"Double-edged sword" effect of reactive oxygen species (ROS) in tumor development and carcinogenesis.

Reactive oxygen species (ROS) are small reactive molecules produced by cellular metabolism and regulate various physiological and pathological functions. Many studies have shown that ROS plays an essential role in the proliferation and inhibition of tumor cells. Different concentrations of ROS can have a "double-edged sword" effect on the occurrence and development of tumors. A certain concentration of ROS can activate growth-promoting signals, enhance the proliferation and invasion of tumor cells, and cause damage to biomacromolecules such as proteins and nucleic acids. However, ROS can enhance the body's antitumor signal at higher levels by initiating oxidative stress-induced apoptosis and autophagy in tumor cells. This review analyzes ROS's unique bidirectional regulation mechanism on tumor cells, focusing on the key signaling pathways and regulatory factors that ROS affect the occurrence and development of tumors and providing ideas for an in-depth understanding of the mechanism of ROS action and its clinical application.

[Clinical observation of drug-coated balloon in the treatment of lower extremity arterial long segment lesions].

Objective: To observe the efficacy of drug -coated balloon (DCB) in the treatment of long -segment arterial stenosis in lower extremity. Methods: Were retrospectively analyzed in February 2017 to January 2018,the First Hospital Affiliated to China Medical University of vascular surgical treated 80 patients with lower limb sclerosis of arterial congee appearance (lesion length>10 cm), accept the DCB and stents (BMS) treatment, compared two groups of patients with preoperative and postoperative issue patency rate of target lesion, ABI, Rutherford, amputation rate and the change of clinical symptoms and quality of life. Results: There were 60 cases in DCB group,20 cases in BMS group and 80 cases in BMS group. The patency rate of DCB group was 83.33% and 75.00% at 6 and 12 months after operation. The patency rate was 85.00% and 65.00% in the BMS group at 6 and 12 months after surgery. ABI, walking distance, Rutherford grade and clinical symptoms were significantly improved in the two groups compared with those before surgery. During the operation, 1 patient in the DCB group presented flow limiting interlayer and 1 patient still had>50% stenosis after predilation, and then underwent stent implantation for remediation. Conclusion: The treatment of lower limb arterial stenosis with DCB can obtain better near -and medium-term clinical efficacy.

[Clinical and pathological differences between papillary thyroid carcinoma with Graves' disease and papillary thyroid carcinoma with Hashimoto's thyroiditis].

Objective: To explore the clinical and pathological differences between papillary thyroid carcinoma (PTC) with Graves' disease (GD) and PTC with Hashimoto's thyroiditis (HT). Methods: A total of 33 PTC patients with GD and 132 PTC patients with HT in the First Affiliated Hospital of China Medical University from January 2009 to December 2015 were enrolled. The clinical and histopathological data were analyzed. Results: The average serum concentration of thyroid stimulating hormone (TSH) of PTCs with GD was significantly lower than PTCs with HT [0.01 (0, 0.10) mU/L vs 2.28(1.51, 3.14) mU/L, P<0.001]. However, there was no significant difference between the two groups in nodule diameter [(15.7±7.0) mm vs (13.5±7.8)mm, P=0.14], percentage of lymph node metastasis (LNM) [33.3%(11/33) vs 39.4%(52/132), P=0.52], TNM stage Ⅲ-Ⅳ disease [12.1%(4/33) vs 11.4% (15/132), P=1.00], papillary thyroid micro-carcinoma (PTMC) [60.6% (20/33) vs 60.6%(80/132), P=1.00]and classic PTC in all its variant patterns [81.8%(27/33) vs 75.0%(99/132), P=0.36]. The age (P<0.01, OR=0.95, 95%CI: 0.92-0.98) and PTMC (P<0.01, OR=0.30, 95%CI: 0.13-0.67), rather than TSH (P=0.08) were independently correlated with LNM. Recurrence rate of PTC with GD was significantly lower than PTC with HT (log-rank test, P=0.03). In Cox proportional hazards regression model, variant pattern of PTC was independently correlated with recurrence rate (P<0.05). Conclusions: GD with PTC wasn't different from HT concomitant with PTC, except for thyroid function test. In addition, recurrence rate of PTC with GD was lower than that of PTC with HT after controlling TSH in the same level.

Complete molecular remission in relapsed and refractory acute myeloid leukaemia with MLL-AF9 treated with chidamide-based chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: The mixed lineage leukaemia (MLL) gene translocations are found in approximately 10% of adults with acute myeloid leukaemia (AML) and are markers of poor prognosis. As the best reported response in relapsed and refractory MLL-rearranged AML is around 40%, reinduction treatment is very challenging for those patients. CASE DESCRIPTION: We report a case of relapsed and refractory AML with MLL-AF9, who did not respond to FLAG (fludarabine, cytarabine, granulocyte colony stimulating factor) regimen reinduction treatment, but achieved complete response and molecular remission after chidamide-based chemotherapy. WHAT IS NEW AND CONCLUSION: Chidamide (CS055/HBI-8000) is a new histone deacetylase (HDAC) inhibitor that is clinically active in relapsed and refractory peripheral T-cell lymphomas. To the best of our knowledge, successful reinduction treatment on relapsed MLL-AF9 by chidamide-based regimen has not been previously reported.

Downregulation of SWI5 and CTC1 genes: hepatitis B virus DNA polymerase transactivated protein 1-mediated inhibition of DNA repair.

Hepatitis B virus (HBV) DNA polymerase transactivated protein 1 (HBVDNAPTP1) is a novel protein upregulated by HBV DNA polymerase, which has been screened by suppression subtractive hybridization technique (SSH) (GenBank Acc. No. AY450389). A vector pcDNA3.1 (-)/myc-His A-HBVDNAPTP1 was constructed and used to transfect acute monocytic leukemia cell line THP-1. HBVDNAPTP1 expression was detected by Western blot analysis in the cells. A cDNA library of genes downregulated by HBVDNAPTP1 in THP-1 cells was made in pGEM-T Easy using SSH. The cDNAs were sequenced and analyzed with BLAST search against the sequences in GenBank. Some sequences, such as DNA repair protein SWI5 homolog (SWI5) and CTS telomere maintenance complex component 1 (CTC1), might be involved in DNA repair. Protein expression of SWI5 and CTC1 was identified by Western blot in THP-1 cells. HBVDNAPTP1 could downregulate the expression of SWI5 and CTC1 at translation level.

The effects of flow on schooling Devario aequipinnatus: school structure, startle response and information transmission.

To assess how flow affects school structure and threat detection, startle response rates of solitary and small groups of giant danio Devario aequipinnatus to visual looming stimuli were compared in flow and no-flow conditions. The instantaneous position and heading of each D. aequipinnatus was extracted from high-speed videos. Behavioural results indicate that (1) school structure is altered in flow such that D. aequipinnatus orient upstream while spanning out in a crosswise direction, (2) the probability of at least one D. aequipinnatus detecting the visual looming stimulus is higher in flow than no flow for both solitary D. aequipinnatus and groups of eight D. aequipinnatus; however, (3) the probability of three or more individuals responding is higher in no flow than in flow. These results indicate a higher probability of stimulus detection in flow but a higher probability of internal transmission of information in no flow. Finally, results were well predicted by a computational model of collective fright response that included the probability of direct detection (based on signal detection theory) and indirect detection (i.e. via interactions between group members) of threatening stimuli. This model provides a new theoretical framework for analysing the collective transfer of information among groups of fishes and other organisms.

Effects of national culture on human failures in container shipping: the moderating role of Confucian dynamism.

Recent reports on work safety in container shipping operations highlight high frequencies of human failures. In this study, we empirically examine the effects of seafarers' perceptions of national culture on the occurrence of human failures affecting work safety in shipping operations. We develop a model adopting Hofstede's national culture construct, which comprises five dimensions, namely power distance, collectivism/individualism, uncertainty avoidance, masculinity/femininity, and Confucian dynamism. We then formulate research hypotheses from theory and test the hypotheses using survey data collected from 608 seafarers who work on global container carriers. Using a point scale for evaluating seafarers' perception of the five national culture dimensions, we find that Filipino seafarers score highest on collectivism, whereas Chinese and Taiwanese seafarers score highest on Confucian dynamism, followed by collectivism, masculinity, power distance, and uncertainty avoidance. The results also indicate that Taiwanese seafarers have a propensity for uncertainty avoidance and masculinity, whereas Filipino seafarers lean more towards power distance, masculinity, and collectivism, which are consistent with the findings of Hofstede and Bond (1988). The results suggest that there will be fewer human failures in container shipping operations when power distance is low, and collectivism and uncertainty avoidance are high. Specifically, this study finds that Confucian dynamism plays an important moderating role as it affects the strength of associations between some national culture dimensions and human failures. Finally, we discuss our findings' contribution to the development of national culture theory and their managerial implications for reducing the occurrence of human failures in shipping operations.

Cloning, expression and identification of the gene of human single-chain variable fragment antibody against Hepatitis B virus surface antigen.

Expression of single-chain variable fragment (scFv) antibodies on the surface of bacteriophage is widely used to prepare antibodies with pre-defined specificities. A phage antibody library containing the gene for scFv antibody against Hepatitis B virus surface antigen (HBsAg) was panned with HBsAg immobilized on microtiter plate wells. After five rounds of panning 30 phage clones specific to HBsAg were obtained and one selected clone was sequenced. It was found to consist of 789 bp and its amino acid sequence and specifically detected the respective antigen in the patients but not in healthy persons.

Targeted Disruption of the Myocilin Gene (Myoc) Suggests that Human Glaucoma-Causing Mutations Are Gain of Function.

Glaucoma is a heterogeneous eye disease and a major cause of blindness worldwide. Recently, primary open angle glaucoma (POAG)-associated mutations have been found in the trabecular meshwork inducible glucocorticoid response gene (TIGR), also known as the myocilin gene (MYOC), at the GLC1A locus on chromosome 1q21-q31. These mutations occurred in a subset of patients with juvenile- and adult-onset POAG and exhibited autosomal dominant inheritance. Ocular expression and its involvement in POAG suggest that TIGR/MYOC may have a role(s) in regulating intraocular pressure (IOP). Here, we report the generation and analysis of mice heterozygous and homozygous for a targeted null mutation in Myoc. Our study shows that Myoc mutant mice are both viable and fertile. Our in vivo findings further demonstrate that Myoc is not required for normal IOP or normal ocular morphology. The lack of a discernable phenotype in both Myoc-heterozygous and Myoc-null mice suggests that haploinsufficiency is not a critical mechanism for POAG in individuals with mutations in MYOC. Instead, disease-causing mutations in humans likely act by gain of function.

Identification and expression of a novel family of bHLH cDNAs related to Drosophila hairy and enhancer of split.

In this report we describe the initial characterization of murine, human, and Drosophila hesr-1 (for hairy and enhancer of split related-1) a novel evolutionary conserved family of hairy/enhancer of split homologs. Hesr-1 cDNAs display features typical of hairy and enhancer of split-type bHLH proteins including a N-terminal bHLH domain a conserved orange domain immediately C-terminal to the bHLH region. Despite their similarity to known hairy/enhancer of split homologs, hesr-1 cDNAs are divergent members of the hairy and enhancer of split bHLH family since the degree of sequence identity within the bHLH and their nearest homologs are relatively low. Moreover, the tetrapeptide motif, WRPW, which is found in all hairy and enhancer of split family members, is not present in hesr-1. Rather, a variant of this motif, YRPW, is found. Analysis of embryonic murine hesr-1 expression by in situ hybridization reveals strong expression in the somitic mesoderm, the central nervous system, the kidney, the heart, nasal epithelium, and limbs indicating a role for hesr-1 in the development of these tissues. Like the enhancer of split cDNAs in Drosophila, we show that hesr-1 expression depends critically on signaling through the notch pathway in murine embryos, suggesting that aspects of hesr-1 regulation and function might also be evolutionary conserved.

lunatic fringe is an essential mediator of somite segmentation and patterning.

The gene lunatic fringe encodes a secreted factor with significant sequence similarity to the Drosophila gene fringe. fringe has been proposed to function as a boundary-specific signalling molecule in the wing imaginal disc, where it is required to localize signalling activity by the protein Notch to the presumptive wing margin. By targeted disruption in mouse embryos, we show here that lunatic fringe is likewise required for boundary formation. lunatic fringe mutants fail to form boundaries between individual somites, the initial segmental unit of the vertebrate trunk. In addition, the normal alternating rostral-caudal pattern of the somitic mesoderm is disrupted, suggesting that intersomitic boundary formation and rostral-caudal patterning of somites are mechanistically linked by a process that requires lunatic fringe activity. As a result, the derivatives of the somitic mesoderm, especially the axial skeleton, are severely disorganized in lunatic fringe mutants. Taken together, our results demonstrate an essential function for a vertebrate fringe homologue and suggest a model in which lunatic fringe modulates Notch signalling in the segmental plate to regulate somitogenesis and rostral-caudal patterning of somites simultaneously.

Multiple calvarial defects in lmx1b mutant mice.

The vertebrate cranial vault, or calvaria, forms during embryonic development from cranial mesenchyme of multiple embryonic origins. Inductive interactions are thought to specify the number and location of the calvarial bones, including interactions between the neuroepithelium and cranial mesenchyme. An important feature of calvarial development is the local inhibition of osteogenic potential which occurs between specific bones and results in the formation of the cranial sutures. These sutures allow for postnatal growth of the skull to accommodate postnatal increase in brain size. The molecular genetic mechanisms responsible for the patterning of individual calvarial bones and for the specification of the number and location of sutures are poorly understood at the molecular genetic level. Here we report on the function and expression pattern of the LIM-homeodomain gene, lmx1b, during calvarial development. Lmx1b is expressed in the neuroepithelium underlying portions of the developing skull and in cranial mesenchyme which contributes to portions of the cranial vault. Lmx1b is essential for proper patterning and morphogenesis of the calvaria since the supraoccipital and interparietal bones of lmx1b mutant mice are either missing or severely reduced. Moreover, lmx1b mutant mice have severely abnormal sutures between the frontal, parietal, and interparietal bones. Our results indicate that lmx1b is required for multiple events in calvarial development and suggest possible genetic interaction with other genes known to regulate skull development and suture formation.

Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome.

Dorsal-ventral limb patterning in vertebrates is thought to be controlled by the LIM-homeodomain protein Lmx1b which is expressed in a spatially and temporally restricted manner along the dorsal-ventral limb axis. Here we describe the phenotype resulting from targeted disruption of Lmx1b. Our results demonstrate that Lmx1b is essential for the specification of dorsal limb fates at both the zeugopodal and autopodal level with prominent phenotypes including an absence of nails and patellae. These features are similar to those present in a dominantly inherited human condition called nail patella syndrome (NPS), which also has renal involvement. Mouse Lmx1b maps to a region syntenic to that of the NPS gene, and kidneys of Lmx1b mutant mice exhibit pathological changes similar to that observed in NPS (refs 5,6). Our results demonstrate an essential function for Lmx1b in mouse limb and kidney development and suggest that NPS might result from mutations in the human LMX1B gene.

Autoactivation of Xenopus MyoD transcription and its inhibition by USF.

Members of the MyoD family of muscle-specific transcription factors play central roles in the formation and differentiation of skeletal muscle; however, steps involved in the initiation and subsequent regulation of myogenic factor expression are poorly understood. To investigate mechanisms underlying muscle cell type-specific MyoD gene expression, the functions of regulatory elements that control Xenopus MyoDa gene transcription were analyzed. We show that E boxes in the XMyoDa promoter have dual functions. These sites bind myogenic basic helix-loop-helix proteins and serve as target sites for direct autoactivation. In addition, these regulatory elements bind other, more widely expressed proteins that repress promoter activity. In particular, the binding of the transcriptional regulatory protein USF to a conserved site in the XMyoDa promoter decreased basal activity of the promoter and inhibited MyoD-dependent autoactivation. The results suggest that XMyoD transcription and myogenic factor activity is governed by a competition between muscle-specific, positive-acting factors and widely expressed repressors for binding to common regulatory sites.