Trends in Head and Neck Cancer Mortality from 1999 to 2019 in Japan : An Observational Analysis

The number of cases of head and neck cancer (HNC) and related deaths has recently increased worldwide. To the best of our knowledge, few studies have examined crude or age-adjusted HNC mortality rates in Japan. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. In Japan, the number of HNC-related deaths increased 1.48-fold. Age-adjusted mortality rates for HNC were four times higher in men than in women, and the rates for both men and women decreased over the 21-year period. This study clarifies the changes in age-adjusted mortality rates of HNC in Japan over time and will aid in developing targeted screening and prevention programs for HNC.Globally, the numbers of head and neck cancer (HNC) cases and related deaths have recently increased. In Japan, few studies have examined crude or age-adjusted HNC mortality rates. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. Data on HNC-associated deaths were extracted from the national death certificate database using the International Classification of Diseases, Tenth Revision (n = 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of −0.7% in men and −0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies

A Role of Aromatase in Sjögren Syndrome

Several autoimmune diseases are known to develop in postmenopausal women. However, the mechanism by which estrogen deficiency influences autoimmunity is unknown. Aromatase is a converting enzyme from androgens to estrogens. In the present study, we used female aromatase gene knockout (ArKO) mice as a model of estrogen deficiency to investigate the molecular mechanism that underlies the onset and development of autoimmunity. Histological analyses showed that inflammatory lesions in the lacrimal and salivary glands of ArKO mice increased with age. Adoptive transfer of spleen cells or bone marrow cells from ArKO mice into recombination activating gene 2 knockout mice failed to induce the autoimmune lesions. Expression of mRNA encoding proinflammatory cytokines and monocyte chemotactic protein-1 (MCP-1) increased in white adipose tissue (WAT) of ArKO mice and was significantly higher than that in wild-type mice. Moreover, an increased number of inflammatory M-1 macrophage was observed in WAT of ArKO mice. A significantly increased MCP-1 mRNA expression of the salivary gland tissue in ArKO was found together with adiposity. Furthermore, the autoimmune lesions in a murine model of Sjögren’s syndrome (SS) were exacerbated by administration of an aromatase inhibitor. These results suggest that aromatase may play in a key role in the pathogenesis of SS-like lesions by controlling the target organ and adipose tissue-associated macrophage

Blocking of interferon regulatory factor 1 reduces tumor necrosis factor α–induced interleukin‐18 bioactivity in rheumatoid arthritis synovial fibroblasts by induction of interleukin‐18 binding protein a: Role of the nuclear interferon regulatory factor 1–NF‐κB–c‐jun complex

Objective To examine the role of interferon regulatory factor 1 (IRF‐1) in tumor necrosis factor α (TNFα)–induced interleukin‐18 binding protein a (IL‐18BPa) expression in rheumatoid arthritis synovial fibroblasts (RASFs). Methods TNFα‐induced IRF‐1 expression was assessed by real‐time quantitative polymerase chain reaction and Western blotting. The effect of TNFα on IRF‐1 was assessed using nuclear and cytoplasmic extracts, Western blots, and immunofluorescence. Chemical inhibitors of NF‐κB or MAP kinases were used to analyze the signaling pathways of TNFα‐induced IRF‐1 expression and IRF‐1 nuclear translocation. Control and IRF‐1 small interfering RNA (siRNA) were used to analyze the effect of IRF‐1 down‐regulation on TNFα‐induced IL‐18BP expression. IL‐18BPa expression was assessed by enzyme‐linked immunosorbent assay, and IL‐18 was assessed at the transcription and bioactivity levels using KG‐1 cells. Results TNFα induced RASF IRF‐1 expression at the messenger RNA and protein levels, with a maximal effect at 2 hours ( P < 0.05; n ≥ 3). Furthermore, TNFα induced nuclear translocation of IRF‐1, with maximal translocation at 2 hours (∼6 fold‐induction) ( P < 0.05; n = 4). Blocking of the NF‐κB or JNK‐2 pathways reduced TNFα‐induced IRF‐1 nuclear translocation by 35% and 50%, respectively ( P < 0.05; n ≥ 4). Using siRNA to knock down IRF‐1, we observed reduced IL‐18BPa expression. Additionally, IL‐18 bioactivity was higher when siRNA was used to knock down IRF‐1 expression. Conclusion These results show that IRF‐1 is a key regulator of IL‐18BPa expression and IL‐18 bioactivity in RASFs. Regulation of IRF‐1 will be a new therapeutic target in RA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88092/1/30583_ftp.pd

NADPH oxidases in cardiovascular disease: insights from in vivo models and clinical studies

NADPH oxidase family enzymes (or NOXs) are the major sources of reactive oxygen species (ROS) that are implicated in the pathophysiology of many cardiovascular diseases. These enzymes appear to be especially important in the modulation of redox-sensitive signalling pathways that underlie key cellular functions such as growth, differentiation, migration and proliferation. Seven distinct members of the family have been identified of which four (namely NOX1, 2, 4 and 5) may have cardiovascular functions. In this article, we review our current understanding of the roles of NOX enzymes in several common cardiovascular disease states, with a focus on data from genetic studies and clinical data where available

Power-Aware Resource Allocation with Guaranteeing Fair QoS

In real-time systems, the execution of tasks with higher Quality of Service (QoS) requires larger resources and higher frequency in CPUs. Dynamic power-aware resource management using dynamic voltage scaling technique is needed to resolve a trade-o# between the QoS maximization and the energy consumption minimization. By taking into the consideration a fairness of QoS levels of all tasks, we formulate the trade-o# as a mathematical programming problem called FQ-PARA (Fair QoS-based Power-Aware Resource Allocation problem). The problem is described by two variables: the QoS level of tasks and the voltage of CPUs. Moreover, under a certain condition, it is reduced to the minimization of a single variable function

Adaptive Resource Allocation Control with

Recently, applications of control theory to avoid overload conditions have been studied. But, in conventional feedback theory, control input is determined by an error between a reference value of a controlled signal and its current value. In real-time systems, a set of active tasks may be time-varying so that the reference value may change according to the set. In this paper, we proposed a novel control method for a fair resource allocation and QoS levels of tasks are used as controlled signals. The proposed adaptation controller allocates a CPU utilization factor to each task with on-line search for the fair QoS level, and the proposed control rule is based on errors between the current QoS levels and their average. Its computation time is small so that it does not yield a heavy overhead

Expression, Purification, and Characterization of AknX Anthrone Oxygenase, Which Is Involved in Aklavinone Biosynthesis in Streptomyces galilaeus

In streptomycete anthracycline biosynthetic gene clusters, small open reading frames are located just upstream of minimal polyketide synthase genes. aknX is such a gene found in the aklavinone-aclacinomycin biosynthetic gene cluster of Streptomyces galilaeus. In order to identify its function, the aknX gene was expressed in Escherichia coli. The cell extract prepared from E. coli cells overexpressing AknX protein exhibited anthrone oxygenase activity, which converted emodinanthrone to anthraquinone emodin. This indicates that AknX and related gene products such as DnrG and SnoaB are involved in the formation of aklanonic acid from its anthrone precursor, as suggested by their homology with TcmH and ActVA6. The AknX protein fused with a His(6) tag was efficiently purified to homogeneity by Ni(2+) affinity and anion-exchange column chromatography. The native molecular mass of AknX was estimated to be 42 kDa by gel filtration. Thus, native AknX is considered to have a homotrimeric subunit structure. AknX, like TcmH and ActVA6, possesses no apparent prosthetic group for oxygen activation. Site-directed mutagenesis was carried out to identify the key amino acid residue(s) involved in the oxygenation reaction. Of seven AknX mutants expressed, the W67F mutant showed significantly reduced oxygenase activity, suggesting the important role of the W67 residue in the AknX reaction. A possible mechanism for the reaction via peroxy anion intermediate is proposed