Attributable fraction of tobacco smoking on cancer using population-based nationwide cancer incidence and mortality data in Korea

Smoking is by far the most important cause of cancer that can be modified at the individual level. Cancer incidence and mortality rates in Korea are the highest among all Asian countries, and smoking prevalence in Korean men is one of the highest in developed countries. The purpose of the current study was to perform a systematic review and provide an evidence-based assessment of the burden of tobacco smoking-related cancers in the Korean population. Sex- and cancer-specific population-attributable fractions (PAF) were estimated using the prevalence of ever-smoking and second-hand smoking in 1989 among Korean adults, respectively, and the relative risks were estimated from the meta-analysis of studies performed in the Korean population for ever-smoking and in the Asian population for passive smoking. National cancer incidence data from the Korea Central Cancer Registry and national cancer mortality data from Statistics Korea for the year 2009 were used to estimate the cancer cases and deaths attributable to tobacco smoking. Tobacco smoking was responsible for 20,239 (20.9%) cancer incident cases and 14,377 (32.9%) cancer deaths among adult men and 1,930 (2.1%) cancer incident cases and 1,351 (5.2%) cancer deaths among adult women in 2009 in Korea. In men, 71% of lung cancer deaths, 55%-72% of upper aerodigestive tract (oral cavity, pharynx, esophagus and larynx) cancer deaths, 23% of liver, 32% of stomach, 27% of pancreas, 7% of kidney and 45% of bladder cancer deaths were attributable to tobacco smoking. In women the proportion of ever-smoking-attributable lung cancer was 8.1%, while that attributable to second-hand smoking among non-smoking women was 20.5%. Approximately one in three cancer deaths would be potentially preventable through appropriate control of tobacco smoking in Korean men at the population level and individual level. For Korean women, more lung cancer cases and deaths were attributable to second-hand than ever-smoking. Effective control programs against tobacco smoking should be further developed and implemented in Korea to reduce the smoking-related cancer burden

Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation

The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as markers of goblet cell metaplasia in lung pathologies. The aim of this study was to investigate the effects of silver NPs on VEGF signaling pathways and mucus hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate the role of silver NPs and the related molecular mechanisms in allergic airway disease. In this study, with an OVA-induced murine model of allergic airway disease, it was found that the increased levels of hypoxia-inducible factor (HIF)-1α, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels, and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially decreased by the administration of silver NPs. In summary, silver NPs substantially suppressed mucus hypersecretion and PI3K/HIF-1α/VEGF signaling pathway in an allergic airway inflammation

Indicators of severe prognosis of scrub typhus: prognostic factors of scrub typhus severity

Abstract Background Scrub typhus is an acute disease, characterized by symptoms of fever, which occurs due to infection by Orientia tsutsugamushi. In most cases, patients recover from the disease with appropriate treatment, but serious and fatal complications may occur. The present study examined laboratory findings and tumor necrosis factor-alpha (TNF-α) levels of scrub typhus patients to identify the prognostic predictors of disease severity. Method Patients whose scrub typhus diagnosis was confirmed by elevated indirect fluorescent antibody (IFA) levels and positive polymerase chain reaction (PCR) results were classified according to disease severity into one of three groups; i.e., deceased (n = 7), severe (n = 15), and mild (n = 15) retrospectively registered. Additionally, the usefulness of modified Acute Physiology and Chronic Health Evaluation II (APACHE II) score, C-reactive protein (CRP) level, white blood cell (WBC) count, and TNF-α level as prognostic predictors were examined. Result The mean TNF-α levels of the deceased, severe, and mild groups were 53.5 (range: 7.8–147.8), 26.0 (1.7–64.4), and 8.8 pg/mL (4.6–16.0), respectively. The results of Kruskal-Wallis tests showed statistically significant differences between the deceased and severe groups versus the mild group (p = 0.005). CRP level and Modified APACHE II score also differed significantly among the groups (p = 0.046 and 0.007, respectively); however, WBC count did not (p = 0.196). Conclusion An elevated serum TNF-α level in patients with scrub typhus could predict a severe condition or death and may be useful in predicting patient prognosis

miR146a-mediated Targeting of FANCM during Inflammation Compromises Genome Integrity

Inflammation is a potent inducer of tumorigenesis. Increased DNA damage or loss of genome integrity is thought to be one of the mechanisms linking inflammation and cancer development. It has been suggested that NF-κB-induced microRNA-146 (miR146a) may be a mediator of the inflammatory response. Based on our initial observation that miR146a overexpression strongly increases DNA damage, we investigated its potential role as a modulator of DNA repair. Here, we demonstrate that FANCM, a component in the Fanconi Anemia pathway, is a novel target of miR146a. miR146a suppressed FANCM expression by directly binding to the 3’ untranslated region of the gene. miR146a-induced downregulation of FANCM was associated with inhibition of FANCD2 monoubiquitination, reduced DNA homologous recombination repair and checkpoint response, failed recovery from replication stress, and increased cellular sensitivity to cisplatin. These phenotypes were recapitulated when miR146a expression was induced by overexpressing the NF-κB subunit p65/RelA or Helicobacter pylori infection in a human gastric cell line; the phenotypes were effectively reversed with an anti-miR146a antagomir. These results suggest that undesired inflammation events caused by a pathogen or over-induction of miR146a can impair genome integrity via suppression of FANCM

miR146a-mediated Targeting of FANCM during Inflammation Compromises Genome Integrity

Inflammation is a potent inducer of tumorigenesis. Increased DNA damage or loss of genome integrity is thought to be one of the mechanisms linking inflammation and cancer development. It has been suggested that NF-κB-induced microRNA-146 (miR146a) may be a mediator of the inflammatory response. Based on our initial observation that miR146a overexpression strongly increases DNA damage, we investigated its potential role as a modulator of DNA repair. Here, we demonstrate that FANCM, a component in the Fanconi Anemia pathway, is a novel target of miR146a. miR146a suppressed FANCM expression by directly binding to the 3’ untranslated region of the gene. miR146a-induced downregulation of FANCM was associated with inhibition of FANCD2 monoubiquitination, reduced DNA homologous recombination repair and checkpoint response, failed recovery from replication stress, and increased cellular sensitivity to cisplatin. These phenotypes were recapitulated when miR146a expression was induced by overexpressing the NF-κB subunit p65/RelA or Helicobacter pylori infection in a human gastric cell line; the phenotypes were effectively reversed with an anti-miR146a antagomir. These results suggest that undesired inflammation events caused by a pathogen or over-induction of miR146a can impair genome integrity via suppression of FANCM

Long wavelength light reduces the negative consequences of dim light at night.

Many patients with autism spectrum disorders (ASD) show disturbances in their sleep/wake cycles, and they may be particularly vulnerable to the impact of circadian disruptors. We have previously shown that a 2-weeks exposure to dim light at night (DLaN) disrupts diurnal rhythms, increases repetitive behaviors and reduces social interactions in contactin-associated protein-like 2 knock out (Cntnap2 KO) mice. The deleterious effects of DLaN may be mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin, which is maximally sensitive to blue light (480 nm). In this study, the usage of a light-emitting diode array enabled us to shift the spectral properties of the DLaN while keeping the intensity of the illumination at 10 lx. First, we confirmed that the short-wavelength enriched lighting produced strong acute suppression of locomotor activity (masking), robust light-induced phase shifts, and cFos expression in the suprachiasmatic nucleus in wild-type (WT) mice, while the long-wavelength enriched lighting evoked much weaker responses. Opn4DTA mice, lacking the melanopsin expressing ipRGCs, were resistant to DLaN effects. Importantly, shifting the DLaN stimulus to longer wavelengths mitigated the negative impact on the activity rhythms and autistic behaviors (i.e. reciprocal social interactions, repetitive grooming) in the Cntnap2 KO as well as in WT mice. The short-, but not the long-wavelength enriched, DLaN triggered cFos expression in in the basolateral amygdala (BLA) as well as in the peri-habenula region raising that possibility that these cell populations may mediate the effects. Broadly, our findings are consistent with the recommendation that spectral properties of light at night should be considered to optimize health in neurotypical as well as vulnerable populations

Accuracy of the qSOFA Score and RED Sign in Predicting Critical Care Requirements in Patients with Suspected Infection in the Emergency Department: A Retrospective Observational Study

Background and objectives: We aimed to compare the accuracy of positive quick sequential organ failure assessment (qSOFA) scores and the RED sign in predicting critical care requirements (CCRs) in patients with suspected infection who presented to the emergency department (ED). Materials and Methods: In this retrospective observational study, we examined adult patients with suspected infection in the ED from June 2018 to September 2018. A positive qSOFA (qSOFA+) was defined as the presence of ≥2 of the following criteria: altered mental status (AMS), systolic blood pressure (SBP) < 100 mmHg, and respiratory rate (RR) ≥ 22 breaths/min. A positive RED sign (RED sign+) was defined as the presence of at least one of the RED sign criteria: AMS, skin mottling, SBP < 90 mmHg, heart rate >130 beats/min, or RR > 30 breaths/min. A qSOFA/RED+ was defined as the presence of qSOFA+ or RED+. We applied these tools twice using the initial values upon ED arrival and all values within 2 h after ED arrival. The accuracy of qSOFA+, RED+, and qSOFA/RED+ in predicting CCR was assessed. Results: Data from 5353 patients with suspected infection were analyzed. The area under the receiver operating characteristic curve (AUC) of RED+ (0.67, 95% confidence interval [CI]: 0.65–0.70) and that of qSOFA/RED+ (0.68, 95% CI: 0.66–0.70, p < 0.01) were higher than the AUC of qSOFA+ (0.59, 95% CI: 0.57–0.60) in predicting CCR on ED arrival. The qSOFA/RED+ within 2 h showed the highest accuracy (AUC 0.72, 95% CI: 0.70–0.75, p < 0.001). Conclusions: The accuracy of the RED sign in predicting CCR in patients with suspected infection who presented at ED was better than that of qSOFA. The combined use of the RED sign and qSOFA (positive qSOFA or RED sign) showed the highest accuracy

Penetrative and Sustained Drug Delivery Using Injectable Hydrogel Nanocomposites for Postsurgical Brain Tumor Treatment

Postsurgical treatment of glioblastoma multiforme (GBM) by systemic chemotherapy and radiotherapy is often inefficient. Tumor cells infiltrating deeply into the brain parenchyma are significant obstacles to the eradication of GBM. Here, we present a potential solution to this challenge by introducing an injectable thermoresponsive hydrogel nanocomposite. As a liquid solution that contains drug-loaded micelles and water-dispersible ferrimagnetic iron oxide nanocubes (wFIONs), the hydrogel nanocomposite is injected into the resected tumor site after surgery. It promptly gelates at body temperature to serve as a soft, deep intracortical drug reservoir. The drug-loaded micelles target residual GBM cells and deliver drugs with a minimum premature release. Alternating magnetic fields accelerate diffusion through heat generation from wFIONs, enabling penetrative drug delivery. Significantly suppressed tumor growth and improved survival rates are demonstrated in an orthotopic mouse GBM model. Our system proves the potential of the hydrogel nanocomposite platform for postsurgical GBM treatment.N

Sustainable Production of Shinorine from Lignocellulosic Biomass by Metabolically Engineered Saccharomyces cerevisiae

Mycosporine-like amino acids (MAAs) have been used in cosmetics and pharmaceuticals. The purpose of this work was to develop yeast strains for sustainable and economical production of MAAs, especially shinorine. First, genes involved in MAA biosynthetic pathway from Actinosynnema mirum were introduced into Saccharomyces cerevisiae for heterologous shinorine production. Second, combinatorial expression of wild and mutant xylose reductase was adopted in the engineered S. cerevisiae to facilitate xylose utilization in the pentose phosphate pathway. Finally, the accumulation of sedoheptulose 7-phosphate (S7P) was attempted by deleting transaldolase-encoding TAL1 in the pentose phosphate pathway to increase carbon flux toward shinorine production. In fed-batch fermentation, the engineered strain (DXdT-M) produced 751 mg/L shinorine in 71 h. Ultimately, 54 mg/L MAAs was produced by DXdT-M from rice straw hydrolysate. The results suggest that shinorine production by S. cerevisiae might be a promising process for sustainable production and industrial applications