Esculetin exerts anti-proliferative effects against non-small-cell lung carcinoma by suppressing specificity protein 1 in vitro.

Esculetin, a coumarin derivative, is a phenolic compound isolated from Artemisia capillaris, Citrus limonia, and Euphorbia lathyris. Although it has been reported to have anti-inflammatory, anti-oxidant, and anti-proliferative activities in several human cancers, its anti-proliferative activity against non-small-cell lung carcinoma (NSCLC) and the molecular mechanisms involved have not been adequately elucidated. In this study, we used two NSCLC cell lines (NCI-H358 and NCI-H1299) to investigate the anti-proliferative activity and apoptotic effect of esculetin. Our data showed that esculetin-treated cells exhibited reduced proliferation and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly suppressed by esculetin in a dose- and time-dependent manner. Furthermore, the levels of p27 and p21, two key regulators of the cell cycle, were up-regulated by the esculetin-mediated down-regulation of Sp1; the level of a third cell-cycle regulator, survivin, was decreased, resulting in caspase-dependent apoptosis. Therefore, we conclude that esculetin could be a potent anti-proliferative agent in patients with NSCLC.

Performance Responses, Nutrient Digestibility, Blood Characteristics, and Measures of Gastrointestinal Health in Weanling Pigs Fed Protease Enzyme.

Although exogenous protease enzymes have been used in poultry diets quite extensively, this has not been the case for pig diets. In general, due to their better gut fermentative capacity and longer transit time, pigs have greater capacity to digest dietary proteins than poultry. However, in early-weaned piglets, the stress brought about by weaning adversely affects the digestion of dietary proteins. Therefore, a study was conducted to determine the effects of a commercial protease enzyme in weanling pigs. Indices of growth, nutrient digestibility, blood profiles, fecal microflora, fecal gas emission and fecal scores were measured during the study. A total of 50 weanling pigs (6.42±0.12 kg) at 28 d of age were randomly assigned to receive 1 of 2 dietary treatments: i) control diet (corn-soy based) with no supplemental protease (CON), and ii) control diet+200 g/ton protease (PROT) for 42 d. A completely randomized design consisting of 2 treatments, 5 replicates, and 5 pigs in each replicate was used. Growth performance in terms of body weight (27.04±0.38 kg vs 25.75±0.39 kg; p<0.05) and average daily gain (491±7.40 g vs 460±7.46 g; p<0.05) in PROT fed pigs were increased significantly, but gain per feed (0.700±0.01 vs 0.678±0.01; p>0.05) was similar between treatments at d 42. Relative to CON pigs, PROT fed pigs had increased (p<0.05) apparent total tract digestibility (84.66%±0.65% vs 81.21%±1.13% dry matter and 84.02%±0.52% vs 80.47%±1.22% nitrogen) and decreased (p<0.05) NH3 emission (2.0±0.16 ppm vs 1.2±0.12 ppm) in the feces at d 42. Except for a decreased (p<0.05) in blood creatinine level, no differences were observed in red blood cell, white blood cell, lymphocyte, urea nitrogen, and IgG concentrations between treatments. Fecal score and fecal microflora (Lactobacillus and E. coli) were also similar between CON and PROT groups. Overall, the supplementation of protease enzyme in weanling pigs resulted in improved growth rate and nutrient digestibility. Exogenous protease enzyme reduced fecal NH3 emission, thus, potentially serving as a tool in lowering noxious gas contribution of livestock production in the environment.

Slits and Robo-2 regulate the coalescence of subsets of olfactory sensory neuron axons within the ventral region of the olfactory bulb.

Olfactory sensory neurons (OSNs) project their axons to second-order neurons in the olfactory bulb (OB) to form a precise glomerular map and these stereotypic connections are crucial for accurate odorant information processing by animals. To form these connections, olfactory sensory neuron (OSN) axons respond to axon guidance molecules that direct their growth and coalescence. We have previously implicated the axon guidance receptor Robo-2 in the accurate coalescence of OSN axons within the dorsal region of the OB (Cho et al., 2011). Herein, we have examined whether Robo-2 and its ligands, the Slits, contribute to the formation of an accurate glomerular map within more ventral regions of the OB. We have ablated expression of Robo-2 in OSNs and assessed the targeting accuracy of axons expressing either the P2 or MOR28 olfactory receptors, which innervate two different regions of the ventral OB. We show that P2-positive axons, which express Robo-2, coalesce into glomeruli more ventrally and form additional glomeruli in the OB of robo-2(lox/lox);OMP-Cre mice. We also demonstrate that Robo-2-mediated targeting of P2 axons along the dorsoventral axis of the OB is controlled by Slit-1 and Slit-3 expression. Interestingly, although MOR28-positive OSNs only express low levels of Robo-2, a reduced number of MOR28-positive glomeruli is observed in the OB of robo-2(lox/lox);OMP-Cre mice. Taken together, our results demonstrate that Slits and Robo-2 are required for the formation of an accurate glomerular map in the ventral region of the OB.

Cellular Mechanisms Mediating the Antinociceptive Effect of Botulinum Toxin A in a Rodent Model of Trigeminal Irritation by a Foreign Body.

Although numerous studies have described botulinum toxin type A (BTX-A) efficacy against trigeminal neuralgia (TN), the underlying cellular mechanisms remain unclear. We have investigated cellular mechanisms that mediate the antinociceptive effect of BTX-A in a rodent model of TN produced by compression of the trigeminal nerve root (TNR). Anesthetized male Sprague-Dawley rats were fixed in a stereotaxic instrument and compression of the TNR was then achieved with a 4% agar solution. This model produced a significant mechanical allodynia and increased the expression of hypoxia-inducible factor (HIF)-1α and cytokines levels including interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the trigeminal ganglion (TG) by postoperative day (POD) 7. Single or double treatments with a high BTX-A dose (3 U/kg) led to significantly prolonged antinociceptive effects. Furthermore, a single treatment with BTX-A (3 U/kg) significantly suppressed the upregulation of HIF-1α expression and IL-1ß, IL-6, and TNF-α concentrations in the TG. Intraganglionic injection of PX-12, a HIF-1α inhibitor, led to significant anti-allodynic effects and lowered the IL-1ß, IL-6, and TNF-α levels in the TG. These findings indicate that the antinociceptive effect of BTX-A is mediated via HIF-1α associated cytokines modulation in the TG and is therefore a potentially relevant treatment strategy for TN. PERSPECTIVE: The antinociceptive properties of BTX-A in a rat model of trigeminal neuralgia are mediated through the regulation of the HIF-1α associated cytokine pathway in the trigeminal ganglion. BTX-A is therefore a potentially effective treatment strategy for trigeminal neuralgia.

Furniture injuries in children.

AIMS: To determine the incidence, type and severity of furniture-related injuries in children in the Sydney region. METHODS: Retrospective analysis of presentations to the emergency departments of two paediatric tertiary hospitals in Sydney over a 4-year period from January 2000 to December 2003 with furniture-related injuries. Deaths of children because of furniture-related injuries reported to the Coroner, from 2000-2002, were also reviewed. The main outcome measures were circumstances of injury, type and number of injuries, morbidity, and mortality. RESULTS: 52 children presented with furniture-related injuries. The median age was 2.5 years (range 9 months-15 years), with a male-to-female ratio of 3:2. Falling televisions accounted for 22 (42%) of the injuries. Median Injury Severity Score was 1 (range 1-25). One child died. The most common regions injured were the limbs and the head. Thirty-one children (60%) required medical imaging, 28 (54%) required admission to hospital and 6 were allowed home in under 12 h. Of the 22 patients admitted for longer than 12 h, 14% required intensive care. Median length of stay was 1 day (range 0-15 days). Eighteen patients (35%) suffered scarring or long-term limitations as a result of their injuries. From 2000 to 2002 there were four additional deaths in NSW because of furniture-related injuries, two because of a falling television. CONCLUSION: Furniture-related injuries represent a cause of serious trauma and death in Australian children. There remains a need for the stability and security of televisions and large furniture items to be improved.

Nanoscale current modulations in Pr(0.7)Ca(0.3)MnO(3) thin films.

Many theoretical and experimental efforts have been focused on the origin of the electric-pulse-induced resistance change effect. However, there are still various reports of the origin supporting either the bulk nature or the interface nature. To resolve the controversies, nanoscale electronic measurements may provide essential clues. In this work, we report microscopic electrical properties of Pr(0.7)Ca(0.3)MnO(3) thin films. The resistance of a single-crystalline grain is not homogeneous in nanometer scale. We deduce that nanoscale inhomogeneity is related to the periodic relaxation of substrate-induced strain, which is caused by the lattice mismatch between the substrate and the thin film.

Olfactory changes after endoscopic endonasal transsphenoidal approach for skull base tumors.

OBJECTIVES/HYPOTHESIS: The increased number of endoscopic endonasal transsphenoidal approaches (EETSA) has been associated with sinonasal complications such as olfactory dysfunction. Current studies have compared preoperative and postoperative olfactory function according to surgical type and age. STUDY DESIGN: Retrospective review of medical records at a tertiary referral center. METHODS: Patients were divided into two groups according to surgical type and into four groups according to age. The two surgical groups were defined based on the bilateral nasoseptal flap technique (group A: right conventional nasoseptal flap and left modified nasoseptal rescure flap; group B: bilateral modified nasoseptal rescue flap). The four age groups were ≤ 30, 31-45, 46-60, and ≥ 61 years. Patients underwent preoperative olfactory function evaluation using a visual analogue scale (VAS), the Connecticut Chemosensory Clinical Research Center Test (CCCRC), and the Cross-Cultural Smell Identification Test (CCSIT). Repeat testing was performed 6-months postoperatively. RESULTS: A total of 226 patients who underwent binostril four-hand EETSA were included in this study. In both groups A and B, the olfactory function was significantly decreased according to CCCRC and CCSIT scores (P < 0.05). The VAS scores were significantly decreased in both groups (P < 0.05). The symptom scores and olfactory test results were significantly changed in >30-year-old patients who had undergone EETSA. CONCLUSION: EETSA might contribute to olfactory dysfunction independent of surgery type. In addition, age may affect the restoration of olfaction after EETSA. Patients who plan to undergo EETSA must be informed that their olfaction may be impaired. LEVEL OF EVIDENCE: 4.

Effects of microencapsulated organic acids and essential oils on growth performance and intestinal flora in weanling pigs / Efecto de los ácidos orgánicos y aceites esenciales microencapsulados sobre el crecimiento y flora intestinal en cerdos destetos / Efeito dos ácidos orgânicos e óleos essenciais microencapsulados sob a flora intestinal e o crescimento em suínos desmamados

Background: dietary supplementation with organic acids and essential oils has positive effects on growth improvement and nutrient digestion. Microencapsulation of nutrients allow for the slow release of core materials in a specific period and/or environment. Objective: to investigate the effect of microencapsulated organic acids and essential oils (MOE) on growth performance, nutrient digestibility, blood and fecal characteristics in weanling pigs. Methods: one-hundred twenty-five weanling pigs [(Yorkshire × Landrace) x Duroc] with an average body weight (BW) of 6.76 ± 0.11 Kg were used in a 42-d experiment. Pigs were allotted to five dietary treatments according to initial body weight, using five replicates per treatment and five pigs per pen. Dietary treatments were: 1) NC (negative control): basal diet free of antibiotics; 2) PC (positive control), basal diet with tiamulin 39 mg/kg; 3) MOE0.5, basal diet with 0.5 g MOE/kg; 4) MOE1, basal diet with 1 g MOE/kg; and 5) MOE2, basal diet with 2 g MOE/kg. Results: final BW was greater in MOE2 and PC treatments compared to NC treatment (p<0.05). Increased feed efficiency (G:F) was observed for MOE treatments during 0 to 7 d compared with NC and PC (p<0.05). During 7 to 21 d, MOE0.5 and MOE1 supplementation decreased average daily feed intake (ADFI) compared with PC (p<0.05). However, there were no differences in average daily gain (ADG) and G:F among treatments (p>0.05). During 22 to 42 d, ADG was greater for PC compared with NC (p<0.05). The G:F of NC and MOE0.5 was lower than that of PC (p<0.05). Overall, ADG and G:F were greater for PC compared to NC (p<0.05). On 42 d, DM and N digestibilities in PC and MOE were greater (p<0.05) than in NC. Fecal scores of pigs fed MOE1 were lower (p<0.05) than those of pigs fed NC. Fecal pH was decreased in MOE0.5 and MOE1 when compared to NC (p<0.05) on day 7. Fecal pH was decreased with MOE compared to NC and PC (p<0.05) on d 21. Conclusion: MOE supplementation improved growth performance and nutrient digestibility while decreasing fecal scores and pH in weanling pigs.

Antecedentes: la suplementación con ácidos orgánicos y aceites esenciales mejora el crecimiento y digestibilidad de los nutrientes. Los microencapsulados permiten la lenta liberación de materiales en periodos y/o ambientes especiales. Objetivo: investigar el efecto de los ácidos orgánicos y aceites esenciales (MOE) microencapsulados sobre el crecimiento, digestibilidad de los nutrientes, y características sanguíneas y de heces en cerdos destetos. Métodos: fueron utilizados 125 cerdos destetos [(Yorkshire × Landrace) x Duroc], con un peso promedio (BW) de 6,76 ± 0,11 kg en un experimento con duración de 42 d. Los cerdos fueron asignados a 5 tratamientos dietarios de acuerdo a su peso inicial, 5 réplicas por tratamiento con 5 cerdos por corral. Los tratamientos fueron: 1) control negativo (NC), dieta básica libre de antibióticos; 2) control positivo (PC), dieta básica + tiamulina 39 mg/ kg; 3) MOE0.5, dieta básica + 0,5 g MOE/kg; 4) MOE1, dieta básica + 1 g MOE/kg; y 5) MOE2, dieta básica + 2 g MOE/kg. Resultados: el peso final fue mayor en MOE2 y PC que en NC (p<0,05). Durante los d 0 al 7, los cerdos tuvieron un incremento de la eficiencia alimenticia (G:F) con MOE en comparación con NC y PC (p<0,05). Durante los d 7 al 21, disminuyó el consumo promedio de alimento (ADFI) en los cerdos sometidos a MOE0.5 y MOE1 en comparación con PC (p<0,05). Sin embargo, no hubo diferencia significativa en la ganancia diaria de peso (ADG) y G:F comparados con PC (p<0,05). Durante los d 22 al 42, la ADG fue mayor en PC que en NC (p<0,05). En NC y MOE0.5 la G:F disminuyó en comparación con PC (p<0,05). La ADG y G:F fue mayor en PC que en NC (p<0,05). En el d 42, la digestibilidad de la materia seca y nitrógeno fue mayor (p<0,05) en PC y los suplementados con MOE que en NC. La calificación de las heces de cerdos alimentados con MOE1 fue menor (p<0,05) que la de NC. El pH fecal disminuyó (p<0,05) en MOE0.5 y MOE1 comparado con NC en el d 7. El pH fecal disminuyó en los tratamientos con MOE comparado con NC y PC en el d 21. Conclusión: la suplementación con MOE puede mejorar el crecimiento y digestibilidad de los nutrientes, y disminuir la calificación fecal y pH en cerdos destetos.

Antecedentes: a suplementação com ácidos orgânicos e óleos essenciais melhora o crescimento e a digestibilidade dos nutrientes. A microencapsulação pode permitir a liberação lenta de materiais em um período e/ou ambiente especial. Objetivo: pesquisar sobre o efeito dos ácidos orgânicos microencapsulados e óleos essenciais (MOE) no desempenho produtivo, a digestibilidade dos nutrientes, as características sanguíneas e fecais em leitões desmamados. Métodos: utilizou-se uma amostra total de 125 leitões desmamados [(York Shire × Landrace) x Duroc] com um peso corporal médio (BW) de 6,76 ± 0,11 kg testados durante 42 d. Os leitões foram distribuídos em cinco tratamentos dietéticos de acordo com seu peso corporal inicial, cinco repetições por tratamento com cinco animais por curral. Os tratamentos foram: 1) NC (controle negativo): dieta basal livre de antibióticos; 2) PC (controle positivo), dieta basal com tiamuline 39 mg/kg; 3) MOE0.5, dieta basal com 0,5 g MOE/kg; 4) MOE1, dieta basal com 1 g MOE/kg; e 5) MOE2, dieta basal com 2 g MOE/kg. Resultados: o peso final foi maior em MOE2 e PC do que NC (p<0,05). Durante 0-7 d, houve um aumento da eficiência alimentar (G: F) com MOE em comparação com NC e PC (p<0,05). Durante o período 7 a 21 d, a suplementação MOE0.5 e MOE1 diminuiu o consumo médio diário de ração (ADFI), em comparação com PC (p<0,05). No entanto, não houve diferenças em ganho de peso médio diário (ADG) e G:F entre os tratamentos (p>0,05). No período entre os 22 e 42 d, ADG foi maior no tratamento PC que NC (p<0,05). Em NC e MOE0.5 a G:F diminui-o em comparação com PC (p<0,05). Em geral, a ADG e G:F foram maiores no PC do que NC (p<0,05). No dia 42, a digestibilidade da matéria seca e nitrogênio foi maior em PC e MOE que em NC (p<0,05). A pontuação fecal de suínos alimentados com MOE1 foi menor que a NC (p<0,05). No dia 7 o pH das fezes diminuiu em MOE0.5 e MOE1 em comparação com NC (p<0,05). O pH fecal no dia 21 diminuiu com MOE em comparação com NC e PC (p<0,05). Conclusão: a suplementação com MOE pode melhorar o desempenho de crescimento e digestibilidade de nutrientes, bem como diminuir o escore fecal e pH em leitões desmamados.

Effect of microencapsulated blends of organic acids and essential oils supplementation on growth performance and nutrient digestibility in finishing pigs / Efecto de mezclas microencapsuladas de ácidos orgánicos y suplementos de aceites esenciales sobre el crecimiento y digestibilidad de nutrientes de cerdos en ceba / Efeito de misturas de ácidos orgânicos microencapsulados e suplementação de óleos essenciais sobre o crescimento e a digestibilidade dos nutrientes em suínos em terminação

Background: positive effects of organic acids and essential oils (MOE) on livestock are well documented. Microencapsulation allows the slow release of core materials in a specific moment or environment. Objective: to evaluate the effect of supplementing finishing pigs with microencapsulated blends of organic acids and essential oils (MOE) on growth performance, nutrient digestibility, fecal noxious gas emissions, and meat quality. Methods: 75 crossbred pigs [(Yorkshire × Landrace) × Duroc, 56.15 ± 3.77 kg] were used in this 10-week trial. Pigs were randomly distributed into 1 of 3 dietary treatments on the basis of body weight (BW) and gender. Each treatment had 5 replicate pens with 5 pigs (2 gilts, 3 barrows) per pen. Treatments were as follows: CON (a basal diet); MOE1 (CON + 0.025% MOE); MOE2 (CON + 0.050% MOE). Results: pigs fed the MOE2 diet had higher final BW at 5th and 10th week than those fed the CON diet (p<0.05). During weeks 0 to 5, MOE1 and MOE2 groups had greater average daily gain (ADG) than the CON group (p<0.05). Overall, ADG in MOE2 was greater than that in CON treatment (p<0.05). MOE2 group had higher dry matter (DM) and energy digestibility than the CON group (p<0.05). Conclusion: the present results indicate that dietary supplementation with 0.05% MOE improves growth performance and nutrient digestibility in finishing pigs.

Antecedentes: los efectos positivos de los ácidos orgánicos y aceites esenciales (MOE) en el ganado han sido documentados. La microencapsulación permite la liberación lenta del material de núcleo en un período o medio ambiente particulares. Objetivo: evaluar el efecto de suplementar cerdos de engorde con mezclas microencapsuladas de ácidos orgánicos y aceites esenciales (MOE) sobre el rendimiento productivo, la digestibilidad de nutrientes, las emisiones de gases fecales, y la calidad de la carne. Métodos: 75 cerdos cruzados [(Yorkshire × Landrace) x Duroc), 56,15 ± 3,77 kg] se utilizaron en las 10 semanas que duró el ensayo. Los cerdos se distribuyeron aleatoriamente en 1 de 3 tratamientos dietarios, de acuerdo con su peso corporal (BW) y género. Cada tratamiento tuvo 5 réplicas (corrales) con 5 cerdos por corral (2 hembras y 3 machos castrados). Los tratamientos fueron: CON (dieta basal); MOE1 (CON + 0,025% MOE); MOE2 (CON + 0,050% MOE). Resultados: los cerdos alimentados con la dieta MOE2 tuvieron mayor BW final en las semanas 5ª y 10ª que los alimentados con la dieta CON (p<0,05). Durante la semana 0 a la 5 los grupos MOE1 y MOE2 tuvieron mayor ganancia media diaria (ADG) que el grupo CON (p<0,05). En general, la ADG de MOE2 fue mayor que en el tratamiento CON (p<0,05). El grupo MOE2 tuvo mayor digestibilidad de la materia seca (DM) y de la energía que el grupo CON (p<0,05). Conclusión: los resultados indican que la suplementación de la dieta con 0,05% MOE mejora el crecimiento y la digestibilidad de nutrientes en cerdos de ceba.

Antecedentes: os efeitos positivos de ácidos orgânicos e óleos essenciais (MOE) para o gado estão bem documentados na literatura. A microencapsulação permite a liberação lenta de materiais centrais num momento ou ambiente específico. Objetivos: avaliar os efeitos de suplementação de suínos em terminação com misturas microencapsuladas de ácidos orgânicos e óleos essenciais (MOE) em pontos como desempenho produtivo, digestibilidade dos nutrientes, emissões de gases nocivos fecais e qualidade da carne. Metodologia: 75 suínos mestiços [(Yorkshire × Landrace) x Duroc), 56,15 ± 3,77 kg] foram utilizados neste teste de 10 semanas. Os animais foram selecionados aleatoriamente em 1 de 3 currais de tratamento dietético, com base no peso corporal (BW) e sexo. Cada curral teve 5 réplicas e cada curral, 5 suínos (2 fêmeas, 3 machos castrados). Os tratamentos foram os seguintes: CON (dieta basal); MOE1 (CON + 0,025% MOE); MOE2 (CON + 0,050% MOE). Resultados: os animais que receberam a dieta MOE2 apresentaram significativamente maior PV final em 5 e 10 semanas do que aqueles alimentados com a dieta CON (p<0,05). Durante 0-5 semanas, os grupos MOE1 e MOE2 tiveram maior GMD que o grupo CON (p<0,05). De um modo geral, ADG de MOE2 foi maior do que no grupo CON (p<0,05). O grupo MOE2 teve a matéria seca (DM) e a digestibilidade de energia maiores do que o grupo CON (p<0,05). Conclusão: os resultados indicam que a suplementação dietética com 0.05% de MOE melhora o desempenho do crescimento e digestibilidade de nutrientes em suínos em terminação.