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Two series of celastrol derivatives were designed and synthesized by modifying carboxylic acid at the 28th position with amino acid, and their intermediates with isobutyrate at the third position. All compounds were evaluated for their antiproliferation activity by four human cancer cell lines (SCG7901, HGC27, HepG2, and Bel7402) and one normal cell LO2. The most promising compound, compound 8, showed superior bioactivity and lower toxicity than others including celastrol. Further underlying tests illustrated that compound 8 induced apoptosis and cell arrest at G2/M and inhibited proliferation and mobility of human hepatoma cells by suppressing the signal transducer and activator of transcription-3 signaling pathway. Besides these, a highly accurate and reproducible high performance liquid chromatography protocol was established to determine celastrol and compound 8 absorption in zebrafish, and results demonstrated that their concentration increased rapidly within 4 hr in a time-dependent manner and the concentration of compound 8 was higher than that of celastrol. In addition, without detection at 12 hr, compound 8 was rapidly metabolized in vivo. These findings are very helpful for the structural modification of celastrol and other bioactive compounds to improve their bioactivity, toxicity, and absorption.
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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis and limited therapies, and transforming growth factor-ß1 (TGF-ß1) plays a central role in the pathogenesis of IPF. Here, we aimed to investigate the chemical constituents and biological activities of Hypericum longistylum and detect whether the isolated compounds inhibit the TGF-ß1/Smad3 signaling pathway to identify candidate compounds for the treatment of pulmonary fibrosis. Fifteen compounds (1-15) were isolated from H. longistylum and their structures were elucidated on the basis of spectroscopic analyses. An in vitro MTT assay was used to test the effect of these fifteen compounds on fibroblast cytotoxicity and vitality. Furthermore, their bioactivities were screened using a TGF-ß1/Smad3 pathway luciferase reporter in vitro. MTT screening found that compounds 1-15 had no deleterious effects on normal mouse lung fibroblasts and no significant inhibition of vitality. Luciferase assay showed that compounds 14 and 15 could significantly inhibit the TGF-ß1/Smad3 pathway with the inhibition rates of 67.92% and 93.10%, respectively. Both compounds can be used as lead compounds for structural modification and optimization to obtain more drug candidates for the treatment of pulmonary fibrosis.
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Antifibrinolíticos/farmacología , Hypericum/química , Extractos Vegetales/farmacología , Fibrosis Pulmonar/tratamiento farmacológico , Animales , Antifibrinolíticos/química , Antifibrinolíticos/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Fibroblastos/efectos de los fármacos , Ratones , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Transducción de Señal/efectos de los fármacos , Proteína smad3/antagonistas & inhibidores , Proteína smad3/metabolismo , Relación Estructura-Actividad , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Vascular calcification is prevalent and associated with adverse outcome without available therapy. The benefits of fibroblast growth factor (FGF)-21 on metabolism and atherosclerosis make it a promising therapeutic agent for vascular calcification. We investigated the effects of FGF21 on vascular smooth muscle cell (VSMC) calcification by culturing rat VSMCs in a calcifying medium for 9days. FGF21 markedly attenuated mineral deposition and apoptosis at the indicated time points. In the presence of FGF21, the expression levels of osteoblastic protein including bone morphogenic protein-2, alkaline phosphatase(ALP), runt-related transcription factor(RUNX)-2 and nuclear factor-kappa B ligand (RANKL) were down-regulated, whereas the expression of osteoprotegerin (OPG) increased. Knockdown of OPG significantly impaired inhibition of FGF21 on apoptosis and the expression of pro-apoptotic genes including caspase-3 and Bax and osteoblastic -promoting markers including ALP, RUNX-2 and RANKL. Furthermore, FGF21 facilitated the phosphoryl of AKT but suppressed P38, while OPG knockdown attenuated the effects. LY29400 (inhibitor of PI3K) abrogated the activation of PI3K/AKT and SB203580 (inhibitor of P38) abolished the inhibition of FGF21 on P38, while alteration was observed in the expression of RUNX-2. FGF21 inhibited VSMCs calcification via OPG/RANKL system, and through P38 andPI3K/AKT pathways.
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Factores de Crecimiento de Fibroblastos/metabolismo , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Animales , Apoptosis , Células Cultivadas , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Protein tyrosine phosphatase 1B (PTP1B) has been regarded asa target for the research and development of new drugs to treat type II diabetes and PTP1B inhibitors are potential lead compounds for this type of new drugs. A phytochemical investigation to obtain new PTP1B inhibitors resulted in the isolation of four new phloroglucinols, longistyliones A-D (1-4) from the aerial parts of Hypericum longistylum. The structures of 1-4 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by comparing their experimental electronic circular dichroism (ECD) spectra with those calculated by the time-dependent density functional theory method. Compounds 1-4 possess a rare polycyclic phloroglucinol skeleton. The following biological evaluation revealed that all of the compounds showed PTP1B inhibitory effects. The further molecular docking studies indicated the strong interactions between these bioactive compounds with the PTP1B protein, which revealed the possible mechanism of PTP1B inhibition of bioactive compounds. All of the results implied that these compounds are potentially useful for the treatment of type II diabetes.
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Inhibidores Enzimáticos/química , Hypericum/química , Floroglucinol/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Sitios de Unión , Dominio Catalítico , Dicroismo Circular , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/metabolismo , Humanos , Hypericum/metabolismo , Espectroscopía de Resonancia Magnética , Conformación Molecular , Simulación del Acoplamiento Molecular , Floroglucinol/aislamiento & purificación , Floroglucinol/metabolismo , Extractos Vegetales/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , TermodinámicaRESUMEN
A bioassay-guided phytochemical investigation of the leaves of Casearia balansae led to the isolation of six new cucurbitane-type triterpenoid derivatives (balanterpenes A-F, 1-6) and four new clerdoane-type diterpenoids (balanterpenes G-J, 7-10). The structures of 1-10 were established on the basis of extensive analysis of NMR spectroscopic data, X-ray crystallography, and experimental and calculated electronic circular dichroism spectra. Compound 1 features a ring-expanded triterpenoid skeleton with the C-19 methyl involved in the ring formation, compound 6 possesses a rare hexanortriterpenoid scaffold, and compounds 7-10 may be four new diterpenoid artifacts presumably formed during the extraction and purification processes. Compounds 3 and 7-10 showed promoting effects on neurite outgrowth of PC12 cells with EC50 values in the range 2.9-10.0 µM.
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Casearia/química , Diterpenos de Tipo Clerodano/aislamiento & purificación , Diterpenos de Tipo Clerodano/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Neuritas/efectos de los fármacos , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Animales , Diterpenos de Tipo Clerodano/química , Medicamentos Herbarios Chinos/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Células PC12 , Hojas de la Planta/química , Ratas , Triterpenos/químicaRESUMEN
A phytochemical investigation to obtain new NO inhibitors resulted in the identification of six new (1-6) and four known (7-10) terpenoids from Salvia plebeia. Compounds 1 and 2 are new diterpenoids, 3-5 are new meroditerpenoids, 6-9 are sesquiterpenoids, and 10 is a known meroditerpenoid. The structures of these isolates were determined by routine NMR experiments and X-ray diffraction, as well as the electronic circular dichroism spectra. Compounds 1-4 are diterpenoids carrying an oxygen bridge, and 6 is a rare copane-type sesquiterpenoid with a bridged tricyclic framework. The isolates inhibited NO generation induced by lipopolysaccharide in BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed interactions of bioactive compounds with the iNOS protein.
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Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Salvia/química , Cristalografía por Rayos X , Diterpenos/química , Medicamentos Herbarios Chinos/química , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Conformación Molecular , Simulación del Acoplamiento Molecular , Estructura Molecular , Óxido Nítrico/biosíntesis , Resonancia Magnética Nuclear Biomolecular , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacologíaRESUMEN
Biologically active substances that promote the neurite outgrowth of nerve cells against neuron degeneration may be useful for the treatment of Alzheimer's disease. In a continuing search for bioactive compounds from plants, an ethyl acetate-soluble extract of the twigs of Casearia graveolens showed moderate stimulatory activity of neurite outgrowth from PC12 cells. Further investigation to obtain bioactive compounds led to the isolation of 10 new clerodane diterpenoids, graveopenes A-J (1-10). Their structures including absolute configurations were elucidated based on analysis of their NMR spectroscopic data and experimental and calculated ECD spectra. Compounds 3-6 and 8 were shown to stimulate NGF-mediated neurite outgrowth from PC12 cells.
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Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Casearia/química , Diterpenos de Tipo Clerodano/aislamiento & purificación , Diterpenos de Tipo Clerodano/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Plantas Medicinales/química , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/química , Diterpenos de Tipo Clerodano/química , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Estructura Molecular , Factor de Crecimiento Nervioso/efectos de los fármacos , Neuritas/efectos de los fármacos , Resonancia Magnética Nuclear Biomolecular , Células PC12 , RatasRESUMEN
The buried interface of the perovskite layer has a profound influence on its film morphology, defect formation, and aging resistance from the outset, therefore, significantly affects the film quality and device performance of derived perovskite solar cells. Especially for FAPbI3 , although it has excellent optoelectronic properties, the spontaneous transition from the black perovskite phase to nonperovskite phase tends to start from the buried interface at the early stage of film formation then further propagate to degrade the whole perovskite. In this work, by introducing âNH3 + rich proline hydrochloride (PF) with a conjugated rigid structure as a versatile medium for buried interface, it not only provides a solid α-phase FAPbI3 template, but also prevents the phase transition induced degradation. PF also acts as an effective interfacial stress reliever to enhance both efficiency and stability of flexible solar cells. Consequently, a champion efficiency of 24.61% (certified 23.51%) can be achieved, which is the highest efficiency among all reported values for flexible perovskite solar cells. Besides, devices demonstrate excellent shelf-life/light soaking stability (advanced level of ISOS stability protocols) and mechanical stability.
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Perovskite solar cells (PSCs) have attracted aggressive attention in the photovoltaic field in light of the rapid increasing power conversion efficiency. However, their large-scale application and commercialization are limited by the toxicity issue of lead (Pb). Among all the lead-free perovskites, tin (Sn)-based perovskites have shown potential due to their low toxicity, ideal bandgap structure, high carrier mobility, and long hot carrier lifetime. Great progress of Sn-based PSCs has been realized in recent years, and the certified efficiency has now reached over 14%. Nevertheless, this record still falls far behind the theoretical calculations. This is likely due to the uncontrolled nucleation states and pronounced Sn (IV) vacancies. With insights into the methodologies resolving both issues, ligand engineering-assisted perovskite film fabrication dictates the state-of-the-art Sn-based PSCs. Herein, we summarize the role of ligand engineering during each state of film fabrication, ranging from the starting precursors to the ending fabricated bulks. The incorporation of ligands to suppress Sn2+ oxidation, passivate bulk defects, optimize crystal orientation, and improve stability is discussed, respectively. Finally, the remained challenges and perspectives toward advancing the performance of Sn-based PSCs are presented. We expect this review can draw a clear roadmap to facilitate Sn-based PSCs via ligand engineering.
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BACKGROUND: Hepatocyte injury is a common pathological cause of various liver diseases. Due to a lack of an effective preventive treatment, gene therapy has become an interesting approach to prevent and alleviate liver injury. AIMS: A protective effect of adenovirus-mediated dual gene expression of human interleukin-10 (hIL-10) and human hepatocyte growth factor (hHGF) was investigated against tetrachloromethane (CCl(4))-induced hepatocyte injury in rats. METHODS: An adenoviral vector carrying the hIL-10 and hHGF genes was constructed, and its protective effect against rat hepatocyte injury was investigated both in vivo and in vitro. RESULTS: In the in vitro CCl(4)-induced cell injury model, simultaneous transfection of hIL-10 and hHGF genes via an adenoviral vector resulted in production of anti-hepatocyte biological factors by an autocrine mechanism, then significantly improved hepatocyte viability. In the in vivo rat model, synergistic effects of these two gene products protected hepatocytes from damage by reducing the CC1(4)-induced hepatocyte degeneration, hepatic fibrosis, and intrahepatic inflammatory cell infiltration, thereby preserving liver function. CONCLUSION: Adenovirus-mediated dual gene expression of hIL-10 and hHGF effectively protected against liver damage by likely regulating immune responses to reduce hepatocyte injury and by promoting hepatocyte regeneration. The hIL-10 and hHGF dual gene expression vector has significant potential in the field of liver disease therapeutics and constitutes one of the most promising current strategies for gene therapy.
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Adenoviridae/genética , Tetracloruro de Carbono/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Regulación Viral de la Expresión Génica/fisiología , Factor de Crecimiento de Hepatocito/fisiología , Interleucina-10/fisiología , Animales , Tetracloruro de Carbono/farmacología , Células Cultivadas , Modelos Animales de Enfermedad , Vectores Genéticos , Factor de Crecimiento de Hepatocito/genética , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Hepatocitos/fisiología , Humanos , Técnicas In Vitro , Interleucina-10/genética , Hígado/efectos de los fármacos , Hígado/patología , Hígado/fisiología , Masculino , Ratas , Ratas Sprague-Dawley , TransfecciónRESUMEN
The signal transducer and activator of transcription 3 (STAT3) oncogene is a promising molecular target and its inhibitors have great potential as anticancer drugs. To identify novel and STAT3-selective inhibitors, a virtual screening based on Specs and Maybridge databases was conducted and a 6,6'-bibenzoxazole type small molecule, compound 3a with a inhibition constant K(i) value of 494.32 nM to STAT3 was explored. Further, a novel series of derivatives originally derived from 3a was synthesized and evaluated through cell-based assays using human breast cancer cell lines, MDA-MB-468 and MCF-7 with or without constitutive expression of STAT3, respectively. In the series, 3a, 3c, 3d and 4e showed a better inhibitory activity with a good selectivity. Among them, 3a and 3c significantly inhibited STAT3 protein level and also displayed binding affinity for STAT3 that detected with flow injection analysis-quartz crystal microbalance (FIA-QCM) analysis system. The results provided a new lead for future design and development of potent STAT3 inhibitors.
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Antineoplásicos/farmacología , Benzoxazoles/farmacología , Descubrimiento de Drogas , Factor de Transcripción STAT3/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Benzoxazoles/síntesis química , Benzoxazoles/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células MCF-7 , Modelos Moleculares , Estructura Molecular , Factor de Transcripción STAT3/metabolismo , Relación Estructura-ActividadRESUMEN
Ewing sarcoma and primitive neuroectodermal tumors (ES/PNETs) are rare tumors that belong to a family of round-cell neuroectodermally derived tumors, and their optimal treatment remains a great challenge. This study presented a case of ES/PNET, arising in the esophagus of a 21-year-old female patient presented with progressive dysphagia. Computed tomography and endoscopic ultrasonography showed a well-defined, submucosal solid mass in the superthoracic esophagus. The accurate diagnosis after surgery was obtained through immunohistochemistry and genetic studies, namely the CD99 immunopositivity as well as the EWSR1/FLI1 gene rearrangement associated with t(11;22)(q24;q12) in tumor cells. The patient underwent localized tumor resection followed by chemotherapy and chest radiotherapy. The patient is doing well with no evidence of tumor recurrence or metastasis 18 months after surgery. Although the esophagus is a rare site for ES/pPNET, we can speculate that the treatment protocol of ES/pPNET should include multi-agent chemotherapy, surgery, and local radiotherapy in order to improve the prognosis based on our report.
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Sn-based perovskite solar cells (PSCs) have received extensive attention for photovoltaic applications. Nevertheless, the low crystallization quality of the film due to rapid crystallization results in high trap density of states, which is one of the main reasons for poor performance of Sn-based PSC devices. In this work, we developed a strategy for the formation of FASnI3 perovskites by introducing the addition of formamidine acetate (FAAc). Benefiting from the iodide-coordinated cation (FA+) and crystallization-regulated anion (AC-), FAAc could achieve the high-quality films with suppressed defects. The champion power conversion efficiency (PCE) of FAAc-modified PSC devices reached 9.96%, reserving 82% of their initial PCE of the light aging test over 1500 h. We hope that our finding could provide implications on the high-performance and stable Sn-based PSCs.
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BACKGROUND: Despite advances in treatment strategies, acute respiratory distress syndrome (ARDS) after cardiac surgery remains associated with high morbidity and mortality. A method of screening patients for risk of ARDS after cardiac surgery is needed. OBJECTIVES: To develop and validate an ARDS prediction score designed to identify patients at high risk of ARDS after cardiac or aortic surgery. METHODS: An ARDS prediction score was derived from a retrospective derivation cohort and validated in a prospective cohort. Discrimination and calibration of the score were assessed with area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test, respectively. A sensitivity analysis was conducted to assess model performance at different cutoff points. RESULTS: The retrospective derivation cohort consisted of 201 patients with and 602 patients without ARDS who had undergone cardiac or aortic surgery. Nine routinely available clinical variables were included in the ARDS prediction score. In the derivation cohort, the score distinguished patients with versus without ARDS with area under the curve of 0.84 (95% CI, 0.81-0.88; Hosmer-Lemeshow P = .55). In the validation cohort, 46 of 1834 patients (2.5%) had ARDS develop within 7 days after cardiac or aortic surgery. Area under the curve was 0.78 (95% CI, 0.71-0.85), and the score was well calibrated (Hosmer-Lemeshow P = .53). CONCLUSIONS: The ARDS prediction score can be used to identify high-risk patients from the first day after cardiac or aortic surgery. Patients with a score of 3 or greater should be closely monitored. The score requires external validation before clinical use.
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Procedimientos Quirúrgicos Cardíacos , Síndrome de Dificultad Respiratoria , Humanos , Estudios Prospectivos , Curva ROC , Síndrome de Dificultad Respiratoria/diagnóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
The purpose of this study is to investigate the effects of melatonin on the radiosensitivity of HeLa cells. Concentration from 10 to 1000 µM of melatonin was used on HeLa cells before X-rays irradiation (IR). The cellular inactivation effect was analyzed by clonogenic assay, and cell growth was measured by MTT assay at various concentrations. Ten micrometer melatonin promoted the cell-killing effects of IR, while 1000-µM melatonin prevented IR-induced cellular inactivation. Further analysis revealed that 1000-µM melatonin protected the cells from IR-induced reactive oxygen species damage, as the oxidative stress measured by fluorescent microscopy and fluorescence-activated cell sorting using 2,7-dichlorofluorescein diacetate staining. This is further confirmed by melatonin receptor agonist, which has no antioxidant capacity. A 10-µM melatonin, on the contrary, enhanced the cell-killing effects of IR by activating c-Jun NH2-terminal kinase (JNK) signaling. c-Jun NH2-terminal kinase signaling activation was indicated by Western blot of phosphorylated JNK. We used JNK inhibitor to further confirm the involvement of JNK signaling in the cell-killing enhancement of 10-µM melatonin administration. Our results suggest the importance of dose-dependent effects in melatonin application for radiotherapy.
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Developing environmentally friendly, stable, and narrow and direct band gap halide perovskite materials has attracted substantial interest because of their wide range of potential applications. Here, an all-inorganic Pb-free halide double perovskite, Cs2NaVCl6, was prepared by the solid-state reaction method and hydrothermal method. Cs2NaVCl6 crystallizes in the cubic Fm3Ì m space group with the unit parameter a = 10.3497(14) Å. The combined density functional theory and experimental study demonstrates that the compound is a direct band gap semiconductor with a band gap of â¼2.64 eV. More importantly, it exhibits strong visible and near-infrared light absorptions and markedly ambient and thermal stability.
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BACKGROUND: Plant natural products have many different biological activities but the precise mechanisms underlying these activities remain largely unknown. Hypericum longistylum has long been recorded in Chinese medicine as a cure for depression and related disorders, but how it repairs neural lineages has not been addressed. METHODS: We extracted compounds from Hypericum longistylum and determined their effect on neural differentiation of embryonic stem cells (ESCs) in vitro by using the Pax6-GFP reporter system. The amount of serotonin released during differentiation was measured by HPLC. The tail suspension test and forced swimming test was performed for determining the effect of compounds on depression-like behaviors in mice. RESULTS: We found that one of the phloroglucinol derivatives not only facilitated differentiation of neural progenitor cells, but also increased the efficiency of differentiation into serotonergic neurons. This compound also improved the behaviors of mice placed in a stressful environment and reduced signs of depression. CONCLUSIONS: This is the first use of Chinese herb derived-natural products to promote neurogenesis of ESCs, including the generation of serotonergic neurons, and the first attempt to identify the active compound in Hypericum longistylum responsible for its beneficial effects on depressive diseases.
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Depresión/tratamiento farmacológico , Hypericum/química , Medicina Tradicional China/métodos , Neurogénesis/efectos de los fármacos , Serotonina , Animales , Diferenciación Celular , Femenino , Masculino , RatonesRESUMEN
Streptococcus suis serotype 2 is an important swine pathogen and an emerging zoonotic agent that causes severe infections. Recent studies have reported a eukaryotic-like Ser/Thr protein kinase (STK) gene and characterized its role in the growth and virulence of different S. suis 2 strains. In the present study, phosphoproteomic analysis was adopted to identify substrates of the STK protein. Seven proteins that were annotated to participate in different cell processes were identified as potential substrates, which suggests the pleiotropic effects of stk on S. suis 2 by targeting multiple pathways. Among them, a protein characterized as cell division initiation protein (DivIVA) was further investigated. In vitro analysis demonstrated that the recombinant STK protein directly phosphorylates threonine at amino acid position 199 (Thr-199) of DivIVA. This effect could be completely abolished by the T199A mutation. To determine the specific role of DivIVA in growth and division, a divIVA mutant was constructed. The ΔdivIVA strain exhibited impaired growth and division, including lower viability, enlarged cell mass, asymmetrical division caused by aberrant septum, and extremely weak pathogenicity in a mouse infection model. Collectively, our results reveal that STK regulates the cell growth and virulence of S. suis 2 by targeting substrates that are involved in different biological pathways. The inactivation of DivIVA leads to severe defects in cell division and strongly attenuates pathogenicity, thereby indicating its potential as a molecular drug target against S. suis.
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Proteínas Bacterianas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Infecciones Estreptocócicas/veterinaria , Streptococcus suis/enzimología , Enfermedades de los Porcinos/microbiología , Secuencias de Aminoácidos , Animales , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , División Celular , Femenino , Regulación Bacteriana de la Expresión Génica , Ratones , Ratones Endogámicos BALB C , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Infecciones Estreptocócicas/microbiología , Streptococcus suis/citología , Streptococcus suis/genética , Streptococcus suis/metabolismo , PorcinosRESUMEN
Genotype 4 hepatitis E virus (HEV) was reportedly transmitted freely between humans and swine in eastern China. The full-length genomic sequence of Shanghai swine isolate (SH-SW-zs1) recovered from feces sample of a pig which was infected with HEV RNA positive swine serum was determined using RT-PCR and RACE (Rapid Amplification of cDNA Ends) methods. The full genome of the SH-SW-zs1 isolate was 7265 nucleotides in length and phylogenetic analysis indicated that this isolate belonged to genotype 4. Comparison of the 3' UTR sequence with the corresponding regions of other 38 HEV strains from different region revealed that the Shanghai swine isolate is 21-49 bp longer than the other stains.
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Genoma Viral , Virus de la Hepatitis E/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Porcinos/virología , Animales , Secuencia de Bases , China , Clonación Molecular , Heces/virología , FilogeniaRESUMEN
BACKGROUND: Most cases of exogenous endophthalmitis occur after intraocular surgery. Although phacoemulsification is quick and convenient, there are some risks involved, and infection is one of them. This study investigated the associated factors and methods of prevention and treatment of endophthalmitis after phacoemulsification. METHODS: A retrospective study was conducted of 84 497 phacoemulsification surgeries with intraocular lens implantation performed in the 10 branches of Mai Ge Ophthalmological Hospital, Tianjin, China, from 1993 to 2003. RESULTS: It was found that 14 patients suffered from postoperative endophthalmitis in 14 eyes. Among them there were 5 cases with rupturing of posterior lens capsule. Postoperative endophthalmitis was culture-positive in 7 cases. After treatment, 5 patients had a visual acuity of 2.0 or above, 4 patients experienced the perception of light or hand movement, and the remaining 5 patients had lost light perception (2 cases ultimately had optic atrophy, and ophthalmectomy was performed on 3 eyes). INTERPRETATION: Endophthalmitis after phacoemulsification surgery led to severe vision loss and blindness, although its incidence was low (0.02%) in this study. The most common organism isolated was Staphylococcus epidermidis, and rupturing of the posterior capsule was one of the main risk factors. Early diagnosis and treatment restored visual acuity in several cases, and improved phacoemulsification technique, including sterilization, helped reduce the incidence of endophthalmitis.