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Domingues, R. R.

Publications and source records attributed to Domingues, R. R..

6 recordsLinked to original sources

Single-cell proteomics maps circulating monocyte dynamics in advanced head and neck squamous cell carcinoma

It remains unclear whether metastatic progression in head and neck squamous cell carcinoma (HNSCC) is accompanied by functional remodeling of circulating immune cells at the proteome level. To address this question, we applied single-cell proteomics (SCP) to cryopreserved peripheral blood mononuclear cells (PBMCs) from three patients with HNSCC representing distinct stages of metastatic progression and two healthy donors. Proteomic analysis of 619 individual PBMCs resolved major immune cell populations, with up to 1,638 proteins quantified per cell. Trajectory inference, clustering, and differential abundance analyses revealed proteomic remodeling associated with disease progression, with the most pronounced changes occurring within a monocyte cluster composed exclusively of cells from patients with nodal metastasis. This population showed increased abundance of interferon-related proteins, HLA molecules, and myeloid immunoregulatory signatures, consistent with an activated, interferon-associated monocyte state. In parallel, lymphocytes showed reduced coordinated abundance of proteins associated with activation, cytotoxicity, and degranulation, consistent with altered cytotoxic effector programs across disease stages. Overall, these findings reveal distinct proteomic states in circulating monocytes and lymphocytes associated with HNSCC progression and identify selective remodeling of the monocyte compartment in nodal metastatic disease.

cancer biology↗

DNA metabarcoding and environmental DNA across Brazilian biomes: trends, challenges, and conservation applications

Brazil harbors the greatest biodiversity on the planet; however, the application of emerging technologies to enhance biodiversity assessment and monitoring remains limited. In recent years, DNA metabarcoding and environmental DNA (eDNA) surveys have revolutionized the assessment of biodiversity, offering new tools to evaluate ecological and conservation trends and patterns worldwide. Yet, their application in Brazil is still in its early stages, underscoring the paradox of a megadiverse country with limited adoption of cutting-edge tools for monitoring its natural wealth. This review provides a comprehensive synthesis of the application of DNA metabarcoding and eDNA analyses across different ecosystems in Brazil, integrating findings from 47 studies published between 2015 and 2025. Trends in ecosystem types, taxonomic groups, molecular markers, geographic distribution, and patterns of authorship and funding were analyzed. Most studies focused on terrestrial (42.5%) and freshwater (34%) environments, followed by marine (19.1%) and estuarine (4.2%) systems. DNA metabarcoding predominated in terrestrial studies (52.1%), while eDNA was more frequent in freshwater, marine, and estuarine environments. The mitochondrial 12S marker was the most widely used, primarily for detecting fish and amphibians. We observed a predominance of Brazilian first and senior authors, with weak signs of parachute science. However, challenges persist, including limited access to funding and underrepresentation of some biomes and taxonomic groups. Our findings highlight a growing national capacity in the use of DNA metabarcoding and eDNA research while underscoring the need for strategic investments in infrastructure, database development, and equitable scientific collaboration.

ecology↗

Tear fluid as noninvasive liquid biopsy reveals proteins associated with malignant transformation of oral lesions

Oral leukoplakias (OLs) are premalignant lesions that can progress into oral squamous cell carcinoma (OSCC). This study hypothesized that tear fluid, as a noninvasive biofluid, reflects proteomic alterations associated with malignant transformation. The tear proteome of 44 individuals, including healthy controls, OL/PVL (proliferative verrucous leukoplakia), and OSCC patients, was deeply profiled, revealing 828 protein groups clustered according to histopathological alterations. N-glycoproteome analysis identified immune-related proteins, while public RNA-seq integration indicated immune imbalance marked by increased B-cell and decreased macrophage signatures during disease progression. Several immune-associated proteins and epithelial markers, including desmoplakin, KRT14, and DSC1, emerged as potential indicators of malignant transformation. These findings demonstrate that tear fluid reflects oral carcinogenic processes, thereby serving as a noninvasive liquid biopsy for early detection and clinical monitoring.

biochemistry↗

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↗

Different biological effects of exposure to far-UVC (222 nm) and near-UVC (254 nm) irradiation

Ultraviolet C (UVC) light has long been used as a sterilizing agent, primarily through devices that emit at 254 nm. Depending on the dose and duration of exposure, UV 254 nm can cause erythema and photokeratitis and potentially cause skin cancer since it directly modifies nitrogenated nucleic acid bases. Filtered KrCl excimer lamps (emitting mainly at 222 nm) have emerged as safer germicidal tools and have even been proposed as devices to sterilize surgical wounds. All the studies that showed the safety of 222 nm analyzed cell number and viability, erythema generation, epidermal thickening, the formation of genetic lesions such as cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproducts (6-4PPs) and cancer-inducing potential. Although nucleic acids can absorb and be modified by both UV 254 nm and UV 222 nm equally, compared to UV 254 nm, UV 222 nm is more intensely absorbed by proteins (especially aromatic side chains), causing photooxidation and cross-linking. Here, in addition to analyzing DNA lesion formation, for the first time, we evaluated changes in the proteome and cellular pathways, reactive oxygen species formation, and metalloproteinase (MMP) levels and activity in full-thickness in vitro reconstructed human skin (RHS) exposed to UV 222 nm. We also performed the longest (40 days) in vivo study of UV 222 nm exposure in the HRS/J mouse model at the occupational threshold limit value (TLV) for indirect exposure (25 mJ/cm2) and evaluated overall skin morphology, cellular pathological alterations, CPD and 6-4PP formation and MMP-9 activity. Our study showed that processes related to reactive oxygen species and inflammatory responses were more altered by UV 254 nm than by UV 222 nm. Our chronic in vivo exposure assay using the TLV confirmed that UV 222 nm causes minor damage to the skin. However, alterations in pathways related to skin regeneration raise concerns about direct exposure to UV 222 nm.

cell biology↗

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↗