Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (3 results)

  • Thesis
  • Peer Reviewed
UC Riverside Electronic Theses and Dissertations (2019)

Developmental toxicology is an ever-changing field dedicated to ensuring the safety and efficacy of foods, drugs and chemicals available to the public, specifically concerned with effects on a developing embryo. While many studies have uncovered the detrimental health effects of tobacco use, a concern to the health problems associated with harm reduction tobacco products (HRTPs) grows as the usage increases, specifically in women who are, or may become pregnant. Using a novel approach analyzing mitochondrial network morphology called Mitochondrial Network Analysis (MiNA), significant changes in mitochondrial network morphology were found in human embryonic stem cells (hESCs) exposed to both Camel and Camel Blue cigarettes, conventional and HRTP respectively. Supplementation with ascorbic acid led to a general improvement of network morphology for both products suggesting ROS as one mechanism of toxicity. To determine if prenatal exposure to Snus, a non-combustible HRTP, causes any increased risk of neurological damage such as anxiety and motor control, pregnant mice were injected with a Snus tobacco extract, and allowed to age into adulthood. The adult mice were then tested for such neurological issues using the elevated plus maze (EPM) and the Suok test. Results suggest female mice are more susceptible to increased behavioral issues such as anxiety and reduced motor control when exposed in utero to Snus tobacco extract than male mice compared to the untreated. This suggest that these neurological concerns may be linked in some way to the X-chromosome, and environmental toxicants such as tobacco may increase chances of occurrence. These studies together suggest that embryonic exposure to HRTPs may lead to other increased risks, not typically evaluated, that may be equal or more detrimental than conventional tobacco and must be taken into consideration when making claims of reduced harm.

    Cover page: Embryonic Exposure to Harm Reduction Tobacco Products Cause Mitochondrial and Behavioral Defects Similar to Conventional Tobacco
    • Article
    • Peer Reviewed
    UC Riverside Previously Published Works (2017)

    Purpose of review

    Osteogenesis is a complex process involving the specification of multiple progenitor cells and their maturation and differentiation into matrix-secreting osteoblasts. Osteogenesis occurs not only during embryogenesis but also during growth, after an injury, and in normal homeostatic maintenance. While much is known about osteogenesis-associated regulatory genes, the role of microRNAs (miRNAs), which are epigenetic regulators of protein expression, is just beginning to be explored. While miRNAs do not abrogate all protein expression, their purpose is to finely tune it, allowing for a timely and temporary protein down-regulation.

    Recent findings

    The last decade has unveiled a multitude of miRNAs that regulate key proteins within the osteogenic lineage, thus qualifying them as "ostemiRs." These miRNAs may endogenously target an activator or inhibitor of differentiation, and depending on the target, may either lead to the prolongation of a progenitor maintenance state or to early differentiation. Interestingly, cellular identity seems intimately coupled to the expression of miRNAs, which participate in the suppression of previous and subsequent differentiation steps. In such cases where key osteogenic proteins were identified as direct targets of miRNAs in non-bone cell types, or through bioinformatic prediction, future research illuminating the activity of these miRNAs during osteogenesis will be extremely valuable. Many bone-related diseases involve the dysregulation of transcription factors or other proteins found within osteoblasts and their progenitors, and the dysregulation of miRNAs, which target such factors, may play a pivotal role in disease etiology, or even as a possible therapy.
      Cover page: microRNA Regulation of Skeletal Development
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2022)
      Epidemiological studies suggest cigarette smoking as a probable environmental factor for a variety of congenital anomalies, including low bone mass, increased fracture risk and poor skeletal health. Human and animal in vitro models have confirmed hypomineralization of differentiating cell lines with sidestream smoke being more harmful to developing cells than mainstream smoke. Furthermore, first reports are emerging to suggest a differential impact of conventional versus harm-reduction tobacco products on bone tissue as it develops in the embryo or in vitro. To gather first insight into the molecular mechanism of such differences, we assessed the effect of sidestream smoke solutions from Camel (conventional) and Camel Blue (harm-reduction) cigarettes using a human embryonic stem cell osteogenic differentiation model. Sidestream smoke from the conventional Camel cigarettes concentration-dependently inhibited in vitro calcification triggered by high levels of mitochondrially generated oxidative stress, loss of mitochondrial membrane potential, and reduced ATP production. Camel sidestream smoke also induced DNA damage and caspase 9-dependent apoptosis. Camel Blue-exposed cells, in contrast, invoked only intermediate levels of reactive oxygen species insufficient to activate caspase 3/7. Despite the absence of apoptotic gene activation, damage to the mitochondrial phenotype was still noted concomitant with activation of an anti-inflammatory gene signature and inhibited mineralization. Collectively, the presented findings in differentiating pluripotent stem cells imply that embryos may exhibit low bone mineral density if exposed to environmental smoke during development.
        Cover page: Sidestream Smoke Extracts from Harm-Reduction and Conventional Camel Cigarettes Inhibit Osteogenic Differentiation via Oxidative Stress and Differential Activation of intrinsic Apoptotic Pathways
        Top