Social determinants related to COVID-19 infection.

This study was aimed at identifying the social determinants related to COVID-19 infection in South Korea. This secondary analysis used data from the 2020 Community Health Survey, a nationwide sample taken to understand the health status of Korean residents. The participants were 220 970 adults 19 years of age or older. COVID-19-related social determinants were age, education level, marital status, household income, hypertension, eating habits, social support, and regional income. The risk of COVID-19 infection increased in those who were under 40 years, were high school graduates or higher, were single, had a household income over US$ 4166.7, ate breakfast 5-7 times a week, had three or more helpers during COVID-19, and lived in a region with above-average income. Hypertension reduced the risk of COVID-19 infection. In conclusion, adults with high socioeconomic activity showed a high risk for COVID-19 infection, which was assumed to include only adults living in residential housing in the community. Further studies are required to include adults living in long-term care or communal living facilities, known to be frequently infected with the corona virus.

Building and evaluating suicide attempt prediction models using risk factors.

This study identified risk factors of suicide attempts for the purpose of building prediction models and evaluating their performance. The participants of this secondary data analysis study were 11 671 adults aged 19 years or older. The prediction models consisted of risk factors identified through multiple logistic regression analysis, and performance was analyzed in terms of calibration, discrimination, and clinical usefulness. The risk factors for suicide attempts were suicide plan and suicidal ideation for males, and suicide plan and depression diagnosis for females. The prediction models constructed with these risk factors showed good calibration and discrimination, with over 0.90 of the area under the curves. At the cutoff point of 0.5%, the sensitivity of the full model was 90.9% for males and 82.4% for females. The net benefit was positive at a threshold probability under 30% for males and 40% for females. Given the acceptable performance of the suicide attempt prediction models, they can be used to assess suicide attempt risk and detect the population at high risk in the community at an early stage, with limited human resources.

SOCS1 Represses Fractionated Ionizing Radiation-Induced EMT Signaling Pathways through the Counter-Regulation of ROS-Scavenging and ROS-Generating Systems.

BACKGROUND/AIMS: Fractionated ionizing radiation (FIR) is an anti-cancer protocol widely applied for the treatment of diverse types of cancers to reduce damage to normal cells. However, cancer cells receiving multiple irradiations at low doses during FIR, often develop resistance to the therapy exhibiting malignant features including epithelial to mesenchymal transition (EMT). The present study has been performed to elucidate the mechanism of FIR-induced EMT signaling pathways and to identify a molecular target for radioresistance modulated by suppressors of cytokine signaling (SOCS)1. METHODS: Colorectal cancer cell lines received FIR with a daily dose of 2 Gy for 3 days. Generation of intracellular reactive oxygen species (ROS) and its role in EMT signaling induced by FIR were analyzed in SOCS1 over-expressing and knock-down cells. ROS were measured by DCF fluorescence using flow cytometry. Expression levels of EMT markers and signaling molecules were analyzed by Western blotting and confocal microscopy. RESULTS: FIR induced ROS and changes in EMT markers including down-regulation of E-cadherin with up-regulation of Twist and Snail. Pretreatment of anti-oxidant N-acetyl cysteine (NAC) abrogated the FIR-induced ROS generation and EMT response. Mechanistic studies indicated that the FIR-induced ROS-mediated EMT signaling proceeded through Akt→Src→Erk pathways. In accordance with the anti-ROS function, SOCS1 blocked the FIR-induced EMT and the associated signaling pathways through thioredoxin (Trx1) up-regulation. This is evidenced by the observation that Trx1 ablation in SOCS1 over-expressing cells negated the inhibitory action of SOCS1 by restoring the FIR-induced ROS and EMT markers. In addition, we have obtained data supporting that the FIR-induced ROS is derived from functional mitochondria and NADPH oxidases (Nox), which are both down-regulated by SOCS1. CONCLUSION: The results demonstrate that ROS signal acts as a mediator of the FIR-induced EMT. The data also suggest a potential anti-tumor function of SOCS1 by blocking the FIR therapy-induced resistance through the counter-regulation of ROS generating and scavenging systems.

Nonwettable Hierarchical Structure Effect on Droplet Impact and Spreading Dynamics.

In this study, the nano/micro hierarchical structure effect of a nonwettable surface on droplet impact was investigated by high-speed visualization. A dual-scale structure of a superhydrophobic surface was designed for manipulating a wide range of capillary pressures (103-106 Pa), and it was supposed to trigger a hierarchical effect on the droplet dynamics. Distilled water droplets of various sizes and initial velocity were subjected to the prepared samples, and the impact behavior, the spreading diameter, and contacted time, were quantitatively measured. The apparent maximum spreading and contact time of the low Weber number ( We#) condition was less dependent on the microscaled design factor of the multiscale-fabricated surface. However, in the high We# condition, the wavy formation shape and the fragmented criteria of the droplet impact were affected by the configuration of the surface morphology. The hierarchical effect from the dual-scale structure on droplet spreading dynamics has been discussed through a balance between capillary pressure induced by the structure and the dynamic pressure of droplet impact.

Ketobacter alkanivorans gen. nov., sp. nov., an n-alkane-degrading bacterium isolated from seawater.

Strain GI5T was isolated from a surface seawater sample collected from Garorim Bay (West Sea, Republic of Korea). The isolated strain was aerobic, Gram-stain-negative, rod-shaped, motile by means of a polar flagellum, negative for catalase and weakly positive for oxidase. The optimum growth pH, salinity and temperature were determined to be pH 7.5-8.0, 3 % NaCl (w/v) and 25 °C, respectively; the growth ranges were pH 6.0-9.0, 1-7 % NaCl (w/v) and 18-40 °C. The results of phylogenetic analysis of 16S rRNA gene sequences indicated that GI5T clustered within the family Alcanivoracaceae, and most closely with Alcanivorax dieseloleiB-5T and Alcanivorax marinusR8-12T (91.9 % and 91.6 % similarity, respectively). The major cellular fatty acids in GI5T were C18 : 1ω7c/C18 : 1ω6c (44.45 %), C16 : 1ω6c/C16 : 1ω7c (14.17 %) and C16 : 0 (10.19 %); this profile was distinct from those of the closely related species. The major respiratory quinone of GI5T was Q-8. The main polar lipids were phosphatidylethanolamine and phosphatidylglycerol. Two putative alkane hydroxylase (alkB) genes were identified in GI5T. The G+C content of the genomic DNA of GI5T was determined to be 51.2 mol%. On the basis of the results of phenotypic, chemotaxonomic and phylogenetic studies, strain GI5T represents a novel species of a novel genus of the family Alcanivoracaceae, for which we propose the name Ketobacter alkanivorans gen. nov., sp. nov.; the type strain is GI5T (=KCTC 52659T=JCM 31835T).

Quantitative analysis of cell proliferation by a dye dilution assay: Application to cell lines and cocultures.

Cell proliferation represents one of the most fundamental processes in biological systems, thus the quantitative analysis of cell proliferation is important in many biological applications such as drug screening, production of biologics, and assessment of cytotoxicity. Conventional proliferation assays mainly quantify cell number based on a calibration curve of a homogeneous cell population, and therefore are not applicable for the analysis of cocultured cells. Moreover, these assays measure cell proliferation indirectly, based on cellular metabolic activity or DNA content. To overcome these shortcomings, a dye dilution assay employing fluorescent cell tracking dyes that are retained within cells was applied and was diluted proportionally by subsequent cell divisions. Here, it was demonstrated that this assay could be implemented to quantitatively analyze the cell proliferation of different types of cell lines, and to concurrently analyze the proliferation of two types of cell lines in coculture by utilizing cell tracking dyes with different spectral characteristics. The mean division time estimated by the dye dilution assay is compared with the population doubling time obtained from conventional methods and values from literature. Additionally, dye transfer between cocultured cells was investigated and it was found that it is a characteristic of the cells rather than a characteristic of the dye. It was suggested that this method can be easily combined with other flow cytometric analyses of cellular properties, providing valuable information on cell status under diverse conditions. © 2017 International Society for Advancement of Cytometry.

Isolation of an exopolysaccharide-producing heavy metal-resistant Halomonas sp. MG.

An exopolysaccharide (EPS)-producing heavy metal-resistant Gram-negative bacterium was isolated from ore-contaminated soil. The selected strain was identified by 16S rDNA sequencing and designated as Halomonas sp. MG. Phylogenetic analysis of the gene sequence showed its close similarity with Halomonas sp. Field emission scanning electron microscopy analysis revealed that the EPS had a porous structure with small pores. X-ray diffractograms showed the non-crystalline nature of the EPS. Further, FTIR spectroscopic analysis revealed the presence of carboxyl, hydroxyl and amide groups corresponding to a typical EPS.

Synergistic effect of chelators and Herbaspirillum sp. GW103 on lead phytoextraction and its induced oxidative stress in Zea mays.

Phytoremediation is an in situ, low-cost strategy for cleanup of the sites contaminated with heavy metals. Experiments were conducted to assess the impact of synthetic chelators and plant growth-promoting rhizosphere bacteria (Herbaspirillum sp. GW103) on heavy metal lead (Pb) uptake in Z. mays cultivated in Pb-contaminated soil. The present study investigated the Pb phytoaccumulation rate and plant antioxidant enzyme activities in Z. mays exposed to 100 mg/kg of PbNO3. The combination of gluconic acid (GA) with Herbaspirillum sp. GW103 treatment showed higher Pb solubility (18.9 mg/kg) compared with other chelators. The chemical chelators showed the significant difference in phytoaccumulation as well as antioxidant enzyme activities. The antioxidant enzymes such as catalase, peroxidase and superoxide dismutase activities changed under Pb stress. The study indicated that increased activity of antioxidant enzymes may play as signal inducers to fight against Pb.

Association analysis of toluene exposure time with high-throughput mRNA expressions and methylation patterns using in vivo samples.

The emission of volatile organic compounds (VOCs) resulting from outdoor air pollution can contribute to major public health problems. However, there has been limited research on the health effects in humans from the inhalation of VOCs. Therefore, this study conducted an in vivo analysis of the effects of toluene, one of the most commonly used chemicals in many industries, on gene expression and methylation over time using the high-throughput technique of microarray analysis. We separated participants into three groups (control, short-term exposure, and long-term exposure) to investigate the influence of toluene exposure time on gene expression. We then comprehensively analyzed and investigated the correlation between variations in gene expression and the occurrence of methylation. Twenty-six genes were upregulated and hypomethylated, while 32 genes were downregulated and hypermethylated. The pathways of these genes were confirmed to be associated with cell survival and the immune system. Based on our findings, these genes can help predict the effects of time-dependent exposure to toluene on human health. Thus, observations from our data may have implications for the identification of biomarkers of toluene exposure.

Notch1 modulates oxidative stress induced cell death through suppression of apoptosis signal-regulating kinase 1.

Notch1 genes encode receptors for a signaling pathway that regulates various aspects of cell growth and differentiation; however, the role of Notch1 signaling in p38 mitogen-activated protein kinase (MAPK) signaling pathway is still not well defined. In this study, we found that Notch1 intracellular domain (Notch1-IC) prevents oxidative stress-induced cell death through the suppression of the Apoptosis signal-regulating kinase (ASK) 1 signaling pathway. Notch1-IC inhibited H2O2-induced activation of ASK1 and the activation of downstream kinases in the p38 MAPK signaling cascade. The results of both in vivo binding and kinase studies have revealed that ASK1 is the direct target of Notch1-IC, whereas it produced no effect on either MAP kinase kinase (MKK) 3 or p38 MAPK. Notch1-IC blocked both the homooligomerization of ASK1 and inhibited ASK1 activity. Furthermore, Notch1-IC facilitated the translocation of activated ASK1 toward the nucleus. Notch1 knockdown was determined to be highly susceptible to oxidative stress-induced activation of ASK1-MKK3/MKK6-p38 MAPK signaling cascade and cell death. Taken together, our findings suggest that Notch1-IC may act as a negative regulator in ASK1 signaling cascades.

Akt1 phosphorylates Nicastrin to regulate its protein stability and activity.

The gamma-secretase is a multiprotein complex that cleaves many type-I membrane proteins, such as the Notch receptor and the amyloid precursor protein. Nicastrin (NCT) is an essential component of the multimeric gamma-secretase complex and functions as a receptor for gamma-secretase substrates. In this study, we found that Akt1 markedly regulated the protein stability of NCT. Importantly, the kinase activity of Akt1 was essential for the inhibition of gamma-secretase activity through degradation of NCT. Notably, the protein level of endogenous NCT was higher in shAkt1-expressing cells than in shCon-expressing cells. Akt1 physically interacted with NCT and mediated its degradation through proteasomal and lysosomal pathways. We also found that Akt1 phosphorylates NCT at Ser437, resulting in a significant reduction in NCT protein stability. Importantly, a phospho-deficient mutation in NCT at Ser437 stabilized its protein levels. Collectively, our results reveal that Akt1 functions as a negative regulator of the gamma-secretase activity through phosphorylation and degradation of NCT. Generation of the amyloid peptide (A-beta) and the amyloid precursor protein (APP) intracellular domain (AICD) can happen by sequential proteolysis of APP by beta and gamma-secretase. The gamma-secretase complex consists of four essential proteins: presenilin (PS1 or PS2), presenilin enhancer 2 (PEN-2), anterior pharynx-defective 1 (APH-1), and the Nicastrin (NCT). NCT can interact and be phosphorylated by Akt1, and phosphorylated NCT promotes its proteasomal and lysosomal degradation. As a result, Akt1 plays role in reducing gamma-secretase activity through phosphorylation-dependent regulation of NCT protein degradation.

Humoral factors in ALS patients during disease progression.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons in the CNS and leading to paralysis and death. There are currently no effective treatments for ALS due to the complexity and heterogeneity of factors involved in motor neuron degeneration. A complex of interrelated effectors have been identified in ALS, yet systemic factors indicating and/or reflecting pathological disease developments are uncertain. The purpose of the study was to identify humoral effectors as potential biomarkers during disease progression. METHODS: Thirteen clinically definite ALS patients and seven non-neurological controls enrolled in the study. Peripheral blood samples were obtained from each ALS patient and control at two visits separated by 6 months. The Revised ALS Functional Rating Scale (ALSFRS-R) was used to evaluate overall ALS-patient functional status at each visit. Eleven humoral factors were analyzed in sera. Cytokine levels (GM-CSF, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNF-α) were determined using the Bio-Rad Bio-Plex® Luminex 200 multiplex assay system. Nitrite, a breakdown product of NO, was quantified using a Griess Reagent System. Glutathione (GSH) concentrations were measured using a Glutathione Fluorometric Assay Kit. RESULTS: ALS patients had ALSFRS-R scores of 30.5 ± 1.9 on their first visit and 27.3 ± 2.7 on the second visit, indicating slight disease progression. Serum multiplex cytokine panels revealed statistically significant changes in IL-2, IL-5, IL-6, and IL-8 levels in ALS patients depending on disease status at each visit. Nitrite serum levels trended upwards in ALS patients while serum GSH concentrations were drastically decreased in sera from ALS patients versus controls at both visits. CONCLUSIONS: Our results demonstrated a systemic pro-inflammatory state and impaired antioxidant system in ALS patients during disease progression. Increased levels of pro-inflammatory IL-6, IL-8, and nitrite and significantly decreased endogenous antioxidant GSH levels could identify these humoral constituents as systemic biomarkers for ALS. However, systemic changes in IL-2, IL-5, and IL-6 levels determined between visits in ALS patients might indicate adaptive immune system responses dependent on current disease stage. These novel findings, showing dynamic changes in humoral effectors during disease progression, could be important for development of an effective treatment for ALS.

Inhibition of notch signalling ameliorates experimental inflammatory arthritis.

OBJECTIVE: To test the hypothesis that Notch signalling plays a role in the pathogenesis of rheumatoid arthritis (RA) and to determine whether pharmacological inhibition of Notch signalling with γ-secretase inhibitors can ameliorate the RA disease process in an animal model. METHODS: Collagen-induced arthritis was induced in C57BL/6 or Notch antisense transgenic mice by immunisation with chicken type II collagen (CII). C57BL/6 mice were administered with different doses of inhibitors of γ-secretase, an enzyme required for Notch activation, at disease onset or after onset of symptoms. Severity of arthritis was monitored by clinical and histological scores, and in vivo non-invasive near-infrared fluorescence (NIRF) images. Micro-CT was used to confirm joint destruction. The levels of CII antibodies and cytokines in serum were determined by ELISA and bead-based cytokine assay. The expression levels of cytokines were studied by quantitative PCR in rheumatoid synovial fibroblasts. RESULTS: The data show that Notch signalling stimulates synoviocytes and accelerates their production of proinflammatory cytokines and immune responses involving the upregulation of IgG1 and IgG2a. Pharmacological inhibition of γ-secretase and antisense-mediated knockdown of Notch attenuates the severity of inflammatory arthritis, including arthritis indices, paw thickness, tissue damage and neutrophil infiltration, and reduces the levels of active NF-κB, ICAM-1, proinflammatory cytokines and matrix metalloproteinase-3 activity in the mouse model of RA. CONCLUSIONS: These results suggest that Notch is involved in the pathogenesis of RA and that inhibition of Notch signalling is a novel approach for treating RA.

Reduction of oxidative stress may play a role in the anti-inflammatory effect of the novel herbal formulation in a rat model of hydrochloric acid-induced cystitis.

AIMS: We investigated the effect of the multi-herbal medicine, WSY-1075 in an animal model of hydrochloric acid (HCl)-induced cystitis. METHODS: Rats were randomly assigned to three groups: sham-operated (control), HCl-induced only (HC), and HC treated with WSY-1075 (HC + WT). Oral administration of either distilled water (control, HC) or WSY-1075 (400 mg/kg) was continued for 4 weeks. In HC and HC + WT groups, cystitis was induced with 0.4 M HCl beginning on the 22nd day. Rats in each group underwent cystometrography, and bladders were examined for evidence of inflammation and oxidative stress. RESULTS: Treatment with WSY-1075 decreased the frequency of urination and reduced inflammation of the bladder tissue in a rat model of HCl-induced cystitis. Compared with the control group, the HC group showed severe chronic inflammatory and fibrosis signs, and the inflammatory grades significantly decreased following WSY-1075 treatment in the HC-WT group. The HC + WT group showed a markedly decreased expression of pro-inflammatory cytokines compared to the HC group. The level of malondialdehyde was significantly greater in the HC group compared to the control group, and it was significantly reduced in the treated (HC + WT) group. The levels of superoxide dismutase increased in the HC + WT group, which confirmed the anti-oxidant effect of WSY-1075. CONCLUSIONS: We suggest that reduction of oxidative stress may play a role in this anti-inflammatory effect.

Identification of cornifelin and early growth response-1 gene as novel biomarkers for in vitro eye irritation using a 3D reconstructed human cornea model MCTT HCE™.

Evaluation of the eye irritation is essential in the development of new cosmetic products. Draize rabbit eye irritation test has been widely used in which chemicals are directly applied to rabbit eye, and the symptoms and signs of eyes are scored. However, due to the invasive procedure, it causes substantial pain and discomfort to animals. Recently, we reported in vitro eye irritation test method using a 3D human corneal epithelial model (MCTT HCE™) which is reconstructed from remaining human tissues after a corneal transplantation. This model exhibited an excellent predictive capacity for 25 reference chemicals (sensitivity 100%, specificity 77% and accuracy 88% vs. GHS). To improve the test performance, we explored new biomarkers for the eye irritation through transcriptomic approach. Three surfactants were selected as model eye irritants that include sodium lauryl sulfate, benzalkonium chloride and triton X-100. After test chemicals were treated, we investigated differentially expressed genes through a whole-gene microarray (Affymetrix GeneChip(®) Human Gene 2.0 ST Array, 48,000 probes). As a result, we identified that mRNAs of cornifelin (CNFN), a constituent of the insoluble cornified cell envelope of stratified squamous epithelia, and early growth response-1 (EGR1), a nuclear transcriptional regulator, were significantly up-regulated by all three irritants. Up-regulation of CNFN and EGR1 was further confirmed by Q-RT-PCR, and immunohistochemistry revealed increased level of CNFN in irritant-treated tissues, supporting the relevance of CNFN and EGR1 as new biomarkers for eye irritation.

Isolation and Characterization of Multi-Metal-Resistant Halomonas sp. MG from Tamil Nadu Magnesite Ore Soil in India.

The aim of the study was to isolate and characterize potential multi-metal-resistant bacteria from ore soils. A total of three bacteria were isolated and assayed for resistance to arsenic (As), copper (Cu), and lead (Pb). Isolate Halomonas sp. MG exhibited maximum resistance to 1000 mg Pb/L, 800 mg As/L, and 500 mg Cu/L and it was identified as Halomonas sp. based on the partial 16S rDNA sequences. The metal(loid)s resistance mechanisms were further confirmed by amplification of arsC (As) copAU (Cu), and pbrT (Pb) genes. Biological transmission electron micrographs and XRD studies showed that the isolate Halomonas sp. MG transformed and/or biomineralized the metals either intracellularly or extracellularly. These results suggest that the isolate could be used as a potential candidate for the bioremediation of As, Cu, and Pb.

Probing Metabolite Space of Escherichia coli via Growth Medium Composition as Monitored by Two-Dimensional NMR Spectroscopy.

As for recombinant protein production, Escherichia coli is one of the most frequently employed hosts because it offers a simple and inexpensive, but rapid and high-yield system in addition to the vast information on its molecular genetics and biology. However, due to its prokaryotic nature, it often fails to produce eukaryotic proteins in a desired form. To devise a systematic way leading to a condition that produces a large amount of usable proteins, we attempted to monitor intracellular metabolites under various conditions, and to link them to recombinant protein production. With such an intention, we identified 31 metabolites from cells grown in different media by using two-dimensional (2D) NMR spectroscopy. Our results revealed that 1) the level of betaine was low, while that of glutamic acid was high when grown in minimal media; 2) the level of glycerol was constantly high in all cases; 3) the level of oxidized glutathione was lower in Luria broth (LB); and 4) the level of leucine was low in minimal media. We hope this work might shed light onto how to improve production of the target proteins by metabolite profiling.

Hand-assisted and pure laparoscopic living donor nephrectomy: a matched-cohort comparison over 10 yr at a single institute.

OBJECTIVE: To compare outcomes between matched patients who underwent hand-assisted laparoscopic donor nephrectomy (HALDN) and pure laparoscopic donor nephrectomy (PLDN) from living donors. METHOD: Between February 2000 and July 2012, 608 consecutive patients underwent laparoscopic living donor nephrectomy at a single center. In September 2003, we began to perform the PLDN for the first time. A matched-pair cohort of 80 patients who underwent PLDN and 80 patients who underwent HALDN was selected for retrospective comparison. RESULT: No significant differences in operative time, warm ischemia time, estimated blood loss, transfusion rate, analgesic requirement, or hospital stay were observed between the HALDN and PLDN groups. No differences were found in the recipient serum creatinine values (mg/dL) and estimated glomerular filtration rate by the Modification of Diet in Renal Disease (MDRD-eGFR; mL/min/1.73 m(2) ). CONCLUSION: No significant differences were observed in surgical outcomes, complication rates, and postoperative parameters between the HALDN and PLDN groups. Moreover, recipient graft function and morbidity between both groups were comparable. Therefore, we believe that PLDN may be a good alternative technique to HALDN.

Suppressors of cytokine signaling promote Fas-induced apoptosis through downregulation of NF-κB and mitochondrial Bfl-1 in leukemic T cells.

Suppressors of cytokine signaling (SOCS) are known as negative regulators of cytokine- and growth factor-induced signal transduction. Recently they have emerged as multifunctional proteins with regulatory roles in inflammation, autoimmunity, and cancer. We have recently reported that SOCS1 has antiapoptotic functions against the TNF-α- and the hydrogen peroxide-induced T cell apoptosis through the induction of thioredoxin, which protects protein tyrosine phosphatases and attenuates Jaks. In this study, we report that SOCS, on the contrary, promote death receptor Fas-mediated T cell apoptosis. The proapoptotic effect of SOCS1 was manifested with increases in Fas-induced caspase-8 activation, truncated Bid production, and mitochondrial dysfunctions. Both caspase-8 inhibitor c-Flip and mitochondrial antiapoptotic factor Bfl-1 were significantly reduced by SOCS1. These proapoptotic responses were not associated with changes in Jak or p38/Jnk activities but were accompanied with downregulation of NF-κB and NF-κB-dependent reporter gene expression. Indeed, p65 degradation via ubiquitination was accelerated in SOCS1 overexpressing cells, whereas it was attenuated in SOCS1 knockdown cells. With high NF-κB levels, the SOCS1-ablated cells displayed resistance against Fas-induced apoptosis, which was abrogated upon siBfl-1 transfection. The results indicate that the suppression of NF-κB-dependent induction of prosurvival factors, such as Bfl-1 and c-Flip, may serve as a mechanism for SOCS action to promote Fas-mediated T cell apoptosis. SOCS3 exhibited a similar proapoptotic function. Because both SOCS1 and SOCS3 are induced upon TCR stimulation, SOCS would play a role in activation-induced cell death by sensitizing activated T cells toward Fas-mediated apoptosis to maintain T cell homeostasis.

Detection and assessment of clarithromycin inducible resistant strains among Korean Mycobacterium abscessus clinical strains: PCR methods.

BACKGROUND: Mycobacterium abscessus group belongs to a group of rapidly growing mycobacteria (RGM) and, following Mycobacterium avium complex, is the second most common pathogen responsible for lung disease caused by nontuberculous mycobacteria (NTM). Clarithromycin is known to be the key drug in the treatment of M. abscessus group disease, but a high failure rate of treatment response is reported due to clarithromycin inducible resistance. METHODS: Using the results from a clarithromycin susceptibility test we examined the proportion of clarithromycin inducible resistant M. abscessus (sensu stricto; hereafter referred to as M. abscessus) clinical strains. Also, we attempted to detect the clarithromycin resistant strains, using the amplification refractory mutation system-PCR (ARMS-PCR) and real-time PCR methods for rapid detection of single-nucleotide polymorphisms (SNPs) at position 28 (T or C) of the erm(41) gene of M. abscessus leading to resistance to clarithromycin. RESULTS: Of the 157 M. abscessus clinical strains, clarithromycin susceptible, resistant, and inducible resistant strains accounted for 10.83% (n = 17), 22.29% (n = 35), and 66.88% (n = 105), respectively. Clarithromycin resistant strains were able to separate from clarithromycin susceptible strains by ARMS-PCR and real-time PCR identical to DNA sequence analysis. CONCLUSION: Most M. abscessus clinical strains in Korea are resistant to clarithromycin, and ARMS-PCR and real-time PCR are useful tools for the rapid detection of single-nucleotide polymorphisms (SNPs) at position 28 of the erm(41) gene.