Molecular subtyping of lung squamous cell carcinoma (LUSC) has been performed at the genomic, transcriptomic, and proteomic level. However, LUSC stratification based on tissue metabolomics is still lacking. Combining high-mass-resolution imaging mass spectrometry with consensus clustering, four tumor- and four stroma-specific subtypes with distinct metabolite patterns were identified in 330 LUSC patients.
View Article and Find Full Text PDFspp. are the causative agents of bacterial dysentery and shigellosis, mainly in children living in developing countries. The study of entire life cycle and the evaluation of vaccine candidates' protective efficacy have been hampered by the lack of a suitable animal model of infection.
View Article and Find Full Text PDFCarbon-bound exogenous compounds, such as polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines, aromatic amines, and organohalogens, are known to affect both tumor characteristics and patient outcomes in lung squamous cell carcinoma (LUSC); however, the roles of these compounds in lung adenocarcinoma (LUAD) remain unclear. We analyzed 11 carbon-bound exogenous compounds in LUAD and LUSC samples using in situ high mass-resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry imaging and performed a cluster analysis to compare the patterns of carbon-bound exogenous compounds between these two lung cancer subtypes. Correlation analyses were conducted to investigate associations among exogenous compounds, endogenous metabolites, and clinical data, including patient survival outcomes and smoking behaviors.
View Article and Find Full Text PDFPatients with the renal phosphate-wasting disease X-linked hypophosphatemia (XLH) and Hyp mice, the murine homolog of XLH, are characterized by loss-of-function mutations in phosphate-regulating endopeptidase homolog X-linked (PHEX), leading to excessive secretion of the bone-derived phosphotropic hormone FGF23. The mineralization defect in patients with XLH and Hyp mice is caused by a combination of hypophosphatemia and local accumulation of mineralization-inhibiting molecules in bone. However, the mechanism by which PHEX deficiency regulates bone cell metabolism remains elusive.
View Article and Find Full Text PDFBackground: COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response.
View Article and Find Full Text PDFBackground: Correct tumor subtyping of primary renal tumors is essential for treatment decision in daily routine. Most of the tumors can be classified based on morphology alone. Nevertheless, some diagnoses are difficult, and further investigations are needed for correct tumor subtyping.
View Article and Find Full Text PDFBackground: The response to neoadjuvant chemotherapy (NAC) differs substantially among individual patients with non-small cell lung cancer (NSCLC). Major pathological response (MPR) is a histomorphological read-out used to assess treatment response and prognosis in patients NSCLC after NAC. Although spatial metabolomics is a promising tool for evaluating metabolic phenotypes, it has not yet been utilized to assess therapy responses in patients with NSCLC.
View Article and Find Full Text PDFHigh mass resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is a suitable method for biomarker detection for several tumor entities. Renal cell carcinoma (RCC) is the seventh most common cancer type and accounts for more than 80% of all renal tumors. Prognostic biomarkers for RCC are still missing.
View Article and Find Full Text PDFPurpose: Current systems of gastric cancer molecular classification include genomic, molecular, and morphological features. Gastric cancer classification based on tissue metabolomics remains lacking. This study aimed to define metabolically distinct gastric cancer subtypes and identify their clinicopathological and molecular characteristics.
View Article and Find Full Text PDFMatrix-assisted laser desorption ionization (MALDI) Fourier transform ion cyclotron resonance (FTICR) imaging mass spectrometry (MS) is a powerful technology used to analyze metabolites in various tissues. However, it faces significant challenges in studying adipose tissues. Poor matrix distribution and crystallization caused by excess liquid lipids on the surface of tissue sections hamper m/z species detection, an adverse effect that particularly presents in lipid-rich white adipose tissue (WAT).
View Article and Find Full Text PDFTissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is not fully defined. To understand how tissues independently and collectively respond to timed exercise, we applied a systems biology approach. We mapped and compared global metabolite responses of seven different mouse tissues and serum after an acute exercise bout performed at different times of the day.
View Article and Find Full Text PDFThe response to neoadjuvant therapy can vary widely between individual patients. Histopathological tumor regression grading (TRG) is a strong factor for treatment response and survival prognosis of esophageal adenocarcinoma (EAC) patients following neoadjuvant treatment and surgery. However, TRG systems are usually based on the estimation of residual tumor but do not consider stromal or metabolic changes after treatment.
View Article and Find Full Text PDFAsymptomatic anthracosis is the accumulation of black carbon particles in adult human lungs. It is a common occurrence, but the pathophysiologic significance of anthracosis is debatable. Using high mass resolution matrix-assisted laser desorption/ionization (MALDI) fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging analysis, we discovered noxious carbon-bound exogenous compounds, such as polycyclic aromatic hydrocarbons (PAH), tobacco-specific nitrosamines, or aromatic amines, in a series of 330 patients with lung cancer in highly variable and unique patterns.
View Article and Find Full Text PDFBackground: Imaging mass spectrometry enables in situ label-free detection of thousands of metabolites from intact tissue samples. However, automated steps for multi-omics analyses and interpretation of histological images have not yet been implemented in mass spectrometry data analysis workflows. The characterization of molecular properties within cellular and histological features is done via time-consuming, non-objective, and irreproducible definitions of regions of interest, which are often accompanied by a loss of spatial resolution due to mass spectra averaging.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
February 2020
Background: Cachexia is the direct cause of at least 20% of cancer-associated deaths. Muscle wasting in skeletal muscle results in weakness, immobility, and death secondary to impaired respiratory muscle function. Muscle proteins are massively degraded in cachexia; nevertheless, the molecular mechanisms related to this process are poorly understood.
View Article and Find Full Text PDFThe domestication of wild emmer wheat led to the selection of modern durum wheat, grown mainly for pasta production. We describe the 10.45 gigabase (Gb) assembly of the genome of durum wheat cultivar Svevo.
View Article and Find Full Text PDFPseudogenes have a reputation of being 'evolutionary relics' or 'junk DNA'. While they are well characterized in mammals, studies in more complex plant genomes have so far been hampered by the absence of reference genome sequences. Barley is one of the economically most important cereals and has a genome size of 5.
View Article and Find Full Text PDFThe prediction of protein sub-cellular localization is an important step toward elucidating protein function. For each query protein sequence, LocTree2 applies machine learning (profile kernel SVM) to predict the native sub-cellular localization in 18 classes for eukaryotes, in six for bacteria and in three for archaea. The method outputs a score that reflects the reliability of each prediction.
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