• Shah McLean posted an update 6 months ago

    The field of organoid engineering promises to revolutionize medicine with wide-ranging applications of scientific, engineering, and clinical interest, including precision and personalized medicine, gene editing, drug development, disease modelling, cellular therapy, and human development. Organoids are a three-dimensional (3D) miniature representation of a target organ, are initiated with stem/progenitor cells, and are extremely promising tools with which to model organ function. The biological basis for organoids is that they foster stem cell self-renewal, differentiation, and self-organization, recapitulating 3D tissue structure or function better than two-dimensional (2D) systems. In this review, we first discuss the importance of epithelial organs and the general properties of epithelial cells to provide a context and rationale for organoids of the liver, pancreas, and gall bladder. Next, we develop a general framework to understand self-organization, tissue hierarchy, and organoid cultivation. For each of these areas, we provide a historical context, and review a wide range of both biological and mathematical perspectives that enhance understanding of organoids. Next, we review existing techniques and progress in hepatobiliary and pancreatic organoid engineering. To do this, we review organoids from primary tissues, cell lines, and stem cells, and introduce engineering studies when applicable. We discuss non-invasive assessment of organoids, which can reveal the underlying biological mechanisms and enable improved assays for growth, metabolism, and function. Applications of organoids in cell therapy are also discussed. Taken together, we establish a broad scientific foundation for organoids and provide an in-depth review of hepatic, biliary and pancreatic organoids.

    Helicobacter pylori (Hpylori) immunoglobulin G (IgG) seropositivity is prevalent but its relation with leukocyte telomere length (LTL), a cellular aging biomarker, is unclear.

    Among 3,472 participants from the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000, LTL was measured with the quantitative polymerase chain reaction. Hpylori IgG was measured by enzyme-linked immunosorbent assays and defined as seropositivity with an immune status ratio score>0.9. We used linear regression models to examine the relation of Hpylori IgG seropositivity with continuous LTL and logistic regression for the relation with short LTL (<10th percentile of the population distribution) adjusting for potential confounders. We stratified the analyses by a priori selected variables.

    Population prevalence of Hpylori IgG seropositivity was 31.5% in the overall population with higher prevalence found in those with older age, other races than non-Hispanic whites, lower education, and being born out of the United States. Continuous LTL was non-significantly shorter in those with HPylori IgG seropositivity versus seronegativity (mean difference=-40.3bp, 95% CI -112.4, 31.9). This difference was not significant after adjusting for potential confounders nor stratifying by potential effect modifiers. HPylori IgG seropositivity was significantly associated with short LTL among the elderly (55-75years, adjusted OR 3.06, 95% CI 1.17, 7.99), but not in the overall population (OR 1.28, 95% CI 0.81-2.02).

    H Pylori IgG seropositivity was not associated with continuous LTL in the general population but may be associated with an excessively short LTL in the elderly.

    H Pylori IgG seropositivity was not associated with continuous LTL in the general population but may be associated with an excessively short LTL in the elderly.

    To advocate for strategic actions by U.S. see more nursing leadership that denote the presence, customs, and implications of racism that has been institutionalized within the structures of U.S. nursing leadership and the profession.

    A racial equity framework is used to examine the barriers to quality health care and equitable health outcomes and to present evidence-based actions to dismantle structural inequities embedded in the nursing profession.

    This article was developed through a comprehensive literature review and synthesis of relevant research, data, peer-reviewed literature, government reports, and organizational guidelines.

    A commitment by U.S. nursing leadership to eradicate structural racism in nursing must be made in order to effect sustainable transformative change toward more equitable systems of health care.

    This article presents recommendations for nursing leadership in the United States to renew its commitment to quality health care through dismantling structural racism at all levels of direct and systems nursing practice and education, at the bedside, and in the boardrooms.

    Structural racism in nursing and health care also persists globally as a key social determinant of health. Its elimination aligns with international health care and nursing’s policy priorities, yet change can only occur when senior leaders clearly understand it as a key barrier to health, and commit to transformative change in how their “systems” work. These recommendations can also be culturally adapted by global nursing for use in antiracism work.

    Structural racism in nursing and health care also persists globally as a key social determinant of health. Its elimination aligns with international health care and nursing’s policy priorities, yet change can only occur when senior leaders clearly understand it as a key barrier to health, and commit to transformative change in how their “systems” work. These recommendations can also be culturally adapted by global nursing for use in antiracism work.Kinases and phosphatases are major players in a variety of cellular events, including cell signaling. Aberrant activity or mutations in kinases and phosphatases can lead to diseases such as cancer, diabetes, and Alzheimer’s. Compared to kinases, phosphatases are understudied; this is partly a result of the limited methods for identifying substrates. As a solution, we developed a proteomics-based method called kinase-catalyzed biotinylation to identify phosphatase substrates (K-BIPS) that previously identified substrates of Ser/Thr phosphatases using small molecule inhibitors. Here, for the first time, K-BIPS was applied to identify substrates of a tyrosine phosphatase, protein tyrosine phosphatase 1B (PTP1B), under siRNA knockdown conditions. Eight possible substrates of PTP1B were discovered in HEK293 cells, including the known substrate pyruvate kinase. In addition, l-lactate dehydrogenase (LDHA) was validated as a novel PTP1B substrate. With the ability to use knockdown conditions with Ser/Thr or Tyr phosphatases, K-BIPS represents a general discovery tool to explore phosphatases biology by identifying unanticipated substrates.

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