RESUMEN
Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.
Asunto(s)
Infarto del Miocardio , Ratones , Animales , Infarto del Miocardio/metabolismo , Arritmias Cardíacas/genética , Miocardio/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Miocitos Cardíacos/metabolismoRESUMEN
This study aimed to establish an effective prognostic nomogram for microvascular decompression (MVD)-treated trigeminal neuralgia (TN). The nomogram was based on a retrospective cohort study of 1054 patients with TN. During the period 2005-2014, 845 patients at our department treated TN with MVD and served as a development cohort. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The model was externally validated by 209 TN patients during 2014-2016. Multivariate cox analysis suggested that the patient's age, atypical pain, vascular type, number of offending vessels, and second MVD were significant factors influencing the prognosis of MVD-treated TN. The C index of nomogram in the development cohort was 0.767 (95% CI, 0.739-0.794), and 0.749 (95% CI, 0.688-0.810) in the validation cohort. We developed and validated a nomogram to predict 3-year overall remission rate after MVD treatment of TN. The nomogram can be used in clinical trials to determine the likelihood of pain recurrence in TN patients treated with MVD for 3 years to aid in the comprehensive treatment of TN.
Asunto(s)
Cirugía para Descompresión Microvascular , Nomogramas , Neuralgia del Trigémino/cirugía , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/etiología , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Neuralgia del Trigémino/diagnóstico , Neuralgia del Trigémino/mortalidadRESUMEN
OBJECT: Microvascular decompression (MVD) is the most popular surgical procedure for treating Trigeminal neuralgia (TN). In this article, the authors conducted a large case series in which patients underwent MVD for TN, and focus on surgical outcomes, intraoperative findings, complications and risk factors. METHODS: From January 2017 to June 2017, a total of 84 patients with TN were treated with MVD in our department. The authors retrospectively analyzed the surgical outcomes and postoperative complications of these patients. Risk factors were analyzed by binary logistic regression analysis. RESULTS: Of the 84 patients, 69 had complete postoperative symptom relief (BNI I-II). A total of 28 patients developed postoperative facial numbness (BNI III-IV) and 1 patient died intraoperatively. With binary logistic regression analysis, significant risk factors for postoperative Facial numbness (FN) were longer operation time (odds ratio [OR] 1.153, Pâ<0.05) and longer hospital stay (OR 1.371, Pâ<0.05). The patients' age, the length of the disease, the gender, and the side of the disease did not affect the occurrence of postoperative FN. CONCLUSIONS: The study found that patients with TN treated with MVD had a good response rate after surgery. The incidence of FN after surgery is not low, and longer duration of surgery and longer hospital stay are risk factors for FN. In the case of ensuring the success rate of surgery, reducing unnecessary operations, reducing the operation time, will help to reduce the occurrence of FN.
Asunto(s)
Hipoestesia/etiología , Cirugía para Descompresión Microvascular/efectos adversos , Complicaciones Posoperatorias , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Neuralgia del Trigémino/etiologíaRESUMEN
1. Diabetes is often accompanied with depression and hypercholesterolemia. It is possible that paroxetine and pravastatin are co-administered to diabetic patients. The aim of this study was to research the differential effect of pravastatin on plasma exposure of paroxetine in normal and diabetic rats. 2. Pharmacokinetics of paroxetine was investigated following oral administration of paroxetine with and without pravastatin in normal and diabetic rats. Effects of pravastatin on metabolism, intestinal absorption and hepatic uptake of paroxetine were investigated. Activity and expression of hepatic Oatp1 and Oatp2 were also assessed. 3. Pravastatin decreased plasma exposure of paroxetine in normal rats, but increased exposure of paroxetine in diabetic rats. Pravastatin neither affected metabolism nor intestinal absorption of paroxetine. Data from hepatocytes demonstrated that hepatic uptake of paroxetine were involved in Oatp1 and Oatp2. Diabetes suppressed Oatp1 activity and expression, but enhanced Oatp2 activity and expression. Pravastatin stimulated Oatp1 but inhibited Oatp2 activity. 4. We concluded that differential effects of pravastatin on plasma exposure of paroxetine in normal and diabetic rats was partly due to the fact that diabetes suppressed Oatp1 activity and expression but enhanced Oatp2 activity and expression as well as that pravastatin stimulated Oatp1 activity but inhibited Oatp2 activity.
Asunto(s)
Anticolesterolemiantes/farmacología , Paroxetina/metabolismo , Pravastatina/farmacocinética , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Animales , Transporte Biológico , Diabetes Mellitus Experimental , Hepatocitos/metabolismo , Hígado/metabolismo , Pravastatina/farmacología , RatasRESUMEN
AIM: Liver failure is associated with dyshomeostasis of efflux transporters at the blood-brain barrier (BBB), which contributes to hepatic encephalopathy. In this study we examined whether breast cancer resistance protein (BCRP), a major efflux transporter at the BBB, was altered during liver failure in rats. METHODS: Rats underwent bile duct ligation (BDL) surgery, and then were sacrificed after intravenous injection of prazosin on d3, d7 and d14. The brains and blood samples were collected. BCRP function at the BBB was assessed by the brain-to-plasma prazosin concentration ratio; Evans Blue extravasation in the brain tissues was used as an indicator of BBB integrity. The protein levels of BCRP in the brain tissues were detected. Human cerebral microvessel endothelial cells (HCMEC/D3) and Madin-Darby canine kidney cells expressing human BCRP (MDCK-BCRP) were tested in vitro. In addition, hyperbilirubinemia (HB) was induced in rats by intravenous injection of unconjugated bilirubin (UCB). RESULTS: BDL rats exhibited progressive decline of liver function and HB from d3 to d14. In the brain tissues of BDL rats, both the function and protein levels of BCRP were progressively decreased, whereas the BBB integrity was intact. Furthermore, BDL rat serum significantly decreased BCRP function and protein levels in HCMEC/D3 cells. Among the abnormally altered components in BDL rat serum tested, UCB (10, 25 µmol/L) dose-dependently inhibit BCRP function and protein levels in HCMEC/D3 cells, whereas 3 bile acids (CDCA, UDCA and DCA) had no effect. Similar results were obtained in MDCK-BCRP cells and in the brains of HB rats. Correlation analysis revealed that UCB levels were negatively correlated with BCRP expression in the brain tissues of BDL rats and HB rats as well as in two types of cells tested in vitro. CONCLUSION: UCB elevation in BDL rats impairs the function and expression of BCRP at the BBB, thus contributing to hepatic encephalopathy.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/biosíntesis , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/fisiología , Bilirrubina/farmacología , Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Fallo Hepático/fisiopatología , Administración Intravenosa , Animales , Conductos Biliares/cirugía , Bilirrubina/administración & dosificación , Células Cultivadas , Perros , Relación Dosis-Respuesta a Droga , Células Endoteliales , Humanos , Hiperbilirrubinemia/inducido químicamente , Ligadura , Fallo Hepático/metabolismo , Células de Riñón Canino Madin Darby , Prazosina/sangre , Prazosina/farmacocinética , RatasRESUMEN
AIM: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. METHODS: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. ß-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. RESULTS: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, ß-glucuronidase activity in small intestinal content was region-dependent: proximal intestineAsunto(s)
Antiinflamatorios no Esteroideos/efectos adversos
, Ciprofloxacina/farmacología
, Diclofenaco/efectos adversos
, Diclofenaco/farmacocinética
, Circulación Enterohepática/efectos de los fármacos
, Glucuronidasa/antagonistas & inhibidores
, Enfermedades Intestinales/prevención & control
, Intestino Delgado/enzimología
, Animales
, Bovinos
, Diclofenaco/sangre
, Relación Dosis-Respuesta a Droga
, Interacciones Farmacológicas
, Escherichia coli/metabolismo
, Enfermedades Intestinales/inducido químicamente
, Intestino Delgado/efectos de los fármacos
, Hígado/metabolismo
, Masculino
, Ratas
RESUMEN
Clozapine (CLZ) was reported to be associated with hepatotoxicity. Glycyrrhetinic acid (GA) has a liver protective effect. Our preliminary experiments showed that GA aggravated rather than attenuated CLZ-induced hepatotoxicity in primary cultured rat hepatocytes. The study aimed to describe the enhancing effect of GA on CLZ-induced hepatotoxicity in vivo and in vitro. Data from primary cultured rat hepatocytes showed the decreased formation of metabolites demethylclozapine (nor-CLZ) and clozapine N-oxide (CLZ N-oxide). The results in vivo showed that 7-day CLZ treatment led to marked accumulation of triglyceride (TG) and increase in γ-glutamyl transpeptidase (γ-GT) activity, liver weight, and serum AST in rats. Co-administration of GA enhanced the increases in hepatic TG, γ-GT, liver weight, and serum total cholesterol induced by CLZ. GA decreased plasma concentrations of nor-CLZ and CLZ N-oxide. Compared with control rats, hepatic microsomes of GA rats exhibited the decreased formations of nor-CLZ and CLZ N-oxide, accompanied by decreases in activities of CYP2C11 and CYP2C19 and increased activity of CYP1A2. QT-PCR analysis demonstrated that GA enhanced expression of CYP1A2, but suppressed expression of CYP2C11 and CYP2C13. All these results support the conclusion that GA aggravated CLZ-induced hepatotoxicity, which was partly via inhibiting CYP2C11 and CYP2C13 or inducing CYP1A2.
Asunto(s)
Antipsicóticos/toxicidad , Clozapina/toxicidad , Ácido Glicirretínico/toxicidad , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Animales , Hidrocarburo de Aril Hidroxilasas/antagonistas & inhibidores , Hidrocarburo de Aril Hidroxilasas/metabolismo , Células Cultivadas , Colesterol/sangre , Clozapina/análogos & derivados , Clozapina/metabolismo , Citocromo P-450 CYP1A2 , Inhibidores Enzimáticos del Citocromo P-450 , Sistema Enzimático del Citocromo P-450/metabolismo , Familia 2 del Citocromo P450 , Citocromos/metabolismo , Sinergismo Farmacológico , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Esteroide 16-alfa-Hidroxilasa/antagonistas & inhibidores , Esteroide 16-alfa-Hidroxilasa/metabolismo , Triglicéridos/metabolismo , gamma-Glutamiltransferasa/metabolismoRESUMEN
High-throughput chromosome conformation capture (Hi-C) technology captures spatial interactions of DNA sequences into matrices, and software tools are developed to identify topologically associating domains (TADs) from the Hi-C matrices. With structural information theory, SuperTAD adopted a dynamic programming approach to find the TAD hierarchy with minimal structural entropy. However, the algorithm suffers from high time complexity. To accelerate this algorithm, we design and implement an approximation algorithm with a theoretical performance guarantee. We implemented a package, SuperTAD-Fast. Using Hi-C matrices and simulated data, we demonstrated that SuperTAD-Fast achieved great runtime improvement compared with SuperTAD. SuperTAD-Fast shows high consistency and significant enrichment of structural proteins from Hi-C data of human cell lines in comparison with the existing six hierarchical TADs detecting methods.
Asunto(s)
Cromatina , Técnicas Genéticas , Programas Informáticos , Cromatina/química , Cromatina/genética , Simulación por Computador , Algoritmos , Entropía , GenomaRESUMEN
OBJECTIVE: To present a bibliometric analysis of global scientific publications on the nondrug and nonsedative hypnotic treatment of insomnia with regard to influential institutions, publications, countries, research hotspots, trends, and frontiers. METHODS: A literature review was conducted by searching the Web of Science Core Collection (WoSCC) and China National Knowledge Infrastructure (CNKI) databases to identify all publications related to the nondrug and nonsedative hypnotic treatment of insomnia from 2000 to 2021. Eligible publications were reviewed, including annual publication increments, citation analyses, international collaborations, and keyword analyses. The data were analysed using CiteSpace (vers5.8.R3, 6.1.R2 and 6.1.6, College of Computing and Informatics, Philadelphia, PA, USA) and virtualized by knowledge maps. RESULTSï¼In total, 9832 publications were included in this analysis. The results from the WoSCC showed that the United States of America (Count = 2268, 40.33%), Stanford University (Count = 141, 2.51%), and the United States Department of Health and Human Services were the leading country, institute, and funding agency regarding the number of publications, respectively. 'Cognitive-behavioural therapy" was the most popular research topic generated from the cocited reference. The most frequently co-occurring keywords were insomnia, cognitive behavioural therapy, disorder, depression, quality of life, Meta-analysis, older adult, sleep, prevalence and efficacy, while keywords including clinical practice guideline, guideline, and Tai Chi remained popular after 2021. Circadian rhythm was the strongest research frontier for 2000-2021. In China, Chengdu University of Traditional Chinese Medicine (Count = 69, 4.79%) was the most productive institute in this field. The most frequently co-occurring keywords from Chinese literature were sleep disorder, sleep quality, acupuncture and moxibustion, Parkinson's disease, transcranial magnetic stimulation, health education, music therapy, chronic insomnia, quality of life, and nonmotor symptoms. Traditional Chinese medicine was the strongest research frontier for 2019-2021. CONCLUSION: This bibliometric study provides an exhaustive mapping encompassing pertinent institute, publications, influential articles, researchers and topics of the global trend of nondrug and nonsedative hypnotic treatment for insomnia. The results show that the research trend has shifted from primary studies on the efficacy and safety of nondrug and nonsedative hypnotic treatment for insomnia to comorbidity studies. Clinical practice guidelines will potentially become the research frontier for this field post-2021. The findings are important for researchers, clinicians, journal editors, and policy-makers working in the field of nondrug and nonsedative hypnotic treatment for insomnia to understand the strengths and potentials in the current studies and guide future clinical practice, research, and science policy.
Asunto(s)
Bibliometría , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Hipnóticos y Sedantes/uso terapéuticoRESUMEN
BACKGROUND: Globally, insomnia has been shown to impact cognitive function, which has prompted the exploration of effective treatments to enhance cognitive outcomes. Both pharmacological and non-pharmacological interventions vary in their effects, indicating that further research for optimized therapeutic strategies is needed. METHODS: Searches of PubMed, EMBASE, Web of Science, the Cochrane Library, and PsychInfo from database inception until August 2024 were conducted to identify relevant randomized controlled studies investigating the impacts of insomnia treatments on cognitive function. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for all studies. Sensitivity analysis, publication bias, and meta-regression were performed. RESULTS: A total of 14,829 records were retrieved, with 24 randomized controlled studies assessing the impact of insomnia treatment on cognition. Pooled analysis indicated that non-pharmacological interventions significantly enhanced cognitive function (SMD: 0.27, 95% CI: 0.04-0.49, p = 0.019), with notable improvements observed in memory (SMD: 1.18, 95% CI: 0.25-2.12, p = 0.013), attention (SMD: 0.32, 95% CI: 0.15-0.50, p < 0.001), and daily living activities (SMD: 0.29, 95% CI: 0.20-0.39, p < 0.001) based on self-reported measures. Longer follow-up periods were associated with more pronounced cognitive benefits (SMD: 0.34, 95% CI: 0.14-0.54, p = 0.001). CONCLUSIONS: The critical role of insomnia treatments, particularly non-pharmacological interventions, in improving cognitive function is highlighted, emphasizing the importance of tailored therapeutic approaches to optimize cognitive outcomes and overall well-being.
RESUMEN
Follicle-stimulating hormone (FSH), luteinizing hormone (LH), miR-23a, apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase (JNK), autophagy and apoptosis play crucial roles in follicular development. However, their role in yak granulosa cells (GCs) remains unknown. Therefore, we examined the effect of miR-23a, ASK1, FSH, and LH on apoptosis, autophagy, and the release and reception of some steroid hormones in these cells. Our results showed that miR-23a overexpression significantly increased the abundance of Beclin1, the LC3II/I ratio, and the number of Ad-mRFP-GFP-LC3-labeled autophagosomes, and decreased p62 abundance. Additionally, Bax abundance and the number of terminal deoxynucleotidyl transferase deoxynucleotide triphosphate nick end labeling-positive cells were reduced, while Bcl2 expression was increased. Overexpression of miR-23a also significantly increased the abundance of estradiol receptor α (ER-α) and ß (ER-ß) and the concentrations of estradiol (E2), progesterone (P4) in yak GCs. Here, treating yak GCs with miR-23a decreased ASK1 expression, which regulates ASK1/JNK-mediated apoptosis, autophagy, E2 and P4 levels, and ER-α/ß abundance. In contrast, treatment of yak GCs with FSH (10 µg/mL) and LH (100 µg/mL) increased miR-23a abundance, regulating the subsequent effect on ASK1/JNK-mediated apoptosis, autophagy, ER-α/ß abundance, and E2 and P4 concentrations. In conclusion, miR-23a enhances autophagy in yak GCs, attenuates apoptosis, and increases ER-α/ß abundance and E2 and P4 concentrations by downregulating ASK1. Additionally, FSH and LH can regulate these effects of miR-23a by altering its expression. These results provide important insights that can inform the development of strategies to reduce abnormal follicular atresia and improve the reproductive rate of yaks.
Asunto(s)
Hormona Luteinizante , MicroARNs , Animales , Bovinos , Femenino , Apoptosis , Autofagia , Estradiol/metabolismo , Hormona Folículo Estimulante/farmacología , Atresia Folicular/fisiología , Células de la Granulosa/metabolismo , Hormona Luteinizante/farmacología , Hormona Luteinizante/metabolismo , MAP Quinasa Quinasa Quinasa 5/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Progesterona/metabolismoRESUMEN
Transition metal carbides/nitrides/carbonitrides, commonly referred to as MXenes, have gained widespread attention since their discovery in 2011 as a promising family of two-dimensional (2D) materials. Their impressive chemical, electrical, thermal, mechanical, and biological properties have fueled a surge in research focused on the synthesis and application of MXenes in various fields, including membrane-based separation. By engineering the materials and membrane structures, MXene-based membranes have demonstrated remarkable separation performance and added functionalities, such as antifouling and photocatalytic properties. In this review, we aim to have a timely and critical review of research on their fabrication strategy and performance in advanced molecular separation and ion exchange, beginning with a brief introduction of the preparation and physicochemical properties of MXenes. Finally, outlooks and future works are outlined with the aims to provide valuable insights and guidance for advancing membranes' applications in different separation domains.
RESUMEN
Long-read sequencing (LRS) facilitates both the genome assembly and the discovery of structural variants (SVs). Here, we built a graph-based pig pangenome by incorporating 11 LRS genomes with an average of 94.01% BUSCO completeness score, revealing 206-Mb novel sequences. We discovered 183,352 nonredundant SVs (63% novel), representing 12.12% of the reference genome. By genotyping SVs in an additional 196 short-read sequencing samples, we identified thousands of population stratified SVs. Particularly, we detected 7,568 Tibetan specific SVs, some of which demonstrate significant population differentiation between Tibetan and low-altitude pigs, which might be associated with the high-altitude hypoxia adaptation in Tibetan pigs. Further integrating functional genomic data, the most promising candidate genes within the SVs that might contribute to the high-altitude hypoxia adaptation were discovered. Overall, our study generates a benchmark pangenome resource for illustrating the important roles of SVs in adaptive evolution, domestication, and genetic improvement of agronomic traits in pigs.
RESUMEN
Polymerase chain reaction (PCR) and sequencing are useful for species identification of Trichinella spp., especially when their morphological characteristics useful for identifying taxa are lacking. In the present study, nine Trichinella isolates from different provinces in mainland China were identified by the PCR-based method using the 5S ribosomal DNA intergene spacer region (5S ISR) and the mitochondrial large subunit ribosomal DNA genes as molecular markers. The results indicated that eight isolates originating from domestic pigs and one isolate originating from civet cat (Paguma larvata) showed identical DNA banding pattern to Trichinella spiralis. Sequence analysis of the 5S ISR gene further confirmed that the nine Trichinella isolates were T. spiralis and revealed the intraspecies genetic variation within T. spiralis.
Asunto(s)
Variación Genética , Trichinella spiralis/clasificación , Trichinella spiralis/aislamiento & purificación , Triquinelosis/veterinaria , Animales , China , Análisis por Conglomerados , ADN de Helmintos/genética , ADN Espaciador Ribosómico/genética , Genotipo , Tipificación Molecular , Filogenia , ARN Ribosómico 5S/genética , Porcinos , Trichinella spiralis/genética , Triquinelosis/parasitología , ViverridaeRESUMEN
OBJECTIVE: To investigate the effect of 10.6-µm laser moxibustion (LM) and traditional moxibustion (TM) on kidney deficiency (KYD) model rats. METHODS: Forty rats were randomly divided into normal, model, 10.6-µm LM, and TM groups. KYD was induced through intramuscular hydrocortisone injections. RESULTS: Hydrocortisone injections decreased the body weight, activity, and temperature and induced changes in the organ coefficients. Compared with the model group, TM and LM treatment prevented body weight loss and improved organ coefficients after treatment ( < 0.05), while the body weight remained lower compared to the normal group ( < 0.01). Additionally, LM and TM significantly increased the levels of urine 17-hydroxycorticosteroid (17-OHCS) compared with the model group ( < 0.01). The LM and TM groups showed a greater distance travelled across the central area, time spent in the central area, and 5-min total distance than the model group in the open field test ( < 0.01). The model group had the lowest anal or surface temperature ( < 0.05); there were no differences among the other three groups ( > 0.05). TM treatment increased the temperature of Mingmen (GV4) and Guanyuan (CV4) compared to the model group ( < 0.05, < 0.01). LM treatment increased Mingmen (GV4) temperature ( < 0.05), while there were no obvious differences in Guanyuan (CV4) temperature compared with the normal group before and after treatment ( > 0.05). There was a positive correlation between Mingmen (GV4)/Guanyuan (CV4) temperature and 17-OHCS levels. CONCLUSIONS: LM and TM treatment can improve KYD symptoms, and acupoint temperature changes may be an objective indicator of KYD.
Asunto(s)
Moxibustión , Ratas , Animales , Hidrocortisona , Puntos de Acupuntura , Riñón , Peso CorporalRESUMEN
Considering the trans-cleavage capabilities, high-specificity and programmability, the CRISPR-Cas system has been recognized as a valuable platform to develop the next-generation diagnostic biosensors. However, due to the natural interaction with nucleic acids, current CRISPR-Cas-based detection mostly applies in nucleic acid analysis rather than non-nucleic acid analysis. By virtue of spherical nucleic acids (SNAs) with programmability and specificity, the Y-shaped DNA nanostructures assembled-SNAs (Y-SNAs) were rationally designed as target converters to achieve the quantitative activation of CRISPR-Cas12a, enabling a highly specific and sensitive electrochemiluminescence (ECL) determination of alpha-methylacyl-CoA racemase (AMACR), a high specific protein biomarker of prostate cancer. Significantly, the Y-shaped DNA nanostructures comprised of assisted DNA (A1), AMACR aptamer and DNA activator of CRISPR-Cas12a were loaded on Au nanoparticles modified Fe3O4 magnetic beads (Au@Fe3O4 MBs) to construct the robust Y-SNAs. In the presence of the target AMACR, the Y-SNAs as target converters could achieve quantitative activation of CRISPR-Cas12a by outputting the DNA activators with a linear relationship to the target. The amplified ECL signals were triggered by the release of the ferrocene-labeled quenching probes (QPs) on the electrode surface due to the trans-cleavage activity of CRISPR-Cas12a, thereby realizing the sensitive ECL determination of AMACR from 10 ng/mL to 100 µg/mL with the detection limit of 1.25 ng/mL. In general, this approach provides novel perspectives on how to design a universal ECL platform of the CRISPR-Cas system to detect the non-nucleic acid targets beyond the traditional methods.
Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Nanoestructuras , Ácidos Nucleicos , Sistemas CRISPR-Cas/genética , ADN/química , Oro/químicaRESUMEN
The first human case with trichinellosis was reported in 1964 in Tibet, China. However, up to the present, the etiological agent of trichinellosis has been unclear. The aim of this study was to identify a Tibet Trichinella isolate at a species level by PCR-based methods. Multiplex PCR revealed amplicon of the expected size (173 bp) for Trichinella spiralis in assays containing larval DNA from Tibet Trichinella isolate from a naturally infected pig. The Tibet Trichinella isolate was also identified by PCR amplification of the 5S ribosomal DNA intergenic spacer region (5S ISR) and mitochondrial large-subunit ribosomal RNA (mt-lsrDNA) gene sequences. The results showed that 2 DNA fragments (749 bp and 445 bp) of the Tibet Trichinella isolate were identical to that of the reference isolates of T. spiralis. The Tibet Trichinella isolate might be classifiable to T. spiralis. This is the first report on T. spiralis in southwestern China.
Asunto(s)
Enfermedades de los Porcinos/parasitología , Trichinella spiralis/clasificación , Triquinelosis/veterinaria , Animales , ADN de Helmintos/química , ADN de Helmintos/genética , ADN Mitocondrial/química , ADN Mitocondrial/genética , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/genética , Genotipo , Humanos , Reacción en Cadena de la Polimerasa Multiplex , ARN Ribosómico 5S/genética , Análisis de Secuencia de ADN , Porcinos , Tibet , Trichinella spiralis/genética , Trichinella spiralis/aislamiento & purificación , Triquinelosis/parasitologíaRESUMEN
Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Hence, we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo. In this study, we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo. Compared with that in normal epidermal melanocytes (PIG1), the expression of SFRP5 was increased in vitiligo melanocytes (PIG3V). To investigate the effect of SFRP5 on melanin synthesis, PIG1 cells were infected with recombinant SFRP5 adenovirus (AdSFRP5), and PIG3V cells were infected with recombinant siSFRP5 adenovirus (AdsiSFRP5). The results showed that SFRP5 overexpression inhibited melanin synthesis in PIG1 cells through downregulation of microphthalmia-associated transcription factor (MITF) and its target proteins via suppression of the Wnt/ß-catenin signaling pathway. Accordingly, SFRP5 silencing increased melanin synthesis and activated the Wnt signaling pathway in PIG3V cells. Moreover, SFRP5 overexpression also downregulated the transcriptional activity of T cell factor/lymphoid enhancer factor (TCF/LEF) in PIG1 cells. Furthermore, this inhibitory effect of SFRP5 on melanin synthesis was reversed by treatment with the ß-catenin agonist, SKL2001. The inhibitory action of SFRP5 in pigmentation was further confirmed in vivo using a nude mouse model. Hence, our results indicate that SFRP5 can inhibit melanogenesis in melanocytes. Additionally, our findings showed that SFRP5 plays a vital role in the development of vitiligo, and thus may serve as a potential therapeutic target for vitiligo.
RESUMEN
OBJECTIVE: To observe the effect of edible vinegar or soy sauce on the infectivity and reproductive capacity of muscle larvae of Trichinella spiralis. METHODS: One hundred and forty male Kunming mice were randomly divided into 14 groups (10 mice per group). Mice in each group were orally fed with 300 muscle larvae in meat (weighing 0.02 g) soaked with edible vinegar (pH 3.05, 4.5% acid), soy (19.3% NaCl) or saline (control) for different time respectively. Half of the infected mice were sacrificed on day 7 and day 42 post-infection respectively. The intestinal adult worms and muscle larvae were observed, and reproductive capacity index (RCI) was determined. RESULTS: The intestinal adult worms (77, 41, 0, and 0, respectively) and RCI (52.48, 18.45, 0, and 0, respectively) in mice fed with 300 muscle larvae treated by vinegar for 3, 6, 12, and 24 h were considerably lower than that in saline control (worm number 121, 121, 116, and 101; RCI 159.10, 124.56, 73.63, and 42.17) (P<0.05). The intestinal adult worms (79.00, 39.00, 3.40, and 0) and RCI (48.75, 20.80, 1.87, and 0) in mice fed with soy-treated larvae for 12, 24, 36, and 48 h were also significantly lower than that in saline control (worm number 116, 101, 95, and 89; RCI 73.63, 42.17, 21.53, and 4.13) (P<0.05). Trend analysis showed that the intestinal adult worms and RCI of the infected mice decreased along with the increase of vinegar- or soy-soaking time (P<0.05). CONCLUSION: The infectivity and fecundity of T. spiralis muscle larvae decrease gradually after the treatment of edible vinegar or soy sauce.
Asunto(s)
Ácido Acético , Alimentos de Soja , Trichinella spiralis/fisiología , Trichinella spiralis/patogenicidad , Animales , Fertilidad , Larva/patogenicidad , Larva/fisiología , Masculino , Ratones , Ratones Endogámicos , TriquinelosisRESUMEN
OBJECTIVE: We explored the remission rate of different branches of the trigeminal nerve after microvascular decompression. METHODS: A retrospective analysis of trigeminal neuralgia patients treated with microvascular decompression in our department from January 2014 to January 2015 was conducted to investigate the prognosis and factors affecting prognosis. RESULTS: One-hundred and fifty-five patients with trigeminal neuralgia including 2 patients with V1 division had a remission rate of 100% at 1 day, 3 months, 1 year, and 3 years after surgery; 93.5%, 93.5%, 90.3%, and 67.7% of patients with V1-2 division. The patients with V1-3 division had rates of 91.7%, 87.5%, 75.0%, and 66.7%; V2 division rates were 88.4%, 81.4%, 76.7%, and 69.8%; V2-3 division rates were 90.2%, 90.2%, 87.8%, and 75.6%; and V3 division were 100%, 100%, 92.9%, and 92.9%. CONCLUSIONS: Postoperative remission rate of non-V2-related branches (V1, V3) are higher than V2-related branches (V2, V1-2, V1-3, V2-3).