Case report of rapidly progressive proliferative verrucous leukoplakia and a proposal for aetiology in mainland China

Proliferative verrucous leukoplakia (PVL) is a rare oral leukoplakia and has four features such as chronic proliferation, multiple occurrences, refractoriness to treatment and high rate of malignant transformation. As mentioned above, most PVL cases processed to malignancy over many years, sometimes 20 years. However, this report described a case of rapid progress, which had malignant transformation in a short period. Additionally, the aetiology of PVL was discussed and immunity was proposed as the possible cause

Expression of indoleamine 2,3-dioxygenase in nasopharyngeal carcinoma impairs the cytolytic function of peripheral blood lymphocytes

<p>Abstract</p> <p>Background</p> <p>Tumor-specific cytotoxic T cells and infiltrating lymphocytes are frequently found in tumor tissues in patients with nasopharyngeal carcinoma (NPC). Most patients with NPC, however, especially those with advanced stages, have a poor clinical prognosis despite conventional immunotherapy. The aim of this work was to examine the effect of indoleamine 2,3-dioxygenase (IDO), an immunosuppressive enzyme, on the lymphocyte function in NPC.</p> <p>Methods</p> <p>The NPC cell line CNE2 was treated by interferon-γ (IFNγ) and the levels of IDO expression was analyzed by Western blotting and reverse phase high-performance liquid chromatography (HPLC). Lymphocytes from health human exposed to the milieu created by IDO-positive CNE2 cells and the lymphocyte cytotoxicity to target tumor cells was analyzed by standard lactate dehydrogenase (LDH) release assay. Additionally, expression of IDO was determined by Immunohistochemical assay in the tumor tissues form clinically evaluated NPC.</p> <p>Results</p> <p>IDO expression was acutely induced in the NPC cell line CNE2 by low dose interferon-γ (IFNγ) or by co-incubation with activated lymphocytes. Exposure to the milieu created by IDO-positive CNE2 cells did not promote lymphocyte death, but lymphocyte cytotoxicity against target tumor cells was impaired. The suppression of lymphocyte cytotoxic function was fully restored when the conditioned medium was replaced by fresh medium for 24 h. In additionally, the IDO-positive cells were found scattered in the tumor tissues from patients with NPC.</p> <p>Conclusion</p> <p>Altogether, these findings suggest that IDO-mediated immunosuppression may be involved in the tumor immune evasion, and that blocking IDO activity in tumor cells may help to re-establish an effective anti-tumor T cell response in NPC.</p

Antimicrobial peptaibols, novel suppressors of tumor cells, targeted calcium-mediated apoptosis and autophagy in human hepatocellular carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is one of the most common cancers in the world which is highly chemoresistant to currently available chemotherapeutic agents. Thus, novel therapeutic targets are needed to be sought for the successful treatment of HCC. Peptaibols, a family of peptides synthesized non-ribosomally by the <it>Trichoderma </it>species and other fungi, exhibit antibiotic activities against bacteria and fungi. Few studies recently showed that peptaibols exerted cytotoxicity toward human lung epithelial and breast carcinoma cells. However, the mechanism involved in peptaibol-induced cell death remains poorly understood.</p> <p>Results</p> <p>Here, we showed that Trichokonin VI (TK VI), a peptaibol from <it>Trichoderma pseudokoningii </it>SMF2, induced growth inhibition of HCC cells in a dose-dependent manner. It did not obviously impair the viability of normal liver cells at lower concentration. Moreover, the suppression of cell viability resulted from the programmed cell death (PCD) with characteristics of apoptosis and autophagy. An influx of Ca²⁺triggered the activation of μ-calpain and proceeded to the translocation of Bax to mitochondria and subsequent promotion of apoptosis. On the other hand, typically morphological characteristics consistent with autophagy were also observed by punctate distribution of MDC staining and the induction of LC3-II, including extensive autophagic vacuolization and enclosure of cell organelles by these autophagosomes. More significantly, specific depletion of Bak expression by small RNA interfering (siRNA) could partly attenuate TK VI-induced autophagy. However, siRNA against Bax led to increased autophagy.</p> <p>Conclusion</p> <p>Taken together, these findings showed for the first time that peptaibols were novel regulators involved in both apoptosis and autophagy, suggesting that the class of peptaibols might serve as potential suppressors of tumor cells.</p

Stemness And Chemotherapeutic Drug Resistance Induced By Eif5a2 Overexpression In Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the digestive tract in East Asian countries. Multimodal therapies, including adjuvant chemotherapy and neo-adjuvant chemotherapy, have become more often used for patients with advanced ESCC. However, the chemotherapy effect is often limited by patients' drug resistance. This study demonstrated that EIF5A2 (eukaryotic translation initiation factor 5A2) overexpression induced stemness and chemoresistance in ESCC cells. We showed that EIF5A2 overexpression in ESCC cells resulted in increased chemoresistance to 5-fluorouracil (5-FU), docetaxel and taxol. In contrast, shRNAs suppressing eIF5A2 increased tumor sensitivity to these chemotherapeutic drugs. In addition, EIF5A2 overexpression was correlated with a poorer overall survival in patients with ESCC who underwent taxane-based chemotherapy after esophagectomy (P > 0.05). Based on these results, we suggest that EIF5A2 could be a predictive biomarker for selecting appropriate chemo-treatment for ESCC patients and EIF5A2 inhibitors might be considered as combination therapy to enhance chemosensitivity in patients with ESCC.published_or_final_versio

Comparison of ischemic stroke diagnosis models based on machine learning

BackgroundThe incidence, prevalence, and mortality of ischemic stroke (IS) continue to rise, resulting in a serious global disease burden. The prediction models have a great value in the early prediction and diagnosis of IS.MethodsThe R software was used to screen the differentially expressed genes (DEGs) of IS and control samples in the datasets GSE16561, GSE58294, and GSE37587 and analyze DEGs for enrichment analysis. The feature genes of IS were obtained by several machine learning algorithms, including the least absolute shrinkage and selector operation (LASSO) logistic regression, the support vector machine-recursive feature elimination (SVM-RFE), and the Random Forest (RF). The IS diagnostic models were constructed based on transcriptomics by machine learning and artificial neural network (ANN).ResultsA total of 69 DEGs, mainly involved in immune and inflammatory responses, were identified. The pathways enriched in the IS group were complement and coagulation cascades, lysosome, PPAR signaling pathway, regulation of autophagy, and toll-like receptor signaling pathway. The feature genes selected by LASSO, SVM-RFE, and RF were 17, 10, and 12, respectively. The area under the curve (AUC) of the LASSO model in the training dataset, GSE22255, and GSE195442 was 0.969, 0.890, and 1.000. The AUC of the SVM-RFE model was 0.957, 0.805, and 1.000, respectively. The AUC of the RF model was 0.947, 0.935, and 1.000, respectively. The models have good sensitivity, specificity, and accuracy. The AUC of the LASSO+ANN, SVM-RFE+ANN, and RF+ANN models was 1.000, 0.995, and 0.997, respectively, in the training dataset. However, the AUC of LASSO+ANN, SVM-RFE+ANN, and RF+ANN models was 0.688, 0.605, and 0.619, respectively, in the GSE22255 dataset. The AUC of the LASSO+ANN and RF+ANN models was 0.740 and 0.630, respectively, in the GSE195442 dataset. In the training dataset, the sensitivity, specificity, and accuracy of the LASSO+ANN model were 1.000, 1.000, and 1.000, respectively; of the SVM-RFE+ANN model were 0.946, 0.982, and 0.964, respectively; and of the RF+ANN model were 0.964, 1.000, and 0.982, respectively. In the test datasets, the sensitivity was very satisfactory; however, the specificity and accuracy were not good.ConclusionThe LASSO, SVM-RFE, and RF models have good prediction abilities. However, the ANN model is efficient at classifying positive samples and is unsuitable at classifying negative samples

Long Non-Coding RNA Expression Profiles for the Characterization of Different Bladder Cancer Grade

Background/Aims: Bladder cancer (BC) is one of the most frequent urologic tumors worldwide. However, long non-coding RNA(lncRNA) expression profiles in BC progression remain unclear. This study aimed to explore lncRNA expression profiles in different grades of bladder cancer and normal urothelium tissues. Methods: We performed high-throughput sequencing in BC tissues of different grade and obtained the expression profiles of its lncRNAs. Then, aberrantly expressed lncRNAs were validated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Gene Ontology (GO) and pathway analyses were used to investigate the potential function of these lncRNAs. Co-expresson network was constructed to explore the relationship between lncRNAs and target mRNAs. Results: We identified 252 aberrantly expressed lncRNAs in high-grade BC while compared to low-grade BC, and 269 lncRNAs in high-grade BC while compared to normal urothelium. Notably, we found 33 overlapped lncRNAs. Subsequently, 7 lncRNAs were selected from the overlapped part and confirmed by RT-PCR. GO and pathway analyses showed that these dysregulated lncRNAs participated in cell migration, cell adhesion, as well as Ras signaling pathway. Co-expression network and The Cancer Genome Atlas (TCGA) data showed LUCAT1 and CCNB1 had positive relationship in regulating the progress of bladder cancer. Conclusion: Our findings revealed the significant role of lncRNAs in the development process of bladder cancer

The neural correlates of value hierarchies: a prospective typology based on personal value profiles of emerging adults

IntroductionValue hierarchies, as motivational goals anchored in the self-schema, may be correlated with spontaneous activity in the resting brain, especially those involving self-relevance. This study aims to investigate the neural correlates of value hierarchies from the perspective of typology.MethodsA total of 610 Chinese college students (30.31% women), aged 18 to 23, completed the personal values questionnaire and underwent resting-state functional magnetic resonance imaging.ResultsThe latent profile analysis revealed three personal value profiles: traditional social orientation, modernized orientation, and undifferentiated orientation. Neuroimaging results revealed that individuals with modernized orientation prioritized openness to change value, and this personal-focus is related to the higher low-frequency amplitude of the posterior insula; individuals with traditional social orientation prioritized self-transcendence and conservation values, and this social-focus is related to the stronger functional connectivity of the middle insula with the inferior temporal gyrus, temporal gyrus, posterior occipital cortex, and basal ganglia, as well as weaker functional connections within the right middle insula.DiscussionTaken together, these findings potentially indicate the intra-generational differentiation of contemporary Chinese emerging adults’ value hierarchies. At the neural level, these are correlated with brain activities involved in processing self- and other-relevance