The fact that cancer is a leading cause of death all around the world has naturally sparked major efforts in the pursuit of novel and more efficient biomarkers that could better serve as diagnostic tools, prognostic predictors, or therapeutical targets in the battle against this type of disease. Mass spectrometry-based proteomics has proven itself as a robust and logical alternative to the immuno-based methods that once dominated the field. Nevertheless, intrinsic limitations of classic proteomic approaches such as the natural gap between shotgun discovery-based methods and clinically applicable results have called for the implementation of more direct, hypothesis-based studies such as those made available through targeted approaches, that might be able to streamline biomarker discovery and validation as a means to increase survivability of affected patients. In fact, the paradigm shifting potential of modern targeted proteomics applied to cancer research can be demonstrated by the large number of advancements and increasing examples of new and more useful biomarkers found during the course of this review in different aspects of cancer research. Out of the many studies dedicated to cancer biomarker discovery, we were able to devise some clear trends, such as the fact that breast cancer is the most common type of tumor studied and that most of the research for any given type of cancer is focused on the discovery diagnostic biomarkers, with the exception of those that rely on samples other than plasma and serum, which are generally aimed toward prognostic markers. Interestingly, the most common type of targeted approach is based on stable isotope dilution-selected reaction monitoring protocols for quantification of the target molecules. Overall, this reinforces that notion that targeted proteomics has already started to fulfill its role as a groundbreaking strategy that may enable researchers to catapult the number of viable, effective, and validated biomarkers in cancer clinical practice.

esquerdo, respectivamente. Para as amostras obtidas com STT os resultados foram 4,45mg/mL ±0,35 and 4,52mg/ mL ±0,29 para olhos direito e esquerdo, respectivamente. Diferenças estatisticamente significativas (p<0,001) foram encontradas entre os dois métodos. Nas condições em que o trabalho foi conduzido, a média da concentração proteica pelo método de Bradford das amostras obtidas através das tiras do STT foi superior à obtida com o tubo microcapilar. Os valores padrão da concentração protéica da lágrima obtida pelo método de Bradford devem ser analisados considerando-se o método de coleta da lágrima, uma vez que este interfere significativamente nos resultados obtidos.

This paper investigated the molecular pathways modulated in past P. falciparum-infected placentas. The proteome, phosphoproteome and glycoproteome analysis of P. falciparum-infected placentas that had developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment, revealed the activation of AKT and ERK signaling pathways and apoptosis. These molecular features open new perspectives towards novel therapeutic solutions.

Background: The mineralocorticoid receptor antagonist spironolactone lowers blood pressure in patients with resistant hypertension despite antihypertensive treatment with angiotensin-converting inhibitors (ACEi) and angiotensin-II receptor blockers (ARB). In preclinical studies, spironolactone suppresses pro-hypertensive interleukin 17A (IL-17A).Objectives: Plasma samples were analysed from a randomized, double-blind placebo-controlled trial with spironolactone given to patients with type 2 diabetes mellitus (T2DM) and resistant hypertension on three antihypertensive drugs. We tested the hypothesis that spironolactone-induced antihypertensive effects are associated with suppression of IL-17A and related cytokines.Methods: Interferon-g (IFN-g), IL-17A, tumor necrosis factor-a (TNF-a), IL-6, IL-1b and IL-10 were assessed in plasma with immunoassay in samples before and after 16 weeks of treatment with placebo or spironolactone (12.5-25-50 mg/day).Results: Spironolactone significantly reduced plasma IFN-g and IL-6 while IL-17A, TNF-a, IL-1b and IL-10 were unchanged. IL-6 was more sensitive to higher doses of spironolactone. At baseline, serum aldosterone correlated positively with diastolic night blood pressure. Urine albumin/creatinine-ratios correlated positively with plasma IL-6 at baseline. There were no relations between aldosterone and cytokine concentrations at baseline; between cytokine concentration and blood pressure at baseline; and between cytokine concentration decrease and blood pressure decrease, except for IFN-g, after treatment. The spironolactone-induced elevation in plasma potassium related inversely to blood pressure but not to changes in cytokines. In macrophages in vitro, spironolactone suppressed lipopolysaccharide (LPS)-induced TNF-a, IL-6, IL-1b and IL-10 levels. Conclusion:The antihypertensive action of spironolactone in resistant hypertensive patients is associated with suppressed IFN-g and IL-6 and not IL-17A. Spironolactone exerts anti-inflammatory actions in vivo on macrophages and T-cells.

This is the pre-peer reviewed version of the following article: The Cytotoxicity of Metal Nanoparticles Depends on Their Synergistic Interactions, which has been published in final form at doi.org/10.1002/ppsc.202000135. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."

Background Combination chemotherapy uses drugs that target different cancer hallmarks, resulting in synergistic or additive toxicity. This strategy enhances therapeutic efficacy as well as minimizes drug resistance and side effects. In this study, we investigated whether silver nanoparticles act as a combinatorial partner to cisplatin. In so doing, we compared post-exposure biological endpoints, intracellular drug accumulation, and changes in the proteome profile of tumoral and normal cell lines. Results Combinatorial exposure corresponded to cytotoxicity and oxidative stress in both cell lines, yet was substantially more effective against tumoral cells. Proteome analysis revealed that proteins related to energy metabolism pathways were upregulated in both cell lines, suggesting that combinatorial exposure corresponded to energetic modulation. However, proteins and upstream regulators involved in the cell cycle were downregulated, indicating reduced cell proliferation. The response to oxidative stress was markedly different in both cell lines; downregulation of antioxidant proteins in tumoral cells, yet upregulation of the antioxidant defense system in normal cells. These outcomes may have avoided higher cell death rates in normal cells. Conclusions Taken together, our results indicate that combining silver nanoparticles with cisplatin increases the biological activity of the latter, and the combination warrants further exploration for future therapies.

Background: Combination chemotherapy uses drugs that target different cancer hallmarks, resulting in synergistic or additive toxicity. This strategy enhances therapeutic efficacy as well as minimizes drug resistance and side effects. In this study, we investigated whether silver nanoparticles act as a combinatorial partner to cisplatin. In so doing, we compared post-exposure biological endpoints, intracellular drug accumulation, and changes in the proteome profile of tumoral and normal cell lines. Results: Combinatorial exposure corresponded to cytotoxicity and oxidative stress in both cell lines, yet was substantially more effective against tumoral cells. Proteome analysis revealed that proteins related to energy metabolism pathways were upregulated in both cell lines, suggesting that combinatorial exposure corresponded to energetic modulation. However, proteins and upstream regulators involved in the cell cycle were downregulated, indicating reduced cell proliferation. The response to oxidative stress was markedly different in both cell lines; downregulation of antioxidant proteins in tumoral cells, yet upregulation of the antioxidant defense system in normal cells. These outcomes may have avoided higher cell death rates in normal cells. Conclusions: Taken together, our results indicate that combining silver nanoparticles with cisplatin increases the biological activity of the latter, and the combination warrants further exploration for future therapies.

RESUMO A avaliação proteica do humor aquoso (HA) pode ser utilizada como método diagnóstico nas uveítes. Entretanto, estudos sobre as proteínas nesse fluido, em equinos hígidos, são escassos e apresentam variações conforme a metodologia empregada. Dessa forma, objetivou-se realizar a análise proteica e citológica do HA nessa espécie, bem como verificar sua correlação com as proteínas plasmáticas. Foram avaliados 13 equinos adultos (26 olhos), sem raça definida, machos ou fêmeas. Mediante aqueocentese, foi coletado 0,5 mL de humor aquoso de cada olho. Cada amostra foi encaminhada para quantificação proteica pelo método de Bradford modificado e pela eletroforese em gel de poliacrilamida - dodecil sulfato de sódio (SDS-PAGE), bem como para avaliação citológica. Por meio de venopunção, coletou-se sangue para determinação da concentração de proteínas séricas. Treze olhos (50% das amostras) apresentaram valor proteico médio de 40,3 mg/dL±6,45 e a eletroforese demonstrou presença de proteínas de massas mais elevadas que 43 KDa. Houve ausência de células em 96,15% das amostras (25 olhos). Equinos hígidos apresentaram baixa concentração de proteínas no HA. Já a correlação entre proteína no humor aquoso/proteína plasmática total foi de 0,56%.