ABSTRACT
Over 400,000 people are estimated to have been exposed to World Trade Center particulate matter (WTCPM) since the attack on the Twin Towers in Lower Manhattan on September 11, 2001. Epidemiological studies have found that exposure to dust may cause respiratory ailments and cardiovascular diseases. However, limited studies have performed a systematic analysis of transcriptomic data to elucidate the biological responses to WTCPM exposure and the therapeutic options. Here, we developed an in vivo mouse exposure model of WTCPM and administered two drugs (i.e., rosoxacin and dexamethasone) to generate transcriptomic data from lung samples. WTCPM exposure increased the inflammation index, and this index was significantly reduced by both drugs. We analyzed the transcriptomics derived omics data using a hierarchical systems biology model (HiSBiM) with four levels, including system, subsystem, pathway, and gene analyses. Based on the selected differentially expressed genes (DEGs) from each group, WTCPM and the two drugs commonly affected the inflammatory responses, consistent with the inflammation index. Among these DEGs, the expression of 31 genes was affected by WTCPM exposure and consistently reversed by the two drugs, and these genes included Psme2, Cldn18, and Prkcd, which are involved in immune- and endocrine-related subsystems and pathways such as thyroid hormone synthesis, antigen processing and presentation, and leukocyte transendothelial migration. Furthermore, the two drugs reduced the inflammatory effects of WTCPM through distinct pathways, e.g., vascular-associated signaling by rosoxacin, whereas mTOR-dependent inflammatory signaling was found to be regulated by dexamethasone. To the best of our knowledge, this study constitutes the first investigation of transcriptomics data of WTCPM and an exploration of potential therapies. We believe that these findings provide strategies for the development of promising optional interventions and therapies for airborne particle exposure.
Subject(s)
Particulate Matter , Pneumonia , Mice , Animals , Particulate Matter/toxicity , Transcriptome , Dust/analysis , Inflammation , Dexamethasone/toxicity , Proteasome Endopeptidase ComplexABSTRACT
Between September to October 1985, 61 male patients with uncomplicated genital gonorrhea, including 33 PPNG urethritis, were treated with single oral dose of rosoxaci, a new oral quinolone derivative, 300 mg Fifty-three patients returned for a test of cure 3 5 days after the treatment. When a patient was found to be not cured, a second course of treatment was given and followed as above. The overall failure rate of initial treatment was 11.3%(6/53). It was 15. 2%(5/33) for PPNG urethritis and 5%(1/20) for non-PPNG urethritis. During the course of this trial the rate af PPNG among pretreatment isolates was exceptionally high(62.2g) compared to 277. during the period of 198l~4. If the PPNG prevalance rate had been a little lower, for instance 30g the overall failure rate would have been much lower(4.9%). When the second treatment was given to the failure cases 4-6 days after the first treatment. The overall failure rate dropped to 3.8%, 3.1% for PPNG urethritis and 5.0% for non-PPNG urethritis. Ten patients (2l, 3p,) developed postgoriococcal urethritie. Susceptibility test, with disks containing rosoxacin 5mcg, showed the inhibition zone to be greater than 34mm. Eight patients developed minor side effects: dizziness or gastritis. The rosoxacin, oral dose of 300 mg, regimen gave the best result yet by oral treatment for gonorrheae in recent years in Korea.
Subject(s)
Humans , Male , Dizziness , Gastritis , Gonorrhea , Korea , UrethritisABSTRACT
Fourty gonococcal urethritis patients were treated with Rosoxacin at the Department of Urology, National Police Hospital from December, 1982 to April, 1983. All patients were male and confirmed as acute gonococcal urethritis by Gram stain and culture. A new bactericidal agent, Rosoxacin, was administered orally in a single dose of 300mg in 40 cases of acute gonococcal urethritis and following results were obtained. 1. Gram negative intracellular diplococci were controlled in 30 patients (100%) among 30 patients with pure gonococcal infection with a single oral dose of Rosoxacin. 2. 7 patients (23.3%) of 30 patients with pure gonococcal infection were revealed to nonspecific urethritis, and they were treated with other antibiotics. 3. Gram negative intracellular diplococci were controlled in 10 patients (100%) among 10 mixed infected patients with a single dose of Rosoxacin. 4. 8 patients (80%) of 10 patients with mixed infection were revealed to nonspecific urethritis, and they were treated with other antibiotics. 5. There was no side effect of Rosoxacin in all patients.