Ultrastructural aspects of cranial and peripheric nerves of cronically diabetic and malnourished rats: a short biochemical panorama

Diabetes Mellitus is one of the most common causes of neuropathies, which can be caused by molecular imbalances that impair metabolic pathways. Studies in rats showed the importance of sirtuins (SIRT), deacetylases that use NAD+ as a cofactor, which have a widespread function in metabolism, and their relation when food deprived or calorie restricted. Additionally, diabetic neuropathy presents different structural biomarkers that cause morphological alterations in fibers that can be partially treated. SIRT1 is the principal sirtuin, which acts on hypothalamus, liver, kidney, among other organs, up regulating or down regulating the expression of some genes or enzymes crucial in the process of glucose absorption

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Progress on Phage Display Technology: Tailoring Antibodies for Cancer Immunotherapy

The search for innovative anti-cancer drugs remains a challenge. Over the past three decades, antibodies have emerged as an essential asset in successful cancer therapy. The major obstacle in developing anti-cancer antibodies is the need for non-immunogenic antibodies against human antigens. This unique requirement highlights a disadvantage to using traditional hybridoma technology and thus demands alternative approaches, such as humanizing murine monoclonal antibodies. To overcome these hurdles, human monoclonal antibodies can be obtained directly from Phage Display libraries, a groundbreaking tool for antibody selection. These libraries consist of genetically engineered viruses, or phages, which can exhibit antibody fragments, such as scFv or Fab on their capsid. This innovation allows the in vitro selection of novel molecules directed towards cancer antigens. As foreseen when Phage Display was first described, nowadays, several Phage Display-derived antibodies have entered clinical settings or are undergoing clinical evaluation. This comprehensive review unveils the remarkable progress in this field and the possibilities of using clever strategies for phage selection and tailoring the refinement of antibodies aimed at increasingly specific targets. Moreover, the use of selected antibodies in cutting-edge formats is discussed, such as CAR (chimeric antigen receptor) in CAR T-cell therapy or ADC (antibody drug conjugate), amplifying the spectrum of potential therapeutic avenues

PREPARO E AVALIAÇÃO DA ESTABILIDADE DE CREMES O/A À BASE DE EMULGENTE ANIÔNICO OU NÃO IÔNICO

<p>Os danos à pele como queimaduras e fotoenvelhecimento, bem como o número de casos de câncer de pele no Brasil aumenta progressivamente com o passar dos anos, isto ocorre por causa dos altos índices de radiações ultravioletas emitidos pelo sol no Brasil durante todo o ano, até mesmo no inverno. Assim, medida de proteção contra a luz solar é de vital importância, o que inclui o uso principalmente de filtros solares de amplo espectro. Com a grande demanda e apelo por cosméticos ecológicos, ou seja, que utilizem de recursos naturais em sua composição, é de fundamental relevância a pesquisa e o desenvolvimento de novos protetores solares que utilizem de matérias-primas vegetais, visto que estas são abundantes na natureza, renováveis, rentáveis e estão associadas a poucos números de casos relacionados às alergias e irritações. A uva é amplamente estudada e conhecida por apresentar compostos bioativos tais como os flavonoides e taninos, que apresentam efeitos antioxidantes e fotoprotetores, pode ser utilizada para incorporação em bases galênicas de caráter aniônica e não iônica para estudo da estabilidade. O bagaço da uva, um subproduto da vinificação, conserva fitocompostos em quantidades elevadas e rotineiramente é descartado por não ter uma utilidade, por isso o seu uso na pesquisa e desenvolvimento de um novo fitocosmético torna-se essencial. A proposta do estudo visou a incorporação do extrato etanólico bruto em cremes O/A com emulgentes diferentes, para avaliar a sua estabilidade, através de teste de pH, viscosidade, características organolépticas, teste de estabilidade acelerada e centrífuga, bem como o estudo do FPS adquirido por essas formulações. As bases galênicas se adaptaram bem com o extrato, uma vez que não houve floculação e/ou separação de fases em nenhum momento da pesquisa, porém reações de oxidação foram observadas a olho nú que podendo ter influenciado na diferença dos valores de pH, bem como do FPS, que deram valores significativos utilizando apenas 5% do extrato. Estudos relacionados a um aumento dessa porcentagem e na aplicação de outros cosméticos multiuso são uma boa alternativa.</p&gt

Validation of the National Institutes of Health Stroke Scale, Modified Rankin Scale and Barthel Index in Brazil: The Role of Cultural Adaptation and Structured Interviewing

Background: We aimed to validate three widely used scales in stroke research in a multiethnic Brazilian population. Methods: The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) were translated, culturally adapted and applied by two independent investigators. The mRS was applied with or without a previously validated structured interview. Interobserver agreement (kappa statistics) and intraclass correlation coefficients were calculated. Results: 84 patients underwent mRS (56 with and 28 without a structured interview), 57 BI and 62 NIHSS scoring. Intraclass correlation coefficient was 0.902 for NIHSS and 0.967 for BI. For BI, interobserver agreement was good (kappa = 0.70). For mRS, the structured interview improved interobserver agreement (kappa = 0.34 without a structured interview; 0.75 with a structured interview). Conclusion: The NIHSS, BI and mRS show good validity when translated and culturally adapted. Using a structured interview for the mRS improves interobserver concordance rates. Copyright (C) 2008 S. Karger AG, Base

DataSheet_1_Altered distribution and function of NK-cell subsets lead to impaired tumor surveillance in JAK2V617F myeloproliferative neoplasms.pdf

In cancer, tumor cells and their neoplastic microenvironment can sculpt the immunogenic phenotype of a developing tumor. In this context, natural killer (NK) cells are subtypes of lymphocytes of the innate immune system recognized for their potential to eliminate neoplastic cells, not only through direct cytolytic activity but also by favoring the development of an adaptive antitumor immune response. Even though the protective effect against leukemia due to NK-cell alloreactivity mediated by the absence of the KIR-ligand has already been shown, and some data on the role of NK cells in myeloproliferative neoplasms (MPN) has been explored, their mechanisms of immune escape have not been fully investigated. It is still unclear whether NK cells can affect the biology of BCR-ABL1-negative MPN and which mechanisms are involved in the control of leukemic stem cell expansion. Aiming to investigate the potential contribution of NK cells to the pathogenesis of MPN, we characterized the frequency, receptor expression, maturation profile, and function of NK cells from a conditional Jak2V617F murine transgenic model, which faithfully resembles the main clinical and laboratory characteristics of human polycythemia vera, and MPN patients. Immunophenotypic analysis was performed to characterize NK frequency, their subtypes, and receptor expression in both mutated and wild-type samples. We observed a higher frequency of total NK cells in JAK2V617F mutated MPN and a maturation arrest that resulted in low-numbered mature CD11b+ NK cells and increased immature secretory CD27+ cells in both human and murine mutated samples. In agreement, inhibitory receptors were more expressed in MPN. NK cells from Jak2V617F mice presented a lower potential for proliferation and activation than wild-type NK cells. Colonies generated by murine hematopoietic stem cells (HSC) after mutated or wild-type NK co-culture exposure demonstrated that NK cells from Jak2V617F mice were deficient in regulating differentiation and clonogenic capacity. In conclusion, our findings suggest that NK cells have an immature profile with deficient cytotoxicity that may lead to impaired tumor surveillance in MPN. These data provide a new perspective on the behavior of NK cells in the context of myeloid malignancies and can contribute to the development of new therapeutic strategies, targeting onco-inflammatory pathways that can potentially control transformed HSCs.</p