Spatial metabolomics in head and neck tumors: a review

The joint analysis of single-cell transcriptomics, proteomics, lipidomics, metabolomics and spatial metabolomics is continually transforming our understanding of the mechanisms of metabolic reprogramming in tumor cells. Since head and neck tumor is the sixth most common tumor in the world, the study of the metabolic mechanism of its occurrence, development and prognosis is still undeveloped. In the past decade, this field has witnessed tremendous technological revolutions and considerable development that enables major breakthroughs to be made in the study of human tumor metabolism. In this review, a comprehensive comparison of traditional metabolomics and spatial metabolomics has been concluded, and the recent progress and challenges of the application of spatial metabolomics combined multi-omics in the research of metabolic reprogramming in tumors are reviewed. Furthermore, we also highlight the advances of spatial metabolomics in the study of metabolic mechanisms of head and neck tumors, and provide an outlook of its application prospects

The Association and Clinical Significance of CDKN2A Promoter Methylation in Head and Neck Squamous Cell Carcinoma: a Meta-Analysis

Background/Aims: The association between cyclin-dependent kinase inhibitor 2A (CDKN2A) hypermethylation and head and neck squamous cell carcinoma (HNSCC) risk has been investigated by a number of studies. However, these studies have not demonstrated consistent results. Moreover, the role of CDKN2A methylation in HNSCC carcinogenesis and its clinical significance remain unclear. Methods: We performed a systematic meta-analysis based on 72 articles (including 3399 HNSCCs, 668 premalignant lesions, and 2393 normal controls) from the PubMed, Google Scholar, Web of Science, Embase, China National Knowledge Infrastructure and Wanfang databases. Results: Our study showed a significant increase in the frequency of CDKN2A methylation during HNSCC carcinogenesis (HNSCC vs. normal controls, odds ratio (OR) = 6.72, P < 0.01; HNSCC vs. precancerous lesions, OR = 1.89, P < 0.05; precancerous lesions vs. normal controls, OR = 14.70, P < 0.01). Moreover, CDKN2A methylation was significantly associated with gender (OR = 1.34; P < 0.05) and lymph node metastasis (OR = 2.32; P < 0.01). The area under summary receiver operating characteristic curve (AUC) for diagnosis of HNSCC based on all samples and saliva sample subgroup were 0.77 and 0.96, respectively. Additionally, CDKN2A hypermethylation was significantly associated with shorter overall survival (OS) (hazard ratio (HR) = 1.01, P < 0.05) and recurrence-free survival (RFS) (HR = 1.77, P < 0.05). Conclusion: Our findings indicate CDKN2A methylation is involved in the carcinogenesis, progression, and metastasis of HNSCC. Furthermore, methylated CDKN2A could be a potential diagnostic and prognostic biomarker for HNSCC

Skeletal Muscle Regeneration on Protein-Grafted and Microchannel-Patterned Scaffold for Hypopharyngeal Tissue Engineering

In the field of tissue engineering, polymeric materials with high biocompatibility like polylactic acid and polyglycolic acid have been widely used for fabricating living constructs. For hypopharynx tissue engineering, skeletal muscle is one important functional part of the whole organ, which assembles the unidirectionally aligned myotubes. In this study, a polyurethane (PU) scaffold with microchannel patterns was used to provide aligning guidance for the seeded human myoblasts. Due to the low hydrophilicity of PU, the scaffold was grafted with silk fibroin (PU-SF) or gelatin (PU-Gel) to improve its cell adhesion properties. Scaffolds were observed to degrade slowly over time, and their mechanical properties and hydrophilicities were improved through the surface grafting. Also, the myoblasts seeded on PU-SF had the higher proliferative rate and better differentiation compared with those on the control or PU-Gel. Our results demonstrate that polyurethane scaffolds seeded with myoblasts hold promise to guide hypopharynx muscle regeneration

ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway

Sepsis is a life-threatening multiple organ dysfunction syndrome (MODS) caused by a microbial infection that leads to high morbidity and mortality worldwide. Sepsis-induced cardiomyopathy (SIC) and coagulopathy promote the progression of adverse outcomes in sepsis. Here, we reported that ACT001, a modified compound of parthenolide, improved the survival of sepsis mice. In this work, we used cecal ligation and puncture (CLP) model to induce SIC. Transthoracic echocardiography and HE staining assays were adopted to evaluate the influence of ACT001 on sepsis-induced cardiac dysfunction. Our results showed that ACT001 significantly improved heart function and reduced SIC. Coagulation accelerates organ damage in sepsis. We found that ACT001 decreased blood clotting in the FeCl3-induced carotid artery thrombosis experiment. ACT001 also reduced the production of neutrophil extracellular traps (NETs). RNA-sequencing of heart tissues revealed that ACT001 significantly downregulated the expression of pro-inflammatory cytokines and the JAK-STAT signaling pathway. These results were confirmed with real-time PCR and ELISA. In summary, we found ACT001 rescued mice from septic shock by protecting the cardiovascular system. This was partially mediated by inhibiting pro-inflammatory cytokine production and down-regulating the JAK-STAT signaling

Study of brain network alternations in non-lesional epilepsy patients by BOLD-fMRI

ObjectiveTo investigate the changes of brain network in epilepsy patients without intracranial lesions under resting conditions.MethodsTwenty-six non-lesional epileptic patients and 42 normal controls were enrolled for BOLD-fMRI examination. The differences in brain network topological characteristics and functional network connectivity between the epilepsy group and the healthy controls were compared using graph theory analysis and independent component analysis.ResultsThe area under the curve for local efficiency was significantly lower in the epilepsy patients compared with healthy controls, while there were no differences in global indicators. Patients with epilepsy had higher functional connectivity in 4 connected components than healthy controls (orbital superior frontal gyrus and medial superior frontal gyrus, medial superior frontal gyrus and angular gyrus, superior parietal gyrus and paracentral lobule, lingual gyrus, and thalamus). In addition, functional connectivity was enhanced in the default mode network, frontoparietal network, dorsal attention network, sensorimotor network, and auditory network in the epilepsy group.ConclusionThe topological characteristics and functional connectivity of brain networks are changed in in non-lesional epilepsy patients. Abnormal functional connectivity may suggest reduced brain efficiency in epilepsy patients and also may be a compensatory response to brain function early at earlier stages of the disease

Realising advanced risk-based port state control inspection using data-driven Bayesian networks

In the past decades, maritime transportation not only contributes to economic prosperity, but also renders many threats to the industry, causing huge casualties and losses. As a result, various maritime safety measures have been developed, including Port State Control (PSC) inspections. In this paper, we propose a data-driven Bayesian Network (BN) based approach to analyse risk factors influencing PSC inspections, and predict the probability of vessel detention. To do so, inspection data of bulk carriers in seven major European countries from 2005 to 2008 1 in Paris MoU is collected to identify the relevant risk factors. Meanwhile, the network structure is constructed via TAN learning and subsequently validated by sensitivity analysis. The results reveal two conclusions: first, the key risk factors influencing PSC inspections include number of deficiencies, type of inspection, Recognised Organisation (RO) and vessel age. Second, the model exploits a novel way to predict the detention probabilities under different situations, which effectively help port authorities to rationalise their inspection regulations as well as allocation of the resources. Further effort will be made to conduct contrastive analysis between ‘Pre-NIR’ period and ‘Post-NIR’ period to test the impact of NIR started in 2008. © 2018 Elsevier Lt

Predicting the prognosis, immune response, and immunotherapy in head and neck squamous cell carcinoma using a novel risk model based on anoikis-related lncRNAs

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is an extremely heterogeneous and metastatic disease. Anoikis, which is a specific type of programmed apoptosis, is involved in tumor metastasis, tissue homeostasis, and development. Herein, we constructed an anoikis-related long non-coding RNA (lncRNA) signature to predict the prognosis, immune responses, and therapeutic effects in HNSCC patients. Methods A total of 501 HNSCC samples were acquired from the TCGA database and randomly classified into the training and validation groups (1:1 ratio). Thereafter, the results derived from the training set were analyzed with the LASSO regression analysis, and a novel anoikis-related lncRNA risk model was constructed. Time-dependent ROC curves and Kaplan–Meier analysis were carried out to assess the diagnostic value and survival outcomes. A nomogram was utilized to predict the prognostic accuracy. Furthermore, we studied the tumor microenvironment, tumor mutation burden, enrichment pathways, and the response to chemotherapy and immunotherapy. Results Seven anoikis-related lncRNAs (AC015878.1, CYTOR, EMSLR, LINC01503, LINC02084, RAB11B-AS1, Z97200.1) were screened to design a novel risk model, which was recognized as the independent prognostic factor for HNSCC patients. The findings implied that low-risk patients showed significantly longer OS, PFS, and DSS compared to those high-risk patients. The two groups that were classified using the risk model showed significant differences in their immune landscape. The risk model also predicted that low-risk HNSCC patients could attain a better response to immunotherapy, while high-risk patients would be more sensitive to gemcitabine, docetaxel, and cisplatin. Conclusions We constructed a novel risk model that could be employed for effectively predicting patient prognosis with a good independent prognostic value for HNSCC patients. Furthermore, this model could be used for designing new immunotherapeutic and chemotherapeutic strategies, and it helps clinicians establish personalized and detailed strategies for HNSCC patients

High molecular weight poly(butylene terephthalate-co-butylene 2,5-furan dicarboxylate) copolyesters: From synthesis to thermomechanical and barrier properties

Poly(butylene terephthalate-co-butylene 2,5-furandicarboxylate) copolyesters (PBTFs) were synthesized from 1,4-butanediol, dimethyl terephthalate (DMT), and 2,5-furandicarboxylic acid (FDCA) by a two-step polymerization method. Their chemical structures were confirmed by Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and carbon nuclear magnetic resonance before thermal properties were explored with differential scanning calorimeter and thermogravimetric analyzer. Results showed that PBTFs changed from semi-crystalline to completely amorphous when the content of FDCA unit was increased to 45 mol% at first, and then became crystallographic again with the further increment of FDCA unit to 75 mol%. For their mechanical properties, the tensile modulus and strength showed the similar trend, decreasing firstly and then increasing later. Their barrier to carbon dioxide and oxygen became better with the increasing of furan content due to the rigidity and higher polarity of furan ring. The performance of PBTFs copolyesters was investigated clearly, and the relative content of FDCA and DMT can be adjusted to satisfy different performance requirements