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Multi-OMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells.
Pinto, SM, Subbannayya, Y, Kim, H, Hagen, L, Górna, MW, Nieminen, AI, Bjørås, M, Espevik, T, Kainov, D, Kandasamy, RK
iScience. 2023;(1):105895
Abstract
COVID-19 pandemic continues to remain a global health concern owing to the emergence of newer variants. Several multi-Omics studies have produced extensive evidence on host-pathogen interactions and potential therapeutic targets. Nonetheless, an increased understanding of host signaling networks regulated by post-translational modifications and their ensuing effect on the cellular dynamics is critical to expanding the current knowledge on SARS-CoV-2 infections. Through an unbiased transcriptomics, proteomics, acetylomics, phosphoproteomics, and exometabolome analysis of a lung-derived human cell line, we show that SARS-CoV-2 Norway/Trondheim-S15 strain induces time-dependent alterations in the induction of type I IFN response, activation of DNA damage response, dysregulated Hippo signaling, among others. We identified interplay of phosphorylation and acetylation dynamics on host proteins and its effect on the altered release of metabolites, especially organic acids and ketone bodies. Together, our findings serve as a resource of potential targets that can aid in designing novel host-directed therapeutic strategies.
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Rehabilitation at the Time of Pandemic: Patient Journey Recommendations.
Negm, AM, Salopek, A, Zaide, M, Meng, VJ, Prada, C, Chang, Y, Zanwar, P, Santos, FH, Philippou, E, Rosario, ER, et al
Frontiers in aging neuroscience. 2022;:781226
Abstract
PURPOSE The World Health Organization (WHO) declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a pandemic in March 2020, causing almost 3.5 million coronavirus disease (COVID-19) related deaths worldwide. The COVID-19 pandemic has imposed a significant burden on healthcare systems, economies, and social systems in many countries around the world. The access and delivery of rehabilitation care were severely disrupted, and patients have faced several challenges during the COVID-19 outbreak. These challenges include addressing new functional impairments faced by survivors of COVID-19 and infection prevention to avoid the virus spread to healthcare workers and other patients not infected with COVID-19. In this scoping review, we aim to develop rehabilitation recommendations during the COVID-19 pandemic across the continuum of rehabilitation care. MATERIALS AND METHODS Established frameworks were used to guide the scoping review methodology. Medline, Embase, Pubmed, CINAHL databases from inception to August 1, 2020, and prominent rehabilitation organizations' websites were searched. STUDY SELECTION We included articles and reports if they were focused on rehabilitation recommendations for COVID-19 survivors or the general population at the time of the COVID-19 pandemic. DATA EXTRACTION Two of our team members used the pre-tested data extraction form to extract data from included full-text articles. The strength and the quality of the extracted recommendations were evaluated by two reviewers using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS We retrieved 6,468 citations, of which 2,086 were eligible after removing duplicates. We excluded 1,980 citations based on the title and the abstract. Of the screened full-text articles, we included 106 studies. We present recommendations based on the patient journey at the time of the pandemic. We assessed the evidence to be of overall fair quality and strong for the recommendations. CONCLUSION We have combined the latest research results and accumulated expert opinions on rehabilitation to develop acute and post-acute rehabilitation recommendations in response to the global COVID-19 pandemic. Further updates are warranted in order to incorporate the emerging evidence into rehabilitation guidelines.
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SILAC-based quantitative proteomic analysis of gastric cancer secretome.
Marimuthu, A, Subbannayya, Y, Sahasrabuddhe, NA, Balakrishnan, L, Syed, N, Sekhar, NR, Katte, TV, Pinto, SM, Srikanth, SM, Kumar, P, et al
Proteomics. Clinical applications. 2013;(5-6):355-66
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Abstract
PURPOSE Gastric cancer is a commonly occurring cancer in Asia and one of the leading causes of cancer deaths. However, there is no reliable blood-based screening test for this cancer. Identifying proteins secreted from tumor cells could lead to the discovery of clinically useful biomarkers for early detection of gastric cancer. EXPERIMENTAL DESIGN A SILAC-based quantitative proteomic approach was employed to identify secreted proteins that were differentially expressed between neoplastic and non-neoplastic gastric epithelial cells. Proteins from the secretome were subjected to SDS-PAGE and SCX-based fractionation, followed by mass spectrometric analysis on an LTQ-Orbitrap Velos mass spectrometer. Immunohistochemical labeling was employed to validate a subset of candidates using tissue microarrays. RESULTS We identified 2205 proteins in the gastric cancer secretome of which 263 proteins were overexpressed greater than fourfold in gastric cancer-derived cell lines as compared to non-neoplastic gastric epithelial cells. Three candidate proteins, proprotein convertase subtilisin/kexin type 9 (PCSK9), lectin mannose binding 2 (LMAN2), and PDGFA-associated protein 1 (PDAP1) were validated by immunohistochemical labeling. CONCLUSIONS AND CLINICAL RELEVANCE We report here the largest cancer secretome described to date. The novel biomarkers identified in the current study are excellent candidates for further testing as early detection biomarkers for gastric adenocarcinoma.
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Glutathionyl hemoglobin is elevated in iron deficiency anemia.
Shet, AS, Pinto, SM, Mitra, G, Mandal, AK
Acta haematologica. 2012;(1):26-30
Abstract
There are few good biomarkers of iron deficiency anemia (IDA). Since IDA patients have evidence for increased oxidative stress, we used mass spectrometry (MS) [i.e. matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization] to identify novel biomarkers. Using MALDI-MS, the following oxidative modifications of hemoglobin with the following mass-to-charge ratios were identified: 1,087.5 (α32-40), 1,545.7 (α17-31), 1,290.0 (β31-40) and 2,076.1 (β41-59). On electrospray ionization MS, the IDA patients had significantly elevated glutathionyl hemoglobin (GSHb) compared with the controls (16.9 ± 9.6 vs. 7.7 ± 3.7%; p = 0.002). GSHb levels correlated inversely with serum ferritin (Spearman rho -0.485; p = 0.003) and positively with serum transferrin receptor (0.460; p = 0.002). GSHb also demonstrated inverse correlations with hemoglobin (-0.512; p = 0.001), mean cell volume (-0.419; p = 0.026), serum iron (-0.446; p = 0.008) and transferrin saturation (-0.460; p = 0.008). For the first time, we show that GSHb is elevated in patients with IDA and has potential as a biomarker of this form of anemia.