Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.
AIMS: The COVID-19 pandemic suddenly and significantly increased hospitalizations for pneumonia with systemic inflammatory disease. Since its appearance, COVID-19 has affected more than 200 countries, with more than 90 million cases and almost 2 million deaths. So far, there is no quality evidence regarding the specific pharmacological therapy for COVID-19; most treatments usually involve off-label use of existing drugs and have unproven efficacy. The global effort converges on the development of a vaccine; however, the greatest challenge is to achieve collective immunization in the face of increasing vaccination hesitancy.METHODS: This study investigated the impact of vaccine hesitancy movements on the goal of COVID-19 immunization in Brazil. An integrative bibliographic review was performed with an electronic search on PubMed and SciELO that yielded 13.535 articles. Inclusion and exclusion criteria were applied which included 29 interventional and descriptive studies.RESULTS: The results of the 29 studies revealed that the most frequent reasons for hesitation is skepticism about the true interests of the industry and politicians, the lack of trust in research, and inaccurate information on social media.CONCLUSION: The main factors that lead the population not to believe in vaccines were the real interests of industry and politicians, lack of confidence in research, and the amount of false information that circulates massively on social media and because of that it is possible that Brazil will face some challenges in achieving collective immunity due to the anti-vaccine movement.
One of the greatest challenges of cancer therapeutics nowadays is to find selective targets
successfully. Prostate apoptosis response-4 (Par-4) is a selective tumor suppressor protein with an interesting
therapeutic potential due to its specificity on inducing apoptosis in cancer cells. Par-4 activity
and levels can be downregulated in several tumors and cancer cell types, indicating poor prognosis
and treatment resistance. Efforts to increase Par-4 expression levels have been studied, including its
use as a therapeutic protein by transfection with adenoviral vectors or plasmids. However, gene therapy
is very complex and still presents many hurdles to be overcome. We decided to review molecules
and drugs with the capacity to upregulate Par-4 and, thereby, be an alternative to reach this druggable
target. In addition, Par-4 localization and function are reviewed in some cancers, clarifying how it can
be used as a therapeutic target.
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