RESUMEN
Complex plasmas consist of ionized gas and charged solid microparticles, representing the plasma state of soft matter. We apply machine learning methods to investigate a melting transition in a two-dimensional complex plasma. A convolutional neural network is constructed and trained with the numerical simulation. The hexatic phase is successfully identified and the evolution of topological defects is studied during melting transition in both simulations and experiments.
RESUMEN
The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.
Asunto(s)
Criopreservación , Ovario , Criopreservación/métodos , Femenino , Humanos , AnimalesRESUMEN
The proportions of the various muscle fiber types are important in the regulation of skeletal muscle metabolism, as well as animal meat production. Four-and-a-half LIM domain protein 3 (FHL3) is highly expressed in fast glycolytic muscle fibers and differentially regulates the expression of myosin heavy chain (MyHC) isoforms at the cellular level. Whether FHL3 regulates the transformation of muscle fiber types in vivo and the regulatory mechanism is unclear. In this study, muscle-specific FHL3 transgenic mice were generated by random integration, and lentivirus-mediated gene knockdown or overexpression in muscles of mice or pigs was conducted. Functional analysis showed that overexpression of FHL3 in muscles significantly increased the proportion of fast-twitch myofibers and muscle mass but decreased muscle succinate dehydrogenase (SDH) activity and whole-body oxygen consumption. Lentivirus-mediated FHL3 knockdown in muscles significantly decreased muscle mass and the proportion of fast-twitch myofibers. Mechanistically, FHL3 directly interacted with the Yin yang 1 (YY1) DNA-binding domain, repressed the binding of YY1 to the fast glycolytic MyHC2b gene regulatory region, and thereby promoted MyHC2b expression. FHL3 also competed with EZH2 to bind the repression domain of YY1 and reduced H3K27me3 enrichment in the MyHC2b regulatory region. Moreover, FHL3 overexpression reduced glucose tolerance by affecting muscle glycolytic metabolism, and its mRNA expression in muscle was positively associated with hemoglobin A1c (HbA1c) in patients with type 2 diabetes. Therefore, FHL3 is a novel potential target gene for the treatment of muscle metabolism-related diseases and improvement of animal meat production.
Asunto(s)
Diabetes Mellitus Tipo 2 , Ratones , Porcinos , Animales , Diabetes Mellitus Tipo 2/metabolismo , Fibras Musculares de Contracción Rápida/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Glucólisis/genética , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismoRESUMEN
Long noncoding RNAs (lncRNAs) play important roles in the spatial and temporal regulation of muscle development and regeneration. Nevertheless, the determination of their biological functions and mechanisms underlying muscle regeneration remains challenging. Here, we identified a lncRNA named lncMREF (lncRNA muscle regeneration enhancement factor) as a conserved positive regulator of muscle regeneration among mice, pigs and humans. Functional studies demonstrated that lncMREF, which is mainly expressed in differentiated muscle satellite cells, promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin accessibility when muscle satellite cells are activated and start to differentiate, thereby facilitating genomic binding of p300/CBP/H3K27ac to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a novel temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration.
Asunto(s)
ARN Largo no Codificante , Adenosina Trifosfatasas , Animales , Diferenciación Celular , Línea Celular , Cromatina/genética , Cromatina/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Epigénesis Genética , Humanos , Ratones , Desarrollo de Músculos , Músculo Esquelético/metabolismo , Proteína MioD/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Regeneración , PorcinosRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that seriously threatens the health of patients. The pathogenesis of IPF is still unclear, and there is a lack of effective therapeutic drugs. Myofibroblasts are the main effector cells of IPF, leading to excessive deposition of extracellular matrix (ECM) and promoting the progression of fibrosis. Inhibiting the excessive activation and relieving autophagy blockage of myofibroblasts is the key to treat IPF. PI3K/Akt/mTOR pathway plays a key regulatory role in promoting fibroblast activation and autophagy inhibition in lung fibrosis. Duvelisib is a PI3K inhibitor that can simultaneously inhibit the activities of PI3K-δ and PI3K-γ, and is mainly used for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma tumour (SLL). In this study, we aimed to examine the effects of Duvelisib on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of Duvelisib on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of Duvelisib in lung fibroblasts in vitro. The in vivo experiments showed that Duvelisib significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro and in vivo pharmacological experiments showed that Duvelisib dose-dependently suppressed lung fibroblast activation and improved autophagy inhibition by inhibiting the phosphorylation of PI3K, Akt and mTOR. Our results indicate that Duvelisib can alleviate the severity of pulmonary fibrosis and provide potential drugs for the treatment of pulmonary fibrosis.
Asunto(s)
Fibrosis Pulmonar Idiopática , Proteínas Proto-Oncogénicas c-akt , Animales , Ratones , Bleomicina/toxicidad , Fibroblastos/metabolismo , Fibrosis Pulmonar Idiopática/metabolismo , Pulmón/patología , Recurrencia Local de Neoplasia/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Schwann cells are functional cells in nerve regeneration and are commonly used as seed cells in tissue engineering. Enhanced Schwann cell migration capacity improves recovery effects, and thus, the identification of Schwann cells with greater migration ability is of great importance. In the present study, we examined the biological activities of Schwann cells collected from rat sciatic nerves (SN) and dorsal root ganglia (DRG). Observations from transwell migration assay and wound healing assay demonstrate that DRG Schwann cells migrate at a faster speed as compared with SN Schwann cells. Sequencing and bioinformatics suggest that differentially expressed genes between SN and DRG Schwann cells are associated with cell motility and migration. miR-140 and miR-200, two microRNAs (miRNAs) that are highly expressed in SN Schwann cells negatively influence Schwann cell migration and thus may be key regulators of Schwann cell phenotype. Igsf10, Plxna2, and Lcp1 are screened as candidate downstream targets of miR-140 and miR-200 based on bioinformatic analysis and their expression correlation with miRNAs. Our comparative analysis displays the unique characteristics of Schwann cells in different anatomical localizations and demonstrates that DRG Schwann cells are suitable seed cells for tissue engineering and regenerative medicine.
Asunto(s)
MicroARNs , Células de Schwann , Animales , Ratas , Movimiento Celular/genética , Células Cultivadas , Ganglios Espinales/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Regeneración Nerviosa/genética , Proteínas del Tejido Nervioso/metabolismo , Ratas Sprague-Dawley , Receptores de Superficie Celular/metabolismo , Células de Schwann/metabolismo , Nervio Ciático/metabolismoRESUMEN
BACKGROUND: Complications and diagnostic efficiency for liver biopsy are main concerns for clinicians. This study aimed to assess the safety and efficacy of transjugular liver biopsy (TJLB) compared with percutaneous liver biopsy (PLB) when patients had equal level of liver function and number of passes, using propensity score matching (PSM). METHODS: The clinical and pathological data of patients who received TJLB or PLB between January 2012 and October 2022 were collected. Matching factors included age, gender, cirrhosis, portal hypertension, liver function, creatinine, number of passes, hemodialysis, history of anti-coagulation and anti-platelet, and comorbidities. Coagulation indexes were not considered as matching factors due to different indications of the two techniques. RESULTS: 2711 PLBs and 30 TJLBs were evaluated. By PSM, 75 patients (50 PLBs, 25 TJLBs) were matched. The complication rates for TJLB and PLB were 4.0% (1/25) and 10.0% (5/50) (P > 0.05). Two PLBs had hepatic hemorrhage, one of which required only close monitoring (Grade 1) and the other needed hemostasis and rehydration therapy (Grade 2). The other 3 cases presented with mild abdominal pain (Grade 1). And only one TJLB presented with mild pain. The median number of complete portal tracts were 6.0 and 10.0 for TJLBs and PLBs (P < 0.05). Moreover, the median length of sample for TJLBs and PLBs were 10.0 and 16.5 mm (P < 0.05). The diagnostic efficiency of hepatopathy of unknown etiology of TJLB versus PLB groups before and after matching were 96.4% vs. 94.1% and 95.7% vs. 93.2%, respectively (P > 0.05). CONCLUSION: TJLB is an effective invasive diagnostic procedure that expands indications for liver biopsy with reliable diagnostic quality.
Asunto(s)
Hipertensión Portal , Hepatopatías , Humanos , Venas Yugulares/patología , Hígado/patología , Biopsia/efectos adversos , Biopsia/métodos , Hepatopatías/patología , Hipertensión Portal/etiología , Hipertensión Portal/patología , Dolor Abdominal/etiologíaRESUMEN
The integration of molecular chain changes on a microscopic scale to achieve macroscopic performance is crucial in degradation processes concerning O-ring seals. Nonetheless, a comprehensive and compelling mathematical model that can describe molecular chains' material properties and macroscopic material properties simultaneously for O-rings under high-pressure conditions is yet to be established. In this paper, we propose a degradation model based on viscoelasticity and molecular chain statistics for hydrogen permeation. The proposed model aims to establish the relationship between the material molecular chains and macroscopic material properties, with a primary focus on accurately recognizing the performance degradation process of rubber sealing rings. We verify the model's reliability through uniaxial tensile strength experiments and high-pressure hydrogen immersion experiments, respectively. Predictions of the model exhibit favorable conformity with the experimental data concerning the above phenomena. Furthermore, we derive the number of molecular chains and maximum strain of the degradation process. Based on the similarity of the degradation process's descent, it is plausible to speculate that NBR properties' degradation can be characterized by the average number of molecular chains.
RESUMEN
Although some tumor has become a curable disease for many patients, involvement of the central nervous system (CNS) is still a major concern. The blood-brain barrier (BBB), a special structure in the CNS, protects the brain from bloodborne pathogens via its excellent barrier properties and hinders new drug development for brain tumor. Recent breakthroughs in nanotechnology have resulted in various nanovehicless (NPs) as drug carriers to cross the BBB by different strategys. Here, the complex compositions and special characteristics of causes of brain tumor formation and BBB are elucidated exhaustively. Additionally, versatile drug nanovehicles with their recent applications and their pathways on different drug delivery strategies to overcome the BBB obstacle for anti-brain tumor are briefly discussed. Customizing nanoparticles for brain tumor treatments is proposed to improve the efficacy of brain tumor treatments via drug delivery from the gut to the brain. This review provides a broad perspective on customizing delivery nano-vehicles characteristics facilitate drug distribution across the brain and pave the way for the creation of innovative nanotechnology-based nanomaterials for brain tumor treatments.
Asunto(s)
Neoplasias Encefálicas , Nanopartículas , Humanos , Encéfalo/fisiología , Barrera Hematoencefálica/metabolismo , Sistema Nervioso Central/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismoRESUMEN
Oral administration is preferred over other drug delivery methods due to its safety, high patient compliance, ease of ingestion without discomfort, and tolerance of a wide range of medications. However, oral drug delivery is limited by the poor oral bioavailability of many drugs, caused by extreme conditions and absorption challenges in the gastrointestinal tract. This review thoroughly discusses the targeted drug vehicles to the intestinal lymphatic system (ILS). It explores the structure and physiological barriers of the ILS, highlighting its significance in dietary lipid and medication absorption and transport. The review presents various approaches to targeting the ILS using spatially precise vehicles, aiming to enhance bioavailability, achieve targeted delivery, and reduce first-pass metabolism with serve in clinic. Furthermore, the review outlines several methods for leveraging these vehicles to open the ILS window, paving the way for potential clinical applications in cancer treatment and oral vaccine delivery. By focusing on targeted drug vehicles to the ILS, this article emphasizes the critical role of these strategies in improving therapeutic efficacy and patient outcomes. Overall, this article emphasizes the critical role of targeted drug vehicles to the ILS and the potential impact of these strategies on improving therapeutic efficacy and patient outcomes.
Asunto(s)
Tracto Gastrointestinal , Sistema Linfático , Humanos , Preparaciones Farmacéuticas , Sistemas de Liberación de Medicamentos , Disponibilidad Biológica , Administración OralRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by alveolar epithelial cell injury and lung fibroblast overactivation. At present, only two drugs are approved by the FDA for the treatment of IPF, including the synthetic pyridinone drug, pirfenidone, and the tyrosine kinase inhibitor, nintedanib. Avitinib (AVB) is a novel oral and potent third-generation tyrosine kinase inhibitor for treating non-small cell lung cancer (NSCLC). However, the role of avitinib in pulmonary fibrosis has not yet been established. In the present study, we used in vivo and in vitro models to evaluate the role of avitinib in pulmonary fibrosis. In vivo experiments first verified that avitinib significantly alleviated bleomycin-induced pulmonary fibrosis in mice. Further in vitro molecular studies indicated that avitinib inhibited myofibroblast activation, migration and extracellular matrix (ECM) production in NIH-3T3 cells, mainly by inhibiting the TGF-ß1/Smad3 signalling pathways. The cellular experiments also indicated that avitinib improved alveolar epithelial cell injury in A549 cells. In conclusion, the present findings demonstrated that avitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting alveolar epithelial cell injury and myofibroblast activation.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Fibrosis Pulmonar Idiopática , Neoplasias Pulmonares , Ratones , Animales , Bleomicina , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmón/metabolismo , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Fibroblastos/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Ratones Endogámicos C57BLRESUMEN
OBJECTIVE: To identify suitable reference genes for gene expression studies in rat dorsal root ganglia (DRG) neurons. METHODS: The raw cycle threshold (Ct) values of 12 selected reference genes were obtained via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in neurons at different developmental stages or under different treatments. Two strategies were employed to screen the most stable reference genes: the genes were ranked according to the coefficient of biological variation and further validated using geNorm and NormFinder programs. The stable and unstable reference genes were subsequently used as internal controls to assess their effects on target gene expression. RESULTS: All reference genes showed varying degrees of fluctuation in Ct values during the growth process of neurons or after different treatments. 18S ribosomal RNA (Rn18s) and ß-actin (Actb) exhibited the most significant changes, while ubiquitin C (Ubc), hypoxanthine phosphoribosyl transferase (Hprt), and mitochondrial ribosomal protein L10 (Mrpl10) showed relatively minor changes. The most stable and unstable genes obtained by different evaluation methods varied slightly. Overall, Actb was found to be the most unstable reference gene, while Hprt was the relatively most stable reference gene. The use of unstable reference genes Actb and ankyrin repeat domain 27 (Ankrd27) as internal controls led to high variability within the control group, ultimately affecting the determination of target gene expression. In contrast, the stable reference gene Hprt had small inter-assay variation and high stability. CONCLUSIONS: Our observations indicate that Hprt is a proper endogenous reference gene for qRT-PCR analysis in rat DRG neurons and thus provides a critical molecular basis for the genetic characterization in neurological disorders.
Asunto(s)
Ganglios Espinales , Transcripción Reversa , Animales , Ratas , Neuronas , Reacción en Cadena de la PolimerasaRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with unknown etiology, high mortality and limited treatment options. It is characterized by myofibroblast proliferation and extensive deposition of extracellular matrix (ECM), which will lead to fibrous proliferation and the destruction of lung structure. Transforming growth factor-ß1 (TGF-ß1) is widely recognized as a central pathway of pulmonary fibrosis, and the suppression of TGF-ß1 or the TGF-ß1-regulated signaling pathway may thus offer potential antifibrotic therapies. JAK-STAT is a downstream signaling pathway regulated by TGF-ß1. JAK1/2 inhibitor baricitinib is a marketed drug for the treatment of rheumatoid arthritis, but its role in pulmonary fibrosis has not been reported. This study explored the potential effect and mechanism of baricitinib on pulmonary fibrosis in vivo and in vitro. The in vivo studies have shown that baricitinib can effectively attenuate bleomycin (BLM)-induced pulmonary fibrosis, and in vitro studies showed that baricitinib attenuates TGF-ß1-induced fibroblast activation and epithelial cell injury by inhibiting TGF-ß1/non-Smad and TGF-ß1/JAK/STAT signaling pathways, respectively. In conclusion, baricitinib, a JAK1/2 inhibitor, impedes myofibroblast activation and epithelial injury via targeting the TGF-ß1 signaling pathway and reduces BLM-induced pulmonary fibrosis in mice.
Asunto(s)
Fibrosis Pulmonar Idiopática , Factor de Crecimiento Transformador beta1 , Ratones , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Bleomicina/farmacología , Pulmón , Transducción de Señal , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibroblastos , Ratones Endogámicos C57BLRESUMEN
The development of disease detection by biosensors represents one of the key components of medical science. However, millions of people are still misdiagnosed each year due to the poor efficacy and thermal instability of biosensors. Using horseradish peroxidase (HRP) as a paradigm, we offer a rational design strategy to optimize the thermostability and activity of biosensors by biomimetic mineralization. To overcome the weak thermostability of the biosensor, the mineralization of Fe-MOF forms an armor on HRP that protects against high temperature. Additionally, the biomimetic mineralization HRP@Fe-MOF can double-catalyze the TMB/H2O2 chromogenic system for color development. The biosensor can also be recycled through simple heat treatment due to the thermally stable aptamer and biomimetic mineralization HRP@Fe-MOF. The optical biosensor based on this sensitive spectral transformation was successfully developed for the measurement of AßO with an outstanding linear range (0.0001-10 nM) and a low limit of detection (LOD) of 0.03 pM. This promising platform will open up new avenues for the detection of AßO in the early diagnosis of Alzheimer's disease (AD).
Asunto(s)
Enfermedad de Alzheimer , Técnicas Biosensibles , Humanos , Peroxidasa de Rábano Silvestre , Biomimética , Peróxido de Hidrógeno , Enfermedad de Alzheimer/diagnósticoRESUMEN
Amyloid-beta (Aß) oligomers causing neuron damage are regarded as potential therapeutic targets and diagnostic markers for Alzheimer's disease (AD). A homogeneous turn-on fluorometric aptasensor is described for Aß oligomers. It is highly selective and non-invasive and based on (a) the use of a luminescent metal-organic framework carrying aptamer-modified AuNPs (L-MOF/Apt-Au) as tracking agent, and (b) enzyme-assisted target recycling signal amplification. The tracking agent does not emit fluoresce by fluorescence resonance energy transfer (FRET) between the luminescent MOF as donor and Apt-Au as the acceptor under the excitation wavelength of 466 nm. When Aß oligomers are added to the tracking agent solution, the Apt-Au on tracking agent can preferentially bind with Aß oligomers and then be released. This turns the "off" signal of the luminescent MOF tracer to the "on" state. The enzyme (Rec Jf exonuclease) added into the supernatant further improves sensitivity due to enzyme-assisted target-recycling signal amplification. The assay has an excellent linear response to Aß oligomers from 1.0 pM to 10 nM, with a detection limit of 0.3 pM. This homogeneous turn-on fluorometric method is expected to have potential and applications in clinical diagnosis. Graphical abstractSchematic representation of fluorometric assay for amyloid-ß oligomers based on luminescence metal-organic framework nanocomposites as tracking agent with exonuclease-assisted target recycling.
Asunto(s)
Péptidos beta-Amiloides/análisis , Aptámeros de Nucleótidos , Fluorometría/métodos , Estructuras Metalorgánicas/química , Reciclaje/métodos , Enfermedad de Alzheimer/diagnóstico , Técnicas Biosensibles/métodos , Exonucleasas , Oro , Humanos , Límite de Detección , Nanopartículas del Metal/químicaRESUMEN
To early effectively detect amyloid-beta (Aß) oligomers, a label-free reusable aptasensor was designed. This aptasensor based on a luminescent nanoscale lanthanum-based metal-organic framework (L-MOF)-armored single-stranded DNA antibody (MOF-armored-anti-DNA antibody) as signal tags and aptamer bound to magnetic beads (Apt-MB) as capture probe. The reusable aptasensor combines signal tag and capture probe with antigen-antibody interaction. When the reusable aptasensor is formed, the strong fluorescence intensity of L-MOF will "turn off" by photo-induced electron transfer from excited states to an unfilled d shell of iron cations on the nanoparticle surface. Upon the presence of Aß oligomers in serum samples, they can be especially distinguished with the Aß oligomers aptamer in capture probes and then signal tags are released into the solution for developing the fluorescence aptasensor under excitation/emission 365 nm/430 nm. Meanwhile, the aptamer was recovered from the complex of Aß oligomers/Apt-MB by heat treatment. When the temperature returns to room temperature, the recovered aptamer in the capture probe can once again bound to the MOF-armored-anti-DNA antibody for reuse. The label-free reusable aptasensor system detection has high sensitivity and selectivity toward Aß oligomers (LOD = 0.4 pg/mL) and an excellent linear range (0.001-100 ng/mL). This strategy is a fruitful step for the development of reusable aptasensor and may turn on new avenues for the applications of Aß oligomer detection in clinical diagnosis.Graphical abstract.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides/sangre , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Péptidos beta-Amiloides/química , Anticuerpos Inmovilizados/inmunología , Aptámeros de Nucleótidos/inmunología , ADN de Cadena Simple/química , ADN de Cadena Simple/inmunología , Colorantes Fluorescentes/química , Humanos , Separación Inmunomagnética , Lantano/química , Límite de Detección , Nanopartículas de Magnetita/química , Estructuras Metalorgánicas/química , Estructura Cuaternaria de Proteína , Espectrometría de FluorescenciaRESUMEN
Genetic iron-overload disorders, mainly hereditary hemochromatosis and untransfused ß-thalassemia, affect a large population worldwide. The primary etiology of iron overload in these diseases is insufficient production of hepcidin by the liver, leading to excessive intestinal iron absorption and iron efflux from macrophages. Hepcidin agonists would therefore be expected to ameliorate iron overload in hereditary hemochromatosis and ß-thalassemia. In the current study, we screened our synthetic library of 210 thiazolidinone compounds and identified three thiazolidinone compounds, 93, 156 and 165, which stimulated hepatic hepcidin production. In a hemochromatosis mouse model with hemochromatosis deficiency, the three compounds prevented the development of iron overload and elicited iron redistribution from the liver to the spleen. Moreover, these compounds also greatly ameliorated iron overload and mitigated ineffective erythropoiesis in ß-thalassemic mice. Compounds 93, 156 and 165 acted by promoting SMAD1/5/8 signaling through differentially repressing ERK1/2 phosphorylation and decreasing transmembrane protease serine 6 activity. Additionally, compounds 93, 156 and 165 targeted erythroid regulators to strengthen hepcidin expression. Therefore, our hepcidin agonists induced hepcidin expression synergistically through a direct action on hepatocytes via SMAD1/5/8 signaling and an indirect action via eythroid cells. By increasing hepcidin production, thiazolidinone compounds may provide a useful alternative for the treatment of iron-overload disorders.
Asunto(s)
Hemocromatosis/tratamiento farmacológico , Sobrecarga de Hierro/tratamiento farmacológico , Tiazolidinedionas/farmacología , Talasemia beta/tratamiento farmacológico , Animales , Química Farmacéutica , Técnicas Químicas Combinatorias , Modelos Animales de Enfermedad , Diseño de Fármacos , Eritropoyesis/efectos de los fármacos , Hepcidinas/agonistas , Hepcidinas/biosíntesis , Hígado/efectos de los fármacos , Masculino , Ratones , Fosforilación , Transducción de SeñalRESUMEN
BACKGROUND: To date no study has compared more specifically the psychotropic medication treatment patterns for patients with schizophrenia living in community between rural and urban areas. This study examined the rural-urban differences of the use of psychotropic drugs among community-dwelling individuals with schizophrenia in China. METHOD: Data on 993 community-dwelling patients with schizophrenia (n = 479 in rural area and n = 514 urban area) were collected by interviews during 2013-2014, and 2015-2016 according to the diagnosis of DSM-IV or ICD-10. Data on patients' socio-demographic and clinical characteristics, prescriptions of psychotropic drugs were collected using a standardized protocol and data acquisition procedure. RESULTS: Multivariate analyses revealed that in comparison with the rural counterparts, the patients from the urban area were significantly more frequently prescribed antipsychotic polypharmacy, clozapine, and benzodiazepines, but the patients from the rural area had more frequently prescribed anticholinergics. CONCLUSIONS: Substantial variations in psychotropic medication treatment patterns for patients with schizophrenia living in community were found between rural and urban areas in China. Common use of antipsychotic polypharmacy, clozapine and benzodiazepines in urban area, and anticholinergics in rural area need to be further addressed.
Asunto(s)
Prescripciones de Medicamentos/estadística & datos numéricos , Psicotrópicos/uso terapéutico , Población Rural/estadística & datos numéricos , Esquizofrenia/tratamiento farmacológico , Población Urbana/estadística & datos numéricos , Adulto , Benzodiazepinas/uso terapéutico , China , Clozapina/uso terapéutico , Demografía , Femenino , Humanos , Vida Independiente/psicología , Vida Independiente/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Polifarmacia , Pautas de la Práctica en Medicina/estadística & datos numéricosRESUMEN
BACKGROUND: The purpose of this study was to evaluate the coverage of HIV health education among rural residents in western China by ascertaining their awareness of HIV/AIDS and its transmission routes, and to investigate how these residents receive health information. METHODS: A survey was conducted through stratified clustered sampling at 99 county hospitals in 11 provinces in western China. Information was collected on awareness of HIV/AIDS and its transmission routes, as well as residents' access to health knowledge. Chi-square analysis was used to analyse the differences in HIV/AIDS awareness (knowing of the existence of HIV/AIDS, hereinafter referred to as "HIV awareness rate") between different subgroups categorized by demographic status, regional factors, and different methods of access to health knowledge. To further analyse the effects of access to health knowledge on HIV awareness, a logistic regression model was established. The relationship between access to health knowledge and transmission routes was also examined using chi-square analysis. RESULTS: The HIV awareness rate of the total 9274 participants was 80.9%. There were statistically significant differences between subgroups classified by age (χ2 = 482.118, p<0.001), education (χ2 = 853.465, p<0.001), occupation (χ2 = 340.553, p<0.001), income (χ2 = 186.448, p<0.001), cumulative HIV cases according to province (χ2 = 59.513, p<0.001), per capita annual net income of rural households according to province (χ2 = 64.676, p<0.001), proportion of minority population according to province (χ2 = 94.898, p<0.001), direct access to health knowledge (medical staff: χ2 = 419.775, p<0.001; mass media: χ2 = 740.238, p<0.001; family members: χ2 = 12.189, p<0.001; socializing: χ2 = 48.780, p<0.001; health education activities: χ2 = 154.400, p<0.001), and indirect access to health knowledge (having a non-communicable disease with medical instructions χ2 = 78.709, p<0.001; physical examinations: χ2 = 135.679, p<0.001). The logistic regression model showed that education and mass media had the strongest impacts on HIV awareness among all methods of access. Participants had the least awareness of HIV's mother-to-child transmission route. CONCLUSION: The HIV awareness rate indicated that previous HIV health education covered 80% of the rural population in western China. Mass media should take greater responsibility in HIV health education for the general population, and special attention should be paid to the elderly, the most impoverished population, minority community as well as the mother-to-child transmission route.
Asunto(s)
Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Conocimientos, Actitudes y Práctica en Salud , Población Rural/estadística & datos numéricos , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/transmisión , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Concienciación , China/epidemiología , Información de Salud al Consumidor/métodos , Estudios Transversales , Femenino , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Adulto JovenRESUMEN
A visualization strategy is described for the detection of clenbuterol (CLB). It is using of antibody against dsDNA and G-quadruplex/hemin labeled on a metal organic framework of type MIL-101(Fe) (G-quadruplex/hemin-anti-DNA/MIL-101) acting as a peroxidase mimetic, and magnetic beads modified with aptamer and complementary DNA (MB/Apt-cDNA) as capture probes. The detection reagent was prepared via the reactions between the double stranded DNA (Apt-cDNA) in capture probes and anti-DNA in peroxidase mimetic. In the presence of CLB, the aptamer on the magnetic beads preferentially binds CLB, and the peroxidase mimetic is released to the supernatant after magnetic separation. The released peroxidase mimetic can catalyze the TMB/H2O2 chromogenic system under mild conditions. This leads to the development of a blue-green coloration whose absorbance is measured at 650 nm. The detection limit is as low as 34 fM of CLB. The method was applied to the determination of CLB in pork samples and gave results that were consistent with data obtained with an ELISA kit. Graphical abstract A visualization strategy is described for the detection of clenbuterol. The selectivity of detection system for clenbuterol is excellent compared with other interferents. The method was applied to the determination of CLB in pork samples.