Capable of mediating efficient transfection and protein production without eliciting innate immune responses, chemically modified mRNA holds great potential to produce paracrine factors at a physiologically beneficial level, in a spatiotemporally controlled manner, and with low toxicity. Although highly promising in cardiovascular medicine and wound healing, effects of this emerging therapeutic on the microvasculature and its bioactivity in disease settings remain poorly understood. Here, we longitudinally and comprehensively characterize microvascular responses to AZD8601, a modified mRNA encoding vascular endothelial growth factor A (VEGF-A), in vivo. Using multi-parametric photoacoustic microscopy, we show that intradermal injection of AZD8601 formulated in a biocompatible vehicle results in pronounced, sustained and dose-dependent vasodilation, blood flow upregulation, and neovessel formation, in striking contrast to those induced by recombinant human VEGF-A protein, a non-translatable variant of AZD8601, and citrate/saline vehicle. Moreover, we evaluate the bioactivity of AZD8601 in a mouse model of diabetic wound healing in vivo. Using a boron nanoparticle-based tissue oxygen sensor, we show that sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing.

Chronic pain (i.e., pain lasting ≥3 months) is a debilitating condition that affects daily work and life activities for many adults in the United States and has been linked with depression (1), Alzheimer disease and related dementias (2), higher suicide risk (3), and substance use and misuse (4). During 2016, an estimated 50 million adults in the United States experienced chronic pain, resulting in substantial health care costs and lost productivity (5,6). Addressing chronic pain and improving the lives of persons living with pain is a public health imperative. Population research objectives in the National Pain Strategy, which was released in 2016 by the Interagency Pain Research Coordinating Committee, call for more precise estimates of the prevalence of chronic pain and high-impact chronic pain (i.e., chronic pain that results in substantial restriction to daily activities) in the general population and within various population groups to guide efforts to reduce the impact of chronic pain (3). Further, a 2022 review of U.S. chronic pain surveillance systems identified the National Health Interview Survey (NHIS) as the best source for pain surveillance data (7). CDC analyzed data from the 2019-2021 NHIS to provide updated estimates of the prevalence of chronic pain and highimpact chronic pain among adults in the United States and within population groups defined by demographic, geographic, socioeconomic, and health status characteristics. During 2021, an estimated 20.9% of U.S. adults (51.6 million persons) experienced chronic pain, and 6.9% (17.1 million persons) experienced high-impact chronic pain. New findings from this analysis include that non-Hispanic American Indian or Alaska Native (AI/AN) adults, adults identifying as bisexual, and adults who are divorced or separated are among the populations experiencing a higher prevalence of chronic pain and highimpact chronic pain. Clinicians, practices, health systems, and payers should vigilantly attend to health inequities and ensure access to appropriate, affordable, diversified, coordinated, and effective pain management care for all persons (8).NHIS is a cross-sectional, household survey of the civilian, noninstitutionalized population conducted annually by the National Center for Health Statistics (NCHS).* Data were analyzed using the 2019-2021 Sample Adult Interviews. † Survey questions used to estimate the prevalence of pain included, "In the past three months, how often did you have pain? Would you say never, some days, most days, or every day?" and "Over the past three months, how often did your pain limit your life or work activities? Would you say never, some days, most days, INSIDE

Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis. Current animal and clinical studies focus on the use of adipose or bone marrow-derived mesenchymal stem cells. We, instead, have established adult lung spheroid cells (LSCs) as an intrinsic source of therapeutic lung stem cells. In the present study, we compared the efficacy and safety of syngeneic and allogeneic LSCs in immunocompetent rats with bleomycin-induced pulmonary inflammation in an effort to mitigate fibrosis development. We found that infusion of allogeneic LSCs reduces the progression of inflammation and fibrotic manifestation and preserves epithelial and endothelial health without eliciting significant immune rejection. Our study sheds light on potential future developments of LSCs as an allogeneic cell therapy for humans with pulmonary fibrosis. STEM CELLS TRANSLATIONAL MEDICINE 2017;9:1905-1916 SIGNIFICANCE STATEMENTWe have demonstrated the safety and efficacy of allogeneic lung spheroid cell (LSC) treatment in attenuating the progression and severity of pulmonary fibrosis, decreasing apoptosis, protecting alveolar structures, and increasing angiogenesis in rats. The use of allogeneic stem cells can potentially change the way we perform cell therapies by allowing for the growth of large quantities of cells from numerous sources, including donated lungs not used for transplantations, surgical discards, and lungs from recently deceased cadavers. Our study demonstrates the potential of allogeneic LSCs as a viable future therapy option for patients suffering from idiopathic pulmonary fibrosis.

No abstract

A multifunctional gold nanorod (AuNR) complex is described with potential utility for theranostic anticancer treatment. The AuNR was functionalized with cyclodextrin for encapsulation of doxorubicin, with folic acid for targeting, and with a photo-responsive dextran-azo compound for intracellular controlled drug release. Interaction of AuNR complex toward HeLa cells was facilitated via the folic acid targeting ligand as displayed in the dark-field images of cells. Enhanced anticancer efficacy was demonstrated through synergistic combination of promoted drug release upon ultraviolet (UV) light irradiation and photothermal therapy upon infrared (IR) irradiation. This multifunctional AuNR-based system represents a novel theranostic strategy for spatiotemporal delivery of anticancer therapeutics.