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1.
J Ethnopharmacol ; 264: 113096, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32693116

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Constipation is a functional gastrointestinal disorder and one of the most prevalent conditions encountered in primary care settings. Rhubarb navel dressings have been used for more than 2,000 years in Chinese medicine to treat constipation. However, the effect of topical rhubarb administration has still not been well recognized and this strategy is not yet established as an evidence-based approach. AIM OF THE STUDY: In this study, we performed a prospective multicentric randomized controlled trial to evaluate the efficacy and safety of rhubarb navel plasters for patients with chronic constipation. MATERIALS AND METHODS: A total of 374 patients from six teaching hospitals were prospectively included between 09/2016 and 10/2017 in the study based on Rome III criteria. All participants were randomly assigned (1:1) into verum/placebo group and given either Rheum officinale rhubarb powder or a placebo flour stick on the navel for 6 h/day/8 days. Primary outcome measures were the Cleveland Constipation Score (CCS) for the feces condition and Bristol Stool Scale (BSS) for stool consistency and 24 h defecation frequency. RESULTS: The groups demonstrated no statistical differences in demographic data, clinical diagnoses and concomitant medication at baseline. In patients treated with the verum CCS was 5.61 (day 8, 95% CI 5.15-6.07) compared to 8.62 (95% CI 8.07-9.18) in placebo-treated controls (P < 0.001). The mean change of CCS at the end of treatment (day 8 versus [vs] day 0) was 6.04 in verum-treated vs 2.73 in placebo-treated controls (P < 0.001). Also 24 h defecation frequency (BSS) showed superior results (day 5: 0.84 vs 0.62, 95% CI 0.67-0.80, P < 0.001; day 6: 0.82 vs 0.60, 95% CI 0.64-0.78, P < 0.01 and day 8: 0.82 vs 0.60, 95% CI 0.64-0.78, P < 0.01) and better BSS type classification during treatment than controls (P < 0.05). No significant differences in adverse events between both groups became obvious. CONCLUSION: Rhubarb navel plaster administration over an 8-day-treatment period resulted in significantly improved bowel function as demonstrated by the CCS, 24 h defecating frequency and BSS. Our results suggest that rhubarb navel plasters represent a feasible, safe and efficient application route for the treatment of patients suffering from chronic constipation.

2.
Tree Physiol ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33104211

RESUMO

Citrus sinensis seedlings were fertigated with nutrient solution containing 2 [magnesium (Mg)-sufficiency] or 0 mM (Mg-deficiency) Mg(NO3)2 for 16 weeks. Thereafter, RNA-Seq was used to investigate Mg-deficiency-responsive genes in the veins of upper and lower leaves in order to understand the molecular mechanisms for Mg-deficiency-induced vein lignification, enlargement and cracking, which appeared only in the lower leaves. In this study, 3,065 upregulated and 1,220 downregulated, and 1,390 upregulated and 375 downregulated genes were identified in Mg-deficiency veins of lower leaves (MDVLL) vs Mg-sufficiency veins of lower leaves (MSVLL) and Mg-deficiency veins of upper leaves (MDVUL) vs Mg-sufficiency veins of upper leaves (MSVUL), respectively. There were 1,473 common differentially expressed genes (DEGs) between MDVLL vs MSVLL and MDVUL vs MSVUL, 1463 of which displayed the same expression trend. Mg-deficiency-induced lignification, enlargement and cracking in veins of lower leaves might be related to the following factors: (a) numerous transciption factors and genes involved in lignin biosynthesis pathways, regulation of cell cycle, and cell wall metabolism were upregulated; and (b) reactive oxygen species (ROS), phytohormone and cell wall integrity (CWI) signalings were activated. Conjoint analysis of proteome and transcriptome indicated that there were 287 and 56 common elements between DEGs and differentially abundant proteins (DAPs) identified in MDVLL vs MSVLL and MDVUL vs MSVUL, respectively, and that among these common elements, the abundances of 198 and 55 DAPs matched well with the transcript levels of the corresponding DEGs in MDVLL vs MSVLL and MDVUL vs MSVUL, respectively, indicating the existence of concordances between protein and transcript levels.

3.
Cell Mol Immunol ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917979

RESUMO

Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Currently, both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear. In this study, we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A (IL-17) stimulation in SLE patients and lupus mice. Using a humanized lupus mouse model, we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs. Moreover, long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+ subsets among IL-17 receptor-expressing plasma cells. Lupus mice deficient in IL-17 or IL-17 receptor C (IL-17RC) exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage, while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice. In reconstituted chimeric mice, IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells. Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization. Together, our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis, which may provide new therapeutic strategies for the treatment of SLE.

4.
J Food Sci ; 85(6): 1793-1798, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32449952

RESUMO

To improve stability of peanut butter, rice bran wax (RBX) was added into peanut butter as a stabilizer by formation of organogel. Effects of addition of RBX, heating temperature, and cooling temperature on stabilization effect of peanut butter by RBX were investigated. The optimum conditions were as follow: addition of RBX at 4.0 wt%; heating temperature at 85 °C, and cooling temperature at 20 °C. Under the optimum conditions, the oil loss of peanut butter decreased from 12.19% to 4.04%, and the adhesiveness of peanut butter increased from 23.5 to 165.9 g·s. After storage for 25 weeks, the acid value (AV) of peanut butter prepared under the optimum conditions increased from 0.65  to 0.80 mg/g, and the peroxide value (PV) increased from 0.116 to 0.127 meq/kg. However, the AV of natural peanut butter increased to 1.73 mg/g, and PV increased to 0.178 meq/kg. The confocal laser scanning microscope images showed that the cooling temperature significantly affected crystallization of RBX and distribution of solid particles. When RBX formed needle-like crystals and peanut solid particles were evenly distributed in the oil phase, stable peanut butter was obtained. These results suggested that the RBX was an effective stabilizer for peanut butter. PRACTICAL APPLICATION: Oil separation often occurred to peanut butter during storage, which reduced the sensory quality of peanut butter and shortened its shelf life. This study stabilized peanut butter by addition of RBX based on the formation of organogel, which was of great practical significance to improve the shelf life of peanut butter.


Assuntos
Arachis/química , Aditivos Alimentares/análise , Manipulação de Alimentos/métodos , Oryza/química , Extratos Vegetais/química , Ceras/análise , Cristalização , Temperatura
5.
Tree Physiol ; 40(9): 1277-1291, 2020 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-32348504

RESUMO

Little is known about the physiological and molecular mechanisms underlying magnesium (Mg)-deficiency-induced enlargement, cracking and lignification of midribs and main lateral veins of Citrus leaves. Citrus sinensis (L.) Osbeck seedlings were irrigated with nutrient solution at a concentration of 0 (Mg-deficiency) or 2 (Mg-sufficiency) mM Mg(NO3)2 for 16 weeks. Enlargement, cracking and lignification of veins occurred only in lower leaves, but not in upper leaves. Total soluble sugars (glucose + fructose + sucrose), starch and cellulose concentrations were less in Mg-deficiency veins of lower leaves (MDVLL) than those in Mg-sufficiency veins of lower leaves (MSVLL), but lignin concentration was higher in MDVLL than that in MSVLL. However, all four parameters were similar between Mg-deficiency veins of upper leaves (MDVUL) and Mg-sufficiency veins of upper leaves (MSVUL). Using label-free, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we identified 1229 and 492 differentially abundant proteins (DAPs) in MDVLL vs MSVLL and MDVUL vs MSVUL, respectively. Magnesium-deficiency-induced alterations of Mg, nonstructural carbohydrates, cell wall components, and protein profiles were greater in veins of lower leaves than those in veins of upper leaves. The increased concentration of lignin in MDVLL vs MSVLL might be caused by the following factors: (i) repression of cellulose and starch accumulation promoted lignin biosynthesis; (ii) abundances of proteins involved in phenylpropanoid biosynthesis pathway, hormone biosynthesis and glutathione metabolism were increased; and (iii) the abundances of the other DAPs [viz., copper/zinc-superoxide dismutase, ascorbate oxidase (AO) and ABC transporters] involved in lignin biosynthesis were elevated. Also, the abundances of several proteins involved in cell wall metabolism (viz., expansins, Rho GTPase-activating protein gacA, AO, monocopper oxidase-like protein and xyloglucan endotransglucosylase/hydrolase) were increased in MDVLL vs MSVLL, which might be responsible for the enlargement and cracking of leaf veins.


Assuntos
Citrus sinensis , Citrus , Cromatografia Líquida , Magnésio , Folhas de Planta , Raízes de Plantas , Espectrometria de Massas em Tandem
6.
J Nat Prod ; 83(5): 1453-1460, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32319765

RESUMO

An enantiomeric pair of rare cyperane-type sesquiterpenoids, (+)- and (-)-gracilistones C (1a, 1b), together with a novel norsesquiterpenoid, gracilistone D (2), bearing a bicyclic lactone system were isolated from the root bark of Acanthopanax gracilistylus using LC-MS-IT-TOF analyses. The structures and absolute configurations of 1a, 1b, and 2 were elucidated by 1D and 2D NMR spectroscopy, X-ray diffraction, and ECD spectroscopic methods. Intermediate 1b suggests a possible biosynthesis process involving compound 2. The bioassay results showed that compounds 1a, 1b, and 2 exhibited significant inhibitory effects against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells, with IC50 values of 7.7 ± 0.6, 6.8 ± 1.5, and 2.6 ± 0.4 µM, respectively. Additional docking analyses provided some perspective of this activity in human inducible nitric oxide synthase.

7.
Environ Pollut ; 262: 114303, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32155556

RESUMO

Low pH and aluminum (Al)-toxicity often coexist in acidic soils. Citrus sinensis seedlings were treated with nutrient solution at a pH of 2.5, 3.0, 3.5 or 4.0 and an Al concentration of 0 or 1 mM for 18 weeks. Thereafter, malate, citrate, isocitrate, acid-metabolizing enzymes, and nonstructural carbohydrates in roots and leaves, and release of malate and citrate from roots were measured. Al concentration in roots and leaves increased under Al-toxicity, but it declined with elevating nutrient solution pH. Al-toxicity increased the levels of glucose, fructose, sucrose and total soluble sugars in leaves and roots at each given pH except for a similar sucrose level at pH 2.5-3.0, but it reduced or did not alter the levels of starch and total nonstructural carbohydrates (TNC) in leaves and roots with the exception that Al improved TNC level in roots at pH 4.0. Levels of nonstructural carbohydrates in roots and leaves rose with reducing pH with a few exceptions with or without Al-toxicity. A potential model for the possible role of root organic acid (OA) metabolism (anions) in C. sinensis Al-tolerance was proposed. With Al-toxicity, the elevated pH upregulated the OA metabolism, and increased the flow of carbon to OA metabolism, and the accumulation of malate and citrate in roots and subsequent release of them, thus reducing root and leaf Al and hence eliminating Al-toxicity. Without Al-toxicity, low pH stimulated the exudation of malate and citrate, an adaptive response of Citrus to low pH. The interactive effects of pH and pH on OA metabolism were different between roots and leaves.


Assuntos
Citrus sinensis , Citrus , Alumínio , Ânions , Concentração de Íons de Hidrogênio , Folhas de Planta , Raízes de Plantas
8.
Nat Prod Res ; : 1-7, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32208773

RESUMO

Two new pregnane alkaloids, (20S)-20α-cinnamoylamino-3ß-dimethylamino-5-en-pregnane (1) and (20S)-20α-cinnamoylamino-3ß-dimethylamino-pregnane (2), and four known alkaloids (+)-(20S)-20-(dimethylamino)-3-(3'R-isopropyl)-lactam-5α-pregn-2-en-4-one (3), axillaridine A (4), pachysamine M (5) and 20α-dimethylamino-16ß-hydroxy-3ß-senecioylamino-pregn-5-ene (6) were obtained from the whole herb of Pachysandra terminalis Sieb. et Zucc. Their structures were determined by various spectral techniques and computed electronic circular dichroism (ECD) data. Compounds 1-4 were tested for cytotoxicity against three human tumor cell lines and a human umbilical vein endothelial cell (HUVEC) line. Compound 4 exhibited moderate cytotoxicity against MCF-7, U251 and A549 cells with IC50 values of 15.01 ± 0.47 µM, 20.13 ± 1.34 µM and 20.04 ± 1.16 µM, respectively; compounds 1-3 showed weak cytotoxic activity against three tumor cells.

9.
J Nanosci Nanotechnol ; 20(7): 4533-4536, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31968514

RESUMO

The hot-injection method was used for the synthesis of ternary metal chalcogenide nanocrystals (NCs) CuInS2 (CIS); this was achieved by using the metal precursors (copper iodide and indium acetate) and four different types of sulfur precursor solutions. It was discovered that CIS NCs synthesized with different sulfur precursor solutions exhibited the chalcopyrite structure with similar particle sizes of ~4.2 nm. As a comparison, CIS NCs synthesized using ODE-S precursor displayed an enhanced luminescence intensity and a long PL decay lifetime, which could be considered as an evidence of improved interior crystallinity.

10.
Phytother Res ; 34(1): 139-152, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31497913

RESUMO

Acute kidney injury (AKI) with high incidence and mortality is the main cause of chronic kidney disease. Previous studies have indicated that quercetin, an abundant flavonoid in plants, exhibited renoprotective role in AKI. However, the underlying mechanism is largely unknown. In this study, we try to explore whether quercetin protects against AKI by inhibiting macrophage inflammation via regulation of Mincle/Syk/NF-κB signaling. The results demonstrated that quercetin can significantly inhibit expression and secretion of IL-1ß, IL-6, and TNF-α in LPS-induced bone marrow-derived macrophages (BMDMs) and reduce activity of Mincle/Syk/NF-κB signaling in vitro. We also found that quercetin can strongly reduce the concentration of serum creatinine, BUN, IL-1ß, IL-6, and TNF-α in cisplatin-induced AKI model. Furthermore, quercetin down-regulated protein levels of Mincle, phosphorylated Syk and NF-κB in kidney macrophages of AKI, as well as inhibited M1, up-regulated M2 macrophage activity. Notably, the down-regulation of LPS-induced inflammation by quercetin was reversed after adding TDB (an agonist of Mincle) in BMDMs, suggesting that quercetin suppresses macrophage inflammation may mainly through inhibiting Mincle and its downstream signaling. In summary, these findings clarified a new mechanism of quercetin improving AKI-induced kidney inflammation and injury, which provides a new drug option for the clinical treatment of AKI.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/tratamento farmacológico , Antioxidantes/uso terapêutico , Cisplatino/efeitos adversos , Inflamação/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Quercetina/farmacologia
11.
Plants (Basel) ; 8(10)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575029

RESUMO

Citrus sinensis seedlings were irrigated with nutrient solution at a concentration of 0 (Mg-deficiency) or 2 (Mg-sufficiency) mM Mg (NO3)2 for 16 weeks. Mg-deficiency-induced interveinal chlorosis, vein enlargement and corkiness, and alterations of gas exchange, pigments, chlorophyll a fluorescence (OJIP) transients and related parameters were observed in middle and lower leaves, especially in the latter, but not in upper leaves. Mg-deficiency might impair the whole photosynthetic electron transport, including structural damage to thylakoids, ungrouping of photosystem II (PSII), inactivation of oxygen-evolving complex (OEC) and reaction centers (RCs), increased reduction of primary quinone electron acceptor (QA) and plastoquinone pool at PSII acceptor side and oxidation of PSI end-electron acceptors, thus lowering energy transfer and absorption efficiency and the transfer of electrons to the dark reactions, hence, the rate of CO2 assimilation in Mg-deficiency middle and lower leaves. Although potassium, Mg, manganese and zinc concentration in blades displayed a significant and positive relationship with the corresponding element concentration in veins, respectively, great differences existed in Mg-deficiency-induced alterations of nutrient concentrations between leaf blades and veins. For example, Mg-deficiency increased boron level in the blades of upper leaves, decreased boron level in the blades of lower leaves, but did not affect boron level in the blades of middle leaves and veins of upper, middle and lower leaves. To conclude, Mg-deficiency-induced interveinal chlorosis, vein enlargement, and corkiness, and alterations to photosynthesis and related parameters increased with increasing leaf age. Mg-deficiency-induced enlargement and corkiness of veins were not caused by Mg-deficiency-induced boron-starvation.

12.
PhytoKeys ; 131: 83-89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576190

RESUMO

A new species, Oreocharis tetrapterus F.Wen, B.Pan & T.V.Do (Gesneriaceae) from Gupo Mountain area, Hezhou city, Guangxi Zhuangzu Autonomous Region, China, is described and illustrated. The new species has a zygomorphic tetramerous corolla with two adaxial and two abaxial lobes and two fertile stamens in the posterior position, making this a unique combination of floral characteristics in the expanded Oreocharis.

13.
Nanoscale Res Lett ; 14(1): 198, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31172299

RESUMO

Copper indium sulfide quantum dots (CuInS2 QDs) were incorporated into a nanocrystalline TiO2 film by using spin coating-assisted successive ionic layer adsorption and reaction process to fabricate CuInS2 QD-sensitized TiO2 photoelectrodes for the solid-state quantum dot-sensitized solar cell (QDSSC) applications. The result shows that the photovoltaic performance of solar cell is extremely dependent on the number of cycles, which has an appreciable impact on the coverage ratio of CuInS2 on the surface of TiO2 and the density of surface defect states. In the following high-temperature annealing process, it is found that annealing TiO2/CuInS2 photoelectrode at a suitable temperature would be beneficial for decreasing the charge recombination and accelerating the charge transport. After annealing at 400 °C, a significantly enhanced photovoltaic properties of solid-state CuInS2 QDSSCs are obtained, achieving the power conversion efficiency (PCE) of 3.13%, along with an open-circuit voltage (VOC) of 0.68 V, a short-circuit photocurrent density (JSC) of 11.33 mA cm-2, and a fill factor (FF) of 0.41. The enhancement in the performance of solar cells is mainly ascribed to the suppression of charge recombination and the promotion of the electron transfer after annealing.

14.
Nat Prod Res ; : 1-8, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31137985

RESUMO

Three new steroidal saponins (1-3), together with four known compounds (4-7), were isolated from the roots and rhizomes of Rohdea chinensis Baker, and their structures were determined as (24S, 25 R)-1ß-hydroxy-3ß-[(ß-D-glucopyranoside)oxy]-spirost-5-en-24-yl-ß-D-glucopyranoside (1) and (24S)-spirost-25(27)-en-1ß, 3ß, 4ß, 5ß, 6ß, 24ß-hexahydroxy-24-O-ß-D-glucopyranoside (2), (22S, 25S)-1ß, 3ß, 4ß, 5ß, 26, 27-hexanol-furospirost-5, 26-O-ß-D-glucopyranoside (3), together with four known compounds 3-epi-diosgenin-3-ß-D-glucopyranosid (4), 3-epiruscogenin (5), 25(R)-1ß-hydroxy-spirost-5-en-3α-yl-O-ß-D-glucopyranoside (6) and tupichinin A (7), on the basis of physico-chemical properties and spectral analysis. In this study, compounds 1-3 and 5-7 were evaluated for their cytotoxic activity against SW620, A549 and HepG2 tumor cell lines. Among them, compound 7 showed moderate cytotoxicity against two human cancer cell lines A549 and HepG 2 with IC50 values of 25.3 ± 2.6 and 26.1 ± 2.5 µM, respectively.

15.
Med Sci Monit ; 25: 3636-3646, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31095532

RESUMO

BACKGROUND The aim of this study was to assess the incidence, clinicopathologic characteristics, prognostic factors, and treatment outcomes in lung large cell neuroendocrine carcinoma (LCNEC). MATERIAL AND METHODS Patients diagnosed with lung LCNEC between 2000 and 2013 were identified using the Surveillance, Epidemiology, and End-Results database. Kaplan-Meier methods and univariate and multivariate analyses were used for statistical analysis. RESULTS A total of 2097 patients were identified. The total age-adjusted incidence rate of lung LCNEC was 0.3/100 000, with a rise in incidence over the study period. The 5-year lung cancer-specific survival (LCSS) and overall survival (OS) were 20.7% and 16.7%, respectively. Multivariate analysis indicated that age ³65 years, male sex, advanced tumor stage, advanced nodal stage, not undergoing surgery. and not undergoing chemotherapy were independent adverse indicators for survival outcomes. After stratification by tumor stage, undergoing surgery was associated with more favorable LCSS and OS compared with those without surgery, regardless of tumor stage. CONCLUSIONS LCNEC is a rare lung cancer subtype with a dismal prognosis. Primary surgical treatment has significant survival benefits, even for stage IV patients. The optimal treatment strategies for lung LCNEC require further investigation.


Assuntos
Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Grandes/patologia , Carcinoma Neuroendócrino/epidemiologia , Neoplasias Pulmonares/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/patologia , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Resultado do Tratamento , Estados Unidos/epidemiologia
16.
Fish Shellfish Immunol ; 84: 1100-1107, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30408601

RESUMO

A primitive adaptive immune system has recently been suggested to be present in a basal chordate amphioxus (Branchiostoma belcheri, Bb), making it an ideal model for studying the origin of adaptive immune. The novel protein kinase C isoform PKC-θ, but not its closest isoform PKC-δ, plays a critical role for mammalian T-cell activation via translocation to immunological synapse (IS) mediated by a unique PKC-θ V3 domain containing one PxxP motif. To understand the evolution of this unique PKC-θ V3 domain and the primitive adaptive immune system in amphioxus, we comparatively studied the orthologs of PKC-δ and -θ from amphioxus and other species. Phylogenetic analysis showed BbPKC-δ/θ to be the common ancestor of vertebrate PKC-δ and PKC-θ, with a V3 domain containing two PxxP motifs. One motif is conserved in both zebrafish and mammalian PKC-θ but is absent in PKC-δ V3 domain of these species, and has already emerged in drosophila PKC-δ. The other non-conserved motif emerged in BbPKC-δ/θ, and only retained in Danio rerio PKC-δ (DrPKC-δ) but lost in mammalian PKC-δ and -θ. Comparative analyses of the sequence and function of BbPKC-δ/θ, DrPKC-δ, DrPKC-θ and Homo sapiens PKC-θ (HsPKC-θ) in IS translocation and T-cell receptor (TCR)-induced NF-κB activation revealed that retention of the conserved PxxP motif and loss of the non-conserved PxxP motif in mammalian PKC-θ and loss of both PxxP motifs in mammalian PKC-δ accomplish the unique function of PKC-θ in T cells. Together, this study suggests an evolutionary mechanism for PKC-θ unique V3 and reveals BbPKC-δ/θ is the common ancestor of PKC-δ and -θ with a functional proto-V3 domain, supplying new evidence for the existence of primitive adaptive immune system in amphioxus.


Assuntos
Imunidade Adaptativa/genética , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Anfioxos/genética , Anfioxos/imunologia , Proteína Quinase C-delta/genética , Proteína Quinase C-delta/imunologia , Proteína Quinase C-theta/genética , Proteína Quinase C-theta/imunologia , Sequência de Aminoácidos , Animais , Perfilação da Expressão Gênica/veterinária , Anfioxos/enzimologia , Filogenia , Proteína Quinase C-delta/química , Proteína Quinase C-theta/química , Alinhamento de Sequência/veterinária
17.
Fitoterapia ; 130: 265-271, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30243779

RESUMO

Gracilistones A (1) and B (2), two new eudesmane-type sesquiterpenoids with an unusual tetrahydrofuran-fused 6/6/5 tricyclic ring system, were obtained from Acanthopanax gracilistylus under the guidance of LC-MS investigation. Their structures and absolute configurations were assigned by extensive spectroscopic analyses and quantum calculation methods. Compounds 1 and 2 showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, compared with the positive control L-NMMA. In addition, compounds 1 and 2 were also evaluated for their antioxidant (DPPH• and ABTS•+) and xanthine oxidase (XO) inhibitory activities, and they exhibited weak inhibitory effects at 100 µM.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Eleutherococcus/química , Sesquiterpenos de Eudesmano/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , China , Cromatografia Líquida , Furanos , Espectrometria de Massas , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Células RAW 264.7 , Sesquiterpenos de Eudesmano/isolamento & purificação
18.
Sci Rep ; 7(1): 1509, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28473706

RESUMO

The well-defined mammalian slp76-signalosome is crucial for T-cell immune response, yet whether slp76-signalosome exists in invertebrates and how it evolved remain unknown. Here we investigated slp76-signalosome from an evolutionary perspective in amphioxus Branchiostoma belcheri (bb). We proved slp76-signalosome components bbslp76, bbGADS and bbItk are present in amphioxus and bbslp76 interacts with bbGADS and bbItk, but differences exist between the interaction manners within slp76-signalosome components of amphioxus and human (h). Specifically, bbslp76 has a unique WW-domain that blocked its association with hItk and decreased TCR-induced tyrosine-phosphorylation and NFAT-activation. Deletion of WW-domain shifted the constitutive association between bbslp76 and hPLCγ1 to a TCR-enhanced association. Among slp76-signalosome, the interaction between slp76 and PLCγ1 is the most conserved and the binding between Itk and slp76 evolved from constitutive to stimulation-regulated. Sequence alignment and 3D structural analysis of slp76-signalosome molecules from keystone species indicated slp76 evolved into a more unfolded and flexible adaptor due to lack of WW-domain and several low-complexity-regions (LCRs) while GADS turned into a larger protein by a LCR gain, thus preparing more space for nucleating the coevolving slp76-signalosome. Altogether, through deletion of WW-domain and manipulation of LCRs, slp76-signalosome evolves from a rigid and stimulation-insensitive to a more flexible and stimulation-responding complex.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Evolução Molecular , Fosfoproteínas/genética , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Regulação da Expressão Gênica , Humanos , Células Jurkat , Anfioxos/genética , Anfioxos/metabolismo , Modelos Moleculares , Mutação/genética , Fatores de Transcrição NFATC/metabolismo , Especificidade de Órgãos/genética , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Fosfotirosina/metabolismo , Filogenia , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Mapeamento de Interação de Proteínas , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/metabolismo
19.
Biometrics ; 73(4): 1311-1320, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28369699

RESUMO

Applications of spatial point processes for large and complex data sets with inhomogeneities as encountered, example, in tropical rain forest ecology call for estimation methods that are both statistically and computationally efficient. We propose a novel second-order quasi-likelihood procedure to estimate the parameters for a second-order intensity reweighted stationary spatial point process. Our approach is to derive first- and second-order estimating functions and then combine them linearly using appropriate weight functions. In the stationary case, we argue that the asymptotically optimal weight functions are respectively a constant and a function of lags between distinct locations in the observation window. This leads to a considerable gain in computational efficiency. We further exploit this simplification in the nonstationary case. Simulations show that, when compared with several existing approaches, our method can achieve significant gains in statistical efficiency. An application to a tropical rain forest data set further illustrates the advantages of our procedure.


Assuntos
Biometria , Ecologia , Modelos Estatísticos , Algoritmos , Simulação por Computador , Floresta Úmida
20.
Springerplus ; 5: 531, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27186495

RESUMO

PURPOSE: Monitoring of key markers for lung cancer detection and tracking of acquired drug resistance is critical for the management of the disease. We aim to ascertain the value of monitoring both total cell free DNA concentrations and mutant EGFR DNA content within diverse groups of individuals most vulnerable to the disease. METHODS: We proposed longitudinal monitoring of circulating DNA using digital PCR. Circulating DNA present in peripheral blood can be obtained non-invasively and provide timely disease status update. 25 heavy smokers and 50 patients undergoing TKI therapy were recruited. Peripheral blood specimens were taken at different time points and their circulating DNA were analyzed and quantified. RESULTS: Significant higher concentrations of total cell free DNA were detected when compared with healthy high-risk individuals. Levels were stable throughout the treatment cycles, which makes it potentially a useful tool for patient stratification. Concurrent mutant T790M DNA detection of lung cancer patients at baseline achieved 82 % concordance with matched tissue analysis. Samples initially negative for the T790M gene mutation that became positive during treatment were corroborated with a repeat biopsy. The results showed its usefulness for serial monitoring. CONCLUSION: Monitoring of circulating DNA addresses the need for disease detection and shows the ability to capture the dynamic changes of the disease.

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