Biology subjects

Paes Leme, A. F.

Publications and source records attributed to Paes Leme, A. F..

4 recordsLinked to original sources

bioRxiv2023

Deacetylation by sirtuins is important for Aspergillus fumigatus pathogenesis and virulence

Protein acetylation is a crucial post-translational modification that controls gene expression and a variety of biological processes. Sirtuins, a prominent class of NAD+-dependent lysine deacetylases, serve as key regulators of protein acetylation and gene expression in eukaryotes. In this study, six single knockout strains of fungal pathogen Aspergillus fumigatus were constructed, in addition to a strain lacking all predicted sirtuins (SIRTKO). Phenotypic assays suggest that sirtuins are involved in cell wall integrity, secondary metabolite production, thermotolerance, and virulence. AfsirE deletion resulted in attenuation of virulence, as demonstrated in murine and Galleria infection models. The absence of AfSirE leads to altered acetylation status of proteins, including histones and non-histones, resulting in significant changes in the expression of genes associated with secondary metabolism, cell wall biosynthesis, and virulence factors. These findings encourage testing sirtuin inhibitors as potential therapeutic strategies to combat A. fumigatus infections or in combination therapy with available antifungals.

microbiology↗

bioRxiv2023

Saliva proteome-wide structural changes are associated with oral cancer aggressiveness

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these potential diagnostic and prognostic factors may be regulated by events that do not imply variation in protein abundance levels, we investigated the hypothesis that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients, with and without lymph node metastasis. Fifty-one proteins with potential structural rearrangements were associated with clinical patient features. Post-translational modifications, such as glycosylation, disulfide bond, and phosphorylation, were also investigated in our data using different search engines and in silico analysis indicating that they might contribute to structural rearrangements of the potential diagnostic and prognostic markers here identified. Altogether, this powerful approach allows for a deep investigation of complex biofluids, such as saliva, advancing the search for targets for oral cancer diagnosis and prognosis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/552034v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@1d0f97dorg.highwire.dtl.DTLVardef@ab9a2borg.highwire.dtl.DTLVardef@16baf1org.highwire.dtl.DTLVardef@4b4a37_HPS_FORMAT_FIGEXP M_FIG Oral cancer progression is associated with potential structural rearrangements. C_FIG

cancer biology↗

bioRxiv2021

Wiring multiple microenvironment proteomes uncovers the biology in head and neck cancer

The poor prognosis of head and neck cancer (HNC) is associated with the presence of metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identified a nodal metastasis signature in the blood and saliva. In summary, we present the deepest proteome characterization wiring multiple sampling sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.

cancer biology↗

bioRxiv2017

Prognostic biomarkers in oral squamous cell carcinoma: a systematic review

Over the years, several tumor biomarkers have been suggested to foresee the prognosis of oral squamous cell carcinoma (OSCC) patients. Here, we present a systematic review to identify, evaluate and summarize the evidence for OSCC reported markers. Eligible studies were identified through a literature search of MEDLINE/PubMed until January 2016. We included primary articles reporting overall survival, disease-free survival and cause-specific survival as outcomes. Our findings were analysed using REporting recommendations for tumor MARKer prognostic studies (REMARK), QuickGo tool and SciCurve trends. We found 41 biomarkers, mostly proteins evaluated by immunohistochemistry. The selected studies are of good quality, although, any study referred to a sample size determination. Considering the lack of follow-up studies, the molecules are still potential biomarkers. Further research is required to validate these biomarkers in well-designed clinical cohort-based studies.

pathology↗