Mass spectrometry and multivariate analysis to classify cervical intraepithelial neoplasia from blood plasma: an untargeted lipidomic study

Cervical cancer is still an important issue of public health since it is the fourth most frequent type of cancer in women worldwide. Much effort has been dedicated to combating this cancer, in particular by the early detection of cervical pre-cancerous lesions. For this purpose, this paper reports the use of mass spectrometry coupled with multivariate analysis as an untargeted lipidomic approach to classifying 76 blood plasma samples into negative for intraepithelial lesion or malignancy (NILM, n = 42) and squamous intraepithelial lesion (SIL, n = 34). The crude lipid extract was directly analyzed with mass spectrometry for untargeted lipidomics, followed by multivariate analysis based on the principal component analysis (PCA) and genetic algorithm (GA) with support vector machines (SVM), linear (LDA) and quadratic (QDA) discriminant analysis. PCA-SVM models outperformed LDA and QDA results, achieving sensitivity and specificity values of 80.0% and 83.3%, respectively. Five types of lipids contributing to the distinction between NILM and SIL classes were identified, including prostaglandins, phospholipids, and sphingolipids for the former condition and Tetranor-PGFM and hydroperoxide lipid for the latter. These findings highlight the potentiality of using mass spectrometry associated with chemometrics to discriminate between healthy women and those suffering from cervical pre-cancerous lesions

Speech Illusions in People at Clinical High Risk for Psychosis Linked to Clinical Outcome

BACKGROUND AND HYPOTHESIS: Around 20% of people at clinical high risk (CHR) for psychosis later develop a psychotic disorder, but it is difficult to predict who this will be. We assessed the incidence of hearing speech (termed speech illusions [SIs]) in noise in CHR participants and examined whether this was associated with adverse clinical outcomes. STUDY DESIGN: At baseline, 344 CHR participants and 67 healthy controls were presented with a computerized white noise task and asked whether they heard speech, and whether speech was neutral, affective, or whether they were uncertain about its valence. After 2 years, we assessed whether participants transitioned to psychosis, or remitted from the CHR state, and their functioning. STUDY RESULTS: CHR participants had a lower sensitivity to the task. Logistic regression revealed that a bias towards hearing targets in stimuli was associated with remission status (OR = 0.21, P = 042). Conversely, hearing SIs with uncertain valence at baseline was associated with reduced likelihood of remission (OR = 7.72. P = .007). When we assessed only participants who did not take antipsychotic medication at baseline, the association between hearing SIs with uncertain valence at baseline and remission likelihood remained (OR = 7.61, P = .043) and this variable was additionally associated with a greater likelihood of transition to psychosis (OR = 5.34, P = .029). CONCLUSIONS: In CHR individuals, a tendency to hear speech in noise, and uncertainty about the affective valence of this speech, is associated with adverse outcomes. This task could be used in a battery of cognitive markers to stratify CHR participants according to subsequent outcomes

Electro-oxidation of the dye azure B: kinetics, mechanism, and by-products

International audienc

Komplex Zinek-Schiffova báze-Novicidin jako potenciální léčba rakoviny prostaty

Prostate cancer cells control energy metabolism by chelating intracellular zinc. Thus, zinc delivery has been a popular therapeutic approach for prostate cancer. Here, we propose the use of the membrane-penetrating peptide Novicidin connected to zinc-Schiff base as a carrier vehicle for the delivery of zinc to prostate cells. Mass spectrometry, electrochemistry and spectrophotometry confirmed the formation/stability of this complex and provided insight regarding the availability of zinc for complex interactions. This delivery system showed minor toxicity in normal PNT1A cells and high potency towards PC3 tumor cells. The complex preferentially penetrated PC3 tumor cells in contrast to confinement to the membranes of PNT1A. Furthermore, zinc uptake was confirmed in both cell lines. Molecular analysis was used to confirm the activation of zinc stress (e.g., ZnT-1) and apoptosis (e.g., CASP-1). Our results strongly suggest that the zinc-Schiff base-Novicidin complex has great potential as a novel anticancer drug.Buňky rakoviny prostaty ovládají energetický metabolismus chelatací intracelulárního zinku. Tedy dodání zinku bylo populární jako terapeutický přístup k léčbě rakoviny prostaty. Zde navrhujeme použití membránou pronikajícího peptidu novicidinu připojeného k Schiffově bázi se zinkem jako nosného prostředku pro dodání zinku do buněk prostaty. Hmotnostní spektrometrie, elektrochemie a spektrofotometrie potvrdily tvorbu a stabilitu tohoto komplexu a poskytly pochopení ohledně dostupnosti zinku pro komplexní interakce. Tento systém ukázal menší toxicitu v normálních buňkách PNT1A a vysokou účinnost vůči nádorovým buňkám PC3. Komplex přednostně pronikl nádorovými buňkami PC3 na rozdíl od uzavření se membránám PNT1A. Dále byl potvrzen příjem zinku v obou buněčných linií. Molekulární analýza byla použita k potvrzení aktivace zinkového stresu (např. ZnT-1) a apoptózy (např. CASP-1). Naše výsledky silně naznačují, že komplex zinek-Schiffova báze-novicidin má velký potenciál jako nové protinádorové léčivo