Background and Aim: Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC who received sorafenib monotherapy. Methods: A total of sixty-five patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender, tumoral characteristics, performance status and NLR were analyzed. Results: Median OS and TTP for the entire cohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLR at baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months) compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (${\leq}4$) (P=0.01). Age ${\leq}65$, NLR>4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariate analysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors of poorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months) compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012). Conclusions: High baseline NLR was associated with worse OS and TTP for patients with advanced HCC treated with sorafenib.
Background: Ginsenoside Rd (GSRd), one of the most abundant ingredients of Panax ginseng, protects the heart via multiple mechanisms including the inhibition of $Ca^{2+}$ influx.We intended to explore the effects of GSRd on L-type $Ca^{2+}$ current ($I_{Ca,L}$) and define the mechanism of the suppression of $I_{Ca,L}$ by GSRd. Methods: Perforated-patch recording and whole-cell voltage clamp techniques were applied in isolated rat ventricular myocytes. Results: (1) GSRd reduced $I_{Ca,L}$ peak amplitude in a concentration-dependent manner [half-maximal inhibitory concentration $(IC_{50})=32.4{\pm}7.1{\mu}mol/L$] and up-shifted the current-voltage (I-V) curve. (2) GSRd ($30{\mu}mol/L$) significantly changed the steady-state activation curve of $I_{Ca,L}$ ($V_{0.5}:-19.12{\pm}0.68$ vs. $-6.26{\pm}0.38mV$; n = 5, p < 0.05) and slowed down the recovery of $I_{Ca,L}$ from inactivation [the time content (${\zeta}$) from 91 ms to 136 ms, n = 5, p < 0.01]. (3) A more significant inhibitive effect of GSRd ($100{\mu}mol/L$) was identified in perforated-patch recording when compared with whole-cell recording [$65.7{\pm}3.2%$ (n = 10) vs. $31.4{\pm}5.2%$ (n = 5), p < 0.01]. (4) Pertussis toxin ($G_i$ protein inhibitor) completely abolished the $I_{Ca,L}$ inhibition induced by GSRd. There was a significant difference in inhibition potency between the two cyclic adenosine monophosphate elevating agents (isoprenaline and forskolin) prestimulation [$55{\pm}7.8%$ (n = 5) vs. $17.2{\pm}3.5%$ (n = 5), p < 0.01]. (5) 1H-[1,2,4]Oxadiazolo[4,3-a]-quinoxalin-1-one (a guanylate cyclase inhibitor) and N-acetyl-$\small{L}$-cysteine (a nitric oxide scavenger) partly recovered the $I_{Ca,L}$ inhibition induced by GSRd. (6) Phorbol-12-myristate-13-acetate (a protein kinase C activator) and GF109203X (a protein kinase C inhibitor) did not contribute to the inhibition of GSRd. Conclusion: These findings suggest that GSRd could inhibit $I_{Ca,L}$ through pertussis toxin-sensitive G protein ($G_i$) and a nitric oxide-cyclic guanosine monophosphate-dependent mechanism.
Wu, Yubo;Lai, Changhua;Qiao, Shiyan;Gong, Limin;Lu, Wenqing;Li, Defa
Asian-Australasian Journal of Animal Sciences
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v.18
no.1
/
pp.66-74
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2005
Three experiments were conducted to study the property of xylanase and the effects of xylanase in wheat-based diets on growth performance of broilers, respectively. Experiment 1 was performed in vitro to evaluate the effect of different pH and temperature on xylanase activity, and to evaluate the enzymic stability under different conditions. The results indicated that the optimum temperature and pH for xylanase activity were $50^{\circ}C$ and 4.5, respectively. The activity of enzyme solution was reduced rapidly after the treatment of water bath above $60^{\circ}C$ for 10 min. The enzyme was relatively stable at pH 3.5 to 8.0 and deteriorated when incubated at pH below 3.5. In Experiment 2, a total of 378 d-old male Arbor Acres broilers were randomly distributed to 7 different treatments with 6 replicates (9 birds) in each treatment. The treatments were as follows: (1) corn based diet (CS), (2) wheat based diet (WS), (3) WS+ 0.05% xylanase, (4) WS+0.15% xylanase, (5) WS+0.25% xylanase, (6) WS+0.35% xylanase, (7) WS+0.45% xylanase. The results showed that the body weight and feed/gain ratio of the broilers fed wheat-based diets have been significantly improved (p<0.05) compared to that fed corn-based diet in the first 3 wk. With regard to the wheat-based diets, the xylanase supplementation had a tendency to improve the growth performance in first 3 wk. After 3 wk, no significant difference (p>0.05) was found among all these different treatments. The supplementation of xylanase and the type of diets did not affect the feed intake but increased the concentration of triglyceride in serum. In Experiment 3, a total of 360 d-old male Arbor Acres broilers were assigned to 30 groups with 12 birds in each group randomly. These groups were then randomly distributed to 5 different treatments with 6 replicates within each treatment. The broilers of each treatment were fed one of the diets as follows: (1) Corn based diet, (2) White wheat based diet (WW) (3) White wheat based diet+0.25% xylanase, (4) Red wheat based diet, (5) Red wheat based diet+0.25% xylanase. The results showed that the body weight and feed/gain ratio had been significantly improved (p<0.05) by xylanase supplementation in the first 2 or 3 wk. The effect of xylanase in red wheat diet is a little higher than that used in white wheat diet. From the results of the present experiments, it can be concluded that the supplementation of Aspergillar xylanase can improve the performance of the broilers fed the wheat-based diet.
Japanese cedar (Cryptomeria japonica) pollinosis is the most popular pollinosis in Japan. It has been reported that Cryptomeria japonica pollen allergenic species are suspended as fine particles in the urban atmosphere. These allergenic fine particles are responsible for inducing asthma by breaking into the lower respiratory tract. It has also been found that pollinosis symptoms on the sufferers appear mainly at night-time by the results from epidemiological studies. However, the exact reason for these phenomena is not yet clarified. In this study, the diurnal and nocturnal behaviours of Cryptomeria japonica pollen grains and their allergenic species in the urban area of Saitama city of Kanto Plain were investigated. Airborne pollen grains and allergenic Cry j 1 concentrations in total suspended particulate matter (TSP) were investigated at two sampling sites, a heavy traffic road (roadside site) and at the balcony of the $10^{th}$ floor of the Building of Research and Project of Saitama University (general urban site). The latter sampling site where located about 300 m away from the roadside site was used as a general urban site unaffected by automobile traffic. The airborne pollen counts were measured with a real-time pollen monitor. Cry j 1 particles were collected with two high volume air samplers, and these concentrations were measured by surface plasmon resonance method with a Biacore J system. The diurnal variation of the airborne pollen counts was similar to the trends of temperature and wind speed during the day-time; whereas its tendency with wind speed trend was not observed during the night-time. Airborne pollen counts were lower with northern wind than with southern wind because the pollen comes from the mountainous areas, and the mountains in the south are closer, about half the distance to the northern mountains. It is suggested that the peaks of airborne pollen counts during night-time in the sampling site occurred by transport of pollen grains released during day-time in the mountainous forest areas, located c.a. 100 km away from the sampling site. On the roadside site the allergenic Cry j 1 concentrations were higher than at the general urban site, nevertheless pollen grains counts were lower. These results suggested that worsening of pollinosis symptoms during night-time in urban area was caused by transport of pollen grains during day-time in the mountainous forest areas. Moreover, pollen allergenic species become different morphology from pollen grain at roadside site, and the subsequent pollen grains re-suspension by automobile traffic.
Objective: To create genetically modified goat as a biopharming source of recombinant human lacotoferrin (hLF) with transcription activator-like effector nucleases. Methods: TALENs and targeting vector were transferred into cultured fibroblasts to insert hLF cDNA in the goat beta-lactoglobulin (BLG) locus with homology-directed repair. The gene targeted efficiency was checked using sequencing and TE7I assay. The bi-allelic gene targeted colonies were isolated and confirmed with polymerase chain reaction, and used as donor cells for somatic cell nuclear transfer (SCNT). Results: The targeted efficiency for BLG gene was approximately 10%. Among 12 Bi-allelic gene targeted colonies, five were used in first round SCNT and 4 recipients (23%) were confirmed pregnant at 30 d. In second round SCNT, 7 (53%), 4 (31%), and 3 (23%) recipients were confirmed to be pregnant by ultrasound on 30 d, 60 d, and 90 d. Conclusion: This finding signifies the combined use of TALENs and SCNT can generate biallelic knock-in fibroblasts that can be cloned in a fetus. Therefore, it might lay the foundation for transgenic hLF goat generation and possible use of their mammary gland as a bioreactor for large-scale production of recombinant hLF.
The volcanic rocks of Ulleungdo reveal very high alkali element abundances and most of them have high K20/Na20 ratios and belong to potassium-series. Ulleungdo volcanics show very wide range of variation in their composition from basalts to trachytic basalt, basaltic trachyandesite, trachyandesite, and finally to trachyte on total alkali-silica diagram. Such a general trend of compositional variation can be explained well by differentiation due to fractional crystallization of various minerals. Olivine, clinopyroxene, plagioclase, ilmenite, and apatite are suggested as the major fractionated minerals. Ulleungdo volcanics show Nb/U and PbICe ratios similar to oceanic volcanics such as MORB and OIB, but significantly different .from volcanic rocks of island arc environments, which suggest that they are not directly related with subduction along the Japanese arc. LREE abundances of Ulleungdo volcanics are highly enriched compared with HREE abundances ((La)N=193-420, (L~)~=7.5-19.5).O nly trachyte-1 show appreciable negative Eu anomalies among various rock types, which suggests significant amount of plagioclase were fractionated. However, trachyte-2, trachyte-3, phonolite, and pumice reveal quite different variation trend of trace and rare earth element abundances from trachyte-1, which suggest that they have originated from different magma batches and have experienced different differentiation processes. A prominent bimodal distribution, thus lacking of intermediate composition, is observed from the Ulleundo volcanics.
MAI (multiple aperture SAR interferometry) method has been recently developed to improve the measurement accuracy of along-track surface deformation. By means of split-beam SAR processing, this novel technique produces forward- and backward-looking interferograms, which are combined to generate an MAI interferogram. The along-track surface deformation can then be derived from the MAI interferogram. The achieved accuracy of the along-track surface deformation is approximately 8 cm for interferograms with a coherence of 0.6. It is commonly recognized that the topographic phase on an MAI interferogram can be ignored. However, in this paper, we have generated an MAI interferogram from an ALOS P ALSAR interferometric pair spanning the 2010 Haiti earthquake, and shown that the topographic phase distortion on the MAI interferogram can reach to about $3.45{\times}10^{-4}$ rad./m. This distortion corresponds to an along-track surface deformation of about 98 cm. We have proposed an efficient method to remove the topographic phase distortion. After correcting the distortion, the topographic phase distortion on the MAI interferogram is reduced to about $7.82{\times}10^{-6}$ rad./m. This means that the proposed method can effectively remove the topographic distortion on the MAI interferogram to improve along-track surface deformation measurement.
Cutaneous evaporative heat loss in Bos indicus and Bos taurus has been well documented. Nonetheless, how crossbreds with different fractional genetic proportions respond to such circumstances is of interest. A study to examine the physiological responses to cutaneous evaporative heat loss, also lactation period and milk yield, were conducted in Sahiwal (Bos indicus, n = 10, $444{\pm}64.8kg$, $9{\pm}2.9years$), Holstein Friesian (Bos taurus, HF100% (n = 10, $488{\pm}97.9kg$, $6{\pm}2.8years$)) and the following crossbreds: HF50% (n = 10, $355{\pm}40.7kg$, $2{\pm}0years$) and HF87.5% (n = 10, $489{\pm}76.8kg$, $7{\pm}1.8years$). They were allocated so as to determine the physiological responses of sweating rate (SR), respiration rate (RR), rectal temperature (RT), and skin temperature (ST) with and without hair from 06:00 h am to 15:00 h pm. And milk yield during 180 days were collected at days from 30 to 180. The ambient temperature-humidity-index (THI) increased from less than 80 in the early morning to more than 90 in the late afternoon. The interaction of THI and breed were highly affected on SR, RR, RT, and ST (p<0.01). The SR was highest in Sahiwal ($595g/m^2/h$) compared to HF100% ($227g/m^2/h$), and their crossbreds both HF50% ($335g/m^2/h$) and HF87.5% ($299g/m^2/h$). On the other hand, RR was higher in HF87.5% (54 bpm) and both HF100% (48 bpm) and HF50% (42 bpm) than Sahiwal (25 bpm) (p<0.01). The RT showed no significant differences as a result of breed (p>0.05) but did change over time. The ST with and without hair were similar, and was higher in HF100% ($37.4^{\circ}C$; $38.0^{\circ}C$) and their crossbred HF50% ($35.5^{\circ}C$; $35.5^{\circ}C$) and HF87.5% ($37.1^{\circ}C$; $37.9^{\circ}C$) than Sahiwal ($34.8^{\circ}C$; $34.8^{\circ}C$) (p<0.01). Moreover, the early lactation were higher at HF100% (25 kg) and 87.5% (25 kg) than HF50% (23 kg) which were higher than Sahiwal (18 kg) while the peak period of lactation was higher at HF100% (35 kg) than crossbreds both HF87.5% and HF50% (32 kg) which was higher than Sahiwal (26 kg) (p<0.05). In conclusion, sweating and respiration were the main vehicle for dissipating excess body heat for Sahiwal, HF and crossbreds, respectively. The THI at 76 to 80 were the critical points where the physiological responses to elevated temperature displayed change.
Purpose: To investigate IQGAP1 and IQGAP2 expression in hepatocellular carcinoma (HCC) and itsassociation with HCC clinicopathological characteristics and survival outcomes. Methods: IQGAP1 and IQGAP2 mRNA and protein were measured in HCC tissues, para-tumor tissues and normal tissues by RT-PCR and Western blotting. We further examined 150 HCC samples with adjacent para-tumor tissues and 11 normal specimens by immunohistochemistry to evaluate the correlation of IQGAP1 and IQGAP2 with clinicopathological features and prognosis. Results: IQGAP1 mRNA and protein were up-regulated while IQGAP2 mRNA and protein were down-regulated in human HCC tissues compared with para-tumor and normal liver tissues (p<0.05). IQGAP1 expression was higher in primary HCC (122/150, 81.3%) than matched adjacent tissues (30/150, 20%, p<0.001), whereas IQGAP2 was lower (31/150, 20.7% as compared to 112/150, 74.7%, P<0.001). Positive IQGAP1 expression correlated with larger tumor size (p=0.002), advanced TNM stage (p=0.002) and tumor differentiation (III and IV, p=0.034). Negative IQGAP2 expression was significantly associated with larger tumor size (p=0.009), multicentric tumor occurrence (p=0.01), advanced TNM stage (0.009) and tumor differentiation (III and IV, p=0.020). Survival analysis revealed that patients with either IQGAP1+ or IQGAP2-tumors had significantly reduced disease-free survival (p<0.001 and 0.006 respectively) and overall survival (p<0.001 for both). Multivariate analysis showed that IQGAP1/2 switch was an independent prognosis factor for disease-free survival (HR=2.824) and overall survival (HR=2.189). Conclusion: Positive IQGAP1 and negative IQGAP2 expression were closely correlated with tumor progression and could be used as adjunctive biomarkers to improve prognostication for HCC patients.
Jiang, Li Juan;Wu, Wen Juan;Wu, Hai;Ryang, Son Sik;Zhou, Jian;Wu, Wei;Li, Tao;Guo, Jian;Wang, Hong Hai;Lu, Shui Hua;Li, Yao
Journal of Microbiology and Biotechnology
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v.22
no.9
/
pp.1301-1306
/
2012
We combined real-time RT-PCR and real-time PCR (R/P) assays using a hydrolysis probe to detect Mycobacterium tuberculosis complex (MTBC)-specific 16S rRNA and its rRNA gene (rDNA). The assay was applied to 28 non-respiratory and 207 respiratory specimens from 218 patients. Total nucleic acids (including RNA and DNA) were extracted from samples, and results were considered positive if the repeat RT-PCR threshold cycle was ${\leq}35$ and the ratio of real-time RT-PCR and real-time PCR load was ${\geq}1.51$. The results were compared with those from existing methods, including smear, culture, and real-time PCR. Following resolution of the discrepant results between R/P assay and culture, the overall sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of all samples (including non-respiratory and respiratory specimens) were 98.2%, 97.2%, 91.7%, and 99.4%, respectively, for R/P assay, and 83.9%, 89.9%, 72.3%, and 94.7%, respectively, for real-time PCR. Furthermore, the R/P assay of four patient samples showed a higher ratio before treatment than after several days of treatment. We conclude that the R/P assay is a rapid and accurate method for direct detection of MTBC, which can distinguish viable and nonviable MTBC, and thus may guide patient therapy and public health decisions.
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