolic acidosis and hypercalcinuria. The genetic knockout or functional inhibition of Kir4.1 suppresses Na-Cl cotransporter (NCC) expression and activity in the DCT. However, the downregulation of Kir4.1 increases epithelial Na+ channel (ENaC) expression in the collecting duct. Recently, factors regulating expression and activity of Kir4.1 and Kir4.1/Kir5.1 were identified, such as cell acidification, dopamine, insulin and insulin-like growth factor-1. The involved mechanisms include PKC, PI3K, Src family protein tyrosine kinases and WNK-SPAK signal transduction pathways. Here we review the progress of renal tubule basolateral Kir, and mainly discuss the function and regulation of Kir4.1 and Kir4.1/Kir5.1.
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Túbulos Renales/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , Animales , Membrana Celular , Humanos , Túbulos Renales Distales , Potenciales de la Membrana , Ratones , Canal Kir5.1RESUMEN
Stimulation of BK2R (bradykinin [BK] B2 receptor) has been shown to increase renal Na+ excretion. The aim of the present study is to explore the role of BK2R in regulating Kir4.1 and NCC (NaCl cotransporter) in the distal convoluted tubule (DCT). Immunohistochemical studies demonstrated that BK2R was highly expressed in both apical and lateral membrane of Kir4.1-positive tubules, such as DCT. Patch-clamp experiments demonstrated that BK inhibited the basolateral 40-pS K+ channel (a Kir4.1/5.1 heterotetramer) in the DCT, and this effect was blocked by BK2R antagonist but not by BK1R (BK B1 receptor) antagonist. Whole-cell recordings also demonstrated that BK decreased the basolateral K+ conductance of the DCT and depolarized the membrane. Renal clearance experiments showed that BK increased urinary Na+ and K+ excretion. However, the BK-induced natriuretic effect was completely abolished in KS-Kir4.1 KO (kidney-specific conditional Kir4.1 knockout) mice, suggesting that Kir4.1 activity is required for BK-induced natriuresis. The continuous infusion of BK with osmotic pump for 3 days decreased the basolateral K+ conductance and the negativity of the DCT membrane. Western blot showed that infusion of BK decreased the expression of total NCC and phosphorylated NCC. Renal clearance experiments demonstrated that thiazide-induced natriuresis was blunted in the mice receiving BK infusion, suggesting that BK inhibited NCC function. Consequently, mice receiving BK infusion for 3 days were hypokalemic. We conclude that stimulation of BK2R inhibits NCC activity, increases urinary K+ excretion, and causes mice hypokalemia and that Kir4.1 is required for BK2R-mediated stimulation of urinary Na+ and K+ excretion.