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Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.
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Péptido Relacionado con Gen de Calcitonina , Centro Germinal , Inmunidad Humoral , Bazo , Animales , Masculino , Ratones , Linfocitos B/inmunología , Linfocitos B/metabolismo , Péptido Relacionado con Gen de Calcitonina/metabolismo , Capsaicina/farmacología , AMP Cíclico/metabolismo , Dinoprostona/metabolismo , Ganglios Espinales/metabolismo , Centro Germinal/inmunología , Ratones Endogámicos C57BL , Nociceptores/metabolismo , Proteína 1 Modificadora de la Actividad de Receptores/metabolismo , Células Receptoras Sensoriales/metabolismo , Células Receptoras Sensoriales/efectos de los fármacos , Transducción de Señal , Bazo/inervación , Bazo/inmunología , FemeninoRESUMEN
Celosia argentea is a manganese (Mn) hyperaccumulator with high ornamental value and strong stress resistance. It is important to understand the molecular mechanism of tolerance to heavy metals of hyperaccumulators to improve the efficiency of phytoremediation. In this study, the effects of different Mn concentrations (0, 0.8, 3, and 10 mM) on physiological characteristics and molecular changes were determined. Low concentrations of Mn increased the growth of C. argentea, while high concentrations of Mn suppressed its growth, A concentration up to 3 mM did not affect the growth of C. argentea, and the highest transfer factor (TF) was 6.16. Oxidative damage of different Mn level treatments in C. argentea was verified through relative water content, electrolyte leakage, MDA content, H2O2 content and superoxide contents. With an increase in Mn concentration, the contents of chlorophyll a, chlorophyll b, and carotenoids decreased. Our results indicated that low-concentration manganese treatment can reduce the reactive oxygen burst and MDA, soluble sugar and proline, making C. argentea have strong abiotic stress tolerance. The molecular mechanism of C. argentea after 10 mM Mn treatment was analysed through transcriptome analysis, and differentially expressed genes (DEGs) in these pathways were further verified by qRTPCR. Plantpathogen interactions, plant hormone signal transduction, the MAPK signalling pathway and the phenylpropanoid biosynthesis pathway were important in the response to Mn stress, and the heavy metal-associated isoprenylated plant protein, metal transporter Nramp, and zinc transporter play key roles in the strong ability of C. argentea to tolerate heavy metals. These results suggest that C. argentea exhibits strong manganese tolerance and provide new insight into the molecular mechanisms of plant responses to heavy metal stress.
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Celosia , Metales Pesados , Manganeso/metabolismo , Clorofila A , Peróxido de Hidrógeno/metabolismo , Metales Pesados/metabolismo , Celosia/metabolismo , Perfilación de la Expresión GénicaRESUMEN
The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length. Genetic ablation of ciliogenesis in NMS neurons enabled a rapid phase shift of the internal clock under jet-lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lost their coherence after external perturbations. Rhythmic cilia changes drive oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression. Inactivation of Shh signaling in NMS neurons phenocopied the effects of cilia ablation. Thus, cilia-Shh signaling in the SCN aids intercellular coupling.
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Cilios , Relojes Circadianos , Ritmo Circadiano , Proteínas Hedgehog , Neuronas del Núcleo Supraquiasmático , Animales , Ratones , Cilios/metabolismo , Cilios/fisiología , Relojes Circadianos/genética , Ritmo Circadiano/fisiología , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Neuronas del Núcleo Supraquiasmático/fisiología , Transducción de Señal , Regulación de la Expresión Génica , Ratones TransgénicosRESUMEN
Aeschynanthus pulcher (Blume) G. Don, the "lipstick plant" is a prized ornamental plant with distinctive flowers. Here, we introduce a novel in vitro regeneration method for A. pulcher using leaf explants and an optimized combination of phytohormone plant growth regulators (PGRs). The optimal conditions for shoot regeneration included 1 mg L-1 polyvinyl pyrrolidone (PVP) plus 3 mg L-1 thidiazuron (TDZ), inducing a response rate of 82.4% and a shoot/explant ratio of 38.6. When the Murashige and Skoog (MS) medium contained indole-3-butyric acid (IBA) alone, leaves first differentiated into adventitious roots and then adventitious shoots. Leaves cultured on MS medium containing 1 g L-1 PVP, 3 mg L-1 TDZ, 5 mg L-1 casein, and 0.1 mg L-1 α-naphthaleneacetic acid (NAA) for 30 d exhibited the highest embryogenic callus (EC) induction rate (95.6%). The optimal shoot proliferation coefficient (21.5) was obtained when shoots derived from EC were cultured on the same medium as that used for EC induction for 5 weeks. The most effective medium for rooting of elongated shoots was MS medium containing 1 g L-1 PVP, 5 mg L-1 casein, 3 mg L-1 6-benzyladenine (BA), and 0.1 mg L-1 NAA, and the number of roots reached 18.8. The regenerated plants grown in a greenhouse had 100% survival following one week of hardening. Overall, our effective and efficient propagation method should result in shortened culture periods and reduced production costs, allowing for the future selective breeding and genetic improvement of A. pulcher.
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Cercidiphyllum japonicum is a deciduous tree belonging to the genus Cercidiphyllum of the family Cercidiphyllaceae (Li et al., 2008). Fossil records indicated that this tree was once distributed throughout the Northern hemisphere during the tertiary period, whereas it is now only found in Japan and China as a consequence of quaternary glaciation. In 1989, C. japonicum was listed as a Rare and Endangered plant in China (Song et al., 1989). It is also highly valued for use in ornamental, medicinal, and research contexts, leading to its widespread planting and cultivation throughout China. In September 2021, a severe leaf spot infection (FigS1.A) was first detected on C. japonicum trees in Meigu County, Sichuan Province, China (N 28°33', E 103°14'). In a survey of twenty 100-year-old C. japonicum trees in this region, the incidence of such leaf spot was found to be approximately 95%. During the early stages of disease, infected leaves exhibited small punctate spots along the leaf center or margins. These spots were brown in the center with black edges. As the disease progressed, these spots expanded until they coalesced to yield large circular or irregularly shaped regions of necrotic tissue, and finally produced mildew. Samples of leaf tissue between symptomatic and healthy regions (5 mm×5 mm) were excised from five symptomatic leaves, surface disinfected for 30 s with 75% ethanol, soaked for 2 min in 3% NaClO, rinsed then plated on potato dextrose agar (PDA) medium supplemented with ampicillin and carbenicillin (50 µg/ml each). After cultured for 3 days in the dark at 25°C, emergent hyphae were purified by subculturing them on fresh PDA medium. In total, single spore culturing was performed by collecting and purifying seven fungal isolates. These isolates exhibited largely comparable morphological characteristics. Aerial hyphae had a cotton-like appearance and were white to pale gray in color (FigS1.B), turning pale reddish-brown with profuse sporulation (FigS1.C). Conidia were present in long chains, with conidiophores being present in clusters or in isolation (FigS1.D), with 1-5 transverse septa, 0-3 oblique and longitudinal septa and an ellipsoidal to obpyriform structure, measuring 9.0-38.6 µm in length and 5.1-12.6 µm in width (n = 40) (FigS1.E). These seven isolates thus exhibited morphological characteristics consistent with those of members of the Alternaria genus (Simmons, 2008). Molecular identification of a representative isolate (LGB9) was performed by amplifying the internal transcribed spacer (ITS) rDNA, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), translation elongation factor 1-alpha (TEF1), and partial RNA polymerase II largest subunit (RPB2) gene sequences with the ITS1/ITS4 (White et al.,1990), GDF/GDR (Templeton et al., 1992), TEF-728F/TEF-986R (Carbone & Kohn 1999) and RPB2-5F2/RPB2-7cR (Sung et al., 1990; Liu et al., 1999), and Bt-2a/Bt-2b (Glass and Donaldson 1995) primer pairs, respectively. The resultant sequences were deposited in GenBank (ITS, OL659190; GAPDH, OL685343; TEF, ON340848; RPB2, OL685344). Further phylogenetic analyses of isolate LGB9 revealed it to cluster in the A. brassicae clade with 97% bootstrap support. To confirm the pathogenicity of isolate LGB9, 15 healthy leaves from five one-year-old C. japonicum plants were spray-inoculated with a suspension containing 3×105 LGB9 conidia/mL, with control leaves instead being sprayed with distilled water. After 8 days, inoculated leaves exhibited symptoms similar to those observed on naturally infected leaves (FigS1.F-I), whereas the mock leaves were free of any symptoms. This is the first report to our knowledge of a case of leaf spot disease caused by A. brassicae affecting C. japonicum in China or anywhere else in the world. To ensure the protection of this living fossil species, appropriate interventional measures should be adopted to manage the development and spread of this disease.
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EZH2 inhibitors that prevent trimethylation of histone lysine 27 (H3K27) are often limited to the treatment of a subset of hematological malignancies. In most solid tumors, EZH2 inhibitors induce reciprocal H3K27 acetylation that subsequently results in acquired drug resistance. The combination of EZH2 and BRD4 inhibitors to resensitize solid cancer cells to EZH2 inhibitors has proven to be effective, underlying the significance of developing dual inhibitors. Herein, we present the design, synthesis, and biological evaluation of first-in-class dual EZH2/BRD4 inhibitors. Our most promising compound, YM458, displays potent inhibitory activity against EZH2 and BRD4 and remarkable antiproliferative capacity against 11 solid cancer cell lines. Its in vivo therapeutic potential is validated in both lung cancer and pancreatic cancer xenograft tumor mice models, highlighting the potential of EZH2/BRD4 dual inhibitors to target a broad scope of EZH2 inhibitor-resistant solid tumors.
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Neoplasias , Proteínas Nucleares , Animales , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proteína Potenciadora del Homólogo Zeste 2 , Histonas , Humanos , Ratones , Neoplasias/tratamiento farmacológico , Factores de TranscripciónRESUMEN
As a valuable ornamental plant, Sinningia hybrida 'Isa's Murmur' (S. hybrida) has genetic flower diversity, which has great potential to develop different flower characters in the horticultural market. The present study focuses on establishing a practical approach for the sustainable propagation of S. hybrida. Compared with aseptic seeding leaves explants, field-grown leaves explants are more suitable for adventitious shoot regeneration. Adding 0.1 mg L-1 NAA and 2.0 mg L-1 TDZ could obtain the highest adventitious shoot proliferation coefficient (24.5), and the induction rate was 91.7%. The shoot proliferation coefficient (20.7) and the greatest shoot length and induction rate (95.3%) were achieved in 0.1 mg L-1 NAA and 2.0 mg L-1 BA medium, accompanied by rooting formation. Adding 0.5 mg L-1 GA3, 1.0 mg L-1 BA, and 0.2 mg L-1 IBA to MS medium can effectively prolong the regenerated buds for rooting. The best for rooting was 1/2 MS medium containing 0.3 mg L-1 IBA, with the maximum number of roots (13.4 per shoot) and survival rate for transplanting (100%). This work aims to build an efficient, definitive, and scalable protocol for S. hybrida regeneration useful for large-scale cultivation and even more protoplast fusion and genetic transformation to develop more colorful or fragrant flowers.
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Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.
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Proteínas de Ciclo Celular/metabolismo , Centriolos/metabolismo , Cilios/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Organogénesis , Fosfoproteínas/metabolismo , Ubiquitina/metabolismo , Animales , Línea Celular , Humanos , Ratones , Complejos Multiproteicos , Proteínas de Unión al ARN/metabolismo , Especificidad por Sustrato , Ubiquitinación , Pez CebraRESUMEN
Cross-coupling reactions between aryl iodide and nucleophiles have been well developed. Iodoniums equipped with a reactive C-I(III) bond accelerate cross-coupling reactions of aryl iodide. Among them, cyclic diaryliodoniums are more atom economical; however; they are often in the trap of metal reliance and encounter regioselectivity issues. Now, we have developed a series of highly reactive cyclic monoaryl-vinyl iodoniums that can be tuned to construct C-N, C-O, and C-C bonds without metal catalysis. Under promotion of triethylamine, coupling reactions with aniline, phenol, aromatic acid, and indole proceed rapidly and regioselectively at room temperature. The carbene species is conceptualized as a key intermediate in our mechanism model. Furthermore, the coupling products enable diversity-oriented synthesis strategy to further build up a chemical library of diverse heterocyclic fragments that are in demand in the drug discovery field. Our current work provides a deep insight into the synthetic application of these highly reactive cyclic iodoniums.
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BACKGROUND: Polymorphisms (rs1801133 or C677T; rs1801131 or A1298C) of the MTHFR gene and rs1801394 (A66G) of the MTRR gene are important genetic determinants of folate metabolism. A convenient, sensitive, and reliable method is required to detect polymorphisms for the precise supplementation of folate. METHODS: A rapid detection method based on molecular beacon probes that can detect rs1801133, rs1801131, and rs1801394 simultaneously was developed in this study. Specific primers and probes were designed, and the amplification system and conditions were optimized. We applied our method to a group of 500 unrelated women of gestational age in the Dongguan region of Guangdong Province in China. The clinical performance of this assay was evaluated by testing 94 samples in comparison with Sanger sequencing. RESULTS: The molecular-beacon-based PCR assay we established is extremely sensitive, with a detection limit of 2 ng/µL of genomic DNA, and validated by direct sequencing in a blind study with 100% concordance. CONCLUSION: The results demonstrate that our molecular-beacon-based asymmetric PCR assay is an easy, reliable, high-yield, and cost-effective method for the simultaneous detection of three polymorphisms related to folate metabolism. It could help evaluate the risk of perinatal-neonatal neural tube malformation, pregnancy hypertension, and other diseases and guide the individualized supplementation of folic acid. Data on the spectrum of mutations in the Dongguan District in this study are beneficial for guiding the supplementation of folic acid.
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Ferredoxina-NADP Reductasa/genética , Ácido Fólico , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo Genético/genética , Adulto , Femenino , Ácido Fólico/genética , Ácido Fólico/metabolismo , Genotipo , Humanos , Límite de Detección , Mutación/genética , Reproducibilidad de los Resultados , Análisis de Secuencia de ADN/métodos , Adulto JovenRESUMEN
Lysine-specific demethylase 1 (LSD1) is frequently elevated in acute myeloid leukemia (AML) and often leads to tumorigenesis. In recent years, numerous LSD1 inhibitors based on tranylcypromine (TCP) scaffolding have reached clinical trials. Most TCP derivatives were modified at the amino site of cyclopropane motif. Herein, we for the first time introduced a sulfonamide group in TCP benzene ring of series a compounds and performed a systematical study on structure and activity relationships by varying sulfonamide groups. The introduction of sulfonamide significantly increased the targeting capacity of TCP against LSD1. Moreover, we discovered that the Boc attached LSD1 inhibitors (labelled as series b compounds) substantially improved their anti-proliferation capacity towards AML cells. The intracellular thermal shift and LC-MS/MS results implied that Boc enhanced the drug lipophilicity and might be removed under the cancerous acidic environment to release the real pharmacophore, evidenced by the fact that a structurally similar but acidic inert pivaloyl to replace Boc dramatically dropped the cellular anti-proliferation effect. Finally, a benzyl group installed at the amino site to appropriately increase lipophilicity led to trans-4-(2-(benzylamino)-cyclopropyl)-N,N-diethylbenzenesulfonamide a10 that showed better anti-proliferation activity in AML cells and enzymatic inhibition against LSD1. Taken together, our work offers a novel TCP-based structure and provides a prodrug strategy for the discovery of potent LSD1 inhibitors by having appropriate lipophilicity.
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Antineoplásicos/farmacología , Diseño de Fármacos , Inhibidores Enzimáticos/farmacología , Histona Demetilasas/antagonistas & inhibidores , Leucemia Mieloide Aguda/tratamiento farmacológico , Sulfonamidas/farmacología , Tranilcipromina/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Histona Demetilasas/metabolismo , Humanos , Leucemia Mieloide Aguda/metabolismo , Estructura Molecular , Relación Estructura-Actividad , Sulfonamidas/química , Tranilcipromina/síntesis química , Tranilcipromina/química , Células Tumorales CultivadasRESUMEN
K-ras (Kirsten ras GTPase) mutations are oncogenic events frequently observed in many cancer types especially in pancreatic cancer. Although mitochondrial dysfunction has been associated with K-ras mutation, the molecular mechanisms by which K-ras impacts mitochondria and maintains metabolic homeostasis are not fully understood. In this study, we used two K-ras inducible cell systems, human pancreatic epithelial/ K-rasG12D (HPNE/K-rasG12D) and human embryonic kidney cells with tetracycline repressorT-Rex/K-rasG12V, to evaluate the role of oncogenic K-ras in regulating mitochondrial function. Among a panel of genes known to affect mitochondria, only the expression of OPA3 (optic atrophy protein 3) was consistently up-regulated by K-ras activation in both cell lines. Importantly, high expression of OPA3 was also observed in clinical pancreatic cancer tissues. Genetic knockdown of OPA3 caused a significant decrease of energy metabolism, manifested by a suppression of oxygen consumption rate (OCR) and a decrease in cellular ATP content, leading to inhibition of cell proliferation capacity and reduced expression of epithelial-mesenchymal transition (EMT) markers. Our study suggests that OPA3 may promote cellular energy metabolism and its up-regulation in K-ras-driven cancer is likely a mechanism to offset the negative impact of K-ras on mitochondria to maintain energy homeostasis. As such, OPA3 could be a potential target to kill cancer cells with K-ras mutations.
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Polycyclic heteroarenes are important scaffolds in the construction of pharmaceuticals. We have previously developed a series of novel heterocyclic iodoniums. In our current work, these unique iodoniums were employed to construct various complex polycyclic heteroarenes with structural diversity via tandem dual arylations. As a result, indole, thiophene and triphenylene motifs were fused into these heterocycles with high molecular quality, which might provide promising fragments in drug discovery. Moreover, these heterocycles could be diversified at a late stage.
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BACKGROUND: The apolipoprotein E gene (APOE) coding polymorphism modifies the risks of Alzheimer's disease, type 2 diabetes, and coronary heart disease. Aside from the coding variants, single nucleotide polymorphism (SNP) of the APOE promoter has also been shown to modify the risk of Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigate the genotype-function relationship of APOE promoter polymorphism at molecular level and at physiological level: i.e., in transcription control of the gene and in the risk of type 2 diabetes. In molecular studies, the effect of the APOE -491A/T (rs449647) polymorphism on gene transcription was accessed by dual-luciferase reporter gene assays. The -491 A to T substitution decreased the activity (p<0.05) of the cloned APOE promoter (-1017 to +406). Using the -501 to -481 nucleotide sequence of the APOE promoter as a 'bait' to screen the human brain cDNA library by yeast one-hybrid system yielded ATF4, an endoplasmic reticulum stress response gene, as one of the interacting factors. Electrophoretic-mobility-shift assays (EMSA) and chromatin immuno-precipitation (ChIP) analyses further substantiated the physical interaction between ATF4 and the APOE promoter. Over-expression of ATF4 stimulated APOE expression whereas siRNA against ATF4 suppressed the expression of the gene. However, interaction between APOE promoter and ATF4 was not -491A/T-specific. At physiological level, the genotype-function relationship of APOE promoter polymorphism was studied in type 2 diabetes. In 630 cases and 595 controls, three APOE promoter SNPs -491A/T, -219G/T (rs405509), and +113G/C (rs440446) were genotyped and tested for association with type 2 diabetes in Hong Kong Chinese. No SNP or haplotype association with type 2 diabetes was detected. CONCLUSIONS/SIGNIFICANCE: At molecular level, polymorphism -491A/T and ATF4 elicit independent control of APOE gene expression. At physiological level, no genotype-risk association was detected between the studied APOE promoter SNPs and type 2 diabetes in Hong Kong Chinese.
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Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Regulación de la Expresión Génica/genética , Genotipo , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Transcripción Genética/genética , Factor de Transcripción Activador 4/metabolismo , Adulto , Diabetes Mellitus Tipo 2/genética , Estrés del Retículo Endoplásmico/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Glucosa/metabolismo , Células HEK293 , Homeostasis/genética , Humanos , Metabolismo de los Lípidos/genética , MasculinoRESUMEN
Porous polyimide (PI) networks with surface area up to 660 m(2) g(-1) were synthesized by planar structure monomers without detrimental catalysts.
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At present, thiol ligands are generally used whenever the classical Brust-Schiffrin two-phase method is employed to prepare metal nanoparticles. In general, the previous research was mainly focused on utilizing small molecular thiol compounds or thiol polymers as the stabilizers in organic phase to obtain small sized and uniform gold nanoparticles (Au NPs). Such preparations are usually associated with the problems of ligand exchange on the nanoparticle's surface due to strong Au-thiol interaction. Herein, we report an approach to produce fairly uniform Au NPs with diameters about 2-6 nm using thioether end-functional polymer ligands (DDT-PVAc and PTMP-PVAc) as the capping agents. These nanoparticles are thoroughly characterized using DLS, TEM, UV-Vis spectroscopy and other complementary techniques. The results indicate that multidentate thioether polymeric ligands (PTMP-PVAc) lead to formation of smaller but special 'multimer' morphology in organic phase; whereas fairly uniform nanoparticles are produced using monodentate thioether functionalized ligands (DDT-PVAc). Further modification of such polymer ligands to introduce the hydrophilic functionalities realizes the phase transfer of Au NPs from organic to aqueous media.
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Cristalización/métodos , Oro/química , Nanoestructuras/química , Nanoestructuras/ultraestructura , Polímeros/química , Sulfuros/química , Sustancias Macromoleculares/química , Ensayo de Materiales , Conformación Molecular , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
PURPOSE: Meta analysis was used to assess the effect of local drug delivery system of chlorhexidine (CHX) as an adjunct to scaling and root planing(SRP) versus SRP alone in patients with chronic periodontitis. METHODS: The selected studies of randomized controlled trials(RCTs) were pooled from six major electronic database up to May,2009 as CHX plus SRP versus SRP with at least 3 months of follow-up. Several English full texts were hand searched. Outcome measures were probing depth(PD) reduction and clinical attachment level (CAL)gain. RESULTS: Seven studies that met inclusion criteria were entered into the Meta analysis. A significant mean reduction of PD in patients with CHX plus SRP was observed, but there were no significant difference in CAL between the two treatment groups. CONCLUSIONS: Chlorhexidine as an adjunct to SRP could reduce probing depth in the treatment of chronic periodontitis. Supported by Research Project of Education Bureau of Liaoning Province(Grant No.20061021).
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Clorhexidina , Aplanamiento de la Raíz , Antiinfecciosos Locales , Periodontitis Crónica , Raspado Dental , Humanos , Índice Periodontal , PeriodontitisRESUMEN
AIM: To explore the therapeutic effectivity and the possible mechanism of triptolide (Tri) on experimental autoimmune encephalomyelitis (EAE). METHODS: All female C57BL/6 mice were randomly divided into EAE group (28), Tri treated group (20) and adjuvant group (18). Mice in EAE and treated groups were immunized with myelin oligodendrocyte glycoprotein peptides 35-55 (MOG(35-55);), adjuvant group was injected at the same time, but instead of MOG(35-55); with normal saline. Tri was intraperitoneally injected in the dosage of 100 microg/(kg.d) in treated group on day 5 post-immunization (p.i.), and mice in EAE and adjuvant group injected with normal saline as control. The clinical feature and pathological changes were observed and the splenic lymphocytes were prepared on days 18-20 p.i. The cell cultures were divided into the control group (only 200 microL of cell suspension) and the experimental group (cell suspension in the presence of 10 mg/L MOG(35-55);). Then all of them were inoculated in 96-well flat-bottom plates under 37 degrees Celsius, 50 mL/L CO(2);. After 48 h, the proliferation assay was determined by MTT, and the supernatants were harvested for the detection of INF-gamma, IL-17, IL-10 and IL-4 by ELISA. RESULTS: Tri treatment showed an significantly protective action on EAE. After the intervention of Tri, the levels of IL-10 were increased (P<0.05), but the secretion of INF-gamma and proliferation response of splenic lymphocytes induced by MOG(35-55); were statistically significantly inhibited(P<0.05 and P<0.01, respectively). There were no influences on the amount of IL-17 and IL-4 by Tri. CONCLUSION: Tri is an effective drug in suppressing murine EAE. This suppression is supposed to be related to downregulation of INF-gamma and upregulation of IL-10 secretion in splenic lymphocytes.
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Diterpenos/farmacología , Encefalomielitis Autoinmune Experimental/prevención & control , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Linfocitos/efectos de los fármacos , Fenantrenos/farmacología , Animales , Antiinflamatorios no Esteroideos/farmacología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo Condicionados/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/metabolismo , Ensayo de Inmunoadsorción Enzimática , Compuestos Epoxi/farmacología , Femenino , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Linfocitos/citología , Linfocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas de la Mielina , Glicoproteína Asociada a Mielina/química , Glicoproteína Asociada a Mielina/inmunología , Glicoproteína Mielina-Oligodendrócito , Fragmentos de Péptidos/inmunología , Distribución Aleatoria , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/patología , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Aromatic amines such as aniline and its derivatives are an important class of environmental water pollutants. A method based on capillary zone electrophoresis with amperometric detection (CZE-AD) at carbon disk electrode was developed for the determination of aromatic amines in water samples. The effects of working potential, pH and concentration of running buffer, separation voltage and injection time were investigated. Under the optimum conditions, 2,3-diaminonaphthalene, aniline, o-phenylenediamine and p-chloroaniline could be separated in 0.16 mol/L Na(2)HPO(4)-citric acid buffer (pH 4.6) within 23 min. The detection limits of them were 1.0 x 10(-7), 3.3 x 10(-8), 5.0 x 10(-8), and 1.3 x 10(-7)mol/L (S/N=3), respectively. The method can be applied directly for the determination of aromatic amines in real water samples with satisfactory results.