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BACKGROUND: COPD is a complex respiratory disorder with high morbidity and mortality rates. Even with the current conventional diagnostic methods, including circulating inflammatory biomarkers, underdiagnosis rates in COPD remain as high as 70%. Our study was a comparative cross-sectional study that aimed to address the diagnostic challenges by identifying future biomarker candidates in COPD variants. METHODS: This study used a label-free plasma proteomics approach that combined mass spectrometric data with bioinformatics to shed light on the functional roles of differentially expressed proteins in the COPD lung microenvironment. The predictive capacity of the screened proteins was assessed using Receiver Operating Characteristic (ROC) curves, with Western blot analysis validating protein expression patterns in an independent cohort. RESULTS: Our study identified three DEPs-reticulocalbin-1, sideroflexin-4, and liprinα-3 that consistently exhibited altered expression in COPD exacerbation. ROC analysis indicated strong predictive potential, with AUC values of 0.908, 0.715, and 0.856 for RCN1, SFXN4, and LIPα-3, respectively. Validation through Western blot analysis confirmed their expression patterns in an independent validation cohort. CONCLUSIONS: Our study discovered a novel duo of proteins reticulocalbin-1, and sideroflexin-4 that showed potential as valuable future biomarkers for the diagnosis and clinical management of COPD exacerbations.

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Neuromyelitis optica spectrum disorders (NMOSD) is a demyelinating autoimmune disease affecting the central nervous system causing inflammatory lesions in the optic nerves, spinal cord and other vital areas of CNS. The clinical manifestations include acute transverse myelitis with paraplegia and optic neuritis with impaired vision. In the present study we focussed on comparative expression of serum proteins between NMOSD variants and control. The study has identified a plethora of novel and unexplored acute phase proteins involved in lipid transport and myelination in perspective of NMOSD. The serum proteins obtained after albumin globulin depletion were subjected to LC-MS/MS. The commonly altered proteins in all NMOSD variants with respect to control were smaug homolog protein and serum amyloid A. Truncated breast and ovarian cancer susceptibility protein and cystic fibrosis transmembrane conductance regulator protein were specifically upregulated and can act as potential biomarkers for neuromyelitis optica with autoantibody negativity to Aquaporin - 4 (AQP-4) and myelin oligodendrocyte (MOG) immunoglobulins. In addition, the uniquely downregulated proteins such as antithrombin III and histidine rich glycoprotein in NMO/MOG autoantibody negative samples can be accounted for its dysregulated fibrinolysis associated with NMO. The differentially expressed proteins were involved in cholesterol transport, synaptic vesicle mediated transport, neurotransmission and immune regulation which are closely associated with myelin formation and protection. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-021-01004-w.

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Cadmium (Cd) is a toxic metal and an important environmental contaminant. We analyzed its effects on oligoelements, oxidative stress, cell death, Hsp expression and the histoarchitecture of rat lung under different diets, using animal models of subchronic cadmium intoxication. We found that Cd lung content augmented in intoxicated groups: Zn, Mn and Se levels showed modifications among the different diets, while Cu showed no differences. Lipoperoxidation was higher in both intoxicated groups. Expression of Nrf-2 and SOD-2 increased only in SoCd. GPx levels showed a trend to increase in Cd groups. CAT activity was higher in intoxicated groups, and it was higher in Soy groups vs. Casein. LDH activity in BAL increased in CasCd and decreased in both soy-fed groups. BAX/Bcl-2 semiquantitative ratio showed similar results than LDH activity, confirmed by Caspase 3 immunofluorescence. The histological analysis revealed an infiltration process in CasCd lungs, with increased connective tissue, fused alveoli and capillary fragility. Histoarchitectural changes were less severe in soy groups. Hsp27 expression increased in both intoxicated groups, while Hsp70 only augmented in SoCd. This show that a soy-diet has a positive impact upon oxidative unbalance, cell death and morphological changes induced by Cd and it could be a good alternative strategy against Cd exposure.

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We present a cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors. All but 1 case predominantly (75%-95% extent) showed histopathologic features of conventional clear cell renal cell carcinoma. In 5 of 7 cases with mostly conventional clear renal cell carcinoma (CRCC) morphology, a diagnosis of CRCC was supported by the molecular genetic findings (presence of von Hippel-Lindau tumor suppressor [VHL] mutation and/or VHL promoter methylation and/or loss of heterozygosity [LOH] for 3p). Of the other 2 cases with predominantly characteristic CRCC morphology, 1 tumor did not reveal any VHL mutation, VHL promoter methylation, or LOH for 3p, and both chromosomes 7 and 17 were disomic, whereas the other tumor displayed polysomy for chromosomes 7 and 17 and no VHL mutation, VHL promoter methylation, or LOH for 3p. One tumor was composed primarily (95%) of distinctly RAT/CCPRCC-like morphology, and this tumor harbored a VHL mutation and displayed polysomy for chromosomes 7 and 17. Of the 5 cases with both histomorphologic features and molecular genetic findings of CRCC, we detected significant immunoreactivity for α-methylacyl-CoA racemase in 2 cases and strong diffuse immunopositivity for cytokeratin 7 in 3 cases. Despite the combination of positivity for α-methylacyl-CoA racemase and cytokeratin 7 in 2 cases, there was nothing to suggest of the possibility of a conventional papillary renal cell carcinoma with a predominance of clear cells.

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