Tissue oxidative stress and expression of chicken UCP and ANT mRNA in laying hens exposed to acute cold stress.

1. Exposure to stress alters normal homoeostasis and, hence, the antioxidant defence system. The aim of this study was to examine the effect of acute cold temperature on the antioxidant defence system in hens.2. Hy-line grey commercial layers (80 40-week-old) were randomly assigned to one of eight groups. In groups 1 to 5, hens were exposed to low temperature at -8.68°C (cool stressed) for 2, 4, 6, 8 and 10 h, respectively. In groups 6 and 7, post 10 h cool stressed, hens were quickly transferred to room at 21°C to recovery for 2 h and 4h, respectively. In treatment groups 6 and 7, post 10 h cool stressed, hens were quickly transferred to room at 21°C for 2 h and 4 h, respectively. Group 8 was the control, where hens were housed under regular condition at 21°C as controls.3. Antioxidant enzymes (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA), in skeletal muscle, the kidney, liver and pancreas were measured. The transcription of avUCP and ANT mRNA was tested by RT-PCR.4. The T-AOC activity was increased in the skeletal muscle of hens cold stressed for 2, 4, 6, 8 and 10 h and the 2 h recovery groups compared with control hens (p < 0.05). The GPx activity was increased in the liver and skeletal muscle after cold stress 4 h and in the pancreas of cold stress 2 h compared with the control group (p < 0.05). Antioxidant SOD activity was increased in the kidney after cold stress 6 h and in the liver after cold stress 10 h compared to the control group (p < 0.05). Measured MDA activity was increased in the pancreas after 2 h cold stress (p < 0.05).5. UCP mRNA expression level was increased in the pectoral muscle for 2 h and 4 h recovery groups compared with the control hens (p < 0.05) and avian uncoupling protein (UPC), adenine nucleotide translocator (ANT) expression level was increased in the leg muscle of hens cold stress for 2, 6, 8 h and recovery 2 and 4 h.6. The observed changes in the antioxidant defence system were tissue specific. Increments in levels of ANT (leg muscle) and UCP (pectoral and leg muscle) mRNA expression may be involved in the regulation of thermogenesis in skeletal muscle.

Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases.

BACKGROUND: Primary tumour location is emerging as an important prognostic factor in localized and metastatic colorectal cancers. However, its prognostic role in colorectal liver metastasis (CRLM) after hepatectomy remains controversial. A systematic review and meta-analysis was undertaken to evaluate its prognostic value. METHODS: References were identified through searches of PubMed, Embase, Web of Science and the Cochrane Library comparing overall or disease-free survival after hepatic resection between patients with CRLM originating from right- or left-sided colorectal cancers. Data were pooled using hazard ratios (HRs) and 95 per cent confidence intervals according to a random-effects model. Meta-regression and subgroup analyses were conducted to assess the effect of underlying confounding factors on HR estimates and to adjust for this. RESULTS: The final analysis included 21 953 patients from 45 study cohorts. Compared with left-sided primary tumour location, right-sided location was associated with worse overall survival (HR 1·39, 95 per cent c.i. 1·28 to 1·51; P < 0·001; prediction interval 1·00 to 1·93), and also tended to have a negative impact on disease-free survival (HR 1·18, 1·06 to 1·32; P = 0·004; prediction interval 0·79 to 1·75). Subgroup analysis showed that the negative effect of right-sided primary tumour location on overall survival was more prominent in the non-Asian population (HR 1·47, 1·33 to 1·62) than the Asian population (HR 1·18, 1·05 to 1·32) (P for interaction <0·01). CONCLUSION: This study demonstrated a prognostic role for primary tumour location in patients with CRLM receiving hepatectomy, especially regarding overall survival. Adding primary tumour location may provide important optimization of prognosis prediction models for CRLM in current use.

ANTECEDENTES: La ubicación del tumor primario (primary tumor location, PTL) ha surgido como un factor pronóstico importante en los cánceres colorrectales (colorectal cancers, CRCs) localizados y metastásicos. Sin embargo, todavía se discute su relevancia como factor pronóstico tras la resección de metástasis hepáticas de cáncer colorrectal (colorectal liver metastases, CRLM). Se realizó una revisión sistemática y un metaanálisis para determinar su valor pronóstico. MÉTODOS: En PubMed, EMBASE, Web of Science y la Biblioteca Cochrane se identificaron los trabajos que compararon la supervivencia global (overall survival, OS) y la supervivencia libre de enfermedad (disease-free survival, DFS) tras la resección hepática de CRLM cuyo CRCs estuviese situado en el lado derecho o izquierdo. Los datos se expresaron en forma del cociente de riesgos instantáneos (hazard ratio, HR) e intervalos de confianza del 95% (i.c. del 95%) de acuerdo con un modelo de efectos aleatorios. Se efectuaron análisis de metarregresión y de subgrupos para evaluar el efecto de los factors de confusión existentes en las estimaciones de HR, ajustando por los mismos. RESULTADOS: El análisis final incluyó 21.953 pacientes de cohortes de 45 estudios. La PTL en el lado derecho en comparación con el lado izquierdo se asoció con una peor supervivencia global (HR 1,39; i.c. del 95% 1,28-1,51; P < 0,001; intervalo de predicción 1,00-1,93) y una tendencia a un impacto negativo en la DFS (HR 1,18; i.c. del 95% 1,06-1,32; P = 0,004; intervalo de predicción 0,79-1,75). El análisis de subgrupos mostró que el efecto negativo de la PTL del lado derecho en la OS fue más prominente en la población no asiática (HR 1,47; i.c. del 95% 1,33-1,62) que en la asiática (HR 1,18; i.c. del 95% 1,05-1,32; Pinteracción < 0,01). CONCLUSIÓN: Este estudio demostró que la PTL tiene un papel pronóstico tras la hepatectomía de las CRLM, especialmente respecto a la OS. La adición de la PTL proporcionaría una optimización importante en los modelos actuales de predicción pronóstica de CRLM.

Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China.

BACKGROUND: The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence. METHODS: A multistage, clustered and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count. RESULTS: A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05). CONCLUSION: Pollen-induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.

Osteogenic potential of three different autogenous bone particles harvested during implant surgery.

OBJECTIVES: The aim was to compare the osteoblast activity and osteogenic potential of autogenous bone particles harvested using three different techniques and determine the most advantageous method of collecting autogenous bone particles. SUBJECTS AND METHODS: Bone particles were harvested from 20 patients during dental implant surgery using bone scraping, low-speed drilling and bone trap filtering. After the osteoblasts were cultured, cell proliferation, migration, mineralization, transcription of osteogenesis-related genes, secretion of osteogenesis-related proteins and osteoinductive protein content in the bone particle matrix were evaluated. RESULTS: Osteoblast activity and osteogenic potential were higher in bone samples harvested by scraper or low-speed drilling than in samples harvested by bone trap filter. Although these parameters were slightly lower in the low-speed drilling group than in the scraper group, significant differences were found only in bone Gla protein levels. However, the levels of osteoinductive proteins in the bone particle matrix were significantly higher in the low-speed drilling group than in the scraper group. CONCLUSIONS: Low-speed drilling is a recommendable and effective technique for collecting autogenous bone particles. In implant operations, low-speed drilling can be considered the first-line option, and if the quantity of harvested bone is insufficient, bone shavings obtained by the scraper may be considered.

Association of 3q13.32 variants with hip trochanter and intertrochanter bone mineral density identified by a genome-wide association study.

We performed a GWAS of trochanter and intertrochanter bone mineral density (BMD) in the Framingham Heart Study and replicated in three independent studies. Our results identified one novel locus around the associated variations at chromosomal region 3q13.32 and replicated two loci at chromosomal regions 3p21 and 8q24. Our findings provide useful insights that enhance our understanding of bone development, osteoporosis, and fracture pathogenesis. INTRODUCTION: Hip trochanter (TRO) and intertrochanter (INT) subregions have important clinical relevance to subtrochanteric and intertrochanteric fractures but have rarely been studied by genome-wide association studies (GWASs). METHODS: Aiming to identify genomic loci associated with BMD variation at TRO and INT regions, we performed a GWAS utilizing the Framingham Heart Study (FHS, N = 6,912) as discovery sample and utilized the Women's Health Initiative (WHI) African-American subsample (N = 845), WHI Hispanic subsample (N = 446), and Omaha osteoporosis study (N = 971), for replication. RESULTS: Combining the evidence from both the discovery and the replication samples, we identified one novel locus around the associated variations at chromosomal region 3q13.32 (rs1949542, discovery p = 6.16 × 10-8, replication p = 2.86 × 10-4 for INT-BMD; discovery p = 1.35 × 10-7, replication p = 4.16 × 10-4 for TRO-BMD, closest gene RP11-384F7.1). We also replicated two loci at chromosomal regions 3p21 (rs148725943, discovery p = 6.61 × 10-7, replication p = 5.22 × 10-4 for TRO-BMD, closest gene CTNNB1) and 8q24 (rs7839059, discovery p = 2.28 × 10-7, replication p = 1.55 × 10-3 for TRO-BMD, closest gene TNFRSF11B) that were reported previously. We demonstrated that the effects at both 3q13.32 and 3p21 were specific to the TRO, but not to the femoral neck and spine. In contrast, the effect at 8q24 was common to all the sites. CONCLUSION: Our findings provide useful insights that enhance our understanding of bone development, osteoporosis, and fracture pathogenesis.

Effects of calcitriol on experimental spinal cord injury in rats.

STUDY DESIGN: Experimental, controlled, animal study. OBJECTIVES: To evaluate the effects of calcitriol on oxidative stress, apoptosis, autophagy and locomotor recovery in rats after spinal cord injury (SCI). SETTING: China. METHODS: Ninety female rats were randomly divided into three groups. Laminectomy only was performed in the control group. The SCI group received laminectomy as well as spinal cord compression injury. In the calcitriol group, SCI rats received an intraperitoneal injection of calcitriol (2 µg kg(-1)day(-1)). Oxidative stress was assessed by the tissue superoxide dismutase (SOD) activity and the contents of glutathione (GSH) and malondialdehyde (MDA). The extent of apoptosis was assessed by immunohistochemistry for C-caspase3, TUNEL staining and western blotting for C-caspase3, Bax and Bcl2. Transmission electron microscopy was used to examine autophagosomes in the injured spinal cord of calcitriol-treated rats. Autophagy was detected by western blotting for LC3-II, Beclin1 and p62. Histological changes were assessed by haematoxylin and eosin staining and Nissl staining. Functional recovery was reflected by the Basso, Beattie and Bresnahan locomotion rating scale and the inclined plane test. RESULTS: With calcitriol treatment, oxidative stress was decreased, SOD activity and GSH content were increased and MDA content was decreased. Moreover, apoptosis was inhibited in the SCI plus calcitriol group. However, a higher level of autophagy was detected in the lesions of the calcitriol group compared with the SCI group. Histological damage and neuron loss after SCI were reduced in calcitriol-treated rats, and functional recovery was significantly promoted in the calcitriol group compared with controls. CONCLUSIONS: Calcitriol promotes locomotor recovery after SCI by reducing oxidative stress and inhibiting apoptosis, as well as promoting autophagy.

Chondroitinase administration and pcDNA3.1-BDNF-BMSC transplantation promote motor functional recovery associated with NGF expression in spinal cord-transected rat.

STUDY DESIGN: We evaluated whether combination of chondroitinase (chABC) administration and brain-derived neurotrophic factor (BDNF)-mesenchymal stem cell (MSC) transplantation could provide an optimal effect for the treatment of spinal cord injury (SCI) subjected to complete transection. OBJECTIVES: Behavioral assessments and DBA tracing were used to evaluate the effects of combination of chABC administration and BDNF-MSC transplantation on axonal regeneration and functional improvement in SCT rats. SETTING: Sichuan, ChinaMethods:Bone mesenchymal stem cells (BMSCs) were cultured and overexpressed BDNF recombinant vector was constructed into MSCs, then transplanted into the impaired spinal cord, together with chABC administration. Finally, the cortical spinal tract regeneration was detected by DBA tracing at 4 weeks post operation, and the expression of nerve growth factor (NGF), BDNF, neurotrophic factor (NT)-3, NT-4, fibroblast growth factor (FGF-2)-2, B cell lymphoma 2 (BCL-2) assaciated X protein (BAX) and BCL-2 in the caudal cord tissues was assessed by reverse transcription-PCR. RESULTS: Animals received both BDNF-BMSC transplantation and chABC administration presented the best functional recovery and obvious axonal regeneration. Moreover, NGF expression was significantly higher than that in the other groups. CONCLUSION: Co-treated strategy could effectively promote motor functional recovery and axonal regeneration in SCT rats associated with NGF upregulation.

Population genetic diversity and genetic structure of Spodoptera exigua around the Bohai Gulf area of China based on mitochondrial DNA signatures.

The beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae), is an economically important pest that causes major losses in some main crop-producing areas of China. To control this pest effectively, it is necessary to investigate its population genetic diversity and genetic structure around the Bohai Gulf area of China. In this study, we used two mitochondrial genes, COI (578 bp) and Cytb (724 bp), to investigate its genetic diversity. We obtained 622 COI sequences and 462 Cytb sequences from 23 populations, and 28 and 73 haplotypes, respectively, were identified. Low to moderate levels of genetic diversity (COI: Hd = 0.267 ± 0.023, Pi = 0.00082 ± 0.00010; Cytb: Hd = 0.689 ± 0.018, Pi = 0.00255 ± 0.00029) for the total populations were observed. Phylogenetic and median-joining network analyses indicated no distinct geographical distribution pattern among the haplotypes. Overall, this study revealed that there was significant differentiation among the populations (COI: FST = 0.158, P < 0.001; Cytb: FST = 0.148, P < 0.001). FST values for Shenyang, Baoding, and Funing were significantly different to those for most of the other populations. Finally, unimodal mismatch distribution analysis, combined with negative neutrality test results, showed a recent population expansion of the beet armyworm around the Bohai Gulf area of China.

Phylogenetic relationships of Pseudohynobius (Urodela, Hynobiidae) inferred from DNA barcoding analysis.

As a proven tool, DNA barcoding can identify species rapidly and unambiguously. In this study, we used mtDNA cyt b, COI, and 16s rRNA sequences of six species of Pseudohynobius, Protohynobius puxiongensis, Liua shihi, Ranodon sibiricus, and Pachyhynobius shangchengensis, to reconstruct the phylogenetic relationships using Bayesian inference and maximum likelihood methods. Approximate lineage divergence times were also estimated, the divergence between them was calculated to have taken place mainly in Miocene. Our results showed that: 1) Ps. guizhouensis is an independent and valid species that is a sister species to Ps. kuankuoshuiensis; 2) five Pseudohynobius species formed a monophyletic group; 3) Ps. tsinpaensis is different from L. shihi, and should be classified as belonging to the Liua genus; and 4) Pr. puxiongensis is the sister lineage to all Pseudohynobius species, and should therefore be named Pseudohynobius puxiongensis.

Rho-kinase inhibitor fasudil reduces allergic airway inflammation and mucus hypersecretion by regulating STAT6 and NFκB.

BACKGROUND: Airway mucus hypersecretion is a key pathophysiological feature in asthma. Fasudil, a selective Rho-A/Rho kinase inhibitor, has been used in clinical trials to treat pulmonary hypertension. However, its function in modulating airway mucus hypersecretion in asthma remains undefined. OBJECTIVE: We examined whether fasudil, a selective Rho-A/Rho kinase inhibitor, affects the mucus hypersecretion by suppressing MUC5AC via signal transducer and activator of transcription factor 6 (STAT6) and nuclear factor-kappa B (NFκB) in mice and cells. METHODS: We measured mucus secretion and the expression of Rho-kinase in the airway tissue of patients with asthma. BALB/c mice were sensitized and challenged with ovalbumin (OVA) followed with fasudil treatment. The lung tissues were assessed for airway inflammation and mucus secretion. Cytokine levels and airway responsiveness were determined. STAT6 and NFκB were quantified by Western blot. 16HBE cells were stimulated with house dust mite (HDM) extracts. MUC5AC and muc5ac promoter activities were measured. Using siRNA to knockdown STAT6 in epithelial cells, we determined the impact of STAT6 on muc5ac promoter activity. NFκB nuclear translocation was observed with immunostaining. RESULTS: Fasudil administration significantly decreased the number of inflammatory cells, inflammation index in the lung and airway responsiveness. Fasudil also reduced mucous secretion and MUC5AC expression in OVA-challenged mice. Fasudil down-regulated the levels of IL-17, IL-4 and IL-13 in the lung tissue of OVA-challenged mice. Fasudil also decreased the expression and phosphorylation of NFκB and STAT6 as well as the nuclear translocation of NFκB. In addition, human airway epithelial cells (16HBE) were challenged with HDM extracts and then treated with fasudil. Fasudil inhibited HDM extract-induced MUC5AC expression, which is associated with a reduction in STAT6 and NFκB in epithelial cells. CONCLUSIONS AND CLINICAL RELEVANCE: These findings indicate that the Rho-A/Rho kinase inhibitor, fasudil, plays a negative regulatory role in allergen-induced mucus secretion and MUC5AC expression by regulating STAT6 and NFκB.

Seroprevalence and associated risk factors of Toxoplasma gondii infection in psychiatric patients: a case-control study in eastern China.

In recent years, the effect of Toxoplasma gondii infection on the cerebrum and neuropsychiatric patients has been increasingly highlighted. However, there is limited information about the epidemiology of T. gondii infection in psychiatric patients in Shandong province, eastern China. Therefore, through a case-control study, 445 patients hospitalized for diacrisis or treatment in Weihai, eastern China, and 445 control subjects from the general population of the same region matched by gender, age, and residence were examined with enzyme-linked immunoassays for the presence of IgG and IgM antibodies to T. gondii and associated sociodemographic and behavioural characteristics in a population of psychiatric patients. Seroprevalence of IgG antibodies to T. gondii in psychiatric patients (77/445, 17·30%) was significantly higher than in control subjects (55/445, 12·36%) (P = 0·038). Fourteen (3·15%) psychiatric patients and 10 (2·25%) control subjects had IgM antibodies to T. gondii (P = 0·408). Multivariate analysis using logic regression showed that T. gondii infection was associated with cats at home and consumption of raw/undercooked meat in psychiatric patients. Considering that most psychiatric patients usually have lower cognitive functioning and additional transmission routes related to their inappropriate behaviours that could enhance the risk of infection, psychiatric patients should be considered as a specific group of T. gondii infection.

Gli1 expression in pancreatic ductal adenocarcinoma and its clinical significance.

The aim of this study was to explore the correlation between the expression levels of Gli1 and p53 in pancreatic ductal adenocarcinoma (PDAC) and its pathological significance. Immunohistochemistry (IHC) was employed to measure the expression level of Gli1 and p53 in 85 sets of paraffin-embedded PDAC and corresponding para-carcinoma tissue specimens. The relationship between these results and the respective patients' clinicopathologic parameters was analyzed. IHC staining revealed that the expression levels of Gli1 and p53 in cancer tissues were evidently higher than that of para-carcinoma tissues (P < 0.05); while Gli1 expression levels correlated with the corresponding TNM stage and tumor infiltration depth, p53 expression level correlated with the respective TNM stage (P < 0.05). Taken together, this study demonstrates increased expression of Gli1 and p53 in PDAC, and proves that Gli1 could be apotential biomarker for prognostic judgment.

Genetic screening and evaluation for chromosomal abnormalities of infertile males in Jilin Province, China.

Chromosomal abnormality is the most common genetic cause of male infertility, particularly in cases of azoospermia, oligozoospermia, and recurrent spontaneous abortion. Chromosomal rearrangement may interrupt an important gene or exert position effects. The functionality of genes at specific breakpoints, perhaps with a specific role in spermatogenesis, may be altered by such rearrangements. Structural chromosome abnormalities are furthermore known to increase the risk of pregnancy loss. In this study, we aimed to assess chromosomal defects in infertile men from Jilin Province, China, by genetic screening and to evaluate the relationship between structural chromosome abnormalities and male infertility. The prevalence of chromosomal abnormalities among the study participants (receiving genetic counseling in Jilin Province, China) was 10.55%. The most common chromosome abnormality was Klinefelter syndrome, and the study findings suggested that azoospermia and oligospermia may result from structural chromosomal abnormalities. Chromosome 1 was shown to be most commonly involved in male infertility and balanced chromosomal translocation was identified as one of the causes of recurrent spontaneous abortion. Chromosomes 4, 7, and 10 were the most commonly involved chromosomes in male partners of women experiencing repeated abortion.

An extremely luminous X-ray outburst at the birth of a supernova.

Massive stars end their short lives in spectacular explosions--supernovae--that synthesize new elements and drive galaxy evolution. Historically, supernovae were discovered mainly through their 'delayed' optical light (some days after the burst of neutrinos that marks the actual event), preventing observations in the first moments following the explosion. As a result, the progenitors of some supernovae and the events leading up to their violent demise remain intensely debated. Here we report the serendipitous discovery of a supernova at the time of the explosion, marked by an extremely luminous X-ray outburst. We attribute the outburst to the 'break-out' of the supernova shock wave from the progenitor star, and show that the inferred rate of such events agrees with that of all core-collapse supernovae. We predict that future wide-field X-ray surveys will catch each year hundreds of supernovae in the act of exploding.

Quantitative evaluation of vertebral marrow adipose tissue in postmenopausal female using MRI chemical shift-based water-fat separation.

AIM: To investigate the feasibility of assessing vertebral marrow adipose tissue using a magnetic resonance imaging (MRI) chemical shift-based water-fat separation technique at 3 T. MATERIAL AND METHODS: A modified Dixon technique was performed to obtain the vertebral marrow fat fraction (FF) in a study of 58 postmenopausal females (age range 49.2-77.4 years), including 24 normal bone density, 19 osteopaenia, and 15 osteoporosis as documented with dual-energy X-ray absorptiometry. The reliability of FF measurements performed by two radiologists independently was evaluated with the intraclass correlation coefficient (ICC). Ten participants were scanned twice to assess the reproducibility of FF measurements. FF values were compared between each vertebral level and between groups. RESULTS: The mean coefficient of variation of FF measurements was 2.1%. According to the ICC, the measurements were reliable (ICC = 0.900 for normal bone density, ICC = 0.937 for osteopaenia and ICC = 0.909 for osteoporosis, p < 0.001 for all). There was an inverse association between mean FF at L1-L4 vertebrae and lumbar spine BMD (r = -0.459, p = 0.006), which remained significant even after controlling for confounders (age, height, and body weight). FF values at different vertebral levels were significantly correlated to each other (r = 0.703-0.921, p < 0.05 for all). There was a general trend toward increased marrow adiposity for more inferior vertebral bodies. Patients with osteopaenia and osteoporosis had a higher marrow fat content compared with normal bone mass after adjusting for confounders, although no significant differences in each vertebral level and average marrow fat content were found between the osteopaenia and osteoporosis groups. CONCLUSION: Chemical shift-based water-fat separation enables the quantitation of vertebral marrow adiposity with excellent reproducibility, which appears to be a useful method to provide complementary information to osteoporosis-related research fields.

Expression of RUNX3 gene in pancreatic adenocarcinoma and its clinical significance.

We investigated the clinical significance of RUNX3 gene expression in human pancreatic carcinoma. Five samples of pancreatic tissues and 30 samples of pancreatic cancer tissues and paracancerous tissues were collected. RUNX3 expression was detected by real-time PCR and immunohistochemistry. The relationships between clinicopathological findings and the expression of RUNX3 were analyzed. The relative quantification level of RUNX3 mRNA expression in human pancreatic carcinoma tissues and paracancerous tissues was 2.60 (0.42-12.82) and 1.02 (0.19-3.58), respectively (P < 0.05). The percentage of positive cells expressing RUNX3 protein in human pancreatic tissues and paracancerous tissues was 45.5 ± 26.2 and 6.9 ± 6.0%, respectively (P < 0.01). The high RUNX3 group (N = 9) with 45.5% or more of the cancer cells staining for RUNX3 and the low RUNX3 group (N = 21) with less than 45.5% cancer cells staining for RUNX3. Low expression of RUNX3 correlated significantly with an advanced TNM stage (χ(2) = 6.897, P = 0.045), lymph node metastasis (χ(2) = 4.739, P = 0.029) and neural invasion (χ(2) = 5.44, P = 0.020). On the other hand, no association could be found between RUNX3 expression and clinicopathological variables including age, gender, tumor location, tumor size, tumor differentiation or the serum concentration of CEA and CA199. The expression of RUNX3 in pancreatic cancer tissues was obviously higher than that in the paracancerous tissues. Low expression of RUNX3 may have an important role in aggressiveness, lymph node metastasis and neural invasion in pancreatic cancer. In pancreatic carcinoma tissues, low expression of RUNX3 may indicate a poor prognosis.

Clinical significance of pituitary tumor transforming gene 1 and transgelin-2 in pancreatic cancer.

Human pituitary tumor transforming gene 1 (PTTG1) is an oncogenic transcription factor that is overexpressed in many malignancies, especially cancers with metastatic potential, while transgelin-2 (TAGLN2) is an actin-binding protein shown to be a tumor suppressor. However, the expression and clinical significance of PTTG1 and TAGLN2 in pancreatic cancer remain unclear. The present study aimed to investigate the expression and clinical significance of PTTG1 and TAGLN2 in human primary pancreatic cancer. Seventy-five cases of human pancreatic cancer tissues were collected. The expression of PTTG1 and TAGLN2 protein was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were analyzed. As a result, the expression of PTTG1 and TAGLN2 in cancerous tissues showed the positive staining mainly in the cytoplasm, and they were found in cancerous tissues with higher strong reactivity rate compared with the adjacent non-cancer tissues (ANCT) (56.0 percent vs 22.7 percent, P less than 0.001; 100 percent vs 84 percent, P=0.002), elevating with the ascending order of tumor malignancy. Furthermore, the positive expression of PTTG1 was associated with the gender of pancreatic cancer patients, but did not correlate with their age, pathological styles, tumor size, tumor sites, TNM staging, perineural infiltration and distant metastasis (each P greater than 0.05). In addition, Spearman rank correlation analysis showed the positive correlation of PTTG1 with TAGLN2 (r=0.624, P less than 0.001). Taken together, PTTG1 and TAGLN2 are highly expressed in human pancreatic cancer, and the positive expression of PTTG1 is associated with the gender of cancer patients, suggesting that it may represent a potential therapeutic target for the treatment of pancreatic cancer.

Successful treatment of thalidomide for recurrent bleeding due to gastric angiodysplasia in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder, which is uncommon anomaly to recurrent gastrointestinal bleeding. Although there are several forms of therapy ranging from local therapy to operations or drug therapy, there is a lack of more effective treatment for the disease. In this report, we presented a Chinese patient with recurrent melena due to gastric angiodysplasia in HHT treated successfully with thalidomide.

Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines.

BACKGROUND: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor and rapamycin analogue that is approved for treating advanced renal cell carcinoma (RCC). It is being actively evaluated in clinical trials for melanoma. The mTOR inhibitors are also immunosuppressants and are used clinically to prevent rejection following solid-organ transplant. Novel immunotherapies are being actively developed for immunoresponsive tumours, such as RCC and melanoma. METHODS: Immune-modulating effects of temsirolimus were characterised when used in combination with cancer vaccines targeting RCC (RENCA) and melanoma (B16). Cancer vaccines were recombinant tumour-specific proteins (CA9 or gp100), and recombinant heat shock protein (HSP; hsp110) served as the immune adjuvant. RESULTS: In murine models, temsirolimus enhanced the anti-tumour activity of cancer vaccines used to treat established RENCA and B16 tumours. A tumour prevention model established that the enhanced anti-tumour activity associated with temsirolimus was immune mediated. In mice treated with an HSP-based anti-tumour vaccine, temsirolimus-treated CD8 T cells had greater interferon-γ and cytotoxic T-cell responses when compared with mice treated with vaccine alone. Temsirolimus also enhanced the formation of CD8 memory cells following administration of HSP-based cancer vaccine. CONCLUSION: These results provide a rationale for combining mTOR inhibitor with immunotherapy when treating immunoresponsive tumours.

Application of allele-specific RNAi in hepatitis B virus lamivudine resistance.

Understanding the consequences of mutation in the tyrosine-methionine-aspartate-aspartate (YMDD) motif of hepatitis B virus (HBV) genome on replication is critical for treating chronic hepatitis B with lamivudine. Allele-specific gene silencing by RNAi (allele-specific RNAi: ASP-RNAi) is an advanced application of RNAi techniques. Use of this strategy as a means for specifically inhibiting an allele expression of interest suggested that it can specifically suppress the expression of alleles causing disease without inhibiting the expression of corresponding wild-type alleles. However, no studies have used ASP-RNAi to address the issue of HBV lamivudine resistance. In this study, we applied ASP-RNAi into two long-term eukaryotic cell lines of full-length HBV containing either lamivudine-resistant mutants (HBV-YIDD) or wild type (HBV-WT) which we generated in previously. The designed siRNAs were also used in this eukaryotic expression system together with lamivudine. ELISA and real-time PCR were performed to monitor virus-specific protein synthesis and viral DNA replication. The results showed that the base substitutions conferring marked ASP-RNAi appeared to be largely present in positions 1, 3, 6, 11, 12, 15 and 19 of the sense strand of siRNAs which were different from the most sensitive positions of this application in eukaryotes. In addition, siRNA-lamivudine combinations did not possess the prominent anti-HBV activity we expected because of some unknown mechanisms. These findings recapitulated many of the features of ASP-RNAi in hepadnaviruses which provided a new insight into the development of a potent strategy against HBV drug resistance.