Urinary proteomics reveals biological processes related to acute kidney injury in Bothrops atrox envenomings.

Acute kidney injury (AKI) is a critical systemic complication caused by Bothrops envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of Bothrops atrox snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI's urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by Bothrops envenoming. This work sheds light on physiological disturbances caused by Bothrops envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication.

Proteomic assessment of colorectal cancers and respective resection margins from patients of the Amazon state of Brazil.

Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival rate and therapeutic efficiency. Tumor surgery implies the removal of an apparently non-tumorous tissue around the tumor in an attempt to reduce recurrence chances; this tissue is referred to as the resection margin. Our analysis employed an 8-plex iTRAQ to label four adenocarcinoma biopsies and their corresponding resection margins at 5cm; our results disclose fifty-six proteins as being differentially abundant. These proteins are mainly involved in energetic metabolism (e.g. S100 calcium binding protein A11), cell migration (e.g. transgelin), formation of the cytoskeleton (e.g. profilin 1) and degradation of extracellular matrix (e.g. carbonic anhydrase 2). A gene ontology enrichment analysis revealed several proteins related to adhesion, invasion, metastasis, death, and recognition cell. Taken together, our results highlight proteins related to invasion, cell proliferation, and linked to the metastasis of colorectal cancer in tumor tissue. Finally, we argue that the expression patterns revealed in our comparison helps shed light on the development of more effective surgical strategies and add to the comprehension of this disease. BIOLOGICAL SIGNIFICANCE: Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival rate and therapeutic efficiency. Tumor surgery implies the removal of an apparently non-tumorous tissue around the tumor in an attempt to reduce recurrence chances; this tissue is also referred to as the resection margin. In this regard, resection margins pose as a treasure trove for investigating the molecular characteristics of the tumorigenesis process. While most studies focus on comparing cancer versus control tissue, this study contrasts the proteomic profiles of colorectal cancer biopsies with their corresponding resection margin at 5cm apart. Our analysis employed an 8-plex iTRAQ labeling and a 4-step offline MudPIT online with a Velos. A gene ontology enrichment analysis revealed several proteins related to adhesion, invasion, metastasis, death, and recognition cell.

Colorectal cancer DNA methylation patterns from patients in Manaus, Brazil.

BACKGROUND: DNA methylation is commonly linked with the silencing of the gene expression for many tumor suppressor genes. As such, determining DNA methylation patterns should aid, in times to come, in the diagnosis and personal treatment for various types of cancers. Here, we analyzed the methylation pattern from five colorectal cancer patients from the Amazon state in Brazil for four tumor suppressor genes, viz.: DAPK, CDH1, CDKN2A, and TIMP2 by employing a polymerase chain reaction (PCR) specific to methylation. Efforts in the study of colorectal cancer are fundamental as it is the third most of highest incidence in the world. RESULTS: Tumor biopsies were methylated in 1/5 (20%), 2/5 (40%), 4/5 (80%), and 4/5 (80%) for CDH1, CDKN2A, DAPK, and TIMP2 genes, respectively. The margin biopsies were methylated in 3/7 (43%), 2/7 (28%), 7/7 (100%), and 6/7 (86%) for CDH1, CDKN2A, DAPK, and TIMP2, respectively. CONCLUSIONS: Our findings showed DAPK and TIMP2 to be methylated in most samples from both tumor tissues and adjacent non-neoplastic margins; thus presenting distinct methylation patterns. This emphasizes the importance of better understanding of the relation of these patterns with cancer in the context of different populations.