Geometric nonlinearity of self-anchored cable-stayed suspension bridges is studied in this paper. The repercussion of shrinkage and creep of concrete, rise-to-span ratio, and girder camber on the system is discussed. A self-anchored cable-stayed suspension bridge with a main span of 800 m is analyzed with linear theory, second-order theory, and nonlinear theory, respectively. In the condition of various rise-to-span ratios and girder cambers, the moments and displacements of both the girder and the pylon under live load are acquired. Based on the results it is derived that the second-order theory can be adopted to analyze a self-anchored cable-stayed suspension bridge with a main span of 800 m, and the error is less than 6%. The shrinkage and creep of concrete impose a conspicuous impact on the structure. And it outmatches suspension bridges for system stiffness. As the rise-to-span ratio increases, the axial forces of the main cable and the girder decline. The system stiffness rises with the girder camber being employed.
MiRNAs are a class of non-coding small RNAs that play important roles in the regulation of gene expression. Although plant miRNAs have been extensively studied in model systems, less is known in other plants with limited genome sequence data, including eggplant (Solanum melongena L.). To identify miRNAs in eggplant and their response to Verticillium dahliae infection, a fungal pathogen for which clear understanding of infection mechanisms and effective cure methods are currently lacking, we deep-sequenced two small RNA (sRNA) libraries prepared from mock-infected and infected seedlings of eggplants. Specifically, 30,830,792 reads produced 7,716,328 unique miRNAs representing 99 known miRNA families that have been identified in other plant species. Two novel putative miRNAs were predicted with eggplant ESTs. The potential targets of the identified known and novel miRNAs were also predicted based on sequence homology search. It was observed that the length distribution of obtained sRNAs and the expression of 6 miRNA families were obviously different between the two libraries. These results provide a framework for further analysis of miRNAs and their role in regulating plant response to fungal infection and Verticillium wilt in particular.
The purpose of this study was to compare perioperative outcomes in patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracoscopic surgery and assess the feasibility of robotic-assisted thymectomy for the treatment of Masaoka stage I.
We evaluated the short-term outcomes of 46 patients who underwent surgery for Masaoka stage I thymoma without myasthenia gravis between January 2009 and June 2012. Of these patients, 25 received unilateral video-assisted thoracoscopic surgery (VATS group) and the rest 21 recieved unilateral robotic-assisted thoracoscopic surgery (RATS group). We evaluated the duration of surgery, amount of intraoperative blood loss, duration of chest drainage, duration of postoperative hospital stay, hospitalization costs, postoperative complications and oncological outcomes.
The duration of surgery was not significantly different between the two groups. Intraoperative blood loss volumes did not differ significantly between the VATS and RATS groups (86.8 mL and 58.6 mL, respectively; P=0.168). The postoperative hospital stay was significantly shorter in the RATS group (3.7 days vs. 6.7 days; P <0.01), and the postoperative pleural drainage volume of the RATS group was significantly less than VATS group (1.1 days vs. 3.6 days; P <0.01). No patients in the RATS group needed conversion to open surgery. However, in the VATS series, one patient had conversion to an open procedure. No surgical complications were observed except that one case had pulmonary atelectasis in the RATS group and one case developed pneumonia after surgery. Use of robot is much more expensive than video. No early recurrence was observed in both groups.
Robotic thymectomy is feasible and safe for Masaoka stage I thymoma. RATS is equally minimally invasive as VATS and results in a shorter drainage period and reduced hospital stay compared with the VATS approach.
Robotics; Thymoma; Minimally invasive surgery; Thymus
For patients with unresectable pancreatic cancer, current chemotherapies have negligible survival benefits. Thus, developing effective minimally invasive therapies is currently underway. This study was conducted to evaluate the efficacy of transarterial chemoembolization plus radiofrequency ablation and/or 125I radioactive seed implantation on unresectable pancreatic cancer. We analyzed the outcome of 71 patients with unresectable pancreatic carcinoma who underwent chemoembolization plus radiofrequency ablation and/or radioactive seed implantation. Of the 71 patients, the median survival was 11 months, and the 1-, 2-, and 3-year overall survival rates were 32.4%, 9.9%, and 6.6% respectively. Patients who had no metastasis, who had oligonodular liver metastases (≤3 lesions), and who had multinodular liver metastases (>3 lesions) had median survival of 12, 18, and 8 months, respectively, and 1-year overall survival rates of 50.0%, 68.8%, and 5.7%, respectively. Although the survival of patients without liver metastases was worse than that of patients with oligonodular liver metastasis, the result was not significant (P = 0.239). In contrast, the metastasis-negative patients had significantly better survival than did patients with multinodular liver metastases (P < 0.001). Patients with oligonodular liver lesions had a significanthg longer median survival than did patients with multinodular lesions (P < 0.001). In conclusion, combined minimally invasive therapies had good efficacy on unresectable pancreatic cancer and resulted in a good control of liver metastases. In addition, the number of liver metastases was a significant factor in predicting prognosis and response to treatment.
Pancreatic cancer; minimally invasive therapies; transarterial chemoembolization; radiofrequency ablation; median survival
Special AT-rich sequence binding protein 1 (SATB1) is a nuclear factor that functions as the global chromatin organizer to regulate chromatin structure and gene expression gene expression. SATB1 has been shown to be abnormally expressed in various types of cancer. However, the expression and role of SATB1 in prostate cancer remain unclear.
120 cases of prostatic carcinoma and 60 cases of benign prostate hyperplasia were analyzed for SATB1 expression by immunohistochemistry. LNCaP, DU-145, and PC3 prostate cancer cells were examined for SATB1 expression by Western blot analysis. Cell proliferation and invasion was evaluated by CCK8 and transwell invasion assay, respectively.
SATB1 staining was stronger in prostatic carcinomas with metastasis than in those without metastasis, but was absent in benign prostate hyperplasia. Furthermore, SATB1 expression was positively correlated with bone metastasis and the Gleason score. SATB1 overexpression promoted the proliferation and invasion of LNCaP cells while SATB1 knockdown inhibited the proliferation and invasion of DU-145 cells.
These findings provide novel insight into oncogenic role of SATB1 in prostate cancer, suggesting that SATB1 is a promising biomarker and therapeutic target for prostate cancer.
SATB1; Prostate cancer; Metastasis; Invasion; Proliferation
No standard therapy for pulmonary epithelioid hemangioendothelioma (PEH) has yet been established due to the rarity of the disease, the lack of clear standards for treatment and the partial-to-complete spontaneous regression. This report describes three cases of PHE manifested as bilateral intrapulmonary masses with an initial diagnosis conducted by thoracoscopic lung biopsy. These patients demonstrated a partial response to combination chemotherapy with carboplatin, paclitaxel, bevacizumab or endostar, and an improvement in clinical status. Furthermore, we reviewed the literature regarding such patients who received chemotherapy and immunotherapy; this indicated that patients with PEH demonstrated a good partial response to chemotherapy with carboplatin, paclitaxel, bevacizumab, thalidomide and α-interferon. Overall, combination chemotherapy regimens may hold therapeutic potential for the treatment of this rare disease.
pulmonary epithelioid hemangioendothelioma; pulmonary tumors; chemotherapy; metastases
RUNX3 (runt-related transcription factor-3) is a known tumor suppressor gene which exhibits potent antitumor activity in several carcinomas. However, little is known about the role of RUNX3 in human renal cell carcinoma (RCC). To investigate the clinical relevance of RUNX3 in RCC patients, immunohistochemistry was performed to detect the clinical relevance of RUNX3 in 75 RCC tissues and paired non-cancerous tissues by using tissue microarray (TMA). We also investigated the role of RUNX3 in RCC cell migration, invasion and angiogenesis. The RUNX3 expression was decreased dramatically in human RCC tissue. The RUNX3 expression was significantly correlated with tumor size (P<0.001), depth of invasion (P<0.001), and of TNM stage (P<0.001). Restoration of RUNX3 significantly decreased renal carcinoma cell migration and invasion capacity compared with controls. In addition, we found that overexpression of RUNX3 reduced the proliferation and tube formation of human umbilical vascular endothelial cells (HUVECs). Gelatin zymography and Western blot showed that RUNX3 expression suppressed matrix metalloproteinase-9 (MMP-9) protein level and enzyme activity. Western blot and ELISA showed that RUNX3 restoration inhibited the expression and secretion of vascular endothelial growth factor (VEGF). Taken together, our studies indicate that decreased expression of RUNX3 in human RCC tissue is significantly correlated with RCC progression. Restoration of RUNX3 expression significantly inhibits RCC cells migration, invasion and angiogenesis. These findings provide new insights into the significance of RUNX3 in migration, invasion and angiogenesis of RCC.
To develop a quantitative PCR method for detecting hookworm infection and quantification.
A real-time PCR method was designed based on the intergenic region II of ribosomal DNA of the hookworm Necator americanus. The detection limit of this method was compared with the microscopy-based Kato-Katz method. The real-time PCR method was used to conduct an epidemiological survey of hookworm infection in southern Fujian Province of China.
The real-time PCR method was specific for detecting Necator americanus infection, and was more sensitive than conventional PCR or microscopy-based method. A preliminary survey for hookworm infection in villages of Fujian Province confirmed the high prevalence of hookworm infections in the resident populations. In addition, the infection rate in women was significantly higher than that of in men.
A real-time PCR method is designed, which has increased detection sensitivity for more accurate epidemiological studies of hookworm infections, especially when intensity of the infection needs to be considered.
Hookworm; Detection method; Epidemiology; Infection rate
A series of modifications have been introduced to the TNM staging system over time for nasopharyngeal carcinoma (NPC), mainly focused on the T (primary tumor) and N (local node) components of the system. The M1 stage is a ‘catch all’ classification, covering a group of patients whose outlook ranges from potentially curable to incurable. Since the current M1 stage does not allow clinicians to stratify patients according to prognosis or guide therapeutic decision-making and allow comparison of results of radical and non-radical treatments, we aimed to subdivide the M1 stage according to a retrospective study of 1027 metastatic NPC patients and to review the relevant literature. Between 1995 and 2007, 1027 inpatients with distant metastasis from NPC were retrospectively analyzed. Various possible subdivisions of the M1 stage were considered, looking at different metastatic sites, the number of metastatic organs and the number of metastases. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. The most frequently involved metastatic sites were the bone, lung and liver. The incidence rates of solitary metastatic lesions and pulmonary metastasis were 16.2 and 41.3%. Despite the poor survival of these patients with a median survival of 30.8 months, patients in the metachronous metastatic group with metastases to the lung and/or solitary lesions, were defined as M1a, and were significantly associated with favorable median survival of 41.5 and 49.1 months in the univariate and multivariate analysis, respectively. Patients in the metachronous metastatic group with metastasis to the lung and/or solitary lesions (M1a) have a more favorable prognosis compared with those patients with multiple metastases located in other anatomic sites (M1b). These data, in one of the largest reported metastatic NPC cohorts, are the first to show the prognostic impact of metastatic status in NPC. As a powerful predictor, the potential clinical value of a modified M1 of the TNM system for NPC will facilitate patient counseling and individualize management.
distant metastasis; M1 stage; nasopharyngeal carcinoma; metastatic survival; prognostic factors
Immunoglobulin A nephropathy (IgAN), an immune-complex-mediated glomerulonephritis defined immunohistologically by the presence of glomerular IgA deposits, is the most common primary glomerular disease worldwide and a significant cause of end-stage renal disease. Familial clustering of patients with IgAN suggests a genetic predisposition.
In this study, 192 patients with IgAN and 192 normal controls in the Sichuan cohort and 935 patients with IgAN and 2,103 normal controls in the Beijing cohort were investigated. HLA-DRB1*01–DRB1*10 specificities were genotyped by the PCR–SSP technique in both cohorts. Based on the HLA-DRB1*04-positive results, the subtypes of HLA-DRB1*04 were analyzed using sequencing-based typing (SBT) in 291 IgAN cases and 420 matched controls.
The frequency of HLA-DRB1*04 in the IgAN group was significantly higher than that in the control group (0.129 vs. 0.092, P = 8.29 × 10-5, odds ratio (OR) =1.381, 95% confidence interval (CI) 1.178–1.619). Other alleles at the HLA-DRB1 locus were observed with no significant differences between the case and control groups. The dominant alleles of the HLA-DRB1*04 subtypes were DRB1*0405 in both cohorts. The frequencies of HLA-DRB1*0405 and 0403 were significantly increased in the patients compared to healthy subjects.
HLA-DRB1*04 was significantly associated with primary IgAN in Chinese population. This result implies that HLA-DRB1 gene plays a major role in primary IgAN.
IgA nephropathy; HLA-DRB1; Association study
Metastasis is the main cause of cancer-related mortality; patients with liver metastases (LM) have the worst prognosis among patients with nasopharyngeal carcinoma (NPC). However, at present, few biomarkers for detecting organ-specific metastasis have been identified. Proteomics, an ultra-sensitive analytical technique, can detect molecular changes before organ-specific metastasis occurs. Analysis with matrix-assisted, laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), combined with magnetic chemical affinity beads is a new technique for evaluating protein separation. We sought to identify potential liver-specific, metastasis-associated proteomic printing in patients with NPC. We examined 64 serum samples from 50 patients who had pathologically confirmed NPC and 14 who had pathologically confirmed non-NPC with LM using MALDI-TOF-MS with weak cation bead protein chips. During follow-up of at least 37 months (maximum, 176 months) following radiotherapy, we confirmed 16 cases of LM (LM NPC), 16 cases without LM (non-LM NPC) and 18 cases without metastasis (non-M NPC). Using comparison analysis, 4 protein mass peaks, 4155.34, 4194.87, 4210.78 and 4249.56 m/z were identified as liver-specific, metastasis-associated protein peaks in NPC and two of them (4155 and 4249 m/z) met two different statistical criteria in both ClinProt software analyses and discriminant analyses. Models based on the 4 potential serum markers of NPC discriminated between LM NPC, non-LM NPC, non-M NPC and non-NPC LM analyzed with sieved markers. The recognition capability and cross-validation of these models for differentiating the above 4 groups are all approximately 80%. MALDI-TOF-MS combined with tree analysis models may provide a clinical diagnostic platform for detecting potential liver-specific, metastasis-associated proteomic printing in NPC. However, markedly differential proteins still need to be identified.
nasopharyngeal carcinoma; organ-specific metastasis; liver metastasis; proteomics
Erythropoietin (EPO) enhances angiogenesis in the ischemic brain. Stroke induces secretion of tumor necrosis factor α (TNF-α). We investigated the effect of TNF-α on EPO-induced in vitro angiogenesis in cerebral endothelial cells. Using a capillary-like tubular formation assay, we found that transient incubation of primary rat cerebral microvascular endothelial cells (RECs) with TNF-α substantially upregulated EPO receptor (EPOR) expression and addition of EPO into TNF-α-treated RECs significantly augmented the capillary-like tube formation. Blockage of TNF receptor 1 (TNFR1) suppressed TNF-α-upregulated EPOR expression and abolished EPO-induced tube formation. Attenuation of endogenous EPOR with small interfering RNA (siRNA) also inhibited EPO-enhanced tube formation. Treatment of RECs with EPO activated nuclear factor-kappa B (NF-κB) and Akt. Incubation of the TNF-α-treated endothelial cells with EPO activated vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), angiopoietin 1 (Ang1), and Tie2. Blockage of VEGFR2 and Tie2 resulted in reduction of EPO-augmented tube formation. These data indicate that interaction of TNF-α with TNFR1 sensitizes cerebral endothelial cells for EPO-induced angiogenesis by upregulation of EPOR, which amplifies the effect of EPO on activation of the VEGF/VEGFR2 and Ang1/Tie2 pathways. Our results provide the evidence for crosslink between TNF and EPOR to coordinate the onset of angiogenesis in cerebral endothelial cells.
angiogenesis; endothelial cell; EPO; EPO receptor; TNF-α
The expression of microRNA-206 (miR-206) is high in skeletal muscle but low in most other tissues. The expression of miR-206 is increased in muscular dystrophy, suggesting its involvement in the pathogenesis of muscle diseases. To determine the role of miR-206 in muscle cell differentiation and explore a possible gene therapy vector, we constructed a miR-206 adenoviral expression vector (AdvmiR-206) and tested for transfection into C2C12 stem cells.
A 355-bp PCR amplicon from C57B6 mouse skeletal muscle genomic DNA was inserted into the adenoviral shuttle vector pAdTrack-CMV, which was then co-transformed with the adenoviral backbone plasmid pAdEasy-1 into competent E. coli BJ5183 bacteria. The specificity and function of this recombinant adenoviral MiR-206 were studied in C2C12 cells by Northern blot, immunofluorescence, Western blot, and flow cytometry.
Increased expression of miR-206 in AdvmiR-206 transfected C2C12 cells (P<0.001) and resulted in morphological and biochemical changes over time that were similar to serum deprivation, including elongated cells and increased myosin heavy chain proteins. Even in the absence of serum deprivation, miR-206 overexpression accounted for a 50% reduction of S-phase cells (P<0.01). Moreover, in untransfected C2C12 cells, the introduction of miR-206-specific antisense oligoribonucleotides inhibited the normal response to serum deprivation. Twenty-four hours after lipofection of antisense oligoribonucleotides, the number of elongated cells was reduced by half (P<0.01).
Collectively, these data support a role for miR-206 in myoblast differentiation. We foresee potential applications for the AdvmiR-206 vector in research and therapy.
microRNA-206; myogenesis; C2C12 cells; adenoviral vector
Among the different extracellular virulence factors produced by Pseudomonas aeruginosa are exotoxin A (ETA) and the pyoverdine and pyochelin siderophores. Production of ETA and the siderophores requires the function of the iron-starvation sigma factor PvdS, the transcriptional activator RegA, and the AraC-activator PchR. Iron represses production of ETA and the siderophores by repressing expression of pvdS, regA, and pchR. PvdS regulates the expression of the ETA gene, toxA, regA, and the pyoverdine synthesis genes. The catecholamine norepinephrine (NE) enhances the growth of pathogenic bacteria by transferring iron from host binding proteins. In this study, we elucidated the mechanism by which NE and other catecholamines induce P. aeruginosa growth. We also investigated if NE regulates expression of toxA and the siderophore genes; and the mechanism of this regulation. NE enhanced the growth of P. aeruginosa by supplying iron from transferrin. This provision of iron repressed expression of toxA, the pyoverdine genes pvdD and pvdE, and their regulators, pvdS, regA, and pchR, suggesting that NE accomplishes this repression through PvdS and PchR. Additionally, NE bypassed PvdS and supported the growth of a pvdS deletion mutant indicating that NE transfers iron to P. aeruginosa independently of pyoverdine. Thus, NE apparently influences the pathogenesis of P. aeruginosa by affecting its pattern of growth and the production of virulence factors.
Stress-related catecholamines; Pseudomonas aeruginosa; gene regulation; siderophores
High myopia is a severe hereditary ocular disease leading to blindness. LAMA1 (alpha subunit of laminin) is a promising candidate gene for high myopia present in the MYP2 (myopia 2) region. The purpose of this study was to determine if high myopia is associated with single nucleotide polymorphism (SNP) variants in LAMA1 in Chinese subjects.
Ninety-seven Chinese subjects with high myopia and ethnically and sexually matched 103 normal controls were enrolled. Genomic DNA was prepared from peripheral blood. The 5 SNPs of LAMA1 were analyzed using PCR and SNaPshot. Allele frequencies were tested for Hardy–Weinberg disequilibrium. The genotype and allele frequencies were evaluated using the χ2 tests or the Fisher exact tests.
One of the 5 SNPs showed a significant difference between patients and control subjects (rs2089760: pgenotype=0.005, pallel=0.003). There were no statistically significant differences between patients and control subjects for the other four SNPs: rs566655, rs11664063, rs607230, and rs3810046.
Our results indicate that the polymorphism of rs2089760, located in the promoter region of LAMA1, may be associated with high myopia in the Chinese population and should be investigated further.
Fusarium species cause rare and severe infections. Their incidence is increasing in immunocompromised patients but they are also observed in healthy hosts. Because of the rapid dissemination of infection and the frequent resistance of Fusarium species to antifungal drugs, histopathologic evidence of hyphae is very helpful to obtain the diagnosis rapidly. We report the clinical and pathological features of two patients with initial cutaneous lesions. Cutaneous early biopsies showed microvessel involvement with hyphae and thrombosis. Fusarium infection was confirmed by skin culture. Hyphae within a microvessel thrombus in the skin were highly suggestive of disseminated fungal infection. These pathological features enabled to establish an early diagnosis and to start efficient antifungal treatment. In early cutaneous biopsies of immunocompromised patients, the presence of cutaneous vessel thrombosis can suggest a fungal infection and may help to start specific therapy without delay for these life-threatening infections.
Skin biopsy; Microvessel; Thrombosis; Fusarium
We designed the current study to determine the protective effects of lornoxicam, a cyclooxygenase (COX) inhibitor, on recurrent herpetic stromal keratitis (HSK) and the nuclear factor-κB (NF-κB)-mediated mechanism in mice.
A corneal latent herpes simplex virus-1 (HSV-1) infected mouse model was established. Six weeks later, Ultraviolet B (UVB) irradiation induced the recurrence. Corneal swabs were obtained and cultured with indicator cells to determine shedding of the virus. Lornoxicam was administered intraperitoneally daily, beginning one day before irradiation and lasting for seven days. Saline-treated and mock-infected control groups were also studied at the same time. Development of corneal inflammation and opacity was scored. Immunohistochemical staining and an electrophoretic mobility shift assay were performed to evaluate the effect of lornoxicam on NF-κB activation in the corneal tissues. The levels of tumor necrosis factor-α (TNF-α) in the cornea were determined by an enzyme-linked immunosorbent assay (ELISA).
HSV-1 reactivation induced stromal edema and opacification concomitantly with elevated activation of NF-κB and elevated production of TNF-α. Lornoxicam treatment significantly decreased the incidence of recurrent HSK, attenuated the corneal opacity scores, and also effectively suppressed both NF-κB activation and TNF-α expression in biological analysis. Histopathology examination revealed a reduced immunostaining positive cell density for NF-κB in the cornea from lornoxicam-treated mice as well as a diminished inflammatory response.
Lornoxicam exerts protective effects against HSK, presumably through the down-regulation of NF-κB activation.
Sorghum [Sorghum bicolor (L.) Moench] is ranked as the fifth most important grain crop and serves as a major food staple and fodder resource for much of the world, especially in arid and semi-arid regions. The recent surge in sorghum research is driven by its tolerance to drought/heat stresses and its strong potential as a bioenergy feedstock. Completion of the sorghum genome sequence has opened new avenues for sorghum functional genomics. However, the availability of genetic resources, specifically mutant lines, is limited. Chemical mutagenesis of sorghum germplasm, followed by screening for mutants altered in important agronomic traits, represents a rapid and effective means of addressing this limitation. Induced mutations in novel genes of interest can be efficiently assessed using the technique known as Targeting Induced Local Lesion IN Genomes (TILLING).
A sorghum mutant population consisting of 1,600 lines was generated from the inbred line BTx623 by treatment with the chemical agent ethyl methanesulfonate (EMS). Numerous phenotypes with altered morphological and agronomic traits were observed from M2 and M3 lines in the field. A subset of 768 mutant lines was analyzed by TILLING using four target genes. A total of five mutations were identified resulting in a calculated mutation density of 1/526 kb. Two of the mutations identified by TILLING and verified by sequencing were detected in the gene encoding caffeic acid O-methyltransferase (COMT) in two independent mutant lines. The two mutant lines segregated for the expected brown midrib (bmr) phenotype, a trait associated with altered lignin content and increased digestibility.
TILLING as a reverse genetic approach has been successfully applied to sorghum. The diversity of the mutant phenotypes observed in the field, and the density of induced mutations calculated from TILLING indicate that this mutant population represents a useful resource for members of the sorghum research community. Moreover, TILLING has been demonstrated to be applicable for sorghum functional genomics by evaluating a small subset of the EMS-induced mutant lines.
Tong-Xin-Luo (TXL) – a mixture of herbal extracts, has been used in Chinese medicine with established therapeutic efficacy in patients with coronary artery disease.
We investigated the protective role of TXL extracts on endothelial cells injured by a known risk factor – palmitic acid (PA), which is elevated in metabolic syndrome and associated with cardiovascular complications. Human aortic endothelial cells (HAECs) were preconditioned with TXL extracts before exposed to PA for 24 hours.
We found that PA (0.5 mM) exposure induced 73% apoptosis in endothelial cells. However, when HAECs were preconditioned with ethanol extracted TXL (100 μg/ml), PA induced only 7% of the endothelial cells into apoptosis. Using antibody-based protein microarray, we found that TXL attenuated PA-induced activation of p38-MAPK stress pathway. To investigate the mechanisms involved in TXL's protective effects, we found that TXL reduced PA-induced intracellular oxidative stress. Through AMPK pathway, TXL restored the intracellular antioxidant system, which was depressed by the PA treatment, with an increased expression of thioredoxin and a decreased expression of the thioredoxin interacting protein.
In summary, our study demonstrates that TXL protects endothelial cells from PA-induced injury. This protection is likely mediated by boosting intracellular antioxidant capacity through AMPK pathway, which may account for the therapeutic efficacy in TXL-mediated cardiovascular protection.
Tumor necrosis factor alpha (TNFα) is implicated in a wide variety of pathological and physiological processes, including chronic inflammatory conditions, coronary artery disease, diabetes, obesity, and cachexia. Transgenic mice expressing human TNFα (hTNFα) have previously been described as a model for progressive rheumatoid arthritis. In this report, we describe extensive characterization of an hTNFα transgenic mouse line.
In addition to arthritis, these hTNFα transgenic mice demonstrated major alterations in body composition, metabolic rate, leptin levels, response to a high-fat diet, bone mineral density and content, impaired fertility and male sexual function. Many phenotypes displayed an earlier onset and a higher degree of severity in males, pointing towards a significant degree of sexual dimorphism in response to deregulated expression of TNFα.
These results highlight the potential usefulness of this transgenic model as a resource for studying the progressive effects of constitutively expressed low levels of circulating TNFα, a condition mimicking that observed in a number of human pathological conditions.