RESUMEN
OBJECTIVE: In the context of postoperative anal pain, understanding the intricate mechanisms and effective interventions is paramount. This study investigates the role of Muscarinic Acetylcholine Receptors (mAChRs) and the IP3-Ca2+-CaM signaling pathway in a rat model of postoperative anal pain, exploring the potential analgesic effects of electroacupuncture. METHODS: Comprehensive approaches involving mechanical sensitivity assays, Western blotting, immunohistochemistry, and intracellular calcium concentration measurement were used. RESULTS: The authors found elevated mAChRs expression in the postoperative pain model. Antagonizing mAChRs reduced pain sensitivity and attenuated the IP3-Ca2+-CaM pathway. Remarkably, electroacupuncture treatment further mitigated pain, potentially by suppressing this signaling cascade. INTERPRETATION: These findings reveal a novel connection between mAChRs and the IP3-Ca2+-CaM pathway in postoperative anal pain and suggest electroacupuncture as a promising avenue for pain relief through these mechanisms, offering insights into innovative strategies for postoperative pain management.
Asunto(s)
Electroacupuntura , Hemorreoidectomía , Dolor Postoperatorio , Ratas Sprague-Dawley , Receptores Muscarínicos , Transducción de Señal , Animales , Electroacupuntura/métodos , Dolor Postoperatorio/terapia , Masculino , Hemorreoidectomía/métodos , Receptores Muscarínicos/metabolismo , Puntos de Acupuntura , Canal Anal/cirugía , Modelos Animales de Enfermedad , Western Blotting , Ratas , Inmunohistoquímica , Calcio/metabolismo , Resultado del TratamientoRESUMEN
The genomes of living lungfishes can inform on the molecular-developmental basis of the Devonian sarcopterygian fish-tetrapod transition. We de novo sequenced the genomes of the African (Protopterus annectens) and South American lungfishes (Lepidosiren paradoxa). The Lepidosiren genome (about 91 Gb, roughly 30 times the human genome) is the largest animal genome sequenced so far and more than twice the size of the Australian (Neoceratodus forsteri)1 and African2 lungfishes owing to enlarged intergenic regions and introns with high repeat content (about 90%). All lungfish genomes continue to expand as some transposable elements (TEs) are still active today. In particular, Lepidosiren's genome grew extremely fast during the past 100 million years (Myr), adding the equivalent of one human genome every 10 Myr. This massive genome expansion seems to be related to a reduction of PIWI-interacting RNAs and C2H2 zinc-finger and Krüppel-associated box (KRAB)-domain protein genes that suppress TE expansions. Although TE abundance facilitates chromosomal rearrangements, lungfish chromosomes still conservatively reflect the ur-tetrapod karyotype. Neoceratodus' limb-like fins still resemble those of their extinct relatives and remained phenotypically static for about 100 Myr. We show that the secondary loss of limb-like appendages in the Lepidosiren-Protopterus ancestor was probably due to loss of sonic hedgehog limb-specific enhancers.
Asunto(s)
Evolución Molecular , Peces , Genoma , Animales , Humanos , África , Aletas de Animales/anatomía & histología , Australia , Elementos Transponibles de ADN/genética , ADN Intergénico/genética , Elementos de Facilitación Genéticos/genética , Extinción Biológica , Peces/anatomía & histología , Peces/clasificación , Peces/genética , Reordenamiento Génico/genética , Genoma/genética , Tamaño del Genoma , Proteínas Hedgehog/genética , Intrones , Cariotipo , Filogenia , ARN de Interacción con Piwi/genética , América del Sur , Factores de Tiempo , Dedos de Zinc/genéticaRESUMEN
The importance of glucokinase (GK) in the regulation of insulin secretion has been highlighted by the phenotypes of individuals with activating and inactivating mutations in the glucokinase gene (GCK). Here we report 10 individuals with congenital hyperinsulinism (HI) caused by eight unique activating mutations of GCK. Six are novel and located near previously identified activating mutations sites. The first recognized episode of hypoglycemia in these patients occurred between birth and 24 years, and the severity of the phenotype was also variable. Mutant enzymes were expressed and purified for enzyme kinetics in vitro. Mutant enzymes had low glucose half-saturation concentration values and an increased enzyme activity index compared with wild-type GK. We performed functional evaluation of islets from the pancreata of three children with GCK-HI who required pancreatectomy. Basal insulin secretion in perifused GCK-HI islets was normal, and the response to glyburide was preserved. However, the threshold for glucose-stimulated insulin secretion in perifused glucokinase hyperinsulinism (GCK-HI) islets was decreased, and glucagon secretion was greatly suppressed. Our evaluation of novel GCK disease-associated mutations revealed that the detrimental effects of these mutations on glucose homeostasis can be attributed not only to a lowering of the glucose threshold of insulin secretion but also to a decreased counterregulatory glucagon secretory response. ARTICLE HIGHLIGHTS: Our evaluation of six novel and two previously published activating GCK mutations revealed that the detrimental effects of these mutations on glucose homeostasis can be attributed not only to a lowering of the glucose threshold of insulin secretion but also to a decreased counterregulatory glucagon secretory response. These studies provide insights into the pathophysiology of GCK-hyperinsulinism and the dual role of glucokinase in ß-cells and α-cells to regulate glucose homeostasis.
Asunto(s)
Hiperinsulinismo Congénito , Hiperinsulinismo , Niño , Humanos , Glucoquinasa/genética , Glucagón , Hiperinsulinismo Congénito/genética , Hiperinsulinismo/genética , Glucosa , Mutación , FenotipoRESUMEN
SUMMARY: To investigate changes of MMP-9 in the rat spleen and hypoxia-induced microvascular basement membrane under high altitude hypoxia. Thirty male specific pathogen-free Sprague Dawley rats were randomly divided into control and hypoxia groups, with 15 rats in each group. The rats in the control group were placed in Dingxi City, Gansu Province (2080 m above sea level) for 30 days. Rats in the hypoxia group were raised in a hypoxic environment in Maduo County, Qinghai Province (4300 m above sea level), for 30 days to establish a hypoxic rat model. Routine blood tests, MMP-9 mRNA, MMP-9 protein, and the spleen microvascular basement membrane were detected. (1) Compared with the control group, the red blood cell count, hemoglobin, and hematocrit levels of the rats in the hypoxia group were all increased; thus, a hypoxia model was successfully established. (2) Compared with the control group, the expression of MMP-9 mRNA and protein was significantly higher in the spleen of rats in the hypoxic group, and the difference was statistically significant (P <0.05). (3) Compared with the control group, the blood vessel basement membrane in the spleen of the hypoxia group was degraded. Under natural low air pressure and high altitude conditions, the expression of MMP-9 in rat spleen tissue increases and participates in the degradation of the microvascular basement membrane.
El objetivo de este trabajo fue investigar los cambios de la MMP-9 en el bazo de la rata y la membrana basal microvascular inducida bajo hipoxia a gran altura. Treinta ratas macho Sprague Dawley, libres de patógenos específicos, se dividieron aleatoriamente en dos grupos de 15 ratas cada uno, un grupo control y un grupo hipoxia. Durante 30 días las ratas del grupo control estuvieron en la ciudad de Dingxi, provincia de Gansu (2080 m sobre el nivel del mar). Las ratas del grupo de hipoxia se criaron en un entorno hipóxico en el condado de Maduo, provincia de Qinghai (4300 m sobre el nivel del mar), durante 30 días para establecer un modelo de rata hipóxica. Se realizaron análisis de sangre de rutina, ARNm de MMP-9, proteína MMP-9 y de la membrana basal microvascular del bazo. En comparación con el grupo control, el recuento de glóbulos rojos, la hemoglobina y los niveles de hematocrito de las ratas del grupo de hipoxia aumentaron; por lo tanto, se estableció con éxito un modelo de hipoxia. En comparación con el grupo control, la expresión de ARNm y proteína de MMP-9 fue significativamente mayor en el bazo de las ratas del grupo hipóxico, siendo la diferencia estadísticamente significativa (P <0,05). En comparación con el grupo control, la membrana basal de los vasos sanguíneos estaba degradada en el bazo del grupo hipoxia. En condiciones naturales de baja presión atmosférica y gran altitud, la expresión de MMP-9 en el tejido del bazo de la rata aumenta y participa en la degradación de la membrana basal microvascular.
Asunto(s)
Animales , Masculino , Ratas , Bazo/patología , Membrana Basal/patología , Metaloproteinasa 9 de la Matriz , Mal de Altura , Western Blotting , Ratas Sprague-Dawley , Microscopía Electrónica de Transmisión , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: To investigate the value of a nomogram based on multiparametric and multiregional MR images to predict Isocitrate Dehydrogenase-1 (IDH1) gene mutations in glioma. DATA AND METHODS: The authors performed a retrospective analysis of 110 MR images of surgically confirmed pathological gliomas; 33 patients with IDH1 gene Mutation (IDH1-M) and 77 patients with Wild-type IDH1 (IDH1-W) were divided into training and validation sets in a 7:3 ratio. The clinical features were statistically analyzed using SPSS and R software. Three glioma regions (rCET, rE, rNEC) were outlined using ITK-SNAP software and projected to four conventional sequences (T1, T2, Flair, T1C) for feature extraction using AI-Kit software. The extracted features were screened using R software. A logistic regression model was established, and a nomogram was generated using the selected clinical features. Eight models were developed based on different sequences and ROIs, and Receiver Operating Characteristic (ROC) curves were used to evaluate the predictive efficacy. Decision curve analysis was performed to assess the clinical usefulness. RESULTS: Age was selected with Radscore to construct the nomogram. The Model 1 AUC values based on four sequences and three ROIs were the highest in these models, at 0.93 and 0.89, respectively. Decision curve analysis indicated that the net benefit of model 1 was higher than that of the other models for most Pt-values. CONCLUSION: A nomogram based on multiparametric and multiregional MR images can predict the mutation status of the IDH1 gene accurately.
Asunto(s)
Glioma , Nomogramas , Humanos , Estudios Retrospectivos , Glioma/diagnóstico por imagen , Glioma/genética , Curva ROC , Mutación/genética , Imagen por Resonancia Magnética/métodos , Isocitrato Deshidrogenasa/genéticaRESUMEN
OBJECTIVE: To evaluate genetic evaluation practices in newborns with the most common birth defect, congenital heart defects (CHD), we determined the prevalence and the yield of genetic evaluation across time and across patient subtypes, before and after implementation of institutional genetic testing guidelines. STUDY DESIGN: This was a retrospective, cross-sectional study of 664 hospitalized newborns with CHD using multivariate analyses of genetic evaluation practices across time and patient subtypes. RESULTS: Genetic testing guidelines for hospitalized newborns with CHD were implemented in 2014, and subsequently genetic testing increased (40% in 2013 and 75% in 2018, OR 5.02, 95% CI 2.84-8.88, P < .001) as did medical geneticists' involvement (24% in 2013 and 64% in 2018, P < .001). In 2018, there was an increased use of chromosomal microarray (P < .001), gene panels (P = .016), and exome sequencing (P = .001). The testing yield was high (42%) and consistent across years and patient subtypes analyzed. Increased testing prevalence (P < .001) concomitant with consistent testing yield (P = .139) added an estimated 10 additional genetic diagnoses per year, reflecting a 29% increase. CONCLUSIONS: In patients with CHD, yield of genetic testing was high. After implementing guidelines, genetic testing increased significantly and shifted to newer sequence-based methods. Increased use of genetic testing identified more patients with clinically important results with potential to impact patient care.
Asunto(s)
Pruebas Genéticas , Cardiopatías Congénitas , Humanos , Recién Nacido , Estudios Retrospectivos , Estudios Transversales , Pruebas Genéticas/métodos , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/epidemiología , Análisis por MicromatricesRESUMEN
Previous studies have shown that peripheral nerve injury can lead to abnormal dendritic spine remodeling in spinal dorsal horn neurons. Inhibition of abnormal dendritic spine remodeling can relieve neuropathic pain. Electroacupuncture (EA) has a beneficial effect on the treatment of neuropathic pain, but the specific mechanism remains unclear. Evidence has shown that slit-robo GTPase activating protein 3 (srGAP3) and Rho GTPase (Rac1) play very important roles in dendritic spine remodeling. Here, we used srGAP3 siRNA and Rac1 activator CN04 to confirm the relationship between SrGAP3 and Rac1 and their roles in improving neuropathic pain with EA. Spinal nerve ligation (SNL) was used as the experimental model, and thermal withdrawal latency (TWL), mechanical withdrawal threshold (MWT), Western blotting, immunohistochemistry and Golgi-Cox staining were used to examine changes in behavioral performance, protein expression and dendritic spines. More dendritic spines and higher expression levels of srGAP3 were found in the initial phase of neuropathic pain. During the maintenance phase, dendritic spines were more mature, which was consistent with lower expression levels of srGAP3 and higher expression levels of Rac1-GTP. EA during the maintenance phase reduced the density and maturity of dendritic spines of rats with SNL, increased the levels of srGAP3 and reduced the levels of Rac1-GTP, while srGAP3 siRNA and CN04 reversed the therapeutic effects of EA. These results suggest that dendritic spines have different manifestations in different stages of neuropathic pain and that EA may inhibit the abnormal dendritic spine remodeling by regulating the srGAP3/Rac1 signaling pathway to alleviate neuropathic pain.
Asunto(s)
Electroacupuntura , Neuralgia , Animales , Ratas , Espinas Dendríticas/metabolismo , GTP Fosfohidrolasas/metabolismo , Guanosina Trifosfato/metabolismo , Neuralgia/metabolismo , Neuralgia/terapia , Proteína de Unión al GTP rac1/metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Nervios Espinales/metabolismoRESUMEN
Abstract Objective To investigate the value of a nomogram based on multiparametric and multiregional MR images to predict Isocitrate Dehydrogenase-1 (IDH1) gene mutations in glioma. Data and methods The authors performed a retrospective analysis of 110 MR images of surgically confirmed pathological gliomas; 33 patients with IDH1 gene Mutation (IDH1-M) and 77 patients with Wild-type IDH1 (IDH1-W) were divided into training and validation sets in a 7:3 ratio. The clinical features were statistically analyzed using SPSS and R software. Three glioma regions (rCET, rE, rNEC) were outlined using ITK-SNAP software and projected to four conventional sequences (T1, T2, Flair, T1C) for feature extraction using AI-Kit software. The extracted features were screened using R software. A logistic regression model was established, and a nomogram was generated using the selected clinical features. Eight models were developed based on different sequences and ROIs, and Receiver Operating Characteristic (ROC) curves were used to evaluate the predictive efficacy. Decision curve analysis was performed to assess the clinical usefulness. Results Age was selected with Radscore to construct the nomogram. The Model 1 AUC values based on four sequences and three ROIs were the highest in these models, at 0.93 and 0.89, respectively. Decision curve analysis indicated that the net benefit of model 1 was higher than that of the other models for most Pt-values. Conclusion A nomogram based on multiparametric and multiregional MR images can predict the mutation status of the IDH1 gene accurately.
RESUMEN
Previous studies have shown that peripheral nerve injury can lead to abnormal dendritic spine remodeling in spinal dorsal horn neurons. Inhibition of abnormal dendritic spine remodeling can relieve neuropathic pain. Electroacupuncture (EA) has a beneficial effect on the treatment of neuropathic pain, but the specific mechanism remains unclear. Evidence has shown that slit-robo GTPase activating protein 3 (srGAP3) and Rho GTPase (Rac1) play very important roles in dendritic spine remodeling. Here, we used srGAP3 siRNA and Rac1 activator CN04 to confirm the relationship between SrGAP3 and Rac1 and their roles in improving neuropathic pain with EA. Spinal nerve ligation (SNL) was used as the experimental model, and thermal withdrawal latency (TWL), mechanical withdrawal threshold (MWT), Western blotting, immunohistochemistry and Golgi-Cox staining were used to examine changes in behavioral performance, protein expression and dendritic spines. More dendritic spines and higher expression levels of srGAP3 were found in the initial phase of neuropathic pain. During the maintenance phase, dendritic spines were more mature, which was consistent with lower expression levels of srGAP3 and higher expression levels of Rac1-GTP. EA during the maintenance phase reduced the density and maturity of dendritic spines of rats with SNL, increased the levels of srGAP3 and reduced the levels of Rac1-GTP, while srGAP3 siRNA and CN04 reversed the therapeutic effects of EA. These results suggest that dendritic spines have different manifestations in different stages of neuropathic pain and that EA may inhibit the abnormal dendritic spine remodeling by regulating the srGAP3/Rac1 signaling pathway to alleviate neuropathic pain.
Asunto(s)
Animales , Ratas , Electroacupuntura , Neuralgia/metabolismo , Neuralgia/terapia , Nervios Espinales/metabolismo , Transducción de Señal , Ratas Sprague-Dawley , Proteína de Unión al GTP rac1/metabolismo , Espinas Dendríticas/metabolismo , GTP Fosfohidrolasas/metabolismo , Guanosina Trifosfato/metabolismoRESUMEN
SUMMARY: The plantaris muscle is located between the soleus and gastrocnemius muscles, within the posterior calf group. Due to degeneration and its loss of plantar-flexion function, the muscle is vestigial in human beings, but it retains clinical significance. Few cases of variation in the plantaris muscle have been reported, and this, therefore, appears to be rare. Nonetheless, absence of this muscle was identified via the dissection of a left lower limb (male), which also indicated the absence of an attachment in the usual position. The present report, which addresses such variation, may provide both inspiration and reference points for the clinical treatment of so-called "tennis leg", and for the use of plantaris muscle for the purposes of clinical, autologous graft repair.
RESUMEN: El músculo plantar se ubica entre los músculos sóleo y gastrocnemio, dentro del grupo posterior de la pierna. Debido a la degeneración y la pérdida de la función de flexión plantar, el músculo es un vestigio en los seres humanos, pero conserva su importancia clínica. Se han informado pocos casos de variación en el músculo plantar y, por lo tanto, esto parece ser raro. No obstante, se observó la ausencia de este músculo durante la disección de un miembro inferior izquierdo (masculino). El presente informe, que aborda dicha variación, puede proporcionar puntos de referencia para el tratamiento clínico de la llamada "pierna de tenista" y para el uso del músculo plantar con fines de reparación clínica con injerto autólogo.
Asunto(s)
Humanos , Masculino , Adulto , Músculo Esquelético/anatomía & histología , Variación AnatómicaRESUMEN
BACKGROUND: Importin 7 (IPO7) belongs to the Importin ß family and is implicated in the progression of diverse human malignancies. This work is performed to probe the role of IPO7 in pancreatic cancer development and its potential downstream mechanisms. METHODS: IPO7 expression in PC and paracancerous tissues were measured using Immunohistochemistry (IHC) staining and qRT-PCR. Western blotting was utilized to detect the expression level of IPO7 in PC cells and immortalize the pancreatic ductal epithelial cell line. After constructing the IPO7 overexpression and knockdown models, the effect of IPO7 on the proliferation of PC cells was analyzed by the CCK-8 and EdU assay. The migration and invasion of PC cells were examined by wound healing assay and Transwell experiment. The apoptosis rate of PC cells was analyzed by flow cytometry and TUNEL assay. The Gene Set Enrichment Analysis (GSEA) was used to determine the enrichment pathways of IPO7. The effect of IPO7 on the ERBB2 expression was determined using Western blotting. A xenograft mouse model was applied to investigate the carcinogenic effect of IPO7 in vivo. RESULTS: IPO7 expression was remarkably elevated in the cancer tissues of PC patients. IPO7 overexpression remarkably enhanced PC cell proliferation, migration and invasion and suppressed apoptosis, while knockdown of IPO7 exerted the opposite effect. Mechanistically, IPO7 facilitated the malignant phenotype of PC cells by up-regulating ERBB2 expression. In addition, knockdown of IPO7 inhibited tumor growth and lung metastasis in vivo. CONCLUSION: IPO7 can act as an oncogenic factor and accelerate PC progression by modulating the ERBB pathway.
Asunto(s)
Carioferinas , Neoplasias Pancreáticas , Receptores Citoplasmáticos y Nucleares , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Carioferinas/genética , Carioferinas/metabolismo , Ratones , Páncreas/patología , Neoplasias Pancreáticas/patología , Receptor ErbB-2 , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Neoplasias PancreáticasRESUMEN
Abstract Background Importin 7 (IPO7) belongs to the Importin β family and is implicated in the progression of diverse human malignancies. This work is performed to probe the role of IPO7 in pancreatic cancer development and its potential downstream mechanisms. Methods IPO7 expression in PC and paracancerous tissues were measured using Immunohistochemistry (IHC) staining and qRT-PCR. Western blotting was utilized to detect the expression level of IPO7 in PC cells and immortalize the pancreatic ductal epithelial cell line. After constructing the IPO7 overexpression and knockdown models, the effect of IPO7 on the proliferation of PC cells was analyzed by the CCK-8 and EdU assay. The migration and invasion of PC cells were examined by wound healing assay and Transwell experiment. The apoptosis rate of PC cells was analyzed by flow cytometry and TUNEL assay. The Gene Set Enrichment Analysis (GSEA) was used to determine the enrichment pathways of IPO7. The effect of IPO7 on the ERBB2 expression was determined using Western blotting. A xenograft mouse model was applied to investigate the carcinogenic effect of IPO7 in vivo. Results IPO7 expression was remarkably elevated in the cancer tissues of PC patients. IPO7 overexpression remarkably enhanced PC cell proliferation, migration and invasion and suppressed apoptosis, while knockdown of IPO7 exerted the opposite effect. Mechanistically, IPO7 facilitated the malignant phenotype of PC cells by up-regulating ERBB2 expression. In addition, knockdown of IPO7 inhibited tumor growth and lung metastasis in vivo. Conclusion IPO7 can act as an oncogenic factor and accelerate PC progression by modulating the ERBB pathway.
RESUMEN
Abstract Objective: To investigate the impact of recombinant human interferon α1b (rhIFNα1b) treatment in infants hospitalized with lower respiratory tract infections on subsequent wheezing. Methods: The clinical data of infants (n = 540) with viral pneumonia, wheezy bronchitis, or bronchiolitis hospitalized in 19 Chinese hospitals from June 2009 to June 2015 were retrospectively analyzed. The parameters relevant to wheezing episodes within the last year were collected by telephone and questionnaires. The rhIFNα1b treatment group (n = 253) and control group (n = 287) were compared in terms of wheezing episodes within the last year. Moreover, the wheezing group (95 cases) and non-wheezing group (445 cases) were compared. Results: Out of 540 cases, 95 (17.6%) experienced wheezing episodes, 13.8% (35/253) cases treated with rhIFNα1b, and 20.9% (60/287) cases without rhIFNα1b experienced wheezing episodes within the last year. The rhIFNα1b treatment significantly improved wheezing episodes within the last year, compared with the control peers (p = 0.031). Single-factor regression showed statistically significant differences between the wheezing and non-wheezing groups in terms of age, rhIFNα1b use, childhood and family history of allergy, housing situation, and feeding history (p < 0.05). Binary logistic regression showed a childhood history of allergy (OR = 2.14, p = 0.004), no rhIFNα1b use (OR = 1.70, p = 0.028), and living in a crowded house (OR = 1.92, p = 0.012) might be risk factors of subsequent wheezing. Accordingly, breastfeeding (OR = 0.44, p = 0.008) and hospitalization age of 1-year-old (OR = 0.58, p = 0.024) were protective factors. Conclusions: Early use of rhIFNα1b in infants hospitalized with lower respiratory tract infections and breastfeeding could prevent subsequent wheezing. Living in a crowded house could promote subsequent wheezing.
Asunto(s)
Humanos , Femenino , Lactante , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Bronquiolitis , Ruidos Respiratorios , Estudios Retrospectivos , Factores de Riesgo , InterferonesRESUMEN
The consideration of ecological and human health risk is an emerging concern with the excessive or inappropriate use of deltamethrin. In this study, the degradation conditions of the newly deltamethrin-degrading strain Stenotrophomonas maltophilia XQ08 were optimized, which were temperature 35 °C, pH 7.5, cell concentration 5.5 × 108 cfu/mL, and substrate concentration 50 mg/L. Strain XQ08 could effectively degrade deltamethrin into three smaller molecular weight and lower toxic compounds. Enriched strain XQ08 was immobilized in a charcoal-alginate matrix and possessed more prominent biodegradability, reusability, storability and thermostability than free XQ08. In a continuous reactor system, immobilized XQ08 could averagely remove 78.81% of deltamethrin at the gradient influent dosages of 50, 75 and 100 mg/L within 30 d. Immobilized XQ08 introduced into the filed brown and yellow soils exhibited a superior degradation potential for deltamethrin with the half-lives of 1.77 and 2.04 d, which were 2.39 and 2.14 folds, or 6.09 and 5.47 folds faster than free XQ08 degradation (4.23 and 4.37 d) or natural dissipation (10.78 and 11.16 d), respectively. Moreover, application of free XQ08 decreased the persistence of deltamethrin in Brassica pekinensis and Brassica chinensis from 5.47 and 6.23 to 2.05 and 2.32 d, or by 62.52% and 62.76%, respectively. This study provides a feasible, effective and rapid biological removal technology for deltamethrin-contaminated environments in situ.
Asunto(s)
Stenotrophomonas maltophilia , Biodegradación Ambiental , Humanos , Nitrilos , Piretrinas , Suelo , Stenotrophomonas maltophilia/genética , Verduras , AguaRESUMEN
OBJECTIVE: To investigate the impact of recombinant human interferon α1b (rhIFNα1b) treatment in infants hospitalized with lower respiratory tract infections on subsequent wheezing. METHODS: The clinical data of infants (n=540) with viral pneumonia, wheezy bronchitis, or bronchiolitis hospitalized in 19 Chinese hospitals from June 2009 to June 2015 were retrospectively analyzed. The parameters relevant to wheezing episodes within the last year were collected by telephone and questionnaires. The rhIFNα1b treatment group (n=253) and control group (n=287) were compared in terms of wheezing episodes within the last year. Moreover, the wheezing group (95 cases) and non-wheezing group (445 cases) were compared. RESULTS: Out of 540 cases, 95 (17.6%) experienced wheezing episodes, 13.8% (35/253) cases treated with rhIFNα1b, and 20.9% (60/287) cases without rhIFNα1b experienced wheezing episodes within the last year. The rhIFNα1b treatment significantly improved wheezing episodes within the last year, compared with the control peers (p=0.031). Single-factor regression showed statistically significant differences between the wheezing and non-wheezing groups in terms of age, rhIFNα1b use, childhood and family history of allergy, housing situation, and feeding history (p<0.05). Binary logistic regression showed a childhood history of allergy (OR=2.14, p=0.004), no rhIFNα1b use (OR=1.70, p=0.028), and living in a crowded house (OR=1.92, p=0.012) might be risk factors of subsequent wheezing. Accordingly, breastfeeding (OR=0.44, p=0.008) and hospitalization age of ≤1-year-old (OR=0.58, p=0.024) were protective factors. CONCLUSIONS: Early use of rhIFNα1b in infants hospitalized with lower respiratory tract infections and breastfeeding could prevent subsequent wheezing. Living in a crowded house could promote subsequent wheezing.
Asunto(s)
Bronquiolitis , Infecciones del Sistema Respiratorio , Femenino , Humanos , Lactante , Interferones , Ruidos Respiratorios/etiología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVES HOXB2 is a new prognostic indicator for lung cancer. But it is unclear whether HOXB2 holds an effect in glioblastoma (GBM) progression. The purpose of this article was to probe the influences of HOXB2 on GBM pathogenesis. METHODS HOXB2 expression level and prognostic power in GBM patients were analyzed. Then the mRNA and protein expression levels of HOXB2 in GBM cell lines were tested by qRT-PCR and western blotting. Cell proliferation, invasion, and migration were determined by CCK8 and transwell assay, severally. The protein levels of PI3K/AKT-pathway associated proteins were analyzed by western blotting. RESULTS The results indicated that HOXB2 was distinctly overexpressed in GBM patients and high expression of HOXB2 was related to a poor prognosis. Moreover, the expression of HOXB2 was higher in all GBM cell lines U251, U-87MG, GOS-3 than that in HEB cells (normal control). Meanwhile, decreased expression of p-PI3K and p-AKT were identified after HOXB2 knockdown. CONCLUSIONS These data demonstrated that HOXB2 had a vital role in GBM progression and could serve as a promising target for GBM treatment.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Genes Homeobox/fisiología , Glioblastoma/diagnóstico , Biomarcadores , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Fosfatidilinositol 3-Quinasas , PronósticoRESUMEN
SUMMARY OBJECTIVES HOXB2 is a new prognostic indicator for lung cancer. But it is unclear whether HOXB2 holds an effect in glioblastoma (GBM) progression. The purpose of this article was to probe the influences of HOXB2 on GBM pathogenesis. METHODS HOXB2 expression level and prognostic power in GBM patients were analyzed. Then the mRNA and protein expression levels of HOXB2 in GBM cell lines were tested by qRT-PCR and western blotting. Cell proliferation, invasion, and migration were determined by CCK8 and transwell assay, severally. The protein levels of PI3K/AKT-pathway associated proteins were analyzed by western blotting. RESULTS The results indicated that HOXB2 was distinctly overexpressed in GBM patients and high expression of HOXB2 was related to a poor prognosis. Moreover, the expression of HOXB2 was higher in all GBM cell lines U251, U-87MG, GOS-3 than that in HEB cells (normal control). Meanwhile, decreased expression of p-PI3K and p-AKT were identified after HOXB2 knockdown. CONCLUSIONS These data demonstrated that HOXB2 had a vital role in GBM progression and could serve as a promising target for GBM treatment.
RESUMO OBJETIVOS A HOXB2 é um novo indicador prognóstico para o câncer de pulmão. Mas não está claro se a HOXB2 tem algum efeito na progressão do glioblastoma (GBM). O objetivo deste artigo foi sondar as influências da HOXB2 na patogênese do GBM. MÉTODOS Foram analisados o nível de expressão e o poder prognóstico da HOXB2 em pacientes com GBM. Em seguida, os níveis de expressão proteica e mRNA da HOXB2 em linhagens de células de GBM foram testados por qRT-PCR e western blotting. A proliferação, a invasão e migração celular foram determinadas por CCK8 e ensaios transwell, várias vezes. Os níveis proteicos das proteínas associadas à via PI3K/AKT foram analisados pelo método western blotting. RESULTADOS Os resultados indicaram que havia uma clara superrexpressão da HOXB2 em pacientes com GBM e que a alta expressão da HOXB2 estava relacionada a um prognóstico negativo. Além disso, a expressão da HOXB2 foi mais elevada em todas as linhagens de células do GBM U251, U-87MG, GOS-3 do que nas células HEB (controle normal). Entretanto, a diminuição da expressão de P-PI3K e p-AKT foi identificada após a redução da expressão da HOXB2. CONCLUSÕES Esses dados demonstram que a HOXB2 desempenha um papel vital na progressão do GBM, podendo ser um alvo promissor para o tratamento do GBM.
Asunto(s)
Humanos , Neoplasias Encefálicas/diagnóstico , Genes Homeobox/fisiología , Glioblastoma/diagnóstico , Pronóstico , Biomarcadores , Regulación Neoplásica de la Expresión Génica , Fosfatidilinositol 3-Quinasas , Línea Celular Tumoral , Proliferación CelularRESUMEN
Four series of novel thieno[3,2-d]pyrimidine and quinazoline derivatives containing N-acylhydrazone or semicarbazone were designed, synthesized, and evaluated for their biological activity. Of which compound 14 showed the most potent antitumor activities with IC50 values of 1.78⯵M, 1.02⯵M, 1.98⯵M, 0.41⯵M and 0.22⯵M against HT-29, MDA-MB-231, U87MG, PC-3 and HCT-116 cell lines respectively. Inhibition of enzymatic assays showed that PI3Kα was very likely to be one of the drug targets of 14 with the IC50 value of 0.20⯵M. According to the results of antitumor activity, the SARs were summarized, which indicated that thieno[3,2-d]pyrimidine and semicarbazone are optimal fragments. In addition, compounds with hydroxyl group at the 4-position on the terminal phenyl ring were more active. Annexin-V and propidium iodide (PI) double staining confirmed that the most active cytotoxic compound 14 can induce cell apoptosis in HCT-116 cells. Moreover, the influence of 14 on the cell cycle distribution was assessed on the HCT-116 cell line, exhibiting a cell cycle arrest at the G2/M phase. Furthermore, molecular docking analysis was also performed to determine possible binding modes between PI3Kα and the target compound. These results will guide us to further refine the structure of the thieno[3,2-d]pyrimidine and quinazoline derivatives to achieve optimal antitumor activity.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Diseño de Fármacos , Hidrazinas/síntesis química , Hidrazinas/farmacología , Neoplasias/tratamiento farmacológico , Pirimidinas/química , Quinazolinas/química , Apoptosis , Ciclo Celular , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
INTRODUCTION AND AIM: Accurately predicting the prognosis of individual patient is crucial in the management of ACLF. We aimed to establish a specific prognostic model for HBV-related ACLF patients treated with nucleoside analog (NA). MATERIAL AND METHODS: We prospectively collected 205 ACLF cases diagnosed according to the APASL criteria. A dynamic prognostic model based on APASL criteria was established and validated. To demonstrate that the model is also applicable to those within EASL criteria, we divided the patients into two groups: met APASL criteria only (group A, n = 123); met both APASL and EASL criteria (group B, n = 82). Its prognostic accuracy was also compared with chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in group B. RESULTS: The model is: R = 0.94 x Bilirubin + 0.53 x evolution of Bilirubin - 0.45 x PT-A - 0.22 x evolution in PT-A -0.1 x PLT + 10 x anti-HBe. The area under receiver operating characteristic curve (AUC) of the model for predicting 90-day mortality was 0.86, which was significantly higher than that of model for end stage liver disease(MELD), MELD-Na, CLIF-SOFA, ΔMELD (7d) and ΔMELD-Na (7d), ΔCLIF- SOFA(7d) (all p < 0.01). The AUC of our model in the validation group was 0.79 which was superior to MELD (0.45) CLIF-SOFA (0.53) score in group B patients (p < 0.01). CONCLUSION: In conclusion, the model was superior to the conventional methods in predicting the outcomes of patients with HBV related ACLF treated with NA. It is the first description of a novel prognostic model using consecutive data in patients with HBV-induced acute-on-chronic liver failure (ACLF) treated by nucleoside analogs.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Antivirales/uso terapéutico , Técnicas de Apoyo para la Decisión , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Modelos Biológicos , Nucleósidos/uso terapéutico , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/virología , Adulto , Antivirales/efectos adversos , Bilirrubina/sangre , Biomarcadores/sangre , China , Progresión de la Enfermedad , Femenino , Anticuerpos contra la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/mortalidad , Hepatitis B Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Nucleósidos/efectos adversos , Puntuaciones en la Disfunción de Órganos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Protrombina/metabolismo , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del TratamientoRESUMEN
A 39-amino acid peptide fragment that is derived from prostatic acidic phosphatase (PAP), PAP248-286 , is secreted in large amounts in human semen and forms amyloid fibrils. These fibrils can capture HIV virions and increase the attachment of virions to target cells; as such, they are called a "semen-derived enhancer of virus infection" (SEVI). Therefore, the inhibition of the formation of PAP248-286 amyloid fibrils is of great significance. Herein, we demonstrate that brazilin effectively inhibits PAP248-286 aggregation. The inhibitory effect increases with increasing brazilin concentration. Thioflavinâ T fluorescence assays and TEM observations confirmed that a few fibrils formed when brazilin was present with PAP248-286 in an equimolar concentration. Circular dichroism spectroscopy indicated that brazilin inhibited the secondary structural transitions from α-helices and random coils into ß-sheets. Cytotoxicity assays showed that brazilin significantly decreased the cytotoxicity of the fibrils at 0.01â mmol L-1 . Isothermal titration calorimetry revealed that hydrophobic interactions were the main driving force for the binding of brazilin to the PAP248-286 monomer (dissociation constant, 4.03â µmol L-1 ), and that the binding affinity of brazilin for the fibrils was at least three orders of magnitude lower than that for the monomer. These results indicate that brazilin holds great potential as a small-molecule agent against SEVIs.