Objective Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance greatly limits the clinical therapeutic efficacy of TRAIL.Elucidating the molecular mechanism underlying TRAIL resistance will be fundamental to resolving this problem.Methods Nuclear and cytoplasmic protein extraction and immunofluorescence (IF) assay were used to detect changes in heterogeneous nuclear ribonucleoprotein K (hnRNPK) localization in H1299 cells.The evaluation of cell apoptosis in cells transfected with GFP-hnRNPK, GFP-hnRNPK S284/353A, or GFP-hnRNPK S284/353D mutant was performed using cleaved caspase-3 antibody.The gene expression of XIAP was tested by quantitative RT-PCR.Results Previously, we reported that hnRNPK antagonized TRAIL-induced apoptosis through inhibition of PKC-mediated GSK3β phosphorylation.In this study, we further demonstrate that TRAIL treatment induces cytoplasmic accumulation of hnRNPK in H1299 cells.The hnRNPK localized in the cytoplasm has a higher capacity to antagonize TRAIL-induced apoptosis.Both ERK1/2 signaling inhibitor U0126 and ERK-phosphoacceptor-site mutant (GFP-hnRNPK S284/353A) diminish cytoplasmic accumulation of hnRNPK induced by TRAIL.Moreover, we show that XIAP is involved in hnRNPK-mediated TRAIL resistance in H1299 cells.Conclusion Taken together, these results give new insights into the understanding of the molecular mechanism associated with TRAIL resistance in lung adenocarcinoma.
Objective Many metals, some of which have been classified as environmental endocrine disruptors, are used extensively in everyday consumer products and are ubiquitous in our living environment.In the present study, we aimed to explore the associations between the prevalence risk of type 2 diabetes and plasma levels of 20 trace elements as well as those of heavy metals in a Han Chinese population.Methods We conducted a case-control study to investigate the associations between plasma concentrations of 20 metals and diabetes in Jiangsu province.A total of 122 newly diagnosed cases of type 2 diabetes and 429 matched controls were recruited from community physical examinations in Suzhou City of Jiangsu Province.Plasma metal levels were measured by inductively-coupled plasma mass spectrometry.Results After adjusting for confounders, plasma vanadium, chromium, manganese, copper, zinc, arsenic, selenium, strontium, palladium, cadmium, cesium, and barium were associated with diabetes risk (P < 0.05).The adjusted OR increased with increasing concentration of vanadium, manganese, copper, zinc, and cesium.Conclusion Many metals, including manganese, copper, zinc, arsenic, selenium, and cadmium in plasma, are associated with the morbidity of diabetes.Monitoring of environmental metal levels and further studies are urgently needed.
Objective To investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors.Methods A total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study.CD4, Foxp3, CD8, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification.Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis.Results Significant differences in 11 factors (age, Ann Arbor stage, B symptom, ECOG performance status, infiltrating CD8+ T cells, PD-L1 expression, absolute blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and serum β2-microglobulin) were observed among patient groups stratified by at least two risk stratification methods[International Prognostic Index (IPI), revised IPI, and NCCN-IPI models](P < 0.05).Concordance rates were high (81.4%-100.0%) when these factors were used for the risk stratification.No difference in the risk stratification results was observed with or without the Ann Arbor stage data.Conclusion We developed a convenient and inexpensive tool for use in risk stratification of aggressive B cell lymphomas, although further studies on the role of immune microenvironmental factors are needed.
Objective In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection.Milk quality and security problems pertaining to the safe consumption of dairy products were also discussed in this study.Methods Milk was preprocessed with 4% NaOH.Then, mycobacteria were isolated from the milk sample on L-J medium.The isolate was identified using multiple loci Polymerase Chain Reaction (PCR) and multi-locus sequence analysis with 16S rRNA, sodA, hsp65, and ITS genes.The drug sensitivity of the isolate to 27 antibiotics was tested through alamar blue assay.Results Smooth, moist, pale yellow colonies appeared on the L-J medium within a week after inoculation.Based on the results of multiple loci PCR analysis, the isolate was preliminarily identified as non-tuberculous mycobacteria.The 16S rRNA, sodA, hsp65, and ITS gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities, respectively, with those of the published reference strains of Mycobacterium elephantis(M.elephantis).The drug sensitivity results showed that the strain is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin, levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin, ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline.Conclusion To the best of our knowledge, this study is initially to report the isolation of M.elephantis from the milk of a cow with mastitis in China.
Objective To evaluate the usefulness of the thyroglobulin (Tg) level in adults as a nutritional biomarker of iodine status and to identify the factors related to the serum Tg level.Methods A cross-sectional study was conducted in adult populations of areas differing in iodine nutrition from three provinces (Autonomous Region) in China.Serum levels of thyroid hormones and Tg as well as thyroid autoantibodies were measured.The thyroid volume and nodule were measured by ultrasound.A multivariate linear regression analysis was used to assess iodine intake and other indeterminate factors associated with the serum Tg level.Results A total of 573 adults were recruited for this study.The serum Tg levels differed significantly among the three groups (22.27 μg/L, 9.73 μg/L and 15.77 μg/L in the excess, more-than-adequate, and deficient groups, respectively).The results of multivariate linear regression analysis indicate that excess and deficient iodine intake, goiter, thyroid nodule, hypothyroidism are significantly related with higher Tg level, and TgAb positivity is significantly related with lower serum Tg.Conclusion The serum Tg level reflects abnormal thyroid function and is a sensitive functional biomarker of iodine nutrition status.
ObjectiveMycobacterium avium(M.avium) and Mycobacterium intracellulare(M.intracellulare) are the major causative agents of nontuberculous mycobacteria (NTM)-related pulmonary infections.However, little is known about the differences in drug susceptibility profiles between these two species.Methods A total of 393 NTM isolates were collected from Shanghai Pulmonary Disease Hospital.Sequencing of partial genes was performed to identify the strains at species level.The minimum inhibitory concentration (MIC) was used to evaluate the drug susceptibility against 20 antimicrobial agents.Variable number of tandem repeat (VNTR) typing was conducted to genotype these two species.Results A total of 173(44.0%)M.avium complex (MAC) isolates were identified, including 41(10.4%)M.avium isolates and 132(33.6%)M.intracellulare isolates.Clarithromycin and amikacin were the two most effective agents against MAC isolates.The Hunter-Gaston Discriminatory Index (HGDI) values for VNTR typing of M.avium and M.intracellulare isolates were 0.993 and 0.995, respectively.Levofloxacin resistance was more common among the unclustered strains than among the clustered strains of M.intracellulare.ConclusionM.intracellulare was the most common NTM species in China.Clarithromycin and amikacin had high antimicrobial activities against MAC.VNTR typing of MAC isolates revealed a high discriminatory power.Levofloxacin resistance was associated with unclustered strains of M.intracellulare.
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