Integrative Proteomic and Pharmacological Analysis of Colon Cancer Reveals the Classical Lipogenic Pathway with Prognostic and Therapeutic Opportunities.

Despite recent advancements, the high mortality rate remains a concern in colon cancer (CAC). Identification of therapeutic markers could prove to be a great asset in CAC management. Multiple studies have reported hyperactivation of de novo lipogenesis (DNL), but its association with the pathology is unclear. This study aims to establish the importance as well as the prognostic and therapeutic potential of DNL in CAC. The key lipogenic enzymes fatty acid synthase along with ATP citrate lyase were quantified using an LC-MS/MS-based targeted proteomics approach in the samples along with the matched controls. The potential capacity of the proteins to distinguish between the tumor and controls was demonstrated using random forest-based class prediction analysis using the peptide intensities. Furthermore, in-depth proteomics of DNL inhibition in the CAC cell line revealed the significance of the pathway in proliferation and metastasis. DNL inhibition affected the major signaling pathways, including DNA repair, PI3K-AKT-mTOR pathway, membrane trafficking, proteasome, etc. The study revealed the upregulation of 26S proteasome machinery as a result of the treatment with subsequent induction of apoptosis. Again, in silico molecular docking-based drug repurposing was performed to find potential drug candidates. Furthermore, we have demonstrated that blocking DNL could be explored as a therapeutic option in CAC treatment.

An early investigative serum Raman spectroscopy study of meningioma.

Meningiomas represent one of the most frequently reported non-glial, primary brain and central nervous system (CNS) tumors. Meningiomas often display a spectrum of anomalous locations and morphological attributes, deterring their timely diagnosis. Majority of them are sporadic in nature and thus the present-day screening strategies, including radiological investigations, often result in misdiagnosis due to their aberrant and equivocal radiological facets. Therefore, it is pertinent to explore less invasive and patient-friendly biofluids such as serum for their screening and diagnostics. The utility of serum Raman spectroscopy in diagnosis and therapeutic monitoring of cancers has been reported in the literature. In the present study, for the first time, to the best of our knowledge, we have explored Raman spectroscopy to classify the sera of meningioma and control subjects. For this exploration, 35 samples each of meningioma and control subjects were accrued and the spectra revealed variance in the levels of DNA, proteins, lipids, amino acids and ß-carotene, i.e., a relatively higher protein, DNA and lipid content in meningioma. Subsequent Principal Component Analysis (PCA) and Principal Component-Linear Discriminant Analysis (PC-LDA) followed by Leave-One-Out Cross-Validation (LOOCV) and limited independent test data, in a patient-wise approach, yielded a classification efficiency of 92% and 80% for healthy and meningioma, respectively. Additionally, in the analogous analysis between healthy and different grades of meningioma, similar results were obtained. These results indicate the potential of Raman spectroscopy in differentiating meningioma. As present methods suffer from known limitations, with the prospective validation on a larger cohort, serum Raman spectroscopy could be an adjuvant/alternative approach in the clinical management of meningioma.

Correction: Comprehensive Analysis of Temporal Alterations in Cellular Proteome of Bacillus subtilis under Curcumin Treatment.

[This corrects the article DOI: 10.1371/journal.pone.0120620.].

Comprehensive analysis of temporal alterations in cellular proteome of Bacillus subtilis under curcumin treatment.

Curcumin is a natural dietary compound with antimicrobial activity against various gram positive and negative bacteria. This study aims to investigate the proteome level alterations in Bacillus subtilis due to curcumin treatment and identification of its molecular/cellular targets to understand the mechanism of action. We have performed a comprehensive proteomic analysis of B. subtilis AH75 strain at different time intervals of curcumin treatment (20, 60 and 120 min after the drug exposure, three replicates) to compare the protein expression profiles using two complementary quantitative proteomic techniques, 2D-DIGE and iTRAQ. To the best of our knowledge, this is the first comprehensive longitudinal investigation describing the effect of curcumin treatment on B. subtilis proteome. The proteomics analysis revealed several interesting targets such UDP-N-acetylglucosamine 1-carboxyvinyltransferase 1, putative septation protein SpoVG and ATP-dependent Clp protease proteolytic subunit. Further, in silico pathway analysis using DAVID and KOBAS has revealed modulation of pathways related to the fatty acid metabolism and cell wall synthesis, which are crucial for cell viability. Our findings revealed that curcumin treatment lead to inhibition of the cell wall and fatty acid synthesis in addition to differential expression of many crucial proteins involved in modulation of bacterial metabolism. Findings obtained from proteomics analysis were further validated using 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) assay for respiratory activity, resazurin assay for metabolic activity and membrane integrity assay by potassium and inorganic phosphate leakage measurement. The gene expression analysis of selected cell wall biosynthesis enzymes has strengthened the proteomics findings and indicated the major effect of curcumin on cell division.