Phenolic constituents of Sanguisorba officinalis and their Nrf2 agonistic effect / 药学学报

Thirty-one phenolic constituents were isolated and purified from the 95% ethanol extract of Sanguisorbae Radix by using various chromatographic techniques, including macroporous resin, silica gel, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated by physicochemical properties, spectroscopic data (MS and NMR) and electronic circular dichroism (ECD) spectra, and identified as 3-methoxyl-2S,3S-epoxyflavanone (1a), 3-methoxyl-2R,3R-epoxyflavanone (1b), longifoin B (2), longifoin C (3), eriodictyol (4), naringenin (5), liquiritigenin (6), 5,3ʹ-dihydroxy-7,4ʹ-dimethoxyflavanone (7), naringenin-7-O-β-D-glucopyranoside (8), dihydroquercetin (9), dihydrokaempferol (10), (-)-garbanzol (11), (2R,3R)-4-methoxyl-distylin (12), kaempferol (13), quercetin (14), α,4,2′,4′-tetrahydroxydihydrochalcone (15), phloretin (16), (+)-catechin (17), ethyl (+)-cyanidan-3-ol-8-carboxylate (18), phyllocoumarin (19), methyl 3-methoxy-4,5-dihydroxybenzoate (20), 4,5-dimethoxy-3-hydroxybenzoic acid methyl ester (21), 3,4′-di-O-methylellagic acid (22), 3,4,3′-O-trimethylellagic acid (23), 3,3ʹ,4ʹ-O-trimethylellagic acid-4-O-β-D-xyloside (24), (3R)-thunberginol C (25), resveratrol (26), 1-hydroxypinoresinol (27), (7S,8S)-3-methoxy-3′,7-epoxy-8,4′-oxyneoligna-4,9,9′-triol (28), emodin-8-O-β-D-glucoside (29), phloracetophenone (30) and 4-(4′-hydroxyphenyl)-butan-2-one (31). Among them, compound 1a and 1b is a pair of new flavonoid enantiomers, compounds 2 and 3 are a pair of new epimers, while compounds 4, 5, 6, 9, 10, 13, 16 and 26 were obtained from S. officinalis for the first time, compounds 7, 8, 27, 30 and 31 were isolated for the first time from the S. officinalis genus, and compounds 11, 12, 15, 18, 19, 25, 28 and 29 were isolated for the first time from the Rosaceae. The antioxidant activities of compounds 1-24 were evaluated by activating the Nrf2 transcriptional pathway, which were measured by the dual-luciferase reporter gene assay in 293T cells. Compounds 4, 6-10, 12, 14, 17, 19, 20 and 22-24 showed significant Nrf2 agonistic effect compared with the control group at 25 μmol·L-1, which provided reference for the research of their antioxidant activity.

BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models / 医学前沿

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.

Effect of electroacupuncture at antagonistic muscle and agonistic muscle on motor function in patients with upper-extremity spasticity after stroke / 中国针灸

OBJECTIVE@#To compare the improvement effect between simultaneous electroacupuncture at antagonistic muscle and agonistic muscle and simple electroacupuncture at antagonistic muscle on spasticity degree, upper-extremity motor function and activity of daily living in patients with upper-extremity spasticity after stroke.@*METHODS@#A total of 60 patients with upper-extremity spasticity after stroke were randomized into a comprehensive group (30 cases, 1 case dropped off) and an antagonistic muscle group (30 cases, 2 cases dropped off). In the antagonistic muscle group, acupuncture was applied at Jianyu (LI 15), Binao (LI 14), Zhouliao (LI 12), Shousanli (LI 10), Waiguan (TE 5) and Houxi (SI 3), electric stimulation was attached to Jianyu (LI 15)-Binao (LI 14), Zhouliao (LI 12)-Shousanli (LI 10) and Waiguan (TE 5)-Houxi (SI 3), with discontinuous wave, 15 Hz in frequency. On the basis of the treatment in the antagonistic muscle group, acupuncture was applied at Tianquan (PC 2), Chize (LU 5), Jianshi (PC 5) and Daling (PC 7) in the comprehensive group, electric stimulation was attached to Tianquan (PC 2)-Chize (LU 5) and Jianshi (PC 5)-Daling (PC 7), with continuous wave, 5 Hz in frequency. The treatment was given once a day, 6 days a week for 4 weeks in the two groups. Before and after treatment, the scores of modified Ashworth scale (MAS), Fugl-Meyer assessment upper extremity scale (FMA-UE) and modified Barthel index (MBI) scale were observed in the two groups.@*RESULTS@#Compared before treatment, the MAS scores of elbow flexors and wrist flexors after treatment were decreased (P<0.05), the scores of FMA-UE and MBI scale after treatment were increased in the two groups (P<0.05). The scores of FMA-UE and MBI scale after treatment in the comprehensive group were higher than those in the antagonistic muscle group (P<0.05).@*CONCLUSION@#Simultaneous electroacupuncture at antagonistic muscle and agonistic muscle and simple electroacupuncture at antagonistic muscle can both improve the spasticity degree in patients with upper-extremity spasticity after stroke, however, the former can better restore motor function and improve activity of daily living.

Alice e os paradoxos da escrita acadêmica / Alice and the academic writing paradoxes / Alice y los paradójicos de la escritura académica

O texto aborda a escrita acadêmica como experiência agonística. Utilizamos o recurso da ficção como estratégia para compor uma narrativa que visa a incidir nos modos de produção de verdades, por meio da convocação de afetos que transcendam o conteúdo da escrita. A experiência agonística é discutida pela personagem Alice, por meio da problematização de três paradoxos: o aspecto informativo e experiencial da escrita na constituição das políticas de produção, o engendramento entre virtualidade e atualização nos processos de subjetivação e a presença-ausente do autor na produção de autoria. Uma posição ético-estético-política é tecida a partir da problematização desses elementos, apostando na potência de um textoexperimentação para provocar fissuras nos modos de produção de conhecimento no âmbito acadêmico.

The text approaches academic writing as an agonistic experience. Fiction discourse is used as a strategy to compose a narrative that aims to delve in truth production modes by means of conjuring affection that transcends the written content. The agonistic experience is discussed by means of three paradoxical problematizations by the character Alice: the informative and personal aspect of writing in constituting production policies, the intertwining between virtuality and the updating of subjectivization processes and the absent-presence of the author on authorship production. An ethical-aesthetical-political approach is woven from the problematization of these elements, leaning on the potency of an experiencing-text to provoke fissures on the production modes of knowledge in the academic scope.

El texto habla de la escritura académica como experiencia agonística. Utilizamos el recurso de la ficción como estrategia para componer una narrativa que busca incidir en los modos de producción de verdades, por medio de la convocatoria de afectos que trasciendan el contenido de la escritura. La experiencia agonística es discutida por el personaje Alice, por medio de la problematización de tres paradojas: el aspecto informativo y experiencial de la escritura en la constitución de las políticas de producción académica, el engendramiento entre virtualidad y actualización en los procesos de subjetivación y la presencia-ausencia del autor en la producción de autoría. Una posición ético-estético-política es tejida a partir de la problematización de estos elementos, apostándose en la potencia de un texto-experimentación para provocar fisuras en los modos de producción de conocimiento en el ámbito académico.

Unusual effect of chemical communication on social aggression in juvenile cichlid fish Cichlasoma paranaense (Cichliformes: Cichlidae)

Some fish species are socially organized and show a social rank order which is achieved through aggressive interactions. After hierarchy is settled, such species communicate their ranks through several sensorial cues; this communication is adaptive because it reduces detrimental effects from physical contests. Cichlid fish are socially organized and signal their social ranks through visual, acoustic and chemical communication. The response to signaling may vary according to the species and environment; the knowledge of different species is fundamental to understand the evolutionary forces upon their social communication. We tested the effect of chemical signaling on social groups of juvenile cichlid Cichlasoma paranaense by renewing the water in the aquarium, a procedure that washes away chemical information and increases aggressive interactions in other cichlid species. Two treatments were designed: 50% and 0% water renewal. Aggressive interactions were video-recorded immediately before water renewal, 1min, 1h, 2h, and 24h after water renewal. The treatment with the water renewal did not increase aggressive interactions within the group. The 50% water renewal apparently reduced aggressive interactions in this species, indicating an interspecific difference on the aggressive response to chemical variation in the social environment.(AU)

Algumas espécies de peixes são organizadas socialmente e apresentam uma ordem de rank social que é alcançada por meio de interações agressivas. Após o estabelecimento da hierarquia, essas espécies comunicam seu rank por diversas pistas sensoriais, essa comunicação é adaptativa, pois reduz os efeitos prejudiciais das lutas físicas. Peixes ciclídeos são socialmente organizados e sinalizam o rank social por comunicação visual, acústica e química. A resposta à sinalização pode variar de acordo com a espécie e o ambiente; o conhecimento sobre diferentes espécies é necessário para entender as forças evolutivas sobre sua comunicação social. Nós testamos o efeito da sinalização química em grupos sociais de juvenis do ciclídeo Cichlasoma paranaense por meio da renovação de água do aquário, um procedimento que dilui informações químicas e aumenta a interação agressiva em outras espécies de ciclídeos. Dois tratamentos foram realizados: 50% e 0% de renovação da água. A interação agressiva foi registrada imediatamente antes da renovação da água, 1min, 1h, 2h e 24h após a renovação da água. O tratamento com renovação não aumenta as interações agressivas dentro do grupo. A renovação de 50% da água do aquário aparentemente diminui as interações agressivas nessa espécie, indicando uma diferença interespecífica na resposta agressiva a variação química no ambiente social.(AU)

Social behavior and group growth of finishing pigs with divergent social breeding values / Comportamiento social y crecimiento grupal de cerdos en etapa de finalización con valores divergentes de crianza sociales / Comportamento social e crescimento grupal de porcos de engorda com valores divergentes de criação social

Abstract Background: Behavioral traits of pigs have been shown to be partly under genetic control, which raises the possibility that behavior might be altered by genetic selection, resulting in pigs with better growth performance. Objective: To evaluate the behavior and growth of finishing pigs and investigate pigs selected for high or low social breeding value (SBV) in relation to social behavior and group growth. Methods: Thirty-five females and 35 boars from five positive and five negative SBV groups of finishing pigs were grown from 30 to 90 kg and housed in 10 test pens (3.0 × 3.3 m, 7 pigs/pen). Pigs were recorded with video technology for nine consecutive hours on days 1, 15, and 30 after mixing. Pigs were weighed at approximately 90 kg body weight and the number of days to reach 90 kg was then calculated. Results: The frequency and duration of behaviors were present in the positive and negative SBV groups after mixing. On day 1 after mixing, agonistic behavior was significantly higher (p=0.027) for the -SBV group compared with the +SBV group. Feeding and feeding-together behaviors were significantly higher (p<0.003) in the +SBV group on days 1 and 30 after mixing. Moreover, growth performance to reach 90 kg body weight was significantly faster (p<0.002) in the +SBV group than in the -SBV group. Conclusion: Social interactions, such as feeding-together behavior, among pen mates might affect their growth rate and feed intake. Selection for SBV could be used as an indirect technique for improving growth performance of pigs.

Resumen Antecedentes: Se ha demostrado que los rasgos conductuales de los cerdos están parcialmente bajo control genético, lo que plantea la posibilidad de que el comportamiento pueda ser alterado vía selección genética y resulte en cerdos con mejores rendimientos de crecimiento. Objetivo: Evaluar el comportamiento y crecimiento de los cerdos en etapa de finalización e investigar cerdos seleccionados por un valor alto o bajo de crianza social (SBV) en relación al comportamiento social y al crecimiento grupal. Métodos: Treinta y cinco hembras y 35 verracos, pertenecientes a cinco grupos positivos y cinco grupos negativos de SBV de cerdos en etapa de finalización, llevados hasta los 90, desde 30 kg de peso, alojados en 10 corrales de prueba (3,0 x 3,3 m, 7 cerdos/corral). Los cerdos fueron observados con la ayuda de tecnología de vídeo por nueve horas consecutivas en los días 1, 15 y 30 luego de ser mezclados. Además, los cerdos se pesaron a los 90 kg de peso aproximadamente y se calculó el número de días para alcanzar dicho peso. Resultados: La frecuencia y duración de los comportamientos de los cerdos en la etapa de finalización se presentaron en los grupos de SBV negativos y positivos luego de ser mezclados. El día 1 luego de la mezcla, el comportamiento agonístico fue significativamente mayor (p=0,027) en el grupo -SBV que en el grupo +SBV. Los comportamientos de consumo de alimento y de consumo en compañía fueron significativamente mayores (p<0,003) en el grupo +SBV en los días 1 y 30 luego de la mezcla. Además, el crecimiento para alcanzar 90 kg de peso corporal fue significativamente más rápido (p=0,002) en el grupo +SBV que el grupo -SBV. Conclusiones: Las interacciones sociales, tales como el comportamiento de consumo de alimento en compañía, entre los compañeros de corral, pueden afectar la tasa de crecimiento y consumo de alimento. La selección por SBV podría usarse como técnica indirecta para mejorar el rendimiento de crecimiento en cerdos.

Resumo Antecedentes: Os traços comportamentais dos porcos demonstraram estar parcialmente sob controle genético, o que aumenta a possibilidade de que o comportamento possa ser alterado pela seleção genética e resulte em porcos com melhor comportamento de crescimento. Objetivo: Avaliar o comportamento e o crescimento dos porcos de engorda e investigar os porcos selecionados para alto ou baixo valor de reprodução social (SBV) em relação ao comportamento social e crescimento do grupo. Métodos: Trinta e cinco fêmeas e 35 machos, pertencentes a cinco grupos de SBV positivos e cinco negativos de porcos de engorda, foram engordados até 90 de 30 kg e alojados em 10 currais de teste (3,0 × 3,3 m, 7 porcos/curral). Os porcos foram observados com o auxílio de tecnologia de vídeo durante nove horas consecutivas nos dias 1, 15 e 30 após a mistura. Além disso, os porcos foram sopesados em aproximadamente 90 kg de peso corporal e o número de dias para atingir 90 kg foi então calculado. Resultados: A frequência e a duração dos comportamentos dos porcos de engorda foram apresentadas com grupos de SBV positivo e negativo após a mistura. No dia 1 após a mistura, o comportamento agonístico foi significativamente maior (p=0,027) no grupo -SBV do que no grupo +SBV. Os comportamentos de alimentação e alimentação conjunta foram significativamente maiores (p<0,003) no grupo +SBV nos dias 1 e 30 após a mistura. Além disso, o comportamento de crescimento do grupo para atingir 90 kg de peso corporal foi significativamente mais rápido (p<0,002) no grupo +SBV do que no grupo -SBV. Conclusão: As interações sociais, como o comportamento de alimentação conjunta, entre companheiros de curral podem afetar a taxa de crescimento e a ingestão alimentar. A seleção para SBV pode ser uma técnica indireta para melhorar o comportamento de crescimento dos porcos.

Water temperature affects aggressive interactions in a Neotropical cichlid fish

Changes in water temperature may affect the aggressive behavior of aquatic organisms, such as fish, either by changing some physiological mechanisms or by increasing the probability of encounters between individuals as a result of variation in their swimming activity. In our study, we evaluated the influence of increasing and decreasing temperature on the aggressive behavior of the Neotropical cichlid fish Cichlasoma paranaense. Firstly, we tested the critical thermal maximum (CTMax) tolerated by this species. Then, we tested the effect of decreasing or increasing the water temperature in 6o C (starting at 27° C) on the aggressive interactions of fish under isolation or housed in groups. We found a CTMax value of 39° C for C. paranaense. We also observe that a 6° C decrease in water temperature lowers swimming activity and aggressive interactions in both isolated and group-housed fish, as expected. On the other hand, the increase in temperature had no effect on the fish's aggressive behavior, neither for isolated nor for grouped fish. We concluded that C. paranaense shows high tolerance to elevated temperatures and, in turn, it does not affect aggressive behavior. Nevertheless, we cannot dismiss possible effects of elevated temperatures on aggressive interactions over longer periods.(AU)

Mudanças na temperatura da água podem afetar o comportamento agressivo de organismos aquáticos, como peixes, seja alterando alguns mecanismos fisiológicos ou aumentando a probabilidade de encontros entre os indivíduos como um resultado da variação na sua atividade natatória. Em nosso estudo, nós avaliamos a influência do aumento e da diminuição da temperatura sobre o comportamento agressivo do peixe ciclídeo neotropical Cichlasoma paranaense. Primeiramente, nós testamos a temperatura crítica máxima (CTMax) tolerada por essa espécie. Depois disso, nós testamos o efeito de reduzir ou aumentar a temperatura da água em 6° C (a partir de 27° C) sobre as interações agressivas de peixes sob isolamento ou alojados em grupos. Nós encontramos um valor de CTMax de 39° C para C. paranaense. Nós também observamos que uma redução de 6° C na temperatura da água diminui a atividade natatória e as interações agressivas tanto em peixes isolados quanto agrupados, como esperado. Por outro lado, o aumento na temperatura não teve efeito no comportamento agressivo dos peixes nem isolados, nem agrupados. Nós concluímos que C. paranaense apresenta alta tolerância a temperaturas elevadas, e que isso, por sua vez, não afeta o comportamento agressivo. No entanto, nós não podemos descartar possíveis efeitos de temperaturas elevadas sobre interações agressivas durante longos períodos.(AU)

Agonistic anti-CD40 single-chain antibody enhances anti-tumor effect of mouse NK cells / 中华微生物学和免疫学杂志

Objective To obtain a mouse CD40-specific single-chain antibody (scFv) with high purity and to investigate its in vivo and in vitro agonistic activity on natural killer(NK) cells against tumor. Methods Agonistic anti-mouse CD40 scFv with high purity was obtained by genetic engineering. Mouse dendritic cells (DCs) were treated with different strategies including anti-CD40 monoclonal antibody (McAb),anti-CD40 scFv and negative control. Expression of IL-12 in the supernatants of DC cultures was measured by ELISA. Then DCs and NK cells were co-cultured to obtain activated NK cells,which were co-cultured with T6-17 cells. WST-8 was used to test the cytotoxic effects of NK cells on T6-17 cells. A mouse tumor model was established by injecting BALB/c nude mice with T6-17 cells. Anti-CD40 scFv was injected into tumor to evaluate its inhibitory effect on tumor growth. Levels of IL-12 and IFN-γ in the tumor microen-vironment were detected by ELISA. Changes in the percentages of tumor-infiltrating NK cells and the expres-sion of NKG2D protein(natural-killer group 2,member D) were detected by flow cytometry and immunohis-tochemistry,respectively. Results The recombinant plasmid CD40 scFv-pET28a was confirmed to be con-structed correctly. Results of SDS-page and His-tag Western blot revealed that anti-CD40 scFv could be ex-pressed successfully with a relative molecular mass of 27×103. The level of IL-12 in the supernatant of DC culture of anti-CD40 scFv group was (555.86 ±40.48) pg/ml, which was significantly higher than that of negative control group (P<0.05). The killing ability of NK cells in anti-CD40 scFv group was (72.23 ± 3.99)%,which was significantly higher than that in negative control group (P<0.05). Anti-CD40 scFv significantly inhibited the tumor growth in BALB/c nude mice as compared with negative control group(P<0.05). The levels of IL-12 and IFN-γ in tumor microenvironment of anti-CD40 scFv group were(188.801± 32.718) pg/ml and(121.428±30.994) pg/ml,respectively,which were significantly higher than those in normal saline(NS) group(P<0.05). The positive rate of NKG2D protein and the percentage of CD3-DX5+cells in anti-CD40 scFv group were respectively(8.18±2.01)% and(19.15±2.24)%,which were signifi-cantly higher than those in NS group (P<0.05). Conclusion Agonistic anti-mouse CD40 scFv could en-hance the anti-tumor ability of NK cells by activating DCs.

Antitumor effect of agonistic CD40 antibody via the regulation of Th1/Th2 balance in the tumor microenvironment / 中国肿瘤临床

Objective:To explore the agonistic CD40 antibody(CD40ScFv and CD40mAb)-mediated suppression of mouse breast cancer cell growth and change in tumor tissue Th1/Th2 balance,as well as the mechanism underlying its antitumor effect.Methods:The re-combinant plasmid containing the CD40ScFv gene fragment was transformed into the Rosetta strain of Escherichia coli to express and purify the recombinant functional CD40ScFv protein.The 4T1 mouse breast cancer cells were cultured in vitro.Balb/C tumor model mice were divided into CD40ScFv,CD40mAb agonist,and saline(NS group)groups,which were administered CD40ScFv,CD40mAb ago-nist,and saline,respectively,to observe the change in tumor volume.The tumor tissues were removed and enzyme-linked immunosor-bent assay(ELISA)was used to determine IL-12 concentration in the tumor tissue supernatants.The tumor infiltrating lymphocytes (TILs)were extracted by enzymatic digestion.The proportion of Th1 and Th2 cells in TILs was determined by flow cytometry.Results:The CD40ScFv protein was successfully identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot.The molecular size and concentration of the purified protein were 27kDa and 1.12 mg/mL,respectively.The tumor sizes of the CD40ScFv and CD40mAb groups were(3.044±0.239)cm3and(2.749±0.261)cm3,respectively,which were significantly smaller(P<0.05)than that of the NS group(3.933±0.326)cm3.The tumor IL-12 concentration(determined by ELISA)in the CD40ScFv group(396.27±48.13)pg/mL and the CD40mAb agonist group(457.63±58.37)pg/mL were significantly higher(P<0.05)than that of the NS group(79.51±14.97) pg/mL.The results of flow cytometry showed that the excited Th1/Th2 cell ratios were 6.32±0.87 and 5.54±0.71 for the CD40ScFv and CD40mAb groups,respectively,which were significantly higher(P<0.05)than that of the NS group(1.79±0.38).Conclusions:The agonis-tic CD40 antibody inhibited tumor growth by regulating the Th1/Th2 ratio and IL-12 secretion via promotion of DC activation,which is one of the important mechanisms affecting Th1/Th2 balance in the tumor microenvironment

The proliferation inhibition of colon cancer cells by agonistic CD40 monoclonal antibody in vitro / 国际生物医学工程杂志

Objective To investigate the inhibitory effect of agonistic CD40 monoclonal antibody on the colon cancer cells (HCT116) proliferation in vitro.Methods The DCs (dendritic cells) loaded with tumor cells (HCT116) antigens were activated by different methods.According to the activation method,the cells were divided into three groups:agonistic CD40 monoclonal antibody group,blank control group and TNF-α positive control group.The cells were cultured for 7 days,and the expression rates of CD80,CD83,CD86 and HLA-DR on DC surface in each group were detected by flow cytometry.The concentration of cytokine IL-12(p70) in DCs culture supernatant was determined by ELISA kit.The proliferation activity of the T lymphocytes was evaluated by MTT (methyl thiazolyl tetrazolium).Then the inhibition rate of colon cancer HCT116 cells proliferation,which induced by the tumor-specific effector T lymphocytes,was assayed.Results Compared with the blank control group,the agonistic CD40 monoclonal antibody group had a significantly higher expression rates of CD80,CD83,CD86 and HLA-DR on DC surface (P＜0.05).The concentration of IL-12 in the supernatant of DC was also much higher in the agonistic CD40 monoclonal antibody group (P＜0.05,(716.80±53.43) pg/ml vs.(405.51 ±12.17) pg/ml).The DCs activated by CD40 monoclonal antibody had stronger ability to stimulate proliferation of T lymphocytes (P＜0.05,the stimulation index was (2.006 2±0.438 3) to (1.365 0±0.209 8)).The tumor-specific CTLs induced by DCs in the agonistic CD40 monoclonal antibody group had stronger ability to inhibit colon cancer HCT116 cells (P＜0.05,the inhibition rate was (66.08±0.41)％ vs.(46.60± 1.10)％).However,there was no statistical significance between the agonistic CD40 monoclonal antibody group and the TNF-α positive control group (P＞0.05).Conclusion Agonistic CD40 monoclonal antibody in vitro can promote activation and mature of DCs,then the activated DCs can induce the production of tumor-specific CTL,which can significantly inhibit the proliferation of colon cancer HCT116 cells.

Dangerous neighborhood: saurophagy between syntopic Tropidurus lizards / Vizinhança perigosa: saurofagia entre lagartos Tropidurus sintópicos

Saurophagy constitutes an important source of mortality among lizards and has been reported for the genus Tropidurus. However, the extension of this behavior remains unknown. Herein, we record the predation of T. jaguaribanus by its congener T. hispidus. This is the first report of saurophagy among different species of syntopicTropidurus. Furthermore, whereas published records of saurophagy tend to be directed against juveniles, this case involved two adult individuals.

A saurofagia constitui uma importante fonte de mortalidade entre lagartos e tem sido reportada para o gênero Tropidurus. Contudo, a extensão deste comportamento permanece desconhecida. Neste estudo registramos a predação de T. jaguaribanus por seu congênere T. hispidus. Este é o primeiro caso de saurofagia entre diferentes espécies de Tropidurus sintópicos. Além disso, embora a saurofagia tenda a ser direcionada contra jovens, este caso envolveu dois indivíduos adultos.

Synthesis and in vitro bioIogicaI activity of 3-phenyI-3-pyrroIyIpentane deriva-tives / 中国药科大学学报

A new series of 3-phenyl-3-pyrrolylpentane derivatives are synthesized through modifying the structure of lead compound LG19055,a nonsecosteroidal vitamin D receptor(VDR)agonist.The VDR-agonistic ability of target compounds was measured indirectly by evaluating the differentiation ability of HL-60 cell.The results showed that compounds 13a,13c,13d,13h,13i,13j have excellent VDR-agonistic ability(EC50 <50 μmol /L), especially for compound 13j (EC50 =0.10 μmol /L),which was more potential than that of lead compound LG190155.Their proliferation inhibitory activities in vitro were evaluated by MTT assay in MCF-7,PC-3,Caco-2, HepG2 and L02 cell lines.Compound 13a exhibited significant inhibitory effects on HepG2 cell line(IC50 =0.11μmol /L).Moreover,the inhibitory effect of compound 13a on non-tumor liver L02 cell line was relatively weak (IC50 =15.24 μmol /L ),suggesting that compound 13a has selective inhibitory effects on liver cancer cells.Additionally,HL-60 cell differentiation-inducing activity and the inhibitory effect of cancer cells were posi-tively related.

Flowers visited by hummingbirds in an urban Cerrado fragment, Mato Grosso do Sul, Brazil

Hummingbirds are the main vertebrate pollinators in the Neotropics, but little is known about the interactions between hummingbirds and flowers in areas of Cerrado. This paper aims to describe the interactions between flowering plants (ornithophilous and non-ornithophilous species) and hummingbirds in an urban Cerrado remnant. For this purpose, we investigated which plant species are visited by hummingbirds, which hummingbird species occur in the area, their visiting frequency and behavior, their role as legitimate or illegitimate visitors, as well as the number of agonistic interactions among these visitors. Sampling was conducted throughout 18 months along a track located in an urban fragment of Cerrado vegetation in Campo Grande, Mato Grosso do Sul, Brasil. We found 15 species of plants visited by seven species of hummingbirds. The main habit for ornithophilous species was herbaceous, with the predominance of Bromeliaceae; among non-ornithophilous most species were trees from the families Vochysiaceae and Malvaceae. Hylocharis chrysura was the hummingbird that visited the largest number of plant species and also attended the greater number of agonistic events. The high proportion (66.7%) of non-ornithophilous species visited by hummingbirds in the present study was similar to that found in other communities analyzed in Brazil. The fact that ornithophilous species in the area does not offer resources continuously throughout the year should induce hummingbirds to search for alternative resources, and contribute to the high proportion of non-ornithophilous species visited. In general, the floral form was not a barrier to floral visits by hummingbirds, although morphological characteristics of flowers from some plant species may be restrictive. Tabebuia aurea, for example, presents flowers with long corollas, hindering the access to floral resources by the pollinators, what may favor the occurrence of illegitimate visits by hummingbirds. Despite of being a small fragment of Cerrado vegetation, the studied remnant can be considered an important refuge, sheltering a great richness of hummingbird species comparable to several forested areas in Brazil.

Os beija-flores são os principais vertebrados polinizadores na região Neotropical, mas pouco ainda se conhece sobre as interações entre beija-flores e flores em áreas de Cerrado. O objetivo deste estudo foi descrever as interações entre espécies de plantas em floração (ornitófilas e não-ornitófilas) e beija-flores, em um fragmento urbano de Cerrado. Para isso, investigamos quais espécies de plantas são visitadas por beija-flores, quais espécies de beija-flores ocorrem na área, seu comportamento e frequência de visitas, sua atuação como visitante legítimo ou ilegítimo, assim como o número de interações agonísticas entre essas aves. Foram realizados 18 meses de amostragem ao longo de uma trilha localizada em um fragmento urbano de Cerrado em Campo Grande, Mato Grosso do Sul, Brasil. Foram encontradas 15 espécies de plantas visitadas por sete espécies de beija-flores. O principal hábito para as espécies ornitófilas foi herbáceo, com a predominância da família Bromeliaceae; entre as não-ornitófilas o principal hábito foi o arbóreo, com a predominância das famílias Vochysiaceae e Malvaceae. Hylocharis chrysura foi o beija-flor que realizou o maior número de visitas às flores e o que participou de maior número de ocorrências agonísticas. A elevada proporção (66,7%) de espécies não-ornitófilas visitadas por beija-flores no presente estudo também vem sendo reportada em outras comunidades analisadas no Brasil. O fato de as espécies ornitófilas da área estudada não oferecerem recurso de forma contínua ao longo de todo o ano deve induzir os beija-flores a procurar recursos alternativos, e contribuir para a alta proporção de espécies não-ornitófilas visitadas. De modo geral, a forma floral não foi obstáculo às visitas dos beija-flores, apesar de as características morfológicas de algumas espécies de plantas poderem ser restritivas. Tabebuia aurea, por exemplo, tem flores de corola longa, o que dificulta o acesso ao néctar pelos beija-flores, podendo favorecer a ocorrência de visitas ilegítimas. Apesar de ser um fragmento de Cerrado pequeno, o remanescente estudado pode ser considerado um importante refúgio, abrigando riqueza de espécies de beija-flores comparável à de diversas formações florestais do Brasil.

Un análisis prosopográfico de algunas formas actuales de movilización armada en Colombia / Prosopographical analysis of some current forms of armed mobilization in Colombia / Prosopografia análise de algumas das atuais formas de mobilização armada na Colômbia

En este artículo sintetizo un análisis de algunas de las formas de la movilización armada en Colombia a finales del siglo XX y comienzos del siglo XXI. Combino el análisis del estado actual del campo y del mercado de la guerra interna en Colombia como condición estructural, con la exploración de una diversidad de formas de movilización armada asociadas en un grupo de reclutas de distintas agrupaciones armadas legales e ilegales en Colombia, sin incluir una referencia a miembros de bandas y agrupaciones de delincuencia común. Trato así de incorporar las relaciones de correspondencia entre las condiciones objetivas y las disposiciones subjetivas que se combinan en un modelo generativo de movilización política armada.

Neste artigo a presenteou ma análise de algumas formas de mobilização armada na Colômbia a final do século XX e começos do século XXI. Combino a analise do atual estado de campo e do mercado da guerra interna na Colômbia como condição estrutural, com a exploração de uma diversidade de formas de mobilização armada associadas num grupo de jovens enrolados em diferentes agrupações armadas legais e ilegais na Colômbia, sem incluir uma referência a bandas e agrupações de delinqüência comum. Tento assim de incorporar as relações de correspondência entre as condições objetivas e as disposições subjetivas que se combinam num modelo generativo de mobilização política armada.

In this paper I summarize the analysis of some armed mobilization ways in Colombiain the beginning of 21th century and ends of the 20th. I put together the analysis of the current state camp and the civil war market in Colombia as a structural condition with the varied armed mobilization ways associated, in a group of recruits from different legal and illegal armed groups in Colombia but without enclose a reference to armed gangs and common crime members. I try to incorporate the agreement relationships between objective conditions and subjective dispositions which are combined in a generative model of political armed mobilization.

Long-term social recognition memory in adult male rats: factor analysis of the social and non-social behaviors

A modified version of the intruder-resident paradigm was used to investigate if social recognition memory lasts at least 24 h. One hundred and forty-six adult male Wistar rats were used. Independent groups of rats were exposed to an intruder for 0.083, 0.5, 2, 24, or 168 h and tested 24 h after the first encounter with the familiar or a different conspecific. Factor analysis was employed to identify associations between behaviors and treatments. Resident rats exhibited a 24-h social recognition memory, as indicated by a 3- to 5-fold decrease in social behaviors in the second encounter with the same conspecific compared to those observed for a different conspecific, when the duration of the first encounter was 2 h or longer. It was possible to distinguish between two different categories of social behaviors and their expression depended on the duration of the first encounter. Sniffing the anogenital area (49.9 percent of the social behaviors), sniffing the body (17.9 percent), sniffing the head (3 percent), and following the conspecific (3.1 percent), exhibited mostly by resident rats, characterized social investigation and revealed long-term social recognition memory. However, dominance (23.8 percent) and mild aggression (2.3 percent), exhibited by both resident and intruders, characterized social agonistic behaviors and were not affected by memory. Differently, sniffing the environment (76.8 percent of the non-social behaviors) and rearing (14.3 percent), both exhibited mostly by adult intruder rats, characterized non-social behaviors. Together, these results show that social recognition memory in rats may last at least 24 h after a 2-h or longer exposure to the conspecific.

Memória de reconhecimento social em ratos / Social recognition memory in rats / Mémoire de reconnaissance sociale chez les rats / Memoria de reconocimiento social en ratones

O paradigma intruso-residente vem sendo intensamente empregado em estudos para avaliar a memória de reconhecimento social em roedores. Tipicamente, ratos adultos (residentes) são expostos a dois encontros de 5 minutos cada com um mesmo intruso juvenil ou com juvenis diferentes; o intervalo entre encontros é usualmente 30 minutos. A quantidade de comportamentos sociais do residente, no segundo encontro, em relação a um intruso familiar é substancialmente menor do que o observado no primeiro encontro, o que não ocorre quando o segundo encontro envolve um juvenil novo; esse resultado caracteriza memória de reconhecimento social. Neste estudo discutimos achados recentes sobre os tipos de comportamentos usualmente incluídos nas categorias social e não-social, a influência da fase temporal, a interferência de rotinas laboratoriais na memória de reconhecimento social, modalidades sensoriais usualmente empregadas por roedores no processamento de informações na memória social e alternativas adicionais para o estudo da socialidade em roedores

The intruder-resident paradigm has been extensively employed in studies of social recognition memory in rodents. Typically, adult rats (residents) are exposed to two 5-min encounters with the same juvenile intruder or with two different juveniles; the interval between the encounters is 30 min. The amount of social behaviors exhibited by the resident rats toward the same intruder juvenile in the second encounter is substantially smaller when compared to both that seen in the first encounter and that seen toward a different juvenile; these results characterize social recognition memory. In this study we discuss recent findings related to behaviors usually included as social and non-social, the influence of the temporal phase on social behavior, the interference of laboratory routines on social recognition memory, sensory modalities usually employed by rodents for processing relevant information in the social memory and additional alternatives to study sociability in these animals

Le paradigme intrus-résident a été employée dans les études de memoire de reconnaissance social chez les rongeurs. Les rats adultes, nommés résidents, sont exposés à deux rencontres de 5min chacun, avec un même intrus juvénile ou avec des différents. L'intervalle de temps parmi les rencontres est 30 min. Le montant des comportements sociaux du résident, à la deuxième rencontre, parrapport a un intrus familiaire est sensiblement inférieur à celui observé à la première rencontre, ce qui ne se produit pas lorsque la deuxième recontre implique un nouveau juvenil. Ce résultat caractérise la mémoire de reconnaissance social. Cette étude discute des récentes conclusions du comportement social et non social, l'influence de la phase temportelle, l'ingérence dês routines de laboratoire dans cette memoire, les modalités sensorielles habituellement utilisées par les rongeurs dans le traitement de l'information sociale dans la mémoire et des solutions alternatifs pour l'étude de la socialité chez eux

El paradigma intruso-residente se viene utilizando extensivamente en estudios de memoria de reconocimiento social en roedores. Típicamente, un ratón adulto (residente) se expone a dos encuentros de 5 minutos cada uno con el mismo intruso juvenil o con dos juveniles diferentes; el intervalo entre los encuentros es de 30 minutos. El número de comportamientos sociales en el segundo encuentro exhibido por el residente y direccionado hacia el mismo intruso es substancialmente menor comparado con el primer encuentro o con un intruso nuevo; este tipo de disminución comportamental caracteriza memoria de reconocimiento social. En este estudio discutimos nuevos resultados relacionados con los comportamientos sociales y no-sociales, influencia de la fase circadiana, interferencia de las rutinas de laboratorio en la memoria de reconocimiento social, modalidades sensoriales empleadas por roedores para procesar información relevante a la memoria social y las alternativas adicionales para estudiar sociabilidad en estos animales

Acciones de endotelina 1 y angiotensina II en embarazos complicados con preeclampsia / Endothelin 1 and angiotensin II in preeeclampsia

Introduction. It is generally thought that development of hypertension in preeclampsia (PE) is due to generalized endothelial dysfunction and/or results from an imbalance in the production and/or action of vasoactive factors, resulting in higher citosolic Ca2+ concentration which in turn leads to vasoconstriction and decreased blood pressure perfusion in organs, including the fetoplacental unit. Among vasoactive factors involved in blood pressure regulation, endothelin 1 (ET-1) and angiotensin II (Ang II) regulate citosolic Ca2+ concentrations and therefore are considered in this review. PE is associated with higher circulating and placental ET-1 levels, observation that explains, at least in part, vasoconstriction and oxidative stress. Higher and lower Ang II sensitivity seen in PE and normal pregnancy, respectively, could not be explained by changes in renin-angiotensin system components, including Ang II receptors (ATI). During normal pregnancy, ATI receptors are found as monomers and are inactivated by reactive oxygen species (ROS) leading to lower Ang II sensitivity. In contrast, PE is associated with increased ATl/bradicinin receptors (B2) heterodimers which are resistant to inactivation by ROS, maintaining increased ATI-receptor stimulated signaling in PE. In adittion, AT-1 agonistic antibodies (AT1-AA) obtained from PE women increases intracellular Ca2+, NADPH oxidase components and ROS, effects not observed with normal pregnancy AT1-AA. Conclusion. High ET-1 levels, the presence of AT1/B2 receptor heterodimers and increased AT1-AA are involved, at least in part, in the hypertensive and oxidative stress states in PE.

Introducción. Se reconoce que el desarrollo de la hipertensión en la preeclampsia (PE) resulta del daño endotelial generalizado y/o de la falta de equilibrio en la producción y/o acción de agentes vasoactivos, lo que conlleva al incremento en la concentración citosólica de Ca2+ que resulta en vasoconstricción y disminución de la perfusión sanguínea en los órganos, incluyendo la unidad fetoplacentaria. Dentro de los factores vaso-activos que regulan la presión arterial, en la presente revisión se consideró a la endotelina 1 (ET-1) y a la angiotensina II (Ang II), factores que regulan la concentración citosólica de Ca2+. En comparación con el embarazo normal, la PE se asocia con mayor concentración en suero y placenta de ET-1, lo que explica en parte la vasoconstricción y el estado de estrés oxidativo. La respuesta exagerada en la PE y el estado de refractariedad en el embarazo normal a la Ang II no pueden explicarse por componentes del sistema renina-angiotensina, incluyendo a los receptores de Ang II (ATI). Durante el embarazo normal los receptores AT-1 se encuentran en forma de monómeros y son inactivados por las especies reactivas de oxígeno (ROS), lo que se asocia con menor respuesta a Ang II. En cambio, la respuesta exagerada a la Ang II durante la PE puede deberse a la heterodimerizacion de los receptores ATI con los de bradicinina (B2), estado que les confiere resistencia a la inactivación por las especies reactivas de oxígeno (ROS), lo que explica el incremento en la concentración del Ca2+ intracelular. Además, los anticuerpos agonistas del receptor ATI (AT1-AA) de mujeres PE aumenta la concentración de Ca2+ intracelular, de la NADPH oxidasa y de ROS, efectos que no se presentan al utilizar AT1-AA de embarazadas normotensas. Conclusión. Las altas concentraciones de ET-1, la presencia de receptores ATI en forma de heterodimeros ATI/ B2 y el aumento en los AT1-AA explican en parte, el estado de hipertensión y de estrés oxidativo de la PE.

Effect of Flexion Angle of Knee Joint on Co-contractions of Agonist and Antagonist Muscles / 中国康复理论与实践

@# Objective To test the effect of different flexion angles of knee joint on the myoelectric activity and torque of quadriceps femoris and hamstring muscle when these muscles contracting.MethodsElectromyographic activities and isometric torque measurements were performed on 10 healthy subjects at 30°, 60° and 90° of knee joint flexion.ResultsThe results indicated that the greatest maximal voluntary isometric contracture-torque of quadriceps femoris occurred during knee extension at 60° of knee flexion ( P<0.01). However, no significant relationship of maximal voluntary isometric contracture-electromyography and maximal voluntary isometric contracture-torque of quadriceps femoris were found in 10 subjects. But when knee joint was at 90° flexion, hamstring muscle had a greatest neuro-myoelectric activity.ConclusionThe exercise of maximal voluntary isometric contraction of quadriceps femoris and hamstrings muscles at certain knee joint angle can help to maintain the stability of knee joint.

Social isolation and aggressiveness in the Amazonian juvenile fish Astronotus ocellatus

We tested the effect of social isolation on the aggressiveness of an Amazonian fish: Astronotus ocellatus. Ten juvenile fishes were transferred from a group aquarium (60 x 60 x 40 cm) containing 15 individuals (without distinguishing sex) to an isolation aquarium (50 x 40 x 40 cm). Aggressiveness was tested by means of attacks on and displays toward the mirror image. The behavior was video-recorded for 10 min at a time on 4 occasions: at 30 min, 1 day, 5 days and 15 days after isolation. The aggressive drive was analyzed in three ways: latency to display agonistic behavior, frequency of attacks and specific attacks toward the mirror image. The latency to attack decreased during isolation, but the frequency of mouth fighting (a high aggressive attack) tended to increase, indicating an augmented aggressive drive. Our findings are congruent with the behavior of the juvenile cichlid, Haplochromis burtoni but differ from the behavior observed in another cichlid, Pterophylum scalare. Increased aggressiveness in A. ocellatus may be mediated by means of the primer effect, the effect of prior residence or processes involving recognition of a conspecific.

Testamos o efeito do isolamento social sobre a agressividade no peixe amazônico, Astronotus ocellatus. Dez peixes juvenis foram transferidos de um aquário de agrupamento (60 x 60 x 40 cm) contendo 15 indivíduos (sem discriminação de sexo) para um aquário de isolamento (50 x 40 x 40 cm). A agressividade foi testada por meio de ataques e exibições direcionadas à imagem do peixe no espelho. O comportamento foi filmado durante 10 min em 4 momentos: 30 min, 1 dia, 5 dias e 15 dias após o isolamento. Nós analisamos a motivação agressiva por meio da latência para início do comportamento agonístico e pela freqüência dos ataques totais e específicos direcionados ao espelho. A latência para o comportamento agonístico reduziu ao longo do isolamento e houve uma tendência de aumento da freqüência de "mouth fighting" (um ataque de alta intensidade de agressão), mostrando-nos um aumento na motivação agressiva. Os resultados estão de acordo com os encontrados para ciclídeos juvenís de Haplochromis burtoni, mas discordam com os encontrados para Pterophylum scalare (acará bandeira). Sugerimos que o aumento da agressividade em A. ocellatus pode ser mediado pelo efeito de exposição prévia, da residência prévia ou por processos envolvendo reconhecimento de co-específicos.

Sensitization of TNF alpha and Agonistic FAS/CD95 Antibody-Induced Apoptosis by INF gamma on Neuroblastoma Cells

PURPOSE: IFN gamma sentitizes many tumor cells to TNF alpha and FASL-mediated apoptosis by enhancing the expression of TNF or FAS/CD95 receptor and modulating the activation of caspase and Bcl-2 family. It has been reported that IFN gamma and TNF alpha synergistically caused differentiation and growth inhibition of neuroblastoma cells. Even though some neuroblastoma cell express FASR/FASL on the cell surface, they could not induce apoptosis by ligation of the FAS/CD95 receptor. But the treatment of IFN gamma is reported to induce apoptosis in some neuroblastoma cell lines through the CD95/ CD95L autocrine circuit. In this study, we examined whether IFN gamma could affect TNF alpha and agonistic FAS/CD95 antibody(CH-11)-induced apoptosis against neuroblastoma cell lines that had shown diverse drug sensitivity and resistance. METHODS: CHLA-15, CHLA-90 and LA-N-2 neuroblastoma cells were cultured in IMDM and treated with recombinant IFN gamma TNF alpha and CH-11 antibody. Cell viability was measured by DIMSCAN with a fluorescent calcein-AM. Apoptosis was analyzed through flow cytometry using Annexin V- PE and 7-ADD staining and confirmed by pancaspase and caspase-8 blocking experiments. The expression of TNF RI and FAS/CD95 receptor was evaluated by flow cytometry using the corresponding antibody and PE-conjugated secondary antibody. RESULTS: IFN gamma or TNF alpha alone had no demonstrable cytotoxic effects, whereas both cytokines in combination induced apoptosis synergistically in CHLA-15 and CHLA-90 cells. Although there was no cytotoxicity with the ligation of CH-11 alone in CHLA-90 cells, pretreatment of IFNgammaincreased the sensitivity of CH-11-mediated apoptosis. The expression of TNFRI and FAS/CD95R were nonspecifically enhanced after treatment of IFN gamma without relation to sensitivity to TNF alpha and CH-11. This finding suggest up-regulation of both receptors may contribute to sensitization of TNFalphaand CH-11-mediated apoptosis by IFN gamma in only sensitive cell lines. CONCLUSION: IFN gamma induced sensitization of TNF alpha and agonistic FAS/CD95 antibody-mediated apoptosis on some neuroblastoma cells through up-regulation of TNFRI and FAS/CD95 receptor.