ABSTRACT
OBJECTIVE: Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs) that provide nutrients to neurons. Adrenal medulla is (ADM) involved in nerve damage. MiR-24 participates in various diseases. However, the regulation and mechanism of miR-24 in oligodendrocyte precursor cell differentiation after spinal injury is unclear. MATERIALS AND METHODS: Wistar rats were divided into sham operation group and model group. Real Time-PCR detects miR-24, PDGFRa and NG2 and MBP expression. OPC cells were cultured and divided into control group, miR-24 group, and si-miR-24 group followed by analysis of miR-24 expression by Real Time-PCR, expression of PDGFRa, NG2 and MBP by Western blot, as well as ADM content and secretion of IL-6 and TNF-α by enzyme-linked immunosorbent assay (ELISA). RESULTS: Expression of miR-24, PDGFRa, and NG2 was increased in the model group and MBP and ADM expression was decreased with increased secretion of IL-6 and TNF-α. Compared with control group, the difference was statistically significant (p<0.05). Upregulation of miR-24 promoted the expression of PDGFRa and NG2, decreased MBP and ADM level, and increased IL-6 and TNF-α secretion. Compared with control group, the difference was statistically significant (p<0.05). Downregulation of miR-24 reversed the above changes, and the difference was statistically significant (p<0.05). CONCLUSIONS: MiR-24 expression is increased in spinal injury. Upregulation of miR-24 expression reduces adrenal medulla expression and inhibits oligodendrocyte precursor cell differentiation.
Subject(s)
Adrenal Medulla/metabolism , MicroRNAs/metabolism , Oligodendrocyte Precursor Cells/metabolism , Spinal Cord Injuries/metabolism , Adrenal Medulla/pathology , Animals , Cell Differentiation , Cells, Cultured , Male , Oligodendrocyte Precursor Cells/pathology , Rats , Rats, Wistar , Spinal Cord Injuries/pathologyABSTRACT
OBJECTIVE: STAT3 has been shown to be involved in the occurrence, progression, and resistance of various tumors. The abnormal expression of miR-29 is associated with the pathogenesis of osteosarcoma. The bioinformatics analysis showed a targeting relationship between miR-29 and STAT3 3'-UTR. This study investigated whether miR-29 regulates the STAT3 expression and affects the proliferation and apoptosis of osteosarcoma cells. PATIENTS AND METHODS: The tumor tissues of osteosarcoma patients were collected, and the adjacent tissues were used as controls to detect the expression of miR-29 and STAT3. The Dual-Luciferase Gene Reporter Assay validated the regulatory relationship between miR-29 and STAT3. The expression of miR-29 and STAT3 in normal osteoblasts hFOB1.19, osteosarcoma SJSA-1, and MG-63 was measured. SJSA-1 cells were divided into miR-NC group and miR-29 mimic group. Cell apoptosis and proliferation were detected by flow cytometry. RESULTS: Compared with adjacent tissues, miR-29 expression was decreased, and STAT3 expression was increased in osteosarcoma. There was a targeted regulation relationship between miR-29 and STAT3. Compared with hFOB1.19 cells, miR-29 expression in osteosarcoma SJSA-1 and MG-63 cells was decreased, with increased STAT3 expression. The transfection of miR-29 mimic significantly decreased the expression of STAT3 and p-STAT3 in SJSA-1 cells, inhibited cell proliferation, and increased cell apoptosis. CONCLUSIONS: Decreased miR-29 expression plays a role in the increase of the STAT3 expression and in the promotion of the pathogenesis of osteosarcoma. Increasing the expression of miR-29 can inhibit the proliferation of osteosarcoma cells and promote apoptosis by decreasing STAT3 expression.
Subject(s)
Bone Neoplasms/genetics , MicroRNAs/genetics , Osteosarcoma/genetics , STAT3 Transcription Factor/genetics , 3' Untranslated Regions , Apoptosis , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Gene Expression Regulation, Neoplastic , HumansABSTRACT
Variations in ear size can be observed in livestock such as sheep; however, the genetic basis of variable ear size in sheep is still poorly understood. To investigate causative genes associated with ear size in sheep, a genome-wide association study was performed in 115 adult Duolang sheep with different-sized floppy ears using the Ovine Infinium HD BeadChip. We found 38 significant SNPs at the genome-wide or chromosome-wise 5% significance level after Bonferroni correction. The most significant association (P = 1.61 × 10-6 ) was found at SNP rs402740419, located in the DCC gene, which plays a critical role in ear development. Also, we observed two additional significant SNPs, rs407891215 in PTPRD and rs407769095 in SOX5, both of which are functionally associated with ear developmental processes. Our results are useful for future sheep breeding and provide insights into the genetic basis of ear size development in sheep and other livestock.
Subject(s)
Ear/anatomy & histology , Genes, DCC , Polymorphism, Single Nucleotide , Sheep, Domestic/genetics , Animals , Breeding , Female , Genetic Association Studies/veterinary , Genotype , MaleABSTRACT
BACKGROUND: Regional anaesthesia may have advantages in preserving immune function. Tumor-infiltrating lymphocytes (TILs) are considered indicators of immune response in the tumor microenvironment and used as a prognostic marker in patients after cancer surgery. This study investigated the effects of combined epidural anaesthesia on the number of TILs in patients undergoing surgery for lung adenocarcinoma. METHODS: Patients undergoing radical resection for primary lung cancer were randomized to receive either combined epidural-general anaesthesia (Epi-GA) or general anaesthesia (GA) in an ongoing randomized controlled trial (ChiCTR-TRC-14004136). Excised adenocarcinoma specimens from patients enrolled between 1 June 2015 and 30 November 2015 were selected for immunohistochemical staining of CD8 and FOXP3 molecules. The numbers of positive lymphocytes were counted and expressed as the number of cells per mm2 tumor area. RESULTS: One hundred and twenty-eight patients were recruited and randomized; 64 patients were included in immunohistochemistry analysis (37 received Epi-GA vs. 27 received GA). The number of CD8+ T cells was higher in the Epi-GA group than in the GA group (median [interquartile range]: 292.8 [198.0-418.3] vs. 204.7 [131.1-305.8], P = 0.036); whereas the number of FOXP3+ T cells was less in the Epi-GA group than in the GA group (37.6 [14.7-92.3] vs. 99.8 [68.9-168.3], P < 0.001). CONCLUSIONS: For patients undergoing surgery for lung adenocarcinoma under general anesthesia, use of epidural anaesthesia increased CD8+ T cells infiltration but decreased FOXP3+ T cells accumulation in tumor tissues. Epidural anaesthesia may affect TILs in a manner that preserves immune function.
Subject(s)
Adenocarcinoma of Lung/surgery , Anesthesia, Epidural , Lung Neoplasms/surgery , Lymphocytes, Tumor-Infiltrating/immunology , Adenocarcinoma of Lung/immunology , Aged , CD8 Antigens/analysis , Female , Forkhead Transcription Factors/analysis , Humans , Immunohistochemistry , Lung Neoplasms/immunology , Male , Middle Aged , Prospective StudiesABSTRACT
Women with chronic hepatitis B should maintain nucleotide analogue treatment to prevent disease progression during pregnancy. The aim of this study was to prospectively evaluate the efficacy and safety of telbivudine used throughout pregnancy for preventing hepatitis B virus (HBV) mother-to-child transmission (MTCT). From January 2012 to June 2014, women who were receiving telbivudine therapy and became pregnant were enrolled in group A at 28 weeks of gestation. Pregnant women with an HBV DNA level >106 IU/mL were enrolled in either group B (telbivudine started at 28 weeks of gestation) or group C (control group without treatment). MTCT was defined as infants who were positive for serum hepatitis B surface antigen at 7 months after birth. There were 41, 179 and 177 pregnant women (397 infants) enrolled in groups A, B and C, respectively. The HBV DNA load at 28 weeks of gestation and delivery was 1.50 ± 0.62 vs 1.45 ± 0.61, 8.05 ± 0.37 vs 4.24 ± 0.89 and 7.94 ± 0.62 vs 7.86 ± 0.73 log10 IU/mL in groups A, B and C, respectively. The rate of MTCT in group C was 4.60%, which was significantly higher than the rates in groups A and B (0% and 0.6%, respectively) (P = .043). The difference between group A and group B was not significant. The rates of neonatal congenital abnormalities were 2.4%, 0.6% and 2.3% in groups A, B and C, respectively, and there were no significant differences (P = .140). Telbivudine used throughout pregnancy may be safe and effective for mothers and infants, but it may not enhance the efficacy of an HBV MTCT block compared with treatment starting at 28 weeks of gestation (NCT02253485).
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B virus , Hepatitis B/drug therapy , Hepatitis B/transmission , Infectious Disease Transmission, Vertical/prevention & control , Thymidine/analogs & derivatives , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Child, Preschool , DNA, Viral , Female , Hepatitis B/blood , Hepatitis B/virology , Hepatitis B Surface Antigens/blood , Humans , Infant , Liver Function Tests , Pregnancy , Prospective Studies , Telbivudine , Thymidine/administration & dosage , Thymidine/adverse effects , Thymidine/therapeutic use , Treatment Outcome , Viral LoadABSTRACT
Fat-tailed sheep (Ovis aries) can survive in harsh environments and satisfy human's intake of dietary fat. However, the animals require more feed, which increases the cost of farming. Thus, most farmers currently prefer thin-tailed, short-tailed or docked sheep. To date, the molecular mechanism of the formation of fat tails in sheep has not been completely elucidated. Here, we conducted a genome-wide association study using phenotypes and genotypes (the Ovine Infinium HD SNP BeadChip genotype data) of two breeds of contrasting tail types (78 Small-tailed and 78 Large-tailed Han sheep breeds) to identify functional genes and variants associated with fat deposition. We identified four significantly (rs416433540, rs409848439, rs408118325 and rs402128848) and three approximately associated autosomal SNPs (rs401248376, rs402445895 and rs416201901). Gene annotation indicated that the surrounding genes (CREB1, STEAP4, CTBP1 and RIP140, also known as NRIP1) function in lipid storage or fat cell regulation. Furthermore, through an X-chromosome-wide association analysis, we detected significantly associated SNPs in the OARX: 88-89 Mb region, which could be a strong candidate genomic region for fat deposition in tails of sheep. Our results represent a new genomic resource for sheep genetics and breeding. In addition, the findings provide novel insights into genetic mechanisms of fat deposition in the tail of sheep and other mammals.
Subject(s)
Adiposity , Sheep, Domestic/genetics , Tail/anatomy & histology , Animals , Breeding , Chromosome Mapping , Female , Genetic Association Studies , Genotype , Male , Molecular Sequence Annotation , Phenotype , Polymorphism, Single Nucleotide , X Chromosome/geneticsABSTRACT
Genome-wide association studies (GWASs) have been widely applied in livestock to identify genes associated with traits of economic interest. Here, we conducted the first GWAS of the supernumerary nipple phenotype in Wadi sheep, a native Chinese sheep breed, based on Ovine Infinium HD SNP BeadChip genotypes in a total of 144 ewes (75 cases with four teats, including two normal and two supernumerary teats, and 69 control cases with two teats). We detected 63 significant SNPs at the chromosome-wise threshold. Additionally, one candidate region (chr1: 170.723-170.734 Mb) was identified by haplotype-based association tests, with one SNP (rs413490006) surrounding functional genes BBX and CD47 on chromosome 1 being commonly identified as significant by the two mentioned analyses. Moreover, Gene Ontology enrichment for the significant SNPs identified by the GWAS analysis was functionally clustered into the categories of receptor activity and synaptic membrane. In addition, pathway mapping revealed four promising pathways (Wnt, oxytocin, MAPK and axon guidance) involved in the development of the supernumerary nipple phenotype. Our results provide novel and important insights into the genetic mechanisms underlying the phenotype of supernumerary nipples in mammals, including humans. These findings may be useful for future breeding and genetics in sheep and other livestock.
Subject(s)
Breast Diseases/veterinary , Genetic Association Studies , Nipples/abnormalities , Sheep, Domestic/genetics , Animals , Breast Diseases/genetics , Breeding , Chromosome Mapping , Female , Genotype , Haplotypes , Linkage Disequilibrium , Molecular Sequence Annotation , Phenotype , Polymorphism, Single Nucleotide , Sheep, Domestic/anatomy & histologyABSTRACT
OBJECTIVE: To explore the role of Id1 in ovarian cancer cell proliferation, invasion and apoptosis. MATERIALS AND METHODS: Lentivirus-based shRNA vectors were constructed to knockdown Id1 expression in SKOV3 ovarian cancer cells. The proliferation, invasion ability and apoptosis of SKOV3 cells were evaluated by CCK-8 assay, transwell assay and flow cytometry, respectively. RESULTS: Compared to control cells, cell proliferation and invasion were significantly inhibited in SKOV3 cells depleted of Id1, while apoptosis was significantly increased in SKOV3 cells depleted of Id1. CONCLUSIONS: Id1 functions to promote ovarian cancer cell proliferation and invasion, and Id1 is a promising therapeutic target for ovarian cancer.
Subject(s)
Apoptosis , Cell Line, Tumor , Cell Proliferation , Female , Humans , Ovarian Neoplasms/genetics , RNA, Small Interfering/geneticsABSTRACT
Administration of corticosteroids to patients affected by influenza virus, especially pandemic avian influenza virus, although relatively common, remains controversial. A systematic review and meta-analysis was performed to assess the impact of corticosteroid treatment on outcomes of patients with influenza virus infection. The PubMed, EMBASE, Web of Science and Cochrane Library databases were searched up to February, 2015. Studies comparing corticosteroid treatment with no corticosteroid treatment in patients with influenza virus infection were included. The primary outcomes assessed were the association of mortality and nosocomial infection with corticosteroid treatment. Two authors independently extracted the data. ORs and weighted mean differences (WMDs) were used to describe dichotomous data and continuous data, respectively. Nineteen studies with 4916 patients were included in this meta-analysis. The results showed that corticosteroid treatment was significantly associated with mortality (OR 1.98, 95% CI 1.62-2.43, p < 0.00001) and nosocomial infection (OR 3.16, 95% CI 2.09-4.78, p < 0.00001). The durations of mechanical ventilation (WMD 3.82, 95% CI 1.49-6.15, p 0.001) and intensive-care unit stay (WMD 4.78, 95% CI 2.27-7.29, p 0.0002) were both markedly longer in the corticosteroid treatment group than in the control group. These findings suggest that routine steroid use may not be ideal for influenza virus infection. However, these results are derived from observational studies, with some important biases. They should be examined in future sufficiently powered randomized trials.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Influenza, Human/drug therapy , Adrenal Cortex Hormones/adverse effects , Anti-Inflammatory Agents/adverse effects , Cross Infection/epidemiology , Humans , Influenza, Human/complications , Influenza, Human/mortality , Length of Stay , Respiration, Artificial , Survival Analysis , Treatment OutcomeABSTRACT
Castleman disease (CD) is a rare reactive lymphoproliferative disorder, first identified in 1954. We recently had the opportunity to analyse the characteristics of two variations of CD with pulmonary involvement. Case 1 had localised retroperitoneal hyaline vascular type CD, while Case 2 was diagnosed as multicentric plasma cell type CD. Both patients had pulmonary symptoms and signs, including cough, dyspnoea, hypoxaemia and ventilatory dysfunction; however, they had different physiological manifestations of their pulmonary abnormalities.
Subject(s)
Castleman Disease/diagnosis , Tuberculosis, Pulmonary/diagnosis , Adult , Antitubercular Agents/therapeutic use , Castleman Disease/complications , Glucocorticoids/therapeutic use , Humans , Hypercapnia/drug therapy , Hypoxia/drug therapy , Lymph Nodes/pathology , Male , Prednisone/therapeutic use , Serum Albumin/metabolism , Tomography, X-Ray Computed , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/drug therapy , Young AdultABSTRACT
Wolbachia 16S rRNA and fbpA genes were twice detected over 5 days in the blood of a patient with high fever. The patient was given fluoroquinolones and the fever resolved. Four weeks later, he was diagnosed with non-Hodgkin's lymphoma and received R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) treatment resulting in complete remission. This is the first report of detection of Wolbachia genes from the blood of human patients with non-Hodgkin's lymphoma.
Subject(s)
Bacteremia/diagnosis , DNA, Bacterial/blood , Gram-Negative Bacterial Infections/diagnosis , Lymphoma, Non-Hodgkin/complications , Wolbachia/genetics , Bacteremia/drug therapy , Cluster Analysis , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Fluoroquinolones/therapeutic use , Gram-Negative Bacterial Infections/drug therapy , Humans , Male , Middle Aged , Molecular Sequence Data , Periplasmic Binding Proteins/genetics , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: The detailed mechanisms of cerebral aneurysm generation remain unclear. Our aim was to investigate whether specific hemodynamic insult in combination with arterial wall degeneration leads to the development of aneurysms in a canine model. MATERIALS AND METHODS: New branch points in the common carotid artery were created in 18 dogs. Nine animals subsequently received elastase insult at the arterial bifurcation apex (elastase-treated bifurcation group); the control bifurcation group (n=9) received saline, and 3 dogs received an elastase insult to both straight common carotid arteries (elastase-treated straight group). Angiographic and hemodynamic analysis was performed immediately and 12 and 24 weeks' postsurgery; histologic response was evaluated at 12 and 24 weeks. RESULTS: Angiography revealed nascent aneurysms (mean, 3.2±0.4 mm) at the arterial bifurcation apices in 5/9 models of the elastase-treated bifurcation group (versus 0 in the control bifurcation group and elastase-treated straight group) without any observed aneurysm rupture. Histologic analysis revealed internal elastic lamina discontinuity, elastic fiber disruption, a thinner muscular layer, reduced smooth-muscle cell proliferation, increased inflammatory cell (macrophage) infiltration, and expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in the media of the elastase-treated bifurcation group compared with that in either the control bifurcation group or the elastase-treated straight group (P<.001). Hemodynamic analysis after surgery indicated that the apex experienced extremely low wall shear stress and flow velocity and the highest relative and total pressure in the elastase-treated bifurcation group, while the values returned to normal after arterial wall remodelling. CONCLUSIONS: In our study, combined hemodynamic insult and arterial wall degeneration at arterial bifurcations are required for the generation of aneurysms in a canine model.
Subject(s)
Carotid Artery, Common/pathology , Hemodynamics/physiology , Intracranial Aneurysm/pathology , Animals , Carotid Artery, Common/metabolism , Cerebral Angiography , Disease Models, Animal , Dogs , Intracranial Aneurysm/metabolism , Stress, MechanicalABSTRACT
OBJECTIVES: The present study was undertaken to investigate the association of peptidyl-arginine-deiminase type IV gene (PADI4) single nucleotide polymorphisms (SNPs) with rheumatoid arthritis (RA) susceptibility, and to determine whether there is any impact of PADI4 polymorphisms on RA subsets or phenotypes in a large Chinese Han cohort. METHODS: Two PADI4 SNPs (rs2240340 and rs1748033) were genotyped in 1216 Chinese Han RA patients and 1040 unaffected controls by TaqMan SNP Assays. Serum anti-CCP antibody and anti-PAD4 antibody levels were measured by ELISA. Bone destruction was scored by Sharp-van der Heijde scores (SHSs) of hands in 463 patients. RESULTS: The two SNPs rs2240340 and rs1748033 of PADI4 showed strong association with RA susceptibility (OR=1.23, 95% CI 1.09-1.38, p=6.66×10â»4; and OR=1.24, 95% CI 1.10-1.41, p=6.98×10â»4, respectively). RA risk genotypes of PADI4 were specifically associated with anti-CCP positive RA (rs2240340: p=5.13×10â»6; rs1748033: p=2.97×10⻳, respectively). Furthermore, there was a trend association between PADI4 rs2240340 and radiographic severity, though it did not reach the statistic significance (p=0.088). CONCLUSIONS: Our data provide strong evidence that PADI4 polymorphisms are risk factors contributed to RA susceptibility, especially for anti-CCP positive RA, and may confer higher risk of RA radiographic severity in Chinese Han population.
Subject(s)
Arthritis, Rheumatoid/genetics , Asian People/genetics , Hydrolases/genetics , Peptides, Cyclic/immunology , Adult , Arthritis, Rheumatoid/ethnology , Arthritis, Rheumatoid/immunology , Asian People/statistics & numerical data , Autoantibodies/blood , Cohort Studies , Female , Gene Frequency , Humans , Linkage Disequilibrium , Male , Middle Aged , Phenotype , Polymorphism, Single Nucleotide , Protein-Arginine Deiminase Type 4 , Protein-Arginine Deiminases , Risk Factors , Seroepidemiologic StudiesABSTRACT
In sheep, coat colour (and pattern) is one of the important traits of great biological, economic and social importance. However, the genetics of sheep coat colour has not yet been fully clarified. We conducted a genome-wide association study of sheep coat colours by genotyping 47 303 single-nucleotide polymorphisms (SNPs) in the Finnsheep population in Finland. We identified 35 SNPs associated with all the coat colours studied, which cover genomic regions encompassing three known pigmentation genes (TYRP1, ASIP and MITF) in sheep. Eighteen of these associations were confirmed in further tests between white versus non-white individuals, but none of the 35 associations were significant in the analysis of only non-white colours. Across the tests, the s66432.1 in ASIP showed significant association (P=4.2 × 10(-11) for all the colours; P=2.3 × 10(-11) for white versus non-white colours) with the variation in coat colours and strong linkage disequilibrium with other significant variants surrounding the ASIP gene. The signals detected around the ASIP gene were explained by differences in white versus non-white alleles. Further, a genome scan for selection for white coat pigmentation identified a strong and striking selection signal spanning ASIP. Our study identified the main candidate gene for the coat colour variation between white and non-white as ASIP, an autosomal gene that has been directly implicated in the pathway regulating melanogenesis. Together with ASIP, the two other newly identified genes (TYRP1 and MITF) in the Finnsheep, bordering associated SNPs, represent a new resource for enriching sheep coat-colour genetics and breeding.
Subject(s)
Agouti Signaling Protein/genetics , Genome-Wide Association Study , Hair Color , Polymorphism, Single Nucleotide , Sheep/genetics , Animals , Female , Genetics, Population , Linkage Disequilibrium , Male , Phenotype , Selection, GeneticABSTRACT
BACKGROUND: Asparagine synthetase (ASNS) is associated with drug resistance in leukaemia, and the function of this enzyme in the context of hepatocellular carcinoma (HCC) is not clear. In this study, the relationship between ASNS expression and clinical outcomes after surgical resection was investigated, and the therapeutic value of ASNS was also evaluated. METHODS: The expression of ASNS was evaluated in HCC samples by real-time PCR and immunohistochemistry assays. The correlation between ASNS expression and clinicopathological features was investigated. Potential clinicopathological prognostic factors were examined by univariate and multivariate survival analysis. Asparagine synthetase was overexpressed and knocked down in HCC cell lines to assess the influence of the enzyme on cell proliferation, migration and tumourigenicity. L-asparaginase was used to treat HCC cells with high or low levels of ASNS in vitro and in vivo to examine the therapeutic efficacy. RESULTS: The expression of ASNS was higher in HCC tumour tissues and was closely correlated with the serum AFP level, tumour size, microscopic vascular invasion, tumour encapsulation, TNM stage and BCLC stage. Patients with low ASNS expression levels had a poor prognosis with respect to overall survival (OS). The multivariate survival analysis indicated that ASNS is an independent prognostic factor for OS. Furthermore, functional studies demonstrated that ASNS significantly inhibits the proliferation, migration and tumourigenicity of HCC cells. The knockdown of ASNS markedly increased sensitivity to L-asparaginase, indicating that cells with different ASNS protein levels have different sensitivities to L-asparaginase. CONCLUSION: The expression of ASNS is an independent factor affecting the survival of HCC patients, and low ASNS expression in HCC was correlated with worse surgical outcomes. The ASNS may be a promising therapeutic target for the treatment of HCC.
Subject(s)
Aspartate-Ammonia Ligase/metabolism , Carcinoma, Hepatocellular , Liver Neoplasms , Adult , Animals , Asparaginase/pharmacology , Aspartate-Ammonia Ligase/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Cell Line, Tumor , Cell Movement , Cell Proliferation , Drug Resistance, Neoplasm , Female , Gene Expression , Humans , Liver Neoplasms/enzymology , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Male , Mice , Mice, Nude , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Staging , Prognosis , RNA Interference , RNA, Small Interfering , Survival , Tissue Array Analysis , Xenograft Model Antitumor Assays , alpha-Fetoproteins/analysisABSTRACT
Global warming and shortage of water have been evidenced in the recent past and are predicted for the future. Climate change will inevitably have considerable impact on plant physiology, growth, productivity and forest ecosystem functions. The present study determined the effects of simulated daytime air warming (+1 to 1.5 °C during the growing season), drought (-40% and -57% of mean precipitation of 728 mm during the 2007 and 2008 growing season, respectively) and their combination, on leaf nitrogen (N) and non-structural carbohydrates (NSC) of two Quercus species (Q. robur and Q. petraea) and provenances (two provenances for each species) grown in two soil types in Switzerland across two treatment years, to test the hypothesis that leaf N and NSC in the more water-sensitive species (Q. robur) and provenances (originating from water-rich locations) will more strongly respond to global warming and water deficit, compared to those in the more drought-tolerant species (Q. petraea) or provenances. No species- and provenance-specific responses in leaf N and NSC to the climate treatment were found, indicating that the results failed to support our hypothesis. The between-species variation of leaf N and NSC concentrations mainly reflected differences in biology of the two species, and the between-provenance variation of N and NSC concentrations apparently mirrored the climate of their origins. Hence, we conclude that (i) the two Quercus species studied are somewhat insensitive, due to their distribution covering a wide geographical and climate range, to moderate climate change within Switzerland, and (ii) a moderate global warming of B1 scenario (IPCC 2007) will not, or at least less, negatively affect the N and carbon physiology in Q. robur and Q. petraea.
Subject(s)
Carbohydrate Metabolism , Ecosystem , Global Warming , Hot Temperature , Nitrogen/metabolism , Plant Leaves/metabolism , Quercus/physiology , Acclimatization , Air , Climate , Droughts , Quercus/metabolism , Rain , Seasons , Soil , Species Specificity , Stress, Physiological , Switzerland , WaterABSTRACT
BACKGROUND AND PURPOSE: A series of benzothiazole derivatives were screened for immunosuppressive activity; of these compounds BD750 was found to be the most effective immunosuppressant. The purpose of the current study was to determine the immunosuppressive activity of BD750 on T cell proliferation and its potential mode of action. EXPERIMENTAL APPROACH: T cell proliferation, CD25 and CD69 expression and cell cycle distribution were measured in vitro by flow cytometry. Cell viability was determined by CCK-8 assay. Cytokine levels were measured by elisa. The activation of signal-regulated molecules was assessed by Western blot analysis. The effects of BD750 were evaluated in vivo in a mouse model of delayed-type hypersensitivity. KEY RESULTS: BD750 significantly inhibited mouse and human T cell proliferation, stimulated either by anti-CD3/anti-CD28 monoclonal antibodies or by an alloantigen, in a dose-dependent manner in vitro. No obvious cytotoxic effects of BD750 were observed in our experimental conditions. Furthermore, BD750 did not inhibit CD25 and CD69 expression or IL-2 and IL-4 secretion, but induced cell cycle arrest at the G(0) /G(1) phase in activated T cells. In IL-2-stimulated CTLL-2 cells and primary activated T cells, BD750 inhibited cell proliferation and STAT5 phosphorylation, but not Akt or p70S6K phosphorylation. BD750 also reduced the T cell-mediated delayed-type hypersensitivity response in mice in a dose-dependent manner. CONCLUSION AND IMPLICATIONS: These data indicate that BD750 inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation. BD750 has the potential to be used as a lead compound for the design and development of new immunosuppressants for preventing graft rejection and treating autoimmune diseases.
Subject(s)
Benzothiazoles/pharmacology , Immunosuppressive Agents/pharmacology , Indazoles/pharmacology , T-Lymphocytes/drug effects , Allergens , Animals , Benzothiazoles/therapeutic use , Cell Cycle/drug effects , Cell Proliferation/drug effects , Dinitrofluorobenzene , Female , Humans , Hypersensitivity, Delayed/chemically induced , Hypersensitivity, Delayed/drug therapy , Hypersensitivity, Delayed/pathology , Immunosuppressive Agents/therapeutic use , Indazoles/therapeutic use , Interleukin-2/pharmacology , Janus Kinase 3/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , STAT5 Transcription Factor/metabolism , Signal Transduction , T-Lymphocytes/metabolismABSTRACT
Microsatellite variation was surveyed to determine the genetic diversity, population structure and admixture of seven North Ethiopian cattle breeds by combining multiple microsatellite data sets of Indian and West African zebu, and European, African and Near-Eastern taurine in genetic analyses. Based on allelic distribution, we identified four diagnostic alleles (HEL1-123 bp, CSSM66-201 bp, BM2113-150 bp and ILSTS6-285 bp) specific to the Near-Eastern taurine. Results of genetic relationship and population structure analyses confirmed the previously established marked genetic distinction between taurine and zebu, and indicated further divergence among the bio-geographical groupings of breeds such as North Ethiopian, Indian and West African zebu, and African, European and Near-Eastern taurine. Using the diagnostic alleles for bio-geographical groupings and a Bayesian method for population structure inference, we estimated the genetic influences of major historical introgressions in North Ethiopian cattle. The breeds have been heavily (>90%) influenced by zebu, followed by African, European and the Near-Eastern taurine. Overall, North Ethiopian cattle show a high level of within-population genetic variation (e.g. observed heterozygosity = 0.659-0.687), which is in the upper range of that reported for domestic cattle and indicates their potential for future breeding applications, even in a global context. Rather low but significant population differentiation (F(ST) = 1.1%, P < 0.05) was recorded as a result of multiple introgression events and strong genetic exchanges among the North Ethiopian breeds.
Subject(s)
Cattle/genetics , Gene Flow , Microsatellite Repeats , Polymorphism, Genetic , Animals , Bayes Theorem , Breeding , Conservation of Natural Resources , Ethiopia , Pedigree , Phylogeography , Polymerase Chain Reaction , Species SpecificityABSTRACT
BACKGROUND AND PURPOSE: Hypertension, one of the most important risk factors for strokes, is associated with altered arterial anatomy and function. In this study, we compared the visualization of the LSAs by 3T 3D-TOF-MRA and DSA and quantitatively examined the LSAs in patients with hypertension by using 3D-TOF-MRA. MATERIALS AND METHODS: We first examined 126 patients with 3D-TOF-MRA and DSA and determined the number of LSAs. In addition, we examined 60 patients with hypertension and 60 nonhypertensive volunteers with 3D-TOF-MRA and determined the quantitative differences between the LSAs of these 2 groups. RESULTS: The mean number of LSA stems visualized by DSA and 3D-TOF-MRA on 1 side was 4.1 ± 0.74 and 3.9 ± 0.94, respectively (P = .0617). The average number of LSA stems on both sides was 4.7 ± 0.8 in patients with hypertension and 6.3 ± 1.9 in nonhypertensive volunteers (P < .0001). The mean number of LSAs in the young hypertensive group (<50 years of age) and its age-matched nonhypertensive group was 4.8 ± 1.1 and 7.6 ± 1.2, respectively (P < .0001) and that in the old hypertensive group (≥50 years of age) and its age-matched nonhypertensive group was 4.6 ± 0.9 and 5.0 ± 1.0, respectively (P = .1088). CONCLUSIONS: LSA detection showed good correlation between 3T 3D-TOF-MRA and DSA. As determined by 3D-TOF-MRA, there was a significant decrease in the number of LSA stems in patients with hypertension compared with that in nonhypertensive volunteers; moreover, the difference in young subjects was more than that in the elderly.
Subject(s)
Cerebral Arteries/pathology , Corpus Striatum/blood supply , Corpus Striatum/pathology , Hypertension/pathology , Magnetic Resonance Angiography/methods , Adult , Aged , Female , Humans , Image Enhancement/methods , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Statistics as Topic , Young AdultABSTRACT
OBJECTIVE: We prospectively investigated the diagnostic accuracy of contrast-free 3-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) with volume rendering (VR) at 3.0 T to detect intracranial aneurysms in a large cohort of patients. METHODS: We conducted a prospective clinical study including 411 patients with suspected aneurysms and other cerebral vascular diseases who were referred for contrast-free 3D-TOF-MRA at 3.0 T prior to digital subtraction angiography (DSA). 2D-DSA and VR-DSA were regarded as the gold standard. Forty-two patients were excluded. Accuracy, sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) as measures to detect or rule out intracranial aneurysms were determined by patient-, aneurysm-, vessel-, and aneurysm size-based evaluations. RESULTS: In all 369 patients investigated, VR-DSA revealed 307 aneurysms in 246 patients (66.7%) and no aneurysm in 123 patients. The patient-based evaluation by VR 3D-TOF-MRA at 3.0 T yielded an accuracy of 97.6%, a sensitivity of 99.2%, specificity of 94.4%, PPV of 97.2%, and NPV of 98.3% in the detection of intracranial aneurysms. The aneurysm-based evaluation yielded an accuracy of 98.3%, sensitivity of 99.3%, specificity of 96.9%, PPV of 97.8%, and NPV of 99.1%. The vessel-based evaluation yielded accuracy of 98.8%, sensitivity of 99.2%, specificity of 98.5%, PPV of 97.5%, and NPV of 99.6%. The evaluation based on aneurysm sizes yielded similar results. CONCLUSIONS: VR 3D-TOF-MRA at 3.0 T accurately identified the presence of intracranial aneurysms. High PPV and NPV indicated that VR 3D-TOF-MRA at 3.0 T may replace DSA as a contrast-free, noninvasive, and non-radiation-based modality for the diagnosis and screening of intracranial aneurysms.