Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3)

BackgroundIncreased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known.Materials and methodsFor this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models.ResultsPAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19–1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36–2.10), men (OR: 1.60, 95% CI: 1.28–2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34–2.23).ConclusionBased on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.     

雷藤舒对TNF-α诱导的人类风湿关节炎滑膜成纤维细胞促凋亡、抗炎及对Ras-MAPKs信号通路的调节作用

目的:观察雷藤舒(LLDT-8)对肿瘤坏死因子-α(TNF-α)诱导的人类风湿关节炎滑膜成纤维细胞(RA-HFLS)的促凋亡、抗炎作用,以及可能的作用机制。方法:在体外培养的RA-HFLS体系中,实验组加入终浓度为50 nmol/L的LLDT-8与终浓度为20 ng/ml TNF-α共孵育,同时设置细胞空白对照组和TNF-α刺激组。采用TUNEL法检测RA-HFLS细胞的凋亡;RT-PCR检测Bcl-2 mRNA表达水平;ELISA和RTPCR分别检测IL-6、MMP-3的表达;Western-blot检测Ras-MAPKs信号通路的磷酸化水平和蛋白表达。结果:与空白对照组比较,LLDT-8组细胞凋亡率明显增加(P0.01)。LLDT-8能显著抑制TNF-α诱导的RA-HFLS分泌IL-6、MMP-3的表达(P0.01);能明显抑制Ras蛋白和p-P38磷酸化水平,而各组之间pERK、p-JNK、c-Fos、c-Jun和c-Myc的磷酸化水平和蛋白表达差异无统计学意义。结论:LLDT-8能够抑制Ras-p38 MAPK信号转导通路的异常活化,从而抑制RA滑膜的增殖,减轻滑膜细胞的炎症。     

Effect of meditation on intracerebral EEG in a patient with temporal lobe epilepsy: A case report

Meditation has been deemed a miracle cure for a wide range of neurological disorders. However, it is unclear whether meditation practice would be beneficial for patients suffering from epilepsy. Here we report on the comparison of the effects of focused-attention meditation and a control task on electroencephalographic (EEG) activity in a patient undergoing stereoencephalographic (SEEG) investigation for drug-resistant epilepsy. The patient routinely practiced focused-attention meditation and reported that she found it beneficial. During the SEEG investigation, intracerebral EEG data were recorded during meditation as well as during mind-wandering task. The EEG data were analyzed for type of electrical activity (labeled) by two expert epileptologists. We found that the proportion of EEG segments containing activity classified as interictal epileptiform discharges (IEDs; abnormal electrical activity that occurs between seizures) increased significantly during meditation practice. Although the finding was surprising, this increase in IEDs may not correlate with an increase in seizure frequency, and the patient might still benefit from practicing meditation. The finding does, however, warrant further studies on the influence of meditation on epileptic activity.     

Development of the decision tree model for distinguishing individuals of Chinese four surnames from Zhanjiang Han population based on Y-STR haplotypes

Co-separation studies between surnames and Y chromosome genetic markers are beneficial to revealing population migrations, surname origins, population formation histories and forensic familial searching. Genetic distributions of 27 Y-STRs in Chinese four surnames (Li, Lin, Chen and Huang) from Zhanjiang Han population were investigated. Meanwhile, we tried to develop a decision tree model for surname predictions based on Y-STR haplotypes. Allelic frequencies of 27 Y-STRs showed that unique alleles were only observed in a certain surname; besides, some alleles displayed higher frequencies in a certain surname than those in other surnames, implying these alleles might be employed as the useful indicators for surname predictions. Haplotype match probability values of 27 Y-STRs in these surnames revealed that the system could be used as a valuable tool for forensic male identification. The developed decision tree model performed well for the training set with the accuracy of 0.9860 and obtained the relatively high accuracy (>0.70) for surname predictions of the testing set. To sum up, we explored the power of the machine learning to the surname predictions based on obtained Y-STR haplotypes, which showed promising application values in forensic familial searching.     

Overview of prospects for inflammation pathways in autism spectrum disorders

Autism spectrum disorders (ASD) represent a heterogeneous group of neurodevelopmental disorders which are both severe and frequent. Understanding its pathophysiology could lead to identifying promising new markers and treatments. For years, a growing number of studies have pointed to an important involvement of the immuno-inflammatory system in ASD. Extensive reviews have already addressed this topic. Yet, this field of investigations is not well known to practitioners even those working with ASD patients. Our main objective is to provide an introduction to these new insights through a mini review of the literature. A first field of antenatal studies connects fetal features and maternal infections to ASD by means of the participation of maternal immune activation (MIA) associated with the production of a particular pro inflammatory cytokinic profile with IL-1, IL-6 and TNF and IL-17. Maternal autoantibodies and other immune-related disorders can also lead to impairment of fetal neurodevelopment. Other postnatal studies have shown the correlation between ASD and autoantibodies and between ASD and inflammatory environment through impaired interleukin levels (IL-6 being the most extensively investigated). Disruption of intestinal microbiota appears to be a possible pathogenic mechanism of ASD. The growing paths opened recently between immunology and psychiatry appear to be promising in the understanding of ASD. It could eventually participate in the development of diagnostic markers and help the emergence of new personalized therapeutics suitable for these patients.     

Cervicovaginal shedding of hepatitis C viral RNA is associated with the presence of menstrual or other blood in cervicovaginal fluids

BackgroundThe role of sexual activity in hepatitis C virus (HCV) transmission remains controversial. Studies to date have not explored the relationship between HCV shedding in cervicovaginal fluids and the presence of menstrual or other blood.ObjectivesSince cross-sectional studies may underestimate the prevalence of viral shedding, we performed a 56-day longitudinal study of cervical HCV shedding.Study designWomen self-collected cervicovaginal swabs for 56 consecutive days, while keeping a diary of menses and genital symptoms. Swabs were tested for HCV RNA and cellular DNA by quantitative PCR, and hemoglobin by spectrophotometry.ResultsSixteen women contributed a total of 701 cervicovaginal swabs (mean collection period 48 days, range 18–56). Detection of HCV RNA was associated with detection of hemoglobin. Premenopausal women were more likely than post-menopausal women to have HCV RNA detected in cervicovaginal fluids. For premenopausal women, detection of HCV RNA was more likely during menstruation (OR = 56.4) or when hemoglobin was detected in cervicovaginal fluids, even if menstruation was not occurring (OR = 35.4). No woman post-hysterectomy had HCV RNA detected in cervicovaginal fluids on any day, regardless of whether hemoglobin was detected.ConclusionsOur findings are consistent with a low likelihood of sexual transmission of HCV. The results suggest that shedding of HCV RNA in the female genital tract is associated with the presence of blood, and requires the presence of a cervix. Clinicians should consider advising premenopausal women who are concerned about transmitting infection that infectivity may increase during menstruation.     

Acquired Antibodies to αIIbβ3 in Glanzmann Thrombasthenia: From Transfusion and Pregnancy to Bone Marrow Transplants and Beyond

Patients with the inherited bleeding disorder Glanzmann thrombasthenia (GT) possess platelets that lack αIIbβ3 integrin and fail to aggregate, and have moderate to severe mucocutaneous bleeding. Many become refractory to platelet transfusions due to the formation of isoantibodies to αIIbβ3 with the rapid elimination of donor platelets and/or a block of function. Epitope characterization has shown isoantibodies to be polyclonal and to recognize different epitopes on the integrin with β3 a major site and αvβ3 on endothelial and vascular cells a newly recognized target. Pregnancy in GT can also lead to isoantibody formation when fetal cells with β3 integrins pass into the circulation of a mother lacking them; a consequence is neonatal thrombocytopenia and a high risk of mortality. Antibody removal prior to donor transfusions can provide transient relief, but all evidence points to recombinant FVIIa as the first choice for GT patients either to stop bleeding or as prophylaxis. Promoting thrombin generation by rFVIIa favors GT platelet interaction with fibrin, and the risk of deep vein thrombosis also associated with prolonged immobilization and catheter use requires surveillance. Although having a high risk, allogeneic bone marrow transplantation associated with different stem cell sources and conditioning regimens has proved successful in many cases of severe GT with antibodies, and often, the associated conditioning and immunosuppressive therapy leads to loss of isoantibody production. Animal models of gene therapy for GT show promising results, but isoantibody production can be stimulated and CRISPR/Cas9 technology has yet to be applied. Up-to-date consensus protocols for dealing with isoantibodies in GT are urgently required, and networks providing patient care should be expanded.