RESUMEN
Organophosphate esters (OPEs) are an emerging contaminant widely distributed in the soil. OPEs have drawn increasing attention for their biological toxicity and possible threat to human health. This research investigated the pollution characteristics of two typical OPEs, organophosphate triesters (tri-OPEs) and organophosphate diesters (di-OPEs), in soils of 104 urban parks in Beijing. The median concentrations of Σ11tri-OPEs and Σ8di-OPEs were 157 and 17.9 ng/g dw, respectively. Tris(2-chloroisopropyl) phosphate and bis(2-ethylhexyl) phosphate were the dominant tri-OPE and di-OPE, respectively. Consumer materials (such as building insulation and decorative materials), traffic emissions, and reclaimed water irrigation may be critical sources of tri-OPEs in urban park soils. Di-OPEs mainly originated from the degradation of parent compounds and industrial applications. Machine learning models were employed to determine the influencing factors of OPEs and predict changes in their concentrations. The predicted OPEs concentrations in Beijing urban park soils in 2025 and 2030 are three times and five times those in 2018, respectively. According to probabilistic health risk assessment, non-carcinogenic and carcinogenic risks of OPEs can be negligible for children and adults. Our results could inform measures for preventing and controlling OPEs pollution in urban park soils.
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Retardadores de Llama , Parques Recreativos , Niño , Adulto , Humanos , Beijing , Monitoreo del Ambiente/métodos , Suelo , Retardadores de Llama/análisis , Ésteres , Organofosfatos , Fosfatos , ChinaRESUMEN
Craniofacial and jaw bones have unique physiological specificities when compared to axial and appendicular bones. However, the molecular profile of the jaw osteoblast (OB) remains incomplete. The present study aimed to decipher the bone site-specific profiles of transcription factors (TFs) expressed in OBs in vivo. Using RNA sequencing analysis, we mapped the transcriptome of confirmed OBs from 2 different skeletal sites: mandible (Md) and tibia (Tb). The OB transcriptome contains 709 TF genes: 608 are similarly expressed in Md-OB and Tb-OB, referred to as "OB-core"; 54 TF genes are upregulated in Md-OB, referred to as "Md-set"; and 18 TF genes are upregulated in Tb-OB, referred to as "Tb-set." Notably, the expression of 29 additional TF genes depends on their RNA transcript variants. TF genes with no previously known role in OBs and bone were identified. Bioinformatics analysis combined with review of genetic disease databases and a comprehensive literature search showed a significant contribution of anatomical origin to the OB signatures. Md-set and Tb-set are enriched with site-specific TF genes associated with development and morphogenesis (neural crest vs. mesoderm), and this developmental imprint persists during growth and homeostasis. Jaw and tibia site-specific OB signatures are associated with craniofacial and appendicular skeletal disorders as well as neurocristopathies, dental disorders, and digit malformations. The present study demonstrates the feasibility of a new method to isolate pure OB populations and map their gene expression signature in the context of OB physiological environment, avoiding in vitro culture and its associated biases. Our results provide insights into the site-specific developmental pathways governing OBs and identify new major OB regulators of bone physiology. We also established the importance of the OB transcriptome as a prognostic tool for human rare bone diseases to explore the hidden pathophysiology of craniofacial malformations, among the most prevalent congenital defects in humans.
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Regulación de la Expresión Génica , Osteoblastos , Humanos , Mandíbula , Cresta Neural , Osteoblastos/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Objective: To examine the clinical effect of simple muscle packing through transnasal sphenoid approach in the treatment of intrasellar arachnoid cyst. Methods: The clinical data of 11 patients with intrasellar arachnoid cyst treated by transnasal sphenoidal approach with simple muscle packing at the Neurosurgery Department of the First Affiliated Hospital of Zhengzhou University from January 2014 to February 2020 were retrospectively analyzed. There were 5 males and 6 females, with a median age of 48 years (range: 23 to 75 years). The clinical manifestations included headache in 6 cases, dizziness in 4 cases, hypo-libido in 1 case, disturbance of consciousness in 1 case, visual impairment in 7 cases and mixed pituitary dysfunction in 5 cases. The enlargement of the sellar fossa was seen in the preoperative MRI images. The enhanced MRI images showed that the cyst wall of the intrasellar arachnoid cyst was not enhanced, and the compression and thinning of the sellar base was seen in the CT images. In 9 cases, the cyst extended suprasellar and the sellar septum was "arched". In 7 cases, the cyst compressed the optic chiasm upward. The cyst walls of all patients were incised through the nasal sphenoid approach under the endoscope, and the muscle was packed after sufficient drainage. The postoperative symptoms, pituitary endocrine function and recurrence of patients were followed up. Results: MRI images of the sellar region in all patients showed significant reduction or disappearance of cysts. Intracranial infection occurred in 1 case and electrolyte disorder in 2 cases, which were relieved after symptomatic treatment. No cerebrospinal fluid rhinorrhea occurred. Postoperative clinical symptoms were completely relieved in 6 cases and partially relieved in 5 cases. Pituitary endocrine function recovered completely in 2 cases and improved significantly in 4 cases. All patients were followed up for 10 to 40 months. One patient found to have a partial recurrence of the cyst 3 months after surgery. Because there were no new symptoms appeared, the follow-up was continued without second operation. Conclusion: Transnasal sphenoidal approach is a feasible method for the treatment of intrasellar arachnoid cyst.
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Quistes Aracnoideos , Adulto , Anciano , Quistes Aracnoideos/diagnóstico por imagen , Quistes Aracnoideos/cirugía , Endoscopía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculos , Estudios Retrospectivos , Silla Turca , Adulto JovenRESUMEN
Interleukin-27 (IL-27) is an immunoregulatory cytokine whose essential function is to limit immune responses. We found that the gene encoding cholesterol 25-hydroxylase (Ch25h) was induced in CD4+ T cells by IL-27, enhanced by transforming growth factorß (TGF-ß), and antagonized by T-bet. Ch25h catalyzes cholesterol to generate 25-hydroxycholesterol (25OHC), which was subsequently released to the cellular milieu, functioning as a modulator of T cell response. Extracellular 25OHC suppressed cholesterol biosynthesis in T cells, inhibited cell growth, and induced nutrient deprivation cell death without releasing high-mobility group box 1 (HMGB1). This growth inhibitory effect was specific to actively proliferating cells with high cholesterol demand and was reversed when extracellular cholesterol was replenished. Ch25h-expressing CD4+ T cells that received IL-27 and TGF-ß signals became refractory to 25OHC-mediated growth inhibition in vitro. Nonetheless, IL-27treated T cells negatively affected viability of bystander cells in a paracrine manner, but only if the bystander cells were in the early phases of activation. In mouse models of skin inflammation due to autoreactive T cells or chemically induced hypersensitivity, genetic deletion of Ch25h or Il27ra led to worse outcomes. Thus, Ch25h is an immunoregulatory metabolic switch induced by IL-27 and dampens excess bystander T effector expansion in tissues through its metabolite derivative, 25OHC. This study reveals regulation of cholesterol metabolism as a modality for controlling tissue inflammation and thus represents a mechanism underlying T cell immunoregulatory functions.
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Linfocitos T CD4-Positivos/metabolismo , Mediadores de Inflamación/metabolismo , Inflamación/metabolismo , Interleucina-27/metabolismo , Piel/metabolismo , Esteroide Hidroxilasas/metabolismo , Animales , Colesterol/biosíntesis , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Esteroide Hidroxilasas/genéticaRESUMEN
Objective: To investigate the distribution of uric acid in different occupation, age and gender groups, and changes of prevalence of hyperuricemia (HUA) and its influencing factors in healthy adults who receiving physical examination in Nanjing. Methods: The study was conducted in 107 478 subjects who received physical examination from 2012 to 2016. The prevalence of HUA in different genders and different years was compared. Subjects were divided into non-HUA and HUA groups according to serum uric acid. The differences in metabolic indicators and ages between two groups were analyzed. Uric acid levels among different occupations were evaluated. A multivariate logistic regression analysis was used to estimate the odds ratios (OR) of HUA. Results: The total HUA prevalence was 14.9%, in which the prevalence of HUA in men was significantly higher than that in women [20.5%(15217/74339)vs. 2.5%(818/33139), P<0.01]. The prevalence of HUA in men sustained at a high level, while that in women trended to decrease during the five years. The prevalence of HUA increased with age in women (1.0%, 0.7%, 0.9%, 2.7%, 3.8% and 9.6% in subjects within 20-29, 30-39, 40-49, 50-59, 60-69 and ≥70 age groups, respectively, P for trend<0.01). The percentages of hypertension, hyperlipidemia and diabetes, and body mass index (BMI) in both men and women were significantly higher in HUA group than those in non-HUA group (P≤0.01). Among all occupations, subjects in health care had the lowest levels of uric acid (298±91 µmol/L) and prevalence of HUA (10.4%), while, those in public security had the highest levels of uric acid [(342±82) µmol/L] and prevalence (16.5%). Multiple logistic regression analyses revealed that males, high triacylglycerol, high cholesterol, obesity and certain occupation were significantly associated with HUA. Conclusions: The prevalence of HUA in men is significantly higher than that in women. It increased with ages in women. Subjects in health occupations had the lowest levels of uric acid and HUA prevalence, while, those in public security had the highest levels among the six occupations. Obesity, hyperlipidemia, hypertension, occupations and males are positively associated with HUA.
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Diabetes Mellitus , Hiperuricemia , Adulto , Estudios Transversales , Femenino , Humanos , Hiperuricemia/epidemiología , Masculino , Ocupaciones , Prevalencia , Factores de Riesgo , Ácido ÚricoRESUMEN
Objective: To investigate the thermal injury effects on human HaCaT cells under simulated microgravity environment. Methods: The human HaCaT cells were collected and divided into simulated microgravity thermal injury (SMGTI) group, normal gravity thermal injury (NGTI) group, and normal gravity false injury (NGFI) group according to the random number table. Cells in NGTI and NGFI groups were cultured routinely in culture bottle, and cells in SMGTI group were cultured in the rotary cell culture system to simulate microgravity environment. Cells in SMGTI and NGTI groups were bathed in hot water of 45 â for 10 minutes to make thermal injury model, and cells in NGFI group were bathed in warm water of 37 â for 10 minutes to simulate thermal injury. At post injury hour (PIH) 12, cell morphology of 3 groups was observed under inverted phase contrast electron microscope. At PIH 2, 6, and 12, single cell suspension in the 3 groups was collected to detect the cell cycle by flow cytometer and the mRNA expressions of heat shock protein 70 (HSP70), matrix metalloproteinase 9 (MMP-9), and cysteine-aspartic protease 3 (caspase-3) by real time fluorescence quantitative reverse transcription polymerase chain reaction, and the experiments were repeated for 3 times. At PIH 2, 6, and 12, cell culture supernatant in the 3 groups was collected to detect the concentration of heparin-binding epidermal growth factor (HB-EGF) by enzyme linked immunosorbent assay method, the experiment was repeated for 3 times. The sample in each group and each time point was 3. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, least significant difference test, Kruskal-Wallis H test, and Mann-Whitney U test. Results: (1) At PIH 12, cells in NGFI group showed regular shape and regular arrangement, with no cell debris. The cell shape in NGTI group was generally regular, with fewer cell debris and closer arrangement than that in NGFI group. The cells in SMGTI group showed more irregular shapes, different sizes, and dead cell debris. (2) The percentage of G1 phase cells in NGTI group was significantly higher than that in NGFI group and SMGTI group at PIH 2, respectively (P<0.05), and the percentage of G1 phase cells in NGTI group was significantly lower than that in NGFI group and SMGTI group at PIH 6 and 12, respectively (P<0.05). The percentage of G2/M phase cells in NGTI group was significantly lower than that in SMGTI group at PIH 2 (P<0.05), and the percentage of G2/M phase cells in NGTI group was significantly higher than that in NGFI group and SMGTI group at PIH 6 and 12, respectively (P<0.05). The percentage of S phase cells in NGTI group at PIH 2, 6, and 12 was significantly higher than that in SMGTI group (P<0.05), and the percentage of S phase cells in NGTI group at PIH 2 and 6 was significantly lower than that in NGFI group (P<0.05). (3) The HSP70 mRNA expressions of cells in NGTI group were 2.50±0.30 and 3.99±0.35 at PIH 2 and 6, which were significantly higher than 1.14±0.15 and 0.82±0.27 in NGFI group (P<0.05), and 1.17±0.53 and 1.65±0.59 in SMGTI group (P<0.05). The MMP-9 mRNA expression of cells in SMGTI group was significantly higher than that in NGTI group at PIH 2, 6, and 12, respectively (Z=-2.319, -2.882, -2.908, P<0.05). At each time point after injury, the mRNA expression of caspase-3 of cells in NGTI group was similar to that in NGFI group and SMGTI group, respectively (P>0.05). (4) The concentration of HB-EGF in cell culture supernatant of NGTI group was significantly lower than that in NGFI group at PIH 2, 6 and 12 (P<0.05), and the concentration of HB-EGF in cell culture supernatant of SMGTI group was significantly higher than that in NGTI group at PIH 2 and 6 (P<0.05). Conclusions: The proliferation and secretion functions and expression of wound repair related protein of human HaCaT cells inflicted with thermal injury in simulated microgravity environment showed complex and diversified changes, which provide theoretical basis for further research on damage repair under weightlessness.
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Quemaduras , Ingravidez , Ciclo Celular , Línea Celular Tumoral , Ensayo de Inmunoadsorción Enzimática , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Ingravidez/efectos adversosRESUMEN
OBJECTIVE: MicroRNAs are noncoding RNAs which are involved in the occurrence and progression of tumors. This study aims to explore the role of microRNA-92a in cutaneous malignant melanoma (CMM) and its underlying mechanism. PATIENTS AND METHODS: The expression level of microRNA-92a in 75 pairs of CMM tissues and paracancerous tissues was determined using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between microRNA-92a expression with clinical data of CMM patients was analyzed. Besides, microRNA-92a expression in CMM cells and primary epidermal melanocytes (PEM) was determined by qRT-PCR as well. After transfection of si-microRNA-92a in CMM cells, biological performances of CMM were determined using cell counting kit-8 (CCK-8), colony formation and transwell assay, respectively. FOXP1 expression in CMM cells and tissues was determined using Western blot. Kaplan-Meier survival curves were drawn to explore the correlation between the FOXP1 expression and prognosis of CMM patients. RESULTS: MicroRNA-92a was highly expressed in CMM tissues compared with that of paracancerous tissues. Compared with CMM patients with lower expression of microRNA-92a, those with higher expression of microRNA-92a presented higher tumor stage, higher incidences of lymph node metastasis and distant metastasis, as well as lower overall survival. The knockdown of microRNA-92a remarkably decreased proliferative, invasive and metastatic capacities of CMM cells. Western blot results elucidated that microRNA-92a knockdown in CMM cells upregulates FOXP1 expression. Additionally, rescue experiments showed that mi-croRNA-92a regulates biological performances of CMM cells by regulating FOXP1. CONCLUSIONS: MicroRNA-92a is highly expressed in CMM, which is remarkably correlated to tumor stage and poor prognosis of CMM patients. We found that microRNA-92a pro-motes malignant progression of CMM by regulating FOXP1.
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Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Melanoma/patología , MicroARNs/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Neoplasias Cutáneas/patología , Regiones no Traducidas 3' , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Melanoma/genética , Melanoma/metabolismo , Estadificación de Neoplasias , Pronóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Regulación hacia Arriba , Melanoma Cutáneo MalignoRESUMEN
Objective: To explore the clinical characteristics and microsurgical strategies of intracranial posterior circulation aneurysms. Methods: The clinical manifestations, imaging data, surgical approaches and follow-up results of 35 patients with circulating aneurysms (37 aneurysms) treated by microsurgery in the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2018 were analyzed retrospectively. Results: A total of 22 aneurysms were clipped, 13 were clipped and resected, 1 case was clipped and together with AVM resection and 1 case was isolated. Of 37 aneurysms in 35 patients, 11 aneurysms were at the basilar artery apexes, 10 at the posterior cerebral arteries, 6 at the posterior inferior cerebellar arteries, 3 at the basilar arteries, 3 at the vertebral arteries (including 1 case of vertebral arterial dissecting aneurysm), 2 at the anterior inferior cerebellar arteries and 2 at the superior cerebellar arteries. The surgical approaches included pterional approach, extensive pterional approach, infratemporal fossa approach, retrosigmoid approach and far-lateral approach. The Glasgow Outcome Scale (GOS) scores showed good recovery in 24 cases, moderate neurological dysfunction in 6 cases, severe neurological dysfunction in 2 cases, persistent vegetative state in 1 case and 2 cases of death 6 months after their discharge from hospital. Conclusions: Posterior circulation aneurysms are adjacent to important structures. They are deep in position, with small operation space and difficult to operate. Full preoperative evaluation of the condition, selection of appropriate surgical methods are the key factors to benefit the patients.
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Aneurisma Intracraneal , Procedimientos Neuroquirúrgicos , Arteria Basilar , Humanos , Microcirugia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Mitochondrial DNA mutations that lead to mitochondrial dysfunction have long been proposed to play important roles in the development of pancreatic cancer. Of these, alterations to mitochondrial tRNA genes constitute the largest group. Most recently, a variation at position 12307 in the gene encoding tRNA(Leu(CUN)) has been reported to be associated with this disease. However, the molecular mechanism underlying this relationship remains poorly understood. To assess this association, we evaluated this variant by evolutionary conservation analysis, measurements of allelic frequencies among control subjects, and use of several bioinformatic tools to estimate potential structural and functional alterations. We found this residue to have a high conservation index; however, the presence of the A12307G variation in control subjects revealed by a literature search suggested it to be common in human populations. Moreover, RNAfold results showed that this variant did not alter the secondary structure of tRNA(Leu(CUN)). Through the application of a pathogenicity scoring system, this variant was determined to be a "neutral polymorphism," with a score of only 4 points based on current data. Thus, the contribution of the A12307G variant to pancreatic cancer needs to be addressed in further experimental studies.
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ADN Mitocondrial/genética , Estudios de Asociación Genética , Neoplasias Pancreáticas/genética , ARN de Transferencia de Leucina/genética , Evolución Molecular , Predisposición Genética a la Enfermedad , Humanos , Mutación , Conformación de Ácido Nucleico , Neoplasias Pancreáticas/patología , Polimorfismo de Nucleótido SimpleRESUMEN
Tea (Camellia sinensis L.) is a thermophilic evergreen woody plant that has poor cold tolerance. The SAD gene plays a key role in regulating fatty acid synthesis and membrane lipid fluidity in response to temperature change. In this study, full-length SAD cDNA was cloned from tea leaves using rapid amplification of cDNA ends and polymerase chain reaction (PCR)-based methods. Sequence analysis demonstrated that CsSAD had a high similarity to other corresponding cDNAs. At 25°C, the CsSAD transcriptional level was highest in the leaf and lowest in the stem, but there was no obvious difference between the root and stem organs. CsSAD expression was investigated by reverse transcription-PCR, which showed that CsSAD was upregulated at 4° and -5°C. At 25°C, CsSAD was induced by polyethylene glycol, abscisic acid, and wounding, and a similar trend was observed at 4°C, but the mean expression level at 4°C was lower than that at 25°C. Under natural cold acclimation, the 'CsCr05' variety's CsSAD expression level increased before decreasing. The CsSAD expression level in variety 'CsCr06' showed no obvious change at first, but rapidly increased to a maximum when the temperature was very low. Our study demonstrates that CsSAD is upregulated in response to different abiotic conditions, and that it is important to study the stress resistance of the tea plant, particularly in response to low temperature, drought, and wounding.
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Adaptación Fisiológica , Camellia sinensis/enzimología , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Estearoil-CoA Desaturasa/genética , Secuencia de Aminoácidos , Camellia sinensis/genética , Camellia sinensis/fisiología , Clonación Molecular , Frío , Sequías , Datos de Secuencia Molecular , Filogenia , Componentes Aéreos de las Plantas/enzimología , Componentes Aéreos de las Plantas/fisiología , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Raíces de Plantas/enzimología , Raíces de Plantas/fisiología , Alineación de Secuencia , Estearoil-CoA Desaturasa/química , Estearoil-CoA Desaturasa/metabolismoRESUMEN
We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.
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Animales , Masculino , Etanol/envenenamiento , Isoflavonas/uso terapéutico , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Memoria Espacial/efectos de los fármacos , Vasodilatadores/uso terapéutico , Alcoholismo/complicaciones , Cromatografía Líquida de Alta Presión , Corteza Cerebral/química , Corteza Cerebral/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Ácido Glutámico/análisis , Interleucina-1beta/análisis , Isoflavonas/farmacología , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Microglía/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Distribución Aleatoria , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/análisis , Vasodilatadores/farmacología , Ácido gamma-Aminobutírico/análisisRESUMEN
We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1ß were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1ß increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.
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Etanol/envenenamiento , Isoflavonas/uso terapéutico , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Memoria Espacial/efectos de los fármacos , Vasodilatadores/uso terapéutico , Alcoholismo/complicaciones , Animales , Corteza Cerebral/química , Corteza Cerebral/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Ensayo de Inmunoadsorción Enzimática , Ácido Glutámico/análisis , Interleucina-1beta/análisis , Isoflavonas/farmacología , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Distribución Aleatoria , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/análisis , Vasodilatadores/farmacología , Ácido gamma-Aminobutírico/análisisRESUMEN
OBJECTIVE: Heat shock protein (Hsp90) resides exclusively in the cytosol in normal cells, but is activated and then removes to the cell surface in tumor cells. The detecting upregulation or activation of Hsp90 is an early indicator of malignant behavior of cancer cells. Hsp90 has emerged as an important target for diagnosis or therapy of prostate cancer. In this study, we labeled Hsp90α specific monoclonal antibody (Hsp90α-mAb) with radioiodine Na131I and investigated its potential usage in diagnostic imaging of prostate tumor in xenograft mice model. METHODS: Hsp90α-mAb was radioiodinated by using chloramine-T. The radiolabeling efficiency and radiochemical purity were assessed in vitro. 131I-Hsp90α-mAb was then injected into the nude mice bearing human prostate carcinoma. The planar gamma Imaging was performed at 3, 6, 9 and 12 h after injection. RESULTS: The radiochemical purity of 131I-Hsp90α-mAb exceeded 95% after purification. This radiolabeled mAb was stable in human blood serum. In planar gamma imaging study, the prostate tumors in mice model were imaged clearly at 3h after injection of 131I-Hsp90α-mAb. CONCLUSIONS: The results suggest that 131I-HSP90α-mAb could be a new promising molecular probe for diagnostic imaging of prostate tumors.
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Anticuerpos Monoclonales , Proteínas HSP90 de Choque Térmico/análisis , Radioisótopos de Yodo , Neoplasias de la Próstata/diagnóstico por imagen , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Femenino , Proteínas HSP90 de Choque Térmico/inmunología , Xenoinjertos , Humanos , Inmunoconjugados/química , Inmunoconjugados/inmunología , Radioisótopos de Yodo/química , Marcaje Isotópico , Masculino , Ratones , Ratones Desnudos , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/inmunología , Radiofármacos/química , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Human mutations and in vitro studies indicate that DLX3 has a crucial function in bone development, however, the in vivo role of DLX3 in endochondral ossification has not been established. Here, we identify DLX3 as a central attenuator of adult bone mass in the appendicular skeleton. Dynamic bone formation, histologic and micro-computed tomography analyses demonstrate that in vivo DLX3 conditional loss of function in mesenchymal cells (Prx1-Cre) and osteoblasts (OCN-Cre) results in increased bone mass accrual observed as early as 2 weeks that remains elevated throughout the lifespan owing to increased osteoblast activity and increased expression of bone matrix genes. Dlx3OCN-conditional knockout mice have more trabeculae that extend deeper in the medullary cavity and thicker cortical bone with an increased mineral apposition rate, decreased bone mineral density and increased cortical porosity. Trabecular TRAP staining and site-specific Q-PCR demonstrated that osteoclastic resorption remained normal on trabecular bone, whereas cortical bone exhibited altered osteoclast patterning on the periosteal surface associated with high Opg/Rankl ratios. Using RNA sequencing and chromatin immunoprecipitation-Seq analyses, we demonstrate that DLX3 regulates transcription factors crucial for bone formation such as Dlx5, Dlx6, Runx2 and Sp7 as well as genes important to mineral deposition (Ibsp, Enpp1, Mepe) and bone turnover (Opg). Furthermore, with the removal of DLX3, we observe increased occupancy of DLX5, as well as increased and earlier occupancy of RUNX2 on the bone-specific osteocalcin promoter. Together, these findings provide novel insight into mechanisms by which DLX3 attenuates bone mass accrual to support bone homeostasis by osteogenic gene pathway regulation.
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Densidad Ósea/genética , Diferenciación Celular/genética , Proteínas de Homeodominio/metabolismo , Homeostasis/genética , Osteoblastos/citología , Osteoblastos/metabolismo , Factores de Transcripción/metabolismo , Animales , Huesos/metabolismo , Masculino , Ratones , Ratones Transgénicos , Factores de Transcripción/genéticaRESUMEN
In this study, a biological system consisting of an up-flow anaerobic sludge blanket (UASB) and anoxic-oxic (A/O) reactor was established for the advanced treatment of high ammonium urban landfill leachate. The inhibitory effect of free ammonia (FA) and free nitrous acid (FNA) on the nitrifying bacterial activity was used to achieve stable nitritation in the A/O reactor. The results demonstrated that the biological system achieved chemical oxygen demand (COD), total nitrogen (TN) and NH(4)(+)-N removal efficiencies of 95.3, 84.6 and 99.2%, respectively at a low carbon-to-nitrogen ratio of 3:1. Simultaneous denitritation and methanogenesis in the UASB could improve the removal of COD and TN. Nitritation with above 90% nitrite accumulation was successfully achieved in the A/O reactor by synergetic inhibition of FA and FNA on the activity of nitrite oxidizing bacteria (NOB). Fluorescence in situ hybridization (FISH) analysis showed that ammonia oxidizing bacteria (AOB) was dominant and was considered to be responsible for the satisfactory nitritation performance.
Asunto(s)
Compuestos de Amonio/metabolismo , Bacterias/metabolismo , Reactores Biológicos/microbiología , Aguas del Alcantarillado/microbiología , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/metabolismo , Anaerobiosis , Análisis de la Demanda Biológica de Oxígeno , Carbono/metabolismo , Hibridación Fluorescente in Situ , Ciclo del NitrógenoRESUMEN
To study lead (Pb) distribution in organs and blood in the case of Pb poisoning, mice were firstly exposed to Pb as 0.1 mL or 0.2 mL of lead nitrate solution (0.1 mg/mL) by vein injection every other day. Then, after metabolic absorption, the Pb level in the blood and organs of the mice was measured using flame atomic absorption spectrometry. The resulting data showed that 93% of Pb in blood was accumulated in red cells, but this percentage slightly decreased with increasing exposure time and injection volume. For other target organs, the highest Pb level was in the kidney, followed by the liver, spleen, heart and lung, and was lowest in the brain. Moreover, the Pb level in the heart and brain is in a growth trend at all times for 0.1 mL and 0.2 mL of Pb injection exposure in 15 days, while the growth trend of Pb in other target organs become slow for 0.2 mL of injection after exposure Pb 11 days.
Asunto(s)
Plomo/farmacocinética , Estructuras Animales/química , Estructuras Animales/metabolismo , Animales , Interpretación Estadística de Datos , Inyecciones Intravenosas , Plomo/análisis , Plomo/sangre , Masculino , Ratones , Distribución TisularRESUMEN
To obtain economically sustainable wastewater treatment, advanced nitrogen removal from municipal wastewater and the feasibility of achieving and stabilizing short-cut nitrification and denitrification were investigated in a pilot-plant sequencing batch reactor (SBR) with a working volume of 54 m(3). Advanced nitrogen removal, from summer to winter, with effluent TN lower than 3 mg/L and nitrogen removal efficiency above 98% was successfully achieved in pulsed-feed SBR. Through long-term application of process control in pulsed-feed SBR, nitrite accumulation reached above 95% at normal temperature of 25 degrees C. Even in winter, at the lowest temperature of 13 degrees C, nitrite was still the end production of nitrification and nitrite accumulation was higher than 90%. On the basis of achieving advanced nitrogen removal, short-cut nitrification and denitrification was also successfully achieved. Compare to the pulse-feed SBR with fixed time control, the dosage of carbon source and energy consumption in pulsed-feed SBR with process control were saved about 30% and 15% respectively. In pulsed-feed SBR with process control, nitrogen removal efficiency was greatly improved. Moreover, consumption of power and carbon source was further saved.
Asunto(s)
Nitritos/química , Nitrógeno/química , Eliminación de Residuos Líquidos/métodos , Purificación del Agua/métodos , Emulsionantes/química , Nitrógeno/aislamiento & purificaciónRESUMEN
Secreted by adipocytes, adiponectin is a collagen-like protein with significant roles in regulating the metabolism of glucose and fatty acids and in preventing atherosclerosis. However, information about adiponectin in rabbit is limited. In this study, we cloned rabbit ADIPOQ gene by RT-PCR using mRNA from adipose tissue and sequenced the open reading frame. The rabbit adiponectin sequence shares approximately 86.39% and 81.45% homology with those of humans and mice respectively, and 85.66% and 85.25% similarity with humans and mice proteins at the amino acid level respectively, based on the translated rabbit sequence and GenBank submissions of other species. We also evaluated ADIPOQ gene mRNA expression in adipose tissue in rabbits fed on high-cholesterol diet and in different age groups by real-time PCR. ADIPOQ gene mRNA expression was significantly different in different age rabbits and correlated positively with the level of plasma HDL in high-cholesterol diet rabbits. These results suggest similar function of ADIPOQ gene in rabbits as in other species and indicate the relationship between ADIPOQ gene mRNA expression and high-cholesterol diet and age.
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Adiponectina/genética , Colesterol en la Dieta/administración & dosificación , Conejos/genética , Adiponectina/biosíntesis , Factores de Edad , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Colesterol en la Dieta/metabolismo , HDL-Colesterol/sangre , Clonación Molecular , ADN Complementario/genética , Masculino , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Conejos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoRESUMEN
Nuclear factor of activated T cells 3 (NFAT3) activities have been implicated in many biological processes, such as breast cancer, cardiac hypertrophy, learning and memory, and adipocyte differentiation. However, how protein factors regulate NFAT3 transcriptional activity is poorly understood. Here, we report that regardless of estrogen, overexpression of estrogen receptor alpha and beta (ERalpha and ERbeta) suppresses NFAT3 transcriptional activity, whereas knockdown of endogenous ERalpha and ERbeta enhances the activity. Estrogen further enhances ER inhibition of NFAT3-dependent transcription. ERalpha and ERbeta interact with NFAT3 independently of the NFAT agonists phorbol myristate acetate (PMA) and ionomycin, and ERalpha is recruited to an NFAT3 target gene promoter. Phosphorylation of ERalpha at different sites differentially affects ERalpha modulation of NFAT3 transcriptional activity. These results suggest that ER may play a critical role in regulation of NFAT3 transcriptional activity.
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Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Regulación de la Expresión Génica/genética , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Transcripción Genética/genética , Línea Celular , Receptor alfa de Estrógeno/genética , Receptor beta de Estrógeno/genética , Regulación de la Expresión Génica/efectos de los fármacos , Genes Reporteros/genética , Humanos , Factores de Transcripción NFATC/agonistas , Fosforilación , Regiones Promotoras Genéticas/genética , Proteínas Quinasas/metabolismo , ARN Interferente Pequeño/genética , Transcripción Genética/efectos de los fármacosRESUMEN
BACKGROUND: Glucocorticoids acting as anti-inflammatory or immunosuppressive drugs have been shown to exert most of their effects genomically. Recent findings suggest that non-genomic activity might be relatively more important in mediating the therapeutic effects of high-dose pulsed glucocorticoid. However, few non-genomic anti-inflammatory effects were reported, much less non-genomic mechanisms. OBJECTIVE: This study was performed to investigate the nongenomic effects of glucocorticoids on human neutrophil degranulation. METHODS: Purified human neutrophils were pretreated with 6 alpha-methylprednisolone or hydrocortisone for 5 min, and then primed with N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10(-6) M) or phorbol myristate acetate (PMA) (50 ng/ml) in the presence of cytochalasin B. The release of two markers of neutrophil granules, lactoferrin and myeloperoxidase, was measured by ELISA and enzymology methods respectively. RESULTS: Both 6 alpha-methylprednisolone (10(-5)-10(-4) M) and hydrocortisone (10(-4) M) showed significant inhibitory effects on neutrophil degranulation within 5 min after fMLP administration. For PMA stimulated degranulation, 6 alpha-methylprednisolone (10(-4) M) showed significant inhibitory effects (p < 0.01), while hydrocortisone (10(-4) M) only showed an inhibitory tendency (P > 0.05). Neither RU486 (10(-5) M) nor cycloheximide (10(-4) M) could alter the inhibitory effects of glucocorticoids. CONCLUSION: Our results demonstrate that megadoses of glucocorticoids exert rapid inhibitory effects on human neutrophil degranulation at the cellular level via a new mechanism that is independent of corticosteroid type II receptor occupation or protein synthesis. We infer that these effects may be very important when glucocorticoids act as anti-inflammatory drugs during pulse therapy.