DESI-MSI and METASPACE indicates lipid abnormalities and altered mitochondrial membrane components in diabetic renal proximal tubules

Zhang, Guanshi; Zhang, Jialing; DeHoog, Rachel J.; Pennathur, Subramaniam; Anderton, Christopher; Venkatachalam, Manjeri A.; Alexandrov, Theodore; Eberlin, Lívia S.; Sharma, Kumar

doi:10.1007/s11306-020-1637-8

Cited by 39 publications

(42 citation statements)

References 65 publications

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“…One group with the purified biofertilizer (average area = 1.52, SD = 0.82) and the second group with the control nodules and non-purified biofertilizer (average area = 3.02, SD = 0.49; average area = 3.08, SD = 0.41, respectively). The mature nodules have a lower amount of phospholipids than the immature ones [ 26 ]. It can be therefore concluded that the nodules from plants treated with purified biofertilizer mature faster than those from the control samples or treated with non-purified biofertilizer.…”

Section: Resultsmentioning

confidence: 99%

Multimodal Spectroscopic Imaging of Pea Root Nodules to Assess the Nitrogen Fixation in the Presence of Biofertilizer Based on Nod-Factors

Suśniak

Krysa

Kidaj

et al. 2021

IJMS

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Multimodal spectroscopic imaging methods such as Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI MSI), Fourier Transform Infrared spectroscopy (FT-IR) and Raman spectroscopy were used to monitor the changes in distribution and to determine semi quantitatively selected metabolites involved in nitrogen fixation in pea root nodules. These approaches were used to evaluate the effectiveness of nitrogen fixation by pea plants treated with biofertilizer preparations containing Nod factors. To assess the effectiveness of biofertilizer, the fresh and dry masses of plants were determined. The biofertilizer was shown to be effective in enhancing the growth of the pea plants. In case of metabolic changes, the biofertilizer caused a change in the apparent distribution of the leghaemoglobin from the edges of the nodule to its centre (the active zone of nodule). Moreover, the enhanced nitrogen fixation and presumably the accelerated maturation form of the nodules were observed with the use of a biofertilizer.

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Section: Resultsmentioning

confidence: 99%

Multimodal Spectroscopic Imaging of Pea Root Nodules to Assess the Nitrogen Fixation in the Presence of Biofertilizer Based on Nod-Factors

Suśniak

Krysa

Kidaj

et al. 2021

IJMS

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“…GPLs are necessary for cells to maintain homeostasis and normal physiological functions. Disorders of GPLs are obviously involved in benign disease and cancers [22][23][24][25]. The identification of dysregulated GPL-related genes may provide a novel perspective for EC therapy.…”

Section: Discussionmentioning

confidence: 99%

Elevated expression of LPCAT1 predicts a poor prognosis and is correlated with the tumour microenvironment in endometrial cancer

Zhao

Han

et al. 2021

Cancer Cell Int

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Background Endometrial cancer (EC) is one of the three malignant reproductive tumours that threaten women’s lives and health. Glycerophospholipids (GPLs) are important bioactive lipids involved in various physiological and pathological processes, including cancer. Immune infiltration of the tumour microenvironment (TME) is positively associated with the overall survival in EC. Exploring GPL-related factors associated with the TME in endometrial cancer can aid in the prognosis of patients and provide new therapeutic targets. Methods Differentially expressed GPL-related genes were identified from TCGA-UCEC datasets and the Molecular Signatures Database (MSigDB). Univariate Cox regression analysis was used to select GPL-related genes with prognostic value. The Random forest algorithm, LASSO algorithm and PPI network were used to identify critical genes. ESTIMATEScore was calculated to identify genes associated with the TME. Then, differentiation analysis and survival analysis of LPCAT1 were performed based on TCGA datasets. GSE17025 and immunohistochemistry (IHC) verified the results of the differentiation analysis. An MTT assay was then conducted to determine the proliferation of EC cells. GO and KEGG enrichment analyses were performed to explore the underlying mechanism of LPCAT1. In addition, we used the ssGSEA algorithm to explore the correlation between LPCAT1 and cancer immune infiltrates. Results Twenty-three differentially expressed GPL-related genes were identified, and eleven prognostic genes were selected by univariate Cox regression analysis. Four significant genes were identified by two different algorithms and the PPI network. Only LPCAT1 was significantly correlated with the tumour microenvironment. Then, we found that LPCAT1 was highly expressed in tumour samples compared with that in normal tissues, and lower survival rates were observed in the groups with high LPCAT1 expression. Silencing of LPCAT1 inhibited the proliferation of EC cells. Moreover, the expression of LPCAT1 was positively correlated with the histologic grades and types. The ROC curve indicated that LPCAT1 had good prognostic accuracy. Receptor ligand activity, pattern specification process, regionalization, anterior/posterior pattern specification and salivary secretion pathways were enriched as potential targets of LPCAT1. By using the ssGSEA algorithm, fifteen kinds of tumor-infiltrating cells (TICs) were found to be correlated with LPCAT1 expression. Conclusion These findings suggested that LPCAT1 may act as a valuable prognostic biomarker and be correlated with immune infiltrates in endometrial cancer, which may provide novel therapy options for and improved treatment of EC.

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“…A limitation of our study is that while the cortex is mainly composed of proximal tubules by volume, it still represents a mixture of different cell types in the kidney, and the spatial localization of 2-HG remains unknown. Mass spectrometry imaging (MSI) with desorption electrospray ionization mass spectrometry (DESI) and matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF) have been used in human and murine models of DKD for compartment-specific expression of metabolites [ 41 , 42 , 43 ], and 2-HG detection with MALDI-TOF has been accomplished in brain tumors with IDH mutations [ 44 ]. However, no current MALDI-TOF data are available for 2-HG levels in DKD.…”

Section: Discussionmentioning

confidence: 99%

Urinary 2-Hydroxyglutarate Enantiomers Are Markedly Elevated in a Murine Model of Type 2 Diabetic Kidney Disease

Baek

Pennathur

2021

Metabolites

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Metabolic reprogramming is a hallmark of diabetic kidney disease (DKD); nutrient overload leads to increased production of metabolic byproducts that may become toxic at high levels. One metabolic byproduct may be 2-hydroxyglutarate (2-HG), a metabolite with many regulatory functions that exists in both enantiomeric forms physiologically. We quantitatively determined the levels of L and D-2HG enantiomers in the urine, plasma, and kidney cortex of db/db mice, a pathophysiologically relevant murine model of type 2 diabetes and DKD. We found increased fractional excretion of both L and D-2HG enantiomers, suggesting increased tubular secretion and/or production of the two metabolites in DKD. Quantitation of TCA cycle metabolites in db/db cortex suggests that TCA cycle overload and an increase in 2-HG precursor substrate, α-ketoglutarate, drive the increased L and D-2HG production in DKD. In conclusion, we demonstrated increased 2-HG enantiomer production and urinary excretion in murine type 2 DKD, which may contribute to metabolic reprogramming and progression of diabetic kidney disease.

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DESI-MSI and METASPACE indicates lipid abnormalities and altered mitochondrial membrane components in diabetic renal proximal tubules

Cited by 39 publications

References 65 publications

Multimodal Spectroscopic Imaging of Pea Root Nodules to Assess the Nitrogen Fixation in the Presence of Biofertilizer Based on Nod-Factors

Multimodal Spectroscopic Imaging of Pea Root Nodules to Assess the Nitrogen Fixation in the Presence of Biofertilizer Based on Nod-Factors

Elevated expression of LPCAT1 predicts a poor prognosis and is correlated with the tumour microenvironment in endometrial cancer

Urinary 2-Hydroxyglutarate Enantiomers Are Markedly Elevated in a Murine Model of Type 2 Diabetic Kidney Disease

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