Epidemiological studies demonstrate an association between breast cancer (BC) and systemic dysregulation of glucose metabolism. However, how BC influences glucose homeostasis remains unknown. We show that BC-derived extracellular vesicles (EVs) suppress pancreatic insulin secretion to impair glucose homeostasis. EV-encapsulated miR-122 targets PKM in β-cells to suppress glycolysis and ATP-dependent insulin exocytosis. Mice receiving high-miR-122 EVs or bearing BC tumours exhibit suppressed insulin secretion, enhanced endogenous glucose production, impaired glucose tolerance, and fasting hyperglycaemia. These effects contribute to tumour growth and are abolished by inhibiting EV secretion or miR-122, restoring PKM in β-cells, or insulin supplementation. Compared to non-cancer controls, BC patients have higher levels of circulating EV-encapsulated miR-122 and fasting glucose concentrations but lower fasting insulin; miR-122 levels are positively associated with glucose and negatively associated with insulin. Therefore, EV-mediated impairment of whole-body glycaemic control may contribute to tumour progression and incidence of type 2 diabetes in some BC patients.
Background Although “clean eating” is widely propagated through social media and anecdotal reports in the popular press, there is almost no scientific research on this potentially risky dietary strategy. The current investigation explored definitions and perceptions of “clean eating” and its associations with indicators of disordered eating among diverse U.S.-based undergraduates. Method Undergraduates ( N = 148, M age = 19.41 years, 70.3% women) were asked to define “clean eating” via an open-ended question and then read vignettes featuring five “clean” diets, all of which caused mild functional impairment across multiple domains. Participants rated the extent to which they believed the diet was 1) “healthy,” 2) reflective of “clean eating,” and 3) likely to be adopted by them. Finally, participants completed questionnaires to assess body appearance evaluation, obsessive-compulsive symptoms, eating disorder symptoms, and symptoms of orthorexia nervosa. Results Open-ended responses indicated that participants defined “clean eating” in varied but overwhelmingly positive terms. Repeated measures ANOVAs indicated that the “meal substitution” vignette was perceived as the least healthy, least “clean,” and least likely to be adopted, whereas the “new” (balanced) diet vignette was rated the highest on these domains. Correlations among diet perceptions and indicators of disordered eating were positive and significant. Conclusions “Clean eating” is likely a heterogeneous phenomenon that is viewed favorably by U.S.-based college students even when it is linked with functional impairment and emotional distress. Ongoing examination of “clean eating” could clarify the potential benefits and risks posed by this dietary strategy and thus inform eating disorder prevention efforts.
Development of new capillary electrophoresis (CE) methodology and instrumentation, as well as application of CE to solve new problems, remains an active research area because of the attractive features of CE compared to other separation techniques. In this review, we focus on the representative works about sample preconcentration, separation media or capillary coating development, detector construction, and multidimensional separation in CE, which are judiciously selected from the papers published in 2018-2020.
An arrayed host:guest fluorescence sensor system can discriminate among and classify multiple different noncanonical DNA structures by exploiting selective molecular recognition. The sensor is highly selective and can discriminate between folds as similar as native Gquadruplexes and those with bulges or vacancies. The host and guest can form heteroternary complexes with DNA strands, with the host acting as mediator between the DNA and dye, modulating the emission. By applying machine learning algorithms to the sensing data, prediction of the folding state of unknown DNA strands is possible with high fidelity.
Metal–organic frameworks (MOFs) have many attractive features, including tunable composition, rigid structure, controllable pore size, and large specific surface area, and thus are highly applicable in molecular analysis. Depending on the MOF structure, a high number of unsaturated metal sites can be exposed to catalyze chemical reactions. In the present work, we report that using both Co(II) and Fe(III) to prepare the MIL-88(NH2) MOF, we can produce the bimetallic MOF that can catalyze the conversion of 3,3′,5,5″-tetramethylbenzidine (TMB) to a color product through a reaction with H2O2 at a higher reaction rate than the monometallic Fe-MIL-88(NH2). The Michaelis constants (K m) of the catalytic reaction for TMB and H2O2 are 3–5 times smaller, and the catalytic constants (k cat) are 5–10 times higher than those of the horseradish peroxidase (HRP), supporting ultrahigh peroxidase-like activity. These values are also much more superior to those of the HRP-mimicking MOFs reported previously. Interestingly, the bimetallic MOF can be coupled with glucose oxidase (GOx) to trigger the cascade enzymatic reaction for highly sensitive detection of extracellular vesicles (EVs), a family of important biomarkers. Through conjugation to the aptamer that recognizes the marker protein on EV surface, the MOF can help isolate the EVs from biological matrices, which are subsequently labeled by GOx via antibody recognition. The cascade enzymatic reaction between MOF and GOx enables the detection of EVs at a concentration as low as 7.8 × 104 particles/mL. The assay can be applied to monitor EV secretion by cultured cells and also can successfully detect the different EV quantities in the sera samples collected from cancer patients and healthy controls. Overall, we prove that the bimetallic Fe/Co-MIL-88(NH2) MOF, with its high peroxidase activity and high biocompatibility, is a valuable tool deployable in clinical assays to facilitate disease diagnosis and prognosis.
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