Summary In this Series paper, we examine how mass incarceration shapes inequality in health. The USA is the world leader in incarceration, which disproportionately affects black populations. Nearly ...one in three black men will ever be imprisoned, and nearly half of black women currently have a family member or extended family member who is in prison. However, until recently the public health implications of mass incarceration were unclear. Most research in this area has focused on the health of current and former inmates, with findings suggesting that incarceration could produce some short-term improvements in physical health during imprisonment but has profoundly harmful effects on physical and mental health after release. The emerging literature on the family and community effects of mass incarceration points to negative health impacts on the female partners and children of incarcerated men, and raises concerns that excessive incarceration could harm entire communities and thus might partly underlie health disparities both in the USA and between the USA and other developed countries. Research into interventions, policies, and practices that could mitigate the harms of incarceration and the post-incarceration period is urgently needed, particularly studies using rigorous experimental or quasi-experimental designs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Förster or fluorescence resonance energy transfer (FRET) technology and genetically encoded FRET biosensors provide a powerful tool for visualizing signaling molecules in live cells with high ...spatiotemporal resolution. Fluorescent proteins (FPs) are most commonly used as both donor and acceptor fluorophores in FRET biosensors, especially since FPs are genetically encodable and live-cell compatible. In this review, we will provide an overview of methods to measure FRET changes in biological contexts, discuss the palette of FP FRET pairs developed and their relative strengths and weaknesses, and note important factors to consider when using FPs for FRET studies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This Viewpoint discusses the health harms to individuals and communities because of mass incarceration in the US and proposes interventions to ensure health equity for all individuals.
Cancer-secreted, extracellular vesicle (EV)-encapsulated miRNAs enable cancer cells to communicate with each other and with noncancerous cells in tumor pathogenesis and response to therapies. Here, ...we show that treatment with a sublethal dose of chemotherapeutic agents induces breast cancer cells to secrete EV with the capacity to stimulate a cancer stem-like cell (CSC) phenotype, rendering cancer cells resistance to therapy. Chemotherapy induced breast cancer cells to secrete multiple EV miRNAs, including miR-9-5p, miR-195-5p, and miR-203a-3p, which simultaneously targeted the transcription factor One Cut Homeobox 2 (ONECUT2), leading to induction of CSC traits and expression of stemness-associated genes, including
, and
. Inhibition of these miRNAs or restoration of ONECUT2 expression abolished the CSC-stimulating effect of EV from chemotherapy-treated cancer cells. In mice bearing xenograft mammary tumors, docetaxel treatment caused elevations of miR-9-5p, miR-195-5p, and miR-203a-3p in circulating EV and decreased ONECUT2 expression and increased levels of stemness-associated genes. These effects following chemotherapy were diminished in tumors deficient in exosome secretion. In human breast tumors, neoadjuvant chemotherapy decreased ONECUT2 expression in tumor cells. Our results indicate a mechanism by which cancer cells communicate with each other and self-adapt to survive in response to cytotoxic treatment. Targeting these adaptation mechanisms along with chemotherapy, such as by blocking the EV miRNA-ONECUT2 axis, represents a potential strategy to maximize the anticancer effect of chemotherapy and to reduce chemoresistance in cancer management. SIGNIFICANCE: These findings reveal a critical mechanism of resistance to chemotherapy by which breast cancer cells secrete miRNA-containing extracellular vesicles to stimulate cancer stem cell-like features.
This study characterizes driving distances to opioid treatment programs in urban vs rural counties in states with the highest rates of opioid mortality and compares them with distances to ...methadone-prescribing federally qualified health centers and dialysis centers.
MicroRNAs （miRNAs） are critical regulators of gene expression, and exert extensive impacts on development, physi- ology, and disease of eukaryotes. A high degree of parallelism is found in the ...molecular basis of miRNA biogenesis and action in plants and animals. Recent studies interestingly suggest a potential cross-kingdom action of plant-de- rived miRNAs, through dietary intake, in regulating mammalian gene expression. Although the source and scope of plant miRNAs detected in mammalian specimens remain controversial, these initial studies inspired us to determine whether plant miRNAs can be detected in Western human sera and whether these plant miRNAs are able to influ- ence gene expression and cellular processes related to human diseases such as cancer. Here we found that Western donor sera contained the plant miRNA miR159, whose abundance in the serum was inversely correlated with breast cancer incidence and progression in patients. In human sera, miR159 was predominantly detected in the extracellular vesicles, and was resistant to sodium periodate oxidation suggesting the plant-originated 2＇-O-methylation on the 3＇ terminal ribose. In breast cancer cells but not non-cancerous mammary epithelial cells, a synthetic mimic of miR159 was capable of inhibiting proliferation by targeting TCF7 that encodes a Wnt signaling transcription factor, leading to a decrease in MYC protein levels. Oral administration of miR159 mimic significantly suppressed the growth of xenograft breast tumors in mice. These results demonstrate for the first time that a plant miRNA can inhibit cancer growth in mammals.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ischemic stroke is a challenging disease with high mortality and disability rates, causing a great economic and social burden worldwide. During ischemic stroke, ionic imbalance and excitotoxicity, ...oxidative stress, and inflammation are developed in a relatively certain order, which then activate the cell death pathways directly or indirectly via the promotion of organelle dysfunction. Neuroprotection, a therapy that is aimed at inhibiting this damaging cascade, is therefore an important therapeutic strategy for ischemic stroke. Notably, phytochemicals showed great neuroprotective potential in preclinical research via various strategies including modulation of calcium levels and antiexcitotoxicity, antioxidation, anti-inflammation and BBB protection, mitochondrial protection and antiapoptosis, autophagy/mitophagy regulation, and regulation of neurotrophin release. In this review, we summarize the research works that report the neuroprotective activity of phytochemicals in the past 10 years and discuss the neuroprotective mechanisms and potential clinical applications of 148 phytochemicals that belong to the categories of flavonoids, stilbenoids, other phenols, terpenoids, and alkaloids. Among them, scutellarin, pinocembrin, puerarin, hydroxysafflor yellow A, salvianolic acids, rosmarinic acid, borneol, bilobalide, ginkgolides, ginsenoside Rd, and vinpocetine show great potential in clinical ischemic stroke treatment. This review will serve as a powerful reference for the screening of phytochemicals with potential clinical applications in ischemic stroke or the synthesis of new neuroprotective agents that take phytochemicals as leading compounds.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This Viewpoint discusses the importance of studying coronavirus disease 2019 (COVID-19) vaccine candidates in prisoners, and proposes a framework for considering how to include them safely, ...ethically, and without coercion in future phase 3 vaccine trials.
Many genetically encoded biosensors use Förster resonance energy transfer (FRET) to dynamically report biomolecular activities. While pairs of cyan and yellow fluorescent proteins (FPs) are most ...commonly used as FRET partner fluorophores, respectively, green and red FPs offer distinct advantages for FRET, such as greater spectral separation, less phototoxicity, and lower autofluorescence. We previously developed the green-red FRET pair Clover and mRuby2, which improves responsiveness in intramolecular FRET reporters with different designs. Here we report the engineering of brighter and more photostable variants, mClover3 and mRuby3. mClover3 improves photostability by 60% and mRuby3 by 200% over the previous generation of fluorophores. Notably, mRuby3 is also 35% brighter than mRuby2, making it both the brightest and most photostable monomeric red FP yet characterized. Furthermore, we developed a standardized methodology for assessing FP performance in mammalian cells as stand-alone markers and as FRET partners. We found that mClover3 or mRuby3 expression in mammalian cells provides the highest fluorescence signals of all jellyfish GFP or coral RFP derivatives, respectively. Finally, using mClover3 and mRuby3, we engineered an improved version of the CaMKIIα reporter Camuiα with a larger response amplitude.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This Viewpoint summarizes a National Academy of Sciences, Engineering, and Medicine (NASEM) consensus panel report recommending ways to reduce populations in prisons and jails as a means to mitigate ...SARS-CoV-2 transmission and the roles clinicians, health systems, and insurers can play in in process.
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