32,396 research outputs found

    Mushroom ő≤-glucan and polyphenol formulations as natural immunity boosters and balancers: nature of the application

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    Mushrooms are experiencing a kind of renaissance as a part of the contemporary human diet. These valuable organisms are more than food, they fi t in perfectly as a novel market group known as nutra-mycoceuticals. Immune-balancing mushroom dietary fibers and secondary metabolites such as polyphenols are the main focus of the healthcare industry. Wellness and cosmetic companies are increasingly using mushroom extracts rich in these ingredients. This review considers the basic molecular immunomodulatory mechanisms of action of the most commonly used mushroom dietary fibers, ő≤-glucans. The literature data on their bioavailability, metabolic transformations, preclinical and human clinical research, and safety are discussed. Immunomodulatory mechanisms of polyphenol ingredients are also considered. These molecules present great potential in the design of the new immunity balancer formulations according to their widespread structural diversity. Finally, we draw attention to the perspectives of modern trends in mushroom nutraceutical and cosmeceutical formulations to strengthen and balance immunity

    Identifizierung prädiktiver und prognostischer Biomarker in unterschiedlichen Tumorkompartimenten des ösophagealen Adenokarzinoms

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    Das √∂sophageale Adenokarzinom zeigt eine global steigende Inzidenz und hat mit einer 5-Jahres-√úberlebensrate von weniger als 25% eine schlechte Prognose. Personalisierte Therapieans√§tze sind selten und prognostische/pr√§diktive Biomarker des Tumormikromilieus sind unzureichend charakterisiert. Die kumulative Promotion n√§hert sich dieser Problematik in drei unterschiedlichen Schwerpunkten. 1. Zur Identifizierung Kompartiment-spezifischer Biomarker wurde eine Methode entwickelt, welche als kosteng√ľnstige Alternative zum sc-Seq Expressionsprofile individueller Zelltypen generiert. Dabei erfolgt die Extraktion der RNA nicht aus Einzelzellen, sondern aus flowzytometrisch-getrennten Zellkompartimenten. Die Separation der Proben in Epithelzellen, Immunzellen und Fibroblasten wurde durch verschiedene Verfahren validiert und eine suffiziente Ausbeute an RNA auch f√ľr kleine Gewebemengen gezeigt. 2. Biomarker des Immunzellkompartiments als therapeutische Angriffspunkte wurden in einem Patientenkollektiv von bis zu 551 Patienten auf ihre Bedeutung beim EAC √ľberpr√ľft. Es zeigte sich eine Expression der Immuncheckpoints LAG3, VISTA und IDO auf TILs durch IHC und RNA-Sonden basierte Verfahren in einem relevanten Anteil (LAG3: 11,4%, VISTA: 29%, IDO: 52,6%). Es konnte eine prognostisch g√ľnstige Bedeutung der VISTA, LAG3 und IDO Expression gezeigt werden. Durch den Vergleich von Genexpressionsprofilen aus therapienaiven und vorbehandelten Tumoren konnte zudem ein immunsuppressiver Effekt von neoadjuvanten Therapiekonzepten auf das Tumormikromilieu des EACs gezeigt werden. Dabei kam es zur verminderten Expression von Checkpoints und Anzahl TILs nach (Radio-) Chemotherapie. 3. Im Tumorzellkompartiment wurde die Rolle von Amplifikationen in ErbB-Rezeptor abh√§ngigen Signalwegen durch FISH-Technik und Immunhistochemie evaluiert. Es fanden sich KRAS Amplifikationen in 17,1%, PIK3CA Amplifikationen in 5% sowie eine HER2/neu-√úberexpression in 14,9% der untersuchten Tumore

    Computational modeling of locoregional recurrence with spatial structure identifies tissue-specific carcinogenic profiles

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    IntroductionLocal and regional recurrence after surgical intervention is a significant problem in cancer management. The multistage theory of carcinogenesis precisely places the presence of histologically normal but mutated premalignant lesions surrounding the tumor - field cancerization, as a significant cause of cancer recurrence. The relationship between tissue dynamics, cancer initiation and cancer recurrence in multistage carcinogenesis is not well known.MethodsThis study constructs a computational model for cancer initiation and recurrence by combining the Moran and branching processes in which cells requires 3 or more mutations to become malignant. In addition, a spatial structure-setting is included in the model to account for positional relativity in cell turnover towards malignant transformation. The model consists of a population of normal cells with no mutation; several populations of premalignant cells with varying number of mutations and a population of malignant cells. The model computes a stage of cancer detection and surgery to eliminate malignant cells but spares premalignant cells and then estimates the time for malignant cells to re-emerge.ResultsWe report the cellular conditions that give rise to different patterns of cancer initiation and the conditions favoring a shorter cancer recurrence by analyzing premalignant cell types at the time of surgery. In addition, the model is fitted to disease-free clinical data of 8,957 patients in 27 different cancer types; From this fitting, we estimate the turnover rate per month, relative fitness of premalignant cells, growth rate and death rate of cancer cells in each cancer type.DiscussionOur study provides insights into how to identify patients who are likely to have a shorter recurrence and where to target the therapeutic intervention

    Anu√°rio cient√≠fico da Escola Superior de Tecnologia da Sa√ļde de Lisboa - 2021

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    √Č com grande prazer que apresentamos a mais recente edi√ß√£o (a 11.¬™) do Anu√°rio Cient√≠fico da Escola Superior de Tecnologia da Sa√ļde de Lisboa. Como institui√ß√£o de ensino superior, temos o compromisso de promover e incentivar a pesquisa cient√≠fica em todas as √°reas do conhecimento que contemplam a nossa miss√£o. Esta publica√ß√£o tem como objetivo divulgar toda a produ√ß√£o cient√≠fica desenvolvida pelos Professores, Investigadores, Estudantes e Pessoal n√£o Docente da ESTeSL durante 2021. Este Anu√°rio √©, assim, o reflexo do trabalho √°rduo e dedicado da nossa comunidade, que se empenhou na produ√ß√£o de conte√ļdo cient√≠fico de elevada qualidade e partilhada com a Sociedade na forma de livros, cap√≠tulos de livros, artigos publicados em revistas nacionais e internacionais, resumos de comunica√ß√Ķes orais e p√≥steres, bem como resultado dos trabalhos de 1¬ļ e 2¬ļ ciclo. Com isto, o conte√ļdo desta publica√ß√£o abrange uma ampla variedade de t√≥picos, desde temas mais fundamentais at√© estudos de aplica√ß√£o pr√°tica em contextos espec√≠ficos de Sa√ļde, refletindo desta forma a pluralidade e diversidade de √°reas que definem, e tornam √ļnica, a ESTeSL. Acreditamos que a investiga√ß√£o e pesquisa cient√≠fica √© um eixo fundamental para o desenvolvimento da sociedade e √© por isso que incentivamos os nossos estudantes a envolverem-se em atividades de pesquisa e pr√°tica baseada na evid√™ncia desde o in√≠cio dos seus estudos na ESTeSL. Esta publica√ß√£o √© um exemplo do sucesso desses esfor√ßos, sendo a maior de sempre, o que faz com que estejamos muito orgulhosos em partilhar os resultados e descobertas dos nossos investigadores com a comunidade cient√≠fica e o p√ļblico em geral. Esperamos que este Anu√°rio inspire e motive outros estudantes, profissionais de sa√ļde, professores e outros colaboradores a continuarem a explorar novas ideias e contribuir para o avan√ßo da ci√™ncia e da tecnologia no corpo de conhecimento pr√≥prio das √°reas que comp√Ķe a ESTeSL. Agradecemos a todos os envolvidos na produ√ß√£o deste anu√°rio e desejamos uma leitura inspiradora e agrad√°vel.info:eu-repo/semantics/publishedVersio

    Metabolomics-based discovery of XHP as a CYP3A4 inhibitor against pancreatic cancer

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    Background: Xihuang Wan (XHW), a purgative and detoxifying agent, is commonly utilized in modern medicine as a treatment and adjuvant therapy for various malignancies, including breast cancer, liver cancer, and lung cancer. A clinical study demonstrated the potential usefulness of the combination of XHW and gemcitabine as a therapy for pancreatic cancer (PC), indicating that XHW‚Äôs broad-spectrum antitumor herbal combination could be beneficial in the treatment of PC. However, the precise therapeutic efficacy of XHW in treating pancreatic cancer remains uncertain.Aim: This study assessed the biological activity of XHW by optimizing the therapeutic concentration of XHW (Xihuang pills, XHP). We performed cell culture and developed an animal test model to determine whether XHP can inhibit pancreatic cancer (PC). We also applied the well-known widely targeted metabolomics analysis and conducted specific experiments to assess the feasibility of our method in PC therapy.Materials and Methods: We used UPLC/Q-TOF-MS to test XHP values to set up therapeutic concentrations for the in vivo test model. SW1990 pancreatic cancer cells were cultured to check the effect the anti-cancer effects of XHP by general in vitro cell analyses including CCK-8, Hoechst 33258, and flow cytometry. To develop the animal model, a solid tumor was subcutaneously formed on a mouse model of PC and assessed by immunohistochemistry and TUNEL apoptosis assay. We also applied the widely targeted metabolomics method following Western blot and RT-PCR to evaluate multiple metabolites to check the therapeutic effect of XHP in our cancer test model.Results: Quantified analysis from UPLC/Q-TOF-MS showed the presence of the following components of XHP: 11-carbonyl-ő≤-acetyl-boswellic acid (AKBA), 11-carbonyl-ő≤-boswellic acid (KBA), 4-methylene-2,8,8-trimethyl-2-vinyl-bicyclo [5.2.0]nonane, and (1S-endo)-2-methyl-3-methylene-2-(4-methyl-3-3-pentenyl)-bicyclo [2.2.1heptane]. The results of the cell culture experiments demonstrated that XHP suppressed the growth of SW1990 PC cells by enhancing apoptosis. The results of the animal model tests also indicated the suppression effect of XHP on tumor growth. Furthermore, the result of the widely targeted metabolomics analysis showed that the steroid hormone biosynthesis metabolic pathway was a critical factor in the anti-PC effect of XHP in the animal model. Moreover, Western blot and RT-PCR analyses revealed XHP downregulated CYP3A4 expression as an applicable targeted therapeutic approach.Conclusion: The results of this study demonstrated the potential of XHP in therapeutic applications in PC. Moreover, the widely targeted metabolomics method revealed CYP3A4 is a potential therapeutic target of XHP in PC control. These findings provide a high level of confidence that XHP significantly acts as a CYP3A4 inhibitor in anti-cancer therapeutic applications

    Liquid Biopsies: The Future of Cancer Early Detection

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    Cancer is a worldwide pandemic. The burden it imposes grows steadily on a global scale causing emotional, physical, and financial strains on individuals, families, and health care systems. Despite being the second leading cause of death worldwide, many cancers do not have screening programs and many people with a high risk of developing cancer fail to follow the advised medical screening regime due to the nature of the available screening tests and other challenges with compliance. Moreover, many liquid biopsy strategies being developed for early detection of cancer lack the sensitivity required to detect early-stage cancers. Early detection is key for improved quality of life, survival, and to reduce the financial burden of cancer treatments which are greater at later stage detection. This review examines the current liquid biopsy market, focusing in particular on the strengths and drawbacks of techniques in achieving early cancer detection. We explore the clinical utility of liquid biopsy technologies for the earlier detection of solid cancers, with a focus on how a combination of various spectroscopic and -omic methodologies may pave the way for more efficient cancer diagnostics

    Macrophages from naked mole-rat possess distinct immunometabolic signatures upon polarization

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    The naked mole-rat (NMR) is a unique long-lived rodent which is highly resistant to age-associated disorders and cancer. The immune system of NMR possesses a distinct cellular composition with the prevalence of myeloid cells. Thus, the detailed phenotypical and functional assessment of NMR myeloid cell compartment may uncover novel mechanisms of immunoregulation and healthy aging. In this study gene expression signatures, reactive nitrogen species and cytokine production, as well as metabolic activity of classically (M1) and alternatively (M2) activated NMR bone marrow-derived macrophages (BMDM) were examined. Polarization of NMR macrophages under pro-inflammatory conditions led to expected M1 phenotype characterized by increased pro-inflammatory gene expression, cytokine production and aerobic glycolysis, but paralleled by reduced production of nitric oxide (NO). Under systemic LPS-induced inflammatory conditions NO production also was not detected in NMR blood monocytes. Altogether, our results indicate that NMR macrophages are capable of transcriptional and metabolic reprogramming under polarizing stimuli, however, NMR M1 possesses species-specific signatures as compared to murine M1, implicating distinct adaptations in NMR immune system

    LDL receptor related protein 1 is an adverse prognostic biomarker that correlates with stromal remodeling and macrophages infiltration in bladder cancer

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    IntroductionBladder cancer (BLCA) is a highly heterogeneous disease influenced by the tumor microenvironment, which may affect patients' response to immune checkpoint blockade therapy. Therefore, identifying molecular markers and therapeutic targets to improve treatment is essential. In this study, we aimed to investigate the prognostic significance of LRP1 in BLCA.MethodsWe analyzed TCGA and IMvigor210 cohorts to investigate the relationship of LRP1 with BLCA prognosis. We utilized gene mutation analysis and enrichment to identify LRP1-associated mutated genes and biological processes. Deconvolution algorithms and single-cell analysis were used to understand the tumor-infiltrated cells and biological pathways associated with LRP1 expression. Immunohistochemistry was conducted to validate the bioinformatics analysis.ResultsOur study revealed that LRP1 was an independent risk factor for overall survival in BLCA patients and was associated with clinicopathological features and FGFR3 mutation frequency. Enrichment analysis demonstrated that LRP1 was involved in extracellular matrix remodeling and tumor metabolic processes. Furthermore, the ssGSEA algorithm revealed that LRP1 was positively correlated with the activities of tumor-associated pathways. Our study also found that high LRP1 expression impaired patients' responsiveness to ICB therapy in BLCA, which was predicted by TIDE prediction and validated by IMvigor210 cohort. Immunohistochemistry confirmed the expression of LRP1 in Cancer-Associated Fibroblasts (CAFs) and macrophages in the tumor microenvironment of BLCA.DiscussionOur study suggests that LRP1 may be a potential prognostic biomarker and therapeutic target in BLCA. Further research on LRP1 may improve BLCA precision medicine and enhance the efficacy of immune checkpoint blockade therapy
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