Potential association factors for developing effective peptide-based cancer vaccines.

Peptide-based cancer vaccines have been shown to boost immune systems to kill tumor cells in cancer patients. However, designing an effective T cell epitope peptide-based cancer vaccine still remains a challenge and is a major hurdle for the application of cancer vaccines. In this study, we constructed for the first time a library of peptide-based cancer vaccines and their clinical attributes, named CancerVaccine (https://peptidecancervaccine.weebly.com/). To investigate the association factors that influence the effectiveness of cancer vaccines, these peptide-based cancer vaccines were classified into high (HCR) and low (LCR) clinical responses based on their clinical efficacy. Our study highlights that modified peptides derived from artificially modified proteins are suitable as cancer vaccines, especially for melanoma. It may be possible to advance cancer vaccines by screening for HLA class II affinity peptides may be an effective therapeutic strategy. In addition, the treatment regimen has the potential to influence the clinical response of a cancer vaccine, and Montanide ISA-51 might be an effective adjuvant. Finally, we constructed a high sensitivity and specificity machine learning model to assist in designing peptide-based cancer vaccines capable of providing high clinical responses. Together, our findings illustrate that a high clinical response following peptide-based cancer vaccination is correlated with the right type of peptide, the appropriate adjuvant, and a matched HLA allele, as well as an appropriate treatment regimen. This study would allow for enhanced development of cancer vaccines.

Delivery of sorafenib by myofibroblast-targeted nanoparticles for the treatment of renal fibrosis.

Fibrosis is an excessive accumulation of the extracellular matrix within solid organs in response to injury and a common pathway that leads functional failure. No clinically approved agent is available to reverse or even prevent this process. Herein, we report a nanotechnology-based approach that utilizes a drug carrier to deliver a therapeutic cargo specifically to fibrotic kidneys, thereby improving the antifibrotic effect of the drug and reducing systemic toxicity. We first adopted in vitro-in vivo combinatorial phage display technology to identify peptide ligands that target myofibroblasts in mouse unilateral ureteral obstruction (UUO)-induced fibrotic kidneys. We then engineered lipid-coated poly(lactic-co-glycolic acid) nanoparticles (NPs) with fibrotic kidney-homing peptides on the surface and sorafenib, a potent antineoplastic multikinase inhibitor, encapsulated in the core. Sorafenib loaded in the myofibroblast-targeted NPs significantly reduced the infiltration of α-smooth muscle actin-expressing myofibroblasts and deposition of collagen I in UUO-treated kidneys and enhanced renal plasma flow measured by Technetium-99m mercaptoacetyltriglycine scintigraphy. This study demonstrates the therapeutic potential of the newly identified peptide fragments as anchors to target myofibroblasts and represents a strategic advance for selective delivery of sorafenib to treat renal fibrosis. SIGNIFICANCE STATEMENT: Renal fibrosis is a pathological feature accounting for the majority of issues in chronic kidney disease (CKD), which may progress to end-stage renal disease (ESRD). This manuscript describes a myofibroblast-targeting drug delivery system modified with phage-displayed fibrotic kidney-homing peptides. By loading the myofibroblast-targeting nanoparticles (NPs) with sorafenib, a multikinase inhibitor, the NPs could suppress collagen synthesis in cultured human myofibroblasts. When given intravenously to mice with UUO-induced renal fibrosis, sorafenib loaded in myofibroblast-targeting NPs significantly ameliorated renal fibrosis. This approach provides an efficient therapeutic option to renal fibrosis. The myofibroblast-targeting peptide ligands and nanoscale drug carriers may be translated into clinical application in the future.

Microalgal extract from thermotolerant Coelastrella sp. F50 retards the liver tumor progression by targeting hepatic cancer stem cells.

Microalgae extracts have shown antitumor activities. However, the antitumor mechanism of them is not yet completely clear, especially the effect on cancer stem cells (CSCs). This study aimed to elucidate the antitumor activity and mechanism of microalgal extract from thermotolerant Coelastrella sp. F50 (F50) in hepatocellular carcinoma (HCC). Oncogenic behaviors were analyzed using cell proliferation, colony formation, invasion, sphere formation, and side population cells (SPCs) assays in HCC cells after F50 treatment. The molecular mechanism was further studied by quantitative real-time PCR, immunoblot, and immunofluorescence analyses. The chemopreventive efficacy of F50 was evaluated in rat orthotopic hepatoma, and the hepatic pathologies were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. F50 specifically suppressed hepatic CSCs (tumor spheres, drug efflux, CD133/ABCG2 CSCs markers) with no cytotoxicity in vitro. In the animal experiments, prophylactic F50 administration significantly attenuated tumor progression and improved liver function in HCC-bearing rats. In the mechanistic analysis, F50 potentially inhibited cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2 ) axis in HCC cells and rat hepatoma, and exogenous PGE2 restored CSCs properties in F50-treated HCC cells. In summary, F50 extract inhibits hepatic CSCs by COX-2/PGE2 downregulation and may facilitate a novel phytotherapy for HCC prevention.

Investigation of biodistribution and tissue penetration of PEGylated gold nanostars and their application for photothermal cancer treatment in tumor-bearing mice.

Gold nanostars (AuNSs), with unique physicochemical properties, are thought to be a promising agent for photothermal therapy (PTT). In this study, we prepared PEGylated gold nanostars (pAuNSs) using the HEPES-reduction method. The high photothermal conversion efficiency (∼80%) and photothermal stability of pAuNSs were demonstrated in vitro and in vivo. 111In-DTPA-pAuNSs were prepared as a radioactive surrogate for the biodistribution studies of pAuNSs. In both microSPECT/CT images and the biodistribution study, the tumor-to-muscle (T/M) ratio reached a maximum at 24 h post intravenous injection of 111In-DTPA-pAuNSs. The high linear correlation between the 111In radioactivity and the gold content in the tumors (R2 0.86-0.99) indicated that 111In-DTPA-pAuNSs were appropriate for noninvasively tracking pAuNSs in vivo after systemic administration. Histological examination after silver enhancement staining clearly illustrated that the accumulated pAuNSs in the tumors were mainly located on the luminal surface of vessels. The mice bearing a SKOV-3 xenograft exhibited remarkable therapeutic efficacy with negligible organ damage after receiving pAuNS-mediated photothermal therapy. Our findings suggested that pAuNSs, together with their radioactive surrogate 111In-DTPA-pAuNSs, are promising for applications in image-guided photothermal therapy.

Neuroprotective effect of surround needling combined with acupoint injection on acute herpetic neuralgia / 中国针灸

OBJECTIVE@#To explore the effect and mechanism of surround needling combined with acupoint injection on acute herpetic neuralgia (AHN).@*METHODS@#Ninety-nine patients with T-T segment AHN were randomly divided into 3 groups, 33 cases in each group, including 2 cases dropped off in the surround needling group, 4 cases dropped off in the acupoint injection group, and 3 cases dropped off in the combined group. Oral valacyclovir was given in each group, 0.3 g each time, 2 times a day for 10 days. Oblique insertion of needle used at points around the herpes in the surround needling group, and continuous wave was stimulated to tolerance for 20 min; the same acupoints were selected as the surround needling group, stimulated with the mixture injection of mecobalamin and lidocaine in the acupoint injection group; After the surround needling, acupoint injection was performed in the combined group. The treatment was given once a day, 14 times for a course, and one course was needed in all groups. The skin healing conditions (blistering, crusting, and dislocation time) of each group were compared after treatment. The pain scores, pain area and quality of life scores in each group were observed before and after treatment. The levels of neuron specific enolase (NSE), substance P (SP) and calcitonin gene-related peptide (CGRP) in the local blister fluid were measured before and after treatment in all groups.@*RESULTS@#The blistering, crusting and dislocation time in the combined group were earlier than the other two groups (all <0.05). The pain score and pain area in the each group were significantly lower than those before treatment, and the quality of life score was significantly higher than that before treatment (all <0.05). The improvements of pain score and quality of life score in the combined group were more obvious than the other two groups (all <0.05). After treatment, the levels of NSE, SP and CGRP in the local blister fluid in each groups were significantly lower than those before treatment (all <0.05). The indexes in the combined group were significantly lower than those in the other two groups (all <0.05).@*CONCLUSION@#Both surround needling and acupoint injection have an adjuvant effect on AHN. The combination of the two is better, the skin is healed quickly, the analgesia is significant, and the contents of local NSE, SP and CGRP are significantly decreased. The mechanism of action is to exert neuroprotective effects.

Práticas corporais, comportamento desviante e consumo de álcool e drogas: uma revisão sistemática / Body practices, deviant behavior and alcohol and drug consumption: a systematic review / Prácticas corporales, el comportamiento desviado y consumo de alcohol y drogas: una revisión sistemática

O estudo objetiva revisar na literatura científica acerca das práticas corporais e o consumo de álcool e drogas a partir do comportamento desviante. Trata-se de uma revisão sistemática nas bases de dados MEDLINE, Scielo, Scopus, Web of Science e SportDiscus, utilizando os descritores e palavras-chave "lazer desviante", "sociologia do desvio", "práticas corporais", "álcool" e "drogas". Os critérios de inclusão foram artigos originais, estudos publicados em periódicos nacionais e internacionais. Vinte estudos publicados em periódicos foram analisados minuciosamente. Os estudos encontrados foram organizados em categorias de acordo com a temática trabalhada: i) lazer, práticas corporais e comportamento desviante em adolescentes e adultos; ii) práticas corporais e comportamento desviante no âmbito do trabalho, e iii) práticas corporais e comportamento desviante em diferentes grupos. As práticas corporais foram vistas como aspecto que podem auxiliar na prevenção de uso de álcool e drogas, mas que sejam direcionadas as formas de prevenção.

The study aims to review in the scientific literature about the corporal practices and the consumption of alcohol and drugs from the deviant behavior. It is a systematic review in the MEDLINE, Scielo, Scopus, Web of Science and SportDiscus databases, using the descriptors and keywords "deviant leisure", "deviant sociology", "corporal practices", "alcohol" and "drugs". The inclusion criteria were original articles, studies published in national and international journals. Twenty studies published in journals were analyzed in detail. The studies were organized in categories according to the theme: i) leisure, body practices and deviant behavior in adolescents and adults; ii) body practices and deviant behavior in the work area; and iii) corporal practices and deviant behavior in different groups. The body practices were seen as aspect that can aid in the prevention of alcohol and drug use, but that are directed the forms of prevention.

El estudio del objetivo es revisar la literatura científica sobre las prácticas corporales y el consumo de alcohol y drogas de la conducta desviada. Se trata de una revisión sistemática en MEDLINE, SciELO, Scopus, Web of Science y SportDiscus utilizando descriptores y palabras clave "ocio desviada", "sociología de la desviación", "prácticas corporales", "alcohol" y "drogas". Los criterios de inclusión fueron artículos originales, estudios publicados en revistas nacionales e internacionales. Se analizaron veinte estudios publicados en revistas. Los estudios encontrados fueron organizados en categorías de acuerdo con la temática trabajado: i) el ocio, las prácticas corporales y la conducta desviada en adolescentes y adultos; ii) el cuerpo y prácticas desviadas en el trabajo, y iii) las prácticas corporales y la conducta desviada en diferentes grupos. Las prácticas corporales fueron vistos como un aspecto que puede ayudar en la prevención de alcohol y drogas, pero que las formas de prevención se dirigen.

Kai-Xin-San series formulae alleviate depressive-like behaviors on chronic mild stressed mice via regulating neurotrophic factor system on hippocampus.

Kai-xin-san (KXS) is a famous Chinese medicinal formula applied for treating stress-related psychiatric diseases with the symptoms such as depression, forgetfulness and dizziness. In clinic, the composition ratio of KXS is always varied and KXS series formulae are created. Here, we aim to compare the anti-depressive effect of different ratios of KXS and reveal its action mechanism on regulation of neurotrophic factor system. Firstly, daily intra-gastric administration of chemically standardized extracts of KXS series formulae for seven days significantly alleviated the depressive symptoms of chronic unpredictable mild stressed mice displayed by enhanced sucrose consumptions and decreased immobile time of forced swimming coupled with increased locomotor activities. KXS might fulfill this effect by up-regulating the expressions of NGF, BDNF and Trk receptors in hippocampus, which were confirmed by the treatment of corresponding blockers tPA-stop and K252a. The ratio with higher amounts of Ginseng Radix et Rhizoma and Polygalae Radix exerted most profound effect on anti-depression and regulation enzymes in metabolic pathway of neurotrophic factors. These findings suggested that KXS was beneficial for enhancing supplies, up-regulating receptors, and restoring the dysfunction of metabolic pathway of neurotrophic factors, which might account for its anti-depression effect.

Saikosaponin d induces cell death through caspase-3-dependent, caspase-3-independent and mitochondrial pathways in mammalian hepatic stellate cells.

BACKGROUND: Saikosaponin d (SSd) is one of the main active triterpene saponins in Bupleurum falcatum. It has a steroid-like structure, and is reported to have pharmacological activities, including liver protection in rat, cell cycle arrest and apoptosis induction in several cancer cell lines. However, the biological functions and molecular mechanisms of mammalian cells under SSd treatment are still unclear. METHODS: The cytotoxicity and apoptosis of hepatic stellate cells (HSCs) upon SSd treatment were discovered by MTT assay, colony formation assay and flow cytometry. The collage I/III, caspase activity and apoptotic related genes were examined by quantitative PCR, Western blotting, immunofluorescence and ELISA. The mitochondrial functions were monitored by flow cytometry, MitoTracker staining, ATP production and XF24 bioenergetic assay. RESULTS: This study found that SSd triggers cell death via an apoptosis path. An example of this path might be typical apoptotic morphology, increased sub-G1 phase cell population, inhibition of cell proliferation and activation of caspase-3 and caspase-9. However, the apoptotic effects induced by SSd are partially blocked by the caspase-3 inhibitor, Z-DEVD-FMK, suggesting that SSd may trigger both HSC-T6 and LX-2 cell apoptosis through caspase-3-dependent and independent pathways. We also found that SSd can trigger BAX and BAK translocation from the cytosol to the mitochondria, resulting in mitochondrial function inhibition, membrane potential disruption. Finally, SSd also increases the release of apoptotic factors. CONCLUSIONS: The overall analytical data indicate that SSd-elicited cell death may occur through caspase-3-dependent, caspase-3-independent and mitochondrial pathways in mammalian HSCs, and thus can delay the formation of liver fibrosis by reducing the level of HSCs.

Reliability of the 6-minute walk test and cardiac autonomic markers in active and sedentary older women / Reprodutibilidade do teste de caminhada de 6 minutos e marcadores autonômicos cardíacos em idosas ativas e sedentárias

Abstract The aim of this study was to examine the reliability of the 6-minute walk test (6MWT) and post-exercise cardiac autonomic markers in physically active and sedentary older women. Eighteen physically active older women (64.2±3.1 years; 63.0±2.7 kg; 1.52±0.06 m; 26.9±2.7 kg.m-2) who performed Tai Chi Chuan for at least 6 months, and 18 sedentary older women (64.0±3.7 years; 63.8±8.9 kg; 1.49±0.05 m; 28.4±3.5 kg.m-2) were submitted to 6MWT in two separate occasions. Immediately after 6MWT, heart rate recovery at one (HRR1’) and two minutes (HRR2’), as well as the heart rate variability (HRV) were recorded. Reliability was verified by intraclass correlation coefficient (ICC) with 95% confidence interval, Bland-Altman plots were used as a measure of agreement, and coefficient of variation (CV) was calculated. High reliability (ICC=0.86) was found for performance in 6MWT (528.8 ± 71.4 m and 473.2 ± 62.4 m; CV=7.9 and VC=8.5%) in both groups. Likewise, high reliability (ICC≥0.84 and ICC≥0.80) was found for HRR 1’ (29.0±11.0 bpm and 17.0±8.0 bpm; VC=30.1% and VC =40.2%) and HRR 2’ (36.0±10.0 bpm and 24.0±9.0 bpm; VC =23.7% and VC =22.8%) in both groups. Regarding HRV, moderate reliability was found in the active group (CCI≥0.57; VC =35-47%), while moderate-high reliability was found in the sedentary group (CCI=0.65-0.76; VC=34-69%). Agreement was found for all variables analyzed. In conclusion, post-exercise 6MWT, HRR, and HRV are reliable tools to assess functional capacity and cardiac autonomic control in physically active and sedentary older women.

Resumo Objetivou-se verificar a reprodutibilidade do teste de caminhada de 6 minutos (TC6) e de marcadores autonômicos cardíacos pós-esforço em idosas fisicamente ativas e sedentárias. Dezoito idosas ativas (64,2 ± 3,1 anos; 63,0 ± 2,7 kg; 1,52 ± 0,06 m; 26,9 ± 2,7 kg.m-2) praticantes de Tai Chi Chuan (≥6 meses de prática) e 18 idosas sedentárias (64,0 ± 3,7 anos; 63,8 ± 8,9 kg; 1,49 ± 0,05 m; 28,4 ± 3,5 kg.m-2) foram submetidas a dois TC6 com uma semana de intervalo. Foram medidas a frequência cardíaca de recuperação (FCR) de um e dois minutos (FCR1’ e FCR2’, respectivamente) e variabilidade da frequência cardíaca (VFC) pós-esforço. A reprodutibilidade foi verificada pelos: coeficiente de correlação intraclasse (CCI) com 95% de intervalo de confiança; análise de concordância de Bland-Altman; e coeficiente de variação (CV). O desempenho no TC6 (528,8±71,4 m e 473,2±62,4 m; CV=7,9% e CV=8,5%) apresentou alta reprodutibilidade (CCI=0,86) em idosas ativas e sedentárias, respectivamente. Similarmente, as medidas pós-esforço da FCR1’ (29,0±11,0 bpm e 17,0±8,0 bpm; CV=30,1% e CV=40,2%) e FCR2’ (36,0±10,0 bpm e 24,0±9,0 bpm; CV=23,7% e CV=22,8%) apresentaram alta reprodutibilidade (CCI≥0,84 e CCI≥0,80) em ambos os grupos. Quanto a VFC verificou-se reprodutibilidade moderada (CCI≥0,57; CV=35-47%) em idosas ativas e moderada-alta nas sedentárias (CCI=0,65-0,76; CV=34-69%). Todas as variáveis apresentaram concordância em ambos os grupos. Conclui-se que o TC6, FCR e VFC pós-esforço são instrumentos reprodutíveis na avaliação da capacidade funcional e controle autonômico cardíaco em idosas ativas e sedentárias.

MDA5 complements TLR3 in suppression of neuroblastoma.

Toll-like receptor3 (TLR3) has been confirmed to be differentially expressed in neuroblastoma (NB), and predicts a favorable prognosis with a high expression in tumor tissues. Treatment with TLR3 agonist--polyinosinic-polycytidylic acid [poly(I:C)] could induce significant but limited apoptosis in TLR3-expressing NB cells, suggesting that other viral RNA sensors, including melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) in the cytosolic compartment might also be implicated in poly(I:C)-induced NB cell death. MDA5 and RIG-I were induced by poly(I:C) to express in two of six NB cell lines, SK-N-AS (AS) and SK-N-FI, which were associated with up-regulation of caspase9 and active caspase3. While knockdown of either MDA5 or RIG-I alone is ineffective to decrease caspase9 and active caspase3, simultaneously targeting MDA5 and TLR3 showed the best effect to rescue poly(I:C) induced up-regulation of mitochondrial antiviral signaling protein (MAVS), caspase9, active caspase3, and apoptosis in AS cells. Over-expression of MDA5 in FaDu cells resulted in significantly less colony formation and more poly(I:C)-induced cell death. Further studies in human NB tissue samples revealed that MDA5 expression in NB tissues predicted a favorable prognosis synergistically with TLR3. Our findings indicate that MDA5 may serve as a complementary role in the TLR3 activated suppression of NB.

Rating of perceived exertion and affective responses during Tai Chi Chuan.

Ratings of perceived exertion (RPE) and affective responses were assessed during Tai Chi Chuan. A total of 16 women (M age = 61.2 yr., SD = 8.8) participated in this study. Individuals practiced Tai Chi Chuan three times/week during seven weeks, and were assessed session-by-session (21 Wu Tai Chi Chuan sessions) in three moments (15, 30, and 45 min.) using Borg's scale (CR 0-10) and the Feeling Scale (+5/-5). With regard to RPE, there was a difference between 15 and 30 min. and between 15 and 45 min. The same pattern of differences was observed for the affective response. The RPE during the seven weeks ranged from "fairly light" to "moderate" and the affective response from "good" to "very good." Thus, Tai Chi Chuan was perceived as a low-moderate intensity and pleasurable (positive affect) exercise by middle-aged and elderly women.

Saikosaponin a and saikosaponin d inhibit proliferation and migratory activity of rat HSC-T6 cells.

The proliferation and migration of hepatic stellate cells (HSCs) profoundly impact the pathogenesis of liver inflammation and fibrogenesis. As a perennial herb native to China, Bupleurum falcatum is administered for its anti-inflammatory, antipyretic, and antihepatotoxic effects. Saikosaponin a (SSa) and Saikosaponin d (SSd) are the major active components of triterpene saponins in Bupleurum falcatum. This study analyzes how SSa and SSd affect rat HSC-T6 cell line proliferation and migration. Experimental results indicate that, in addition to suppressing HSC-T6 proliferation, wound healing activity and cell migration in a time- and dose-dependent manner, SSa and SSd significantly induce apoptosis. Additionally, SSa and SSd decreased the expressions of extracellular matrix-regulated kinase 1/2 (ERK1/2), platelet-derived growth factor receptor 1 (PDGFR1), and subsequently transforming growth factor-ß1 receptor (TGF-ß1R), α-smooth muscle actin, TGF-ß1 and connective tissue growth factor. They also decreased phosphorylation of p38 (p-p38) and ERK1/2 (p-ERK1/2) of HSC-T6. Furthermore, both SSa and SSd can block PDGF-BB and TGF-ß1-induced cell proliferation and migration of HSC-T6. These results suggest that SSa and SSd may inhibit proliferation and activation of HSC-T6, and the modulated mechanisms warrant further study.

Evaluation of EGFR-targeted radioimmuno-gold-nanoparticles as a theranostic agent in a tumor animal model.

This study evaluated the tumor targeting and therapeutic efficacy of a novel theranostic agent (131)I-labeled immuno-gold-nanoparticle ((131)I-C225-AuNPs-PEG) for high epidermal growth factor receptor (EGFR)-expressed A549 human lung cancer. Confocal microscopy demonstrated the specific uptake of C225-AuNPs-PEG in A549 cells. (131)I-C225-AuNPs-PEG induced a significant reduction in cell viability, which was not observed when incubated with AuNPs-PEG and C225-AuNPs-PEG. MicroSPECT/CT imaging of tumor-bearing mice after intravenous injection of (123)I-C225-AuNPs-PEG revealed significant radioactivity retention in tumor suggested that (131)I-labeled C225-conjugated radioimmuno-gold-nanoparticles may provide a new approach of targeted imaging and therapy towards high EGFR-expressed cancers.

Percepção subjetiva do esforço, resposta afetiva e hipotensão pós-exercício em sessão de Tai Chi Chuan / Rating of perceived exertion, affective response and post-exercise hypotension in Tai Chi Chuan session

O objetivo do estudo foi analisar a percepção subjetiva do esforço (PSE), resposta afetiva (RA) e pressão arterial pós-exercício em sessão aguda de Tai Chi Chuan (TCC). Vinte e quatro mulheres (47-79 anos; 9 normotensas e 15 hipertensas) foram submetidas a uma sessão de TCC e uma sessão controle (delineamento cruzado). A PSE foi avaliada pela escala de Borg (CR10), a RA pela escala de valência afetiva (+5/-5) e a pressão arterial (PA) pelo método oscilométrico (5, 10, 25, 20, 25 e 30 min pós-sessão). Redução significante da PA sistólica foi identificada aos 20 e 25 min após a sessão de TCC somente nas hipertensas. Os valores de RA e PSE foram +2,8 ± 1,9 e 3,5 ± 1,2, respectivamente. Os resultados sugerem que uma sessão de TCC de intensidade moderada foi prazerosa para as voluntárias (hipertensas e normotensas), embora tenha induzido discreto efeito hipotensor agudo na PA sistólica somente das hipertensas.

The aim of the study was to analyze the rating of perceived exertion (RPE), affective response (AR), and blood pressure (BP) post-exercise in acute Tai Chi Chuan (TCC) session. Twenty-four women (47-79 years; 9 normotensive and 15 hypertensive) performed one TCC and one control session (cross-over design). The RPE was assessed using the Borg's scale (CR10), the AR was assessed by the Feeling Scale (+5/-5) and the BP by the oscillometric method (5, 10, 15, 20, 25, and 30min post-TCC session). A significant systolic BP reduction was observed in the 20 and 25min post-TCC session only in the hypertensive women. The AR and RPE values were +2.8 ± 1.9 e 3.5 ± 1.2, respectively. The results suggest that a moderate TCC exercise bout was pleasurable for the volunteers (normotensive and hypertensive), although it has induced a slight acute hypotensive effect on the systolic BP only in the hypertensive women.

Efeito da prática do Tai Chi Chuan sobre a resistência aeróbia de idosas sedentárias / Effect of Tai Chi Chuan practice on aerobic resistance of sedentary elderly women

OBJETIVO: Investigar o efeito da prática do Tai Chi Chuan (TCC) sobre a resistência aeróbia de idosas sedentárias. Métodos: Fizeram parte do estudo 11 idosas sedentárias (67,9 ± 6,8 anos; 25,9 ± 2,8 kg/m²), as quais foram submetidas aos testes de marcha estacionária de dois minutos e teste de caminhada de seis minutos pré e pós-intervenção de 12 semanas de TCC. RESULTADOS: Houve aumento da resistência aeróbia das idosas analisadas após 12 semanas de prática de TCC, demonstrado tanto por meio do teste de caminhada de seis minutos (510 ± 64 vs. 536 ± 63 metros; p = 0,006) quanto no teste de marcha estacionária de dois minutos (83 ± 20 vs. 110 ± 19 execuções; p = 0,001). CONCLUSÃO: De acordo com os resultados obtidos, é possível concluir que a prática do TCC é capaz de promover aumento da resistência aeróbia de idosas sedentárias.

OBJECTIVE: To investigate the effect of Tai Chi Chuan(TCC) practice on cardiorespiratory fitness of sedentary elderly women. Methods:A total of 11 sedentary elderly women (67.9 ± 6.8 years; 25.9 ± 2.8 kg·m-2)were submitted to six-minute walk test and two-minute step testbefore and after a 12-week TCC training program. RESULTS: Improvements were observed on cardiorespiratory fitness of elderly women analyzed after a 12-week TCC training program, through six-minute walk test (510 ± 64 vs. 536 ± 63 meters; p= 0.006)and two-minute step test(83 ± 20 vs. 110 ± 19 executions; p= 0.001). CONCLUSION: According with obtained results, itis possible to conclude that the TCC practice may promote an increase in cardiorespiratory fitness in sedentary elderly women.

Genistein and genistein-containing dietary supplements accelerate the early stages of cataractogenesis in the male ICR/f rat.

Cataract-related loss of vision affects large numbers of people in today's aging populations and presents a healthcare burden to many nations. The role of dietary supplements within the lens is largely unknown, although benefits from dietary anti-oxidants are expected. In this study, the effects of genistein as its aglycone, a genistein-containing dietary supplement (Novasoy(®)200), and a genistein-containing food (soy protein isolate, PRO-FAM 932) on the development of lens opacity were examined in the hereditary cataractous ICR/f rat. These studies were carried out in a background diet of semi-purified, isoflavone-free AIN-76A with casein as its protein source. The amount of genistein for the experimental diets was standardized to its concentration (as genistein aglycone as well as simple and complex ß-glucoside conjugates) in the soy protein isolate supplement. Also tested was a high-dose genistein diet containing an 11-fold higher amount of genistein aglycone. The composition of each diet was verified by reverse-phase HPLC and blood plasma isoflavone concentrations were determined by LC-tandem mass spectrometry. The development of opacity in each lens was monitored and digitally recorded using slit-lamp examination over the course of the study. Each of the genistein-containing diets caused a significantly more rapid development of fibrous opacification in the anterior cortical region and development of apparent water clefts or vacuoles in the posterior subcapsular region than the AIN-76A control diet; however, the establishment of dense lens opacification was not significantly different between each of the diets. There was also no significant difference observed between the low-dose and high-dose genistein aglycone groups. These data suggest that genistein-containing dietary supplements accelerate the early stages of cataractogenesis in the male ICR/f rat, with no dose-dependent effects.

[Optimization of molding technics of xiaochuang granules by central composite design-response surface methodology].

OBJECTIVE: The optimal molding technics of Xiaochuang granules was selected. METHODS: The main influential factors of the molding technics included the mixed excipients' ratio, the quantity times of excipients and the ethanol concentration. The molding effect was evaluated with the yield of qualified granules and solubility. The optimal technics of Xiaochuang granules was selected by central composite design-response surface methodology. RESULTS: The optimal molding technics were as follows: the quantity times of excipients was 2.0, the proportion between mixed excipents (dextrin: lactose) was 1:1, and the ethanol concentration was 65%. CONCLUSION: The molding technics of Xiaochuang granules is reasonable, stable and reliable.

[Study on the optimal extracion craft of Xiaochuang gel by central composite design-response surface methodology].

OBJECTIVE: To optimize the extraction craft of Xiaochuang gel by central composite design-response surface methodology. METHODS: The main influential factors of extraction effect included the quantity of ethanol, the concentration of ethanol and the extraction time. The conditions of the extraction were evaluated by the yield of the extracts and the total content of rheum emodin and chrysophanol. The optimal extraction craft of Xiaochuang gel was chosen by central composite design-response surface methodology. RESULTS: The optimal conditions were extracting two times, two hours each time with ten volume multiples of 60% ethanol. CONCLUSIONS: It is simple, convenient and highly predictive to optimize the extraction craft of Xiaochuang gel by central composite design-response surface methodology.

Intraprostatic capsaicin injection as a novel model for nonbacterial prostatitis and effects of botulinum toxin A.

OBJECTIVES: An animal model for nonbacterial prostatitis in rats was developed with the use of intraprostatic injection of capsaicin, an agent thought to excite C-afferent fibers and cause neurogenic inflammation. The analgesic and anti-inflammatory properties of botulinum toxin type A (BoNT-A) was tested in this model. METHODS: Adult male Spraque-Dawley rats were injected with varying doses of capsaicin into the prostate. The nociceptive effects of capsaicin were evaluated for 30min by using a behavior approach; then the prostate was removed for histology and cyclooxygenase (COX) 2 protein concentration measurement. Evans blue (50mg/kg) was also injected intravenously to assess for plasma protein extravasation. A second set of animals were injected with up to 20U of BoNT-A into the prostates 1 wk prior to intraprostatic injection of 1000micromol/l capsaicin. RESULTS: Capsaicin dose dependently induced modifications in pain behavior: closing of the eyes, hypolocomotion, and inflammatory changes: increase of inflammatory cell accumulation, COX2 expression, and plasma extravasation at the acute stage, but completely recovered at 1 wk. BoNT-A pretreatment dose dependently reversed pain behavior and inflammation. BoNT-A 20U significantly decreased inflammatory cell accumulation, COX2 expression, and Evans blue extraction (82.1%, 83.0%, and 50.4%, respectively), and reduced pain behavior (66.7% for eye score and 46.5% for locomotion score). CONCLUSIONS: Intraprostatic capsaicin injection induced neurogenic prostatitis and prostatic pain, and may be a useful research model. BoNT-A produced anti-inflammatory and analgesic effects, and support clinical evaluation in prostatitis.

Effect of Tongxinluo superfine on experimental anginal model (contraction of collaterals) in rat with endothelial dysfunction / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of Tongxinluo superfine (TXL) on experimental anginal model induced by Arginine Vasopressin in rats with endothelial dysfunction.</p><p><b>METHOD</b>First, the endothelial dysfunction rat model was made by methionine-induced hyperhomocysteinemia (HHcy). The thoracic aorta were excised, and acetylcholine (Ach)-induced endothelium dependent relaxation and sodium nitroprusside (SNP) induced endothelium-independent relaxation were measured. Total plasma homocysteine (Hcy) concentrations were measured with automated fluorescence polarization immunoassay (FPIA). Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma von Willebrand factor (vWF) level. Plasma nitric oxide (NO) contents were assayed by method of nitrate reductase. Then, the rat model of collaterals contraction (model group) was established by AVP intravenous injection in rats with endothelial dysfunction and the S wave change (DeltaS) and T wave depression in Lead II ECG were used as the index of angina severity. The nitric oxide (NO) contents in serum and the expression of myocardium eNOS mRNA were measured.</p><p><b>RESULT</b>Ach (0. 1-1000 nmol L(-1))-induced endothelium dependent relaxation (EDR) of aortic rings was significantly decreased in HHcy group. The endothelium-independent relaxation induced by SNP (0.001-10 micromol L(-1)) was not significantly different between the two groups. Plasma homocysteine concentrations and vWF levels in rats treated with methionine were higher than those of control group, while NO contents were significantly decreased in HHcy group compared with control. The results showed that L-methionine intake induced hyperhomocysteinemia in rats. Impaired EDR, increased vWF and decreased NO suggested the exist of endothelial dysfunction. DeltaS of model group increased from 1 min to 5 min and T wave of model group depressed at 2 min compared with that of control after the administration of vasopressin (0.5 U kg(-1)). The intragastric administration of TXL inhibited vasopressin-induced S wave change at 4 min and 5 min and T wave depression from 30 s to 3 min after AVP injection. The NO contents in serum and the expression of myocardium eNOS mRNA of TXL group were increased compared with model group.</p><p><b>CONCLUSION</b>Experimental angina induced by AVP injection is more severe in rats with endothelial dysfunction. Tongxinluo Superfine can protect against collaterals contraction in rats maybe by increasing the NO contents in serum and the expression of myocardium eNOS mRNA.</p>