Deep serum lipidomics identifies evaluative and predictive biomarkers for individualized glycemic responses following low-energy diet-induced weight loss: a PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) substudy.

Background: Weight loss through lifestyle interventions, notably low-energy diets, offers glycemic benefits in populations with overweight-associated prediabetes. However, >50% of these individuals fail to achieve normoglycemia after weight loss. Circulating lipids hold potential for evaluating dietary impacts and predicting diabetes risk.

ReTimeML: a retention time predictor that supports the LC-MS/MS analysis of sphingolipids.

The analysis of ceramide (Cer) and sphingomyelin (SM) lipid species using liquid chromatography-tandem mass spectrometry (LC-MS/MS) continues to present challenges as their precursor mass and fragmentation can correspond to multiple molecular arrangements. To address this constraint, we developed ReTimeML, a freeware that automates the expected retention times (RTs) for Cer and SM lipid profiles from complex chromatograms. ReTimeML works on the principle that LC-MS/MS experiments have pre-determined RTs from internal standards, calibrators or quality controls used throughout the analysis.

Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis.

Background: Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantly overexpressed in a multitude of malignancies, including HCC. Our previous research has shown that genetic ablation of Sphk1 mitigates HCC progression in mice.

Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein.

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC.

Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer.

Sphingolipids are a class of essential lipids implicated in constructing cellular membranes and regulating nearly all cellular functions. Sphingolipid metabolic network is centered with the ceramide-sphingomyelin axis. Ceramide is well-recognized as a pro-apoptotic signal; while sphingomyelin, as the most abundant type of sphingolipids, is required for cell growth.

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers.

Prostate cancer is the second most prevalent malignancy worldwide. In the early stages, the development of prostate cancer is dependent on androgens. Over time with androgen deprivation therapy, 20% of prostate cancers progress to a castration-resistant form.

Integrated Glycoproteomics Identifies a Role of N-Glycosylation and Galectin-1 on Myogenesis and Muscle Development.

Many cell surface and secreted proteins are modified by the covalent addition of glycans that play an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signaling. Aberrant protein glycosylation has been associated with the development of several muscular diseases, suggesting essential glycan- and lectin-mediated functions in myogenesis and muscle development, but our molecular understanding of the precise glycans, catalytic enzymes, and lectins involved remains only partially understood.

Regulation of hepatic insulin signaling and glucose homeostasis by sphingosine kinase 2.

Sphingolipid dysregulation is often associated with insulin resistance, while the enzymes controlling sphingolipid metabolism are emerging as therapeutic targets for improving insulin sensitivity. We report herein that sphingosine kinase 2 (SphK2), a key enzyme in sphingolipid catabolism, plays a critical role in the regulation of hepatic insulin signaling and glucose homeostasis both in vitro and in vivo. Hepatocyte-specific knockout mice exhibit pronounced insulin resistance and glucose intolerance.

The Interaction of the Metallo-Glycopeptide Anti-Tumour Drug Bleomycin with DNA.

The cancer chemotherapeutic drug, bleomycin, is clinically used to treat several neoplasms including testicular and ovarian cancers. Bleomycin is a metallo-glycopeptide antibiotic that requires a transition metal ion, usually Fe(II), for activity. In this review, the properties of bleomycin are examined, especially the interaction of bleomycin with DNA.

The sequence specificity of UV-induced DNA damage in a systematically altered DNA sequence.

The sequence specificity of UV-induced DNA damage was investigated in a specifically designed DNA plasmid using two procedures: end-labelling and linear amplification. Absorption of UV photons by DNA leads to dimerisation of pyrimidine bases and produces two major photoproducts, cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). A previous study had determined that two hexanucleotide sequences, 5'-GCTC*AC and 5'-TATT*AA, were high intensity UV-induced DNA damage sites.

An extended sequence specificity for UV-induced DNA damage.

The sequence specificity of UV-induced DNA damage was determined with a higher precision and accuracy than previously reported. UV light induces two major damage adducts: cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). Employing capillary electrophoresis with laser-induced fluorescence and taking advantages of the distinct properties of the CPDs and 6-4PPs, we studied the sequence specificity of UV-induced DNA damage in a purified DNA sequence using two approaches: end-labelling and a polymerase stop/linear amplification assay.

RecBCD (Exonuclease V) is inhibited by DNA adducts produced by cisplatin and ultraviolet light.

The presence of adducts on the DNA double-helix can have major consequences for the efficient functioning of DNA repair enzymes. E. coli RecBCD (exonuclease V) is involved in recombinational repair of double-strand breaks that are caused by defective DNA replication, DNA damaging agents and other factors.

The mitochondrial DNA sequence specificity of the anti-tumour drug bleomycin using end-labeled DNA and capillary electrophoresis and a comparison with genome-wide DNA sequencing.

The DNA sequence specificity of the cancer chemotherapeutic agent, bleomycin, was investigated in two human mitochondrial DNA sequences. Bleomycin was found to cleave preferentially at 5'-TGT*A-3' DNA sequences (where * is the cleavage site). The bleomycin analysis using capillary electrophoresis with laser-induced fluorescence was determined on both DNA strands and each strand was independently fluorescently labelled at the 3'- and 5'-ends.