Glycyrrhizic Acid Attenuates Balloon-Induced Vascular Injury Through Inactivation of RAGE Signaling Pathways

Percutaneous coronary intervention is a well-established technique used to treat coronary artery disease, but the risk of coronary artery in-stent restenosis following percutaneous coronary intervention is still high. Previous studies revealed that high mobility group protein B1 (HMGB1) plays a critical role in neointima formation. In this study, we aimed to investigate the role of glycyrrhizic acid (GA), an HMGB1 inhibitor, in the process of neointima formation and the potential mechanisms. We investigated the role of GA in neointima formation through an iliac artery balloon injury model in rabbits. Proliferation, migration, and phenotype transformation of human vascular smooth muscle cells (VSMCs) were observed. Besides, inflammation and receptor for advanced glycosylation end products (RAGE) signaling pathways were studied. The results indicate that GA attenuated neointima formation and downregulated HMGB1 expression in injured artery in rabbits. HMGB1 promoted proliferation, migration, and phenotype transformation through the activation of RAGE signaling pathways in VSMCs, and blockade of HMGB1 by GA (1, 10, and 100 μM) could attenuate those processes and reduce proliferation of human VSMCs. In conclusion, the HMGB1 inhibitor GA might be useful to treat proliferative vascular diseases by downregulating RAGE signaling pathways. Our results indicate a new and promising therapeutic agent for restenosis

Human Norovirus NS3 has RNA Helicase and Chaperoning Activities

RNA remodeling proteins, including RNA helicases and chaperones, act to remodel RNA structures and/or protein-RNA interactions, and are required for all processes involving RNAs. Although many viruses encode RNA helicases and chaperones, their in vitro activities and their roles in infected cells largely remain elusive. Noroviruses are a diverse group of positive-stranded RNA viruses in the family Caliciviridae, and constitute a significant and potentially fatal threat to human health. Here we report that protein NS3 encoded by human norovirus has both ATP-dependent RNA helicase activity that unwinds RNA helices and ATP-independent RNA chaperoning activity that can remodel structured RNAs and facilitate strand-annealing. Moreover, NS3 can facilitate viral RNA synthesis in vitro by norovirus polymerase. NS3 may therefore play an important role in norovirus RNA replication. Lastly, we demonstrate that the RNA remodeling activity of NS3 is inhibited by guanidine hydrochloride, an FDA-approved compound and, more importantly, that it reduces the replication of norovirus replicon in cultured human cells. Altogether, these findings are the first to demonstrate the presence of RNA remodeling activities encoded by Caliciviridae, and highlight the functional significance of NS3 in noroviral life cycle

Roadmap on Label-Free Super-resolution Imaging

Label-free super-resolution (LFSR) imaging relies on light-scattering processes in nanoscale objects without a need for fluorescent (FL) staining required in super-resolved FL microscopy. The objectives of this Roadmap are to present a comprehensive vision of the developments, the state-of-the-art in this field, and to discuss the resolution boundaries and hurdles that need to be overcome to break the classical diffraction limit of the label-free imaging. The scope of this Roadmap spans from the advanced interference detection techniques, where the diffraction-limited lateral resolution is combined with unsurpassed axial and temporal resolution, to techniques with true lateral super-resolution capability that are based on understanding resolution as an information science problem, on using novel structured illumination, near-field scanning, and nonlinear optics approaches, and on designing superlenses based on nanoplasmonics, metamaterials, transformation optics, and microsphere-assisted approaches. To this end, this Roadmap brings under the same umbrella researchers from the physics and biomedical optics communities in which such studies have often been developing separately. The ultimate intent of this paper is to create a vision for the current and future developments of LFSR imaging based on its physical mechanisms and to create a great opening for the series of articles in this field.Peer reviewe

Crystalline Modification and Its Effects on Dielectric Breakdown Strength and Space Charge Behavior in Isotactic Polypropylene

Adding nucleating agents (NAs) is one of the most efficient ways to obtain improved mechanical, optical, and thermal properties of isotactic polypropylene (iPP). While it is well appreciated that electrical property is critically affected by crystalline modification, the role between them remains unclear. Here, we address this issue by incorporating commercial α-NA and β-NA into iPP, both of which exhibit strong nucleation ability, e.g., reducing the size of crystalline agglomerates from 45.3 μm (Pure-iPP) to 2.5 μm (α-iPP) and 7.6 μm (β-iPP), respectively. Mechanical testing results show that while β-modification decreases the tensile strength a little, it does enhance the elongation at break (200%) and toughness (25.3% higher), relative to its unfilled counterparts. Moreover, a well-dispersed β-iPP system obtains a comprehensive improvement of electrical properties, including dielectric breakdown strength, space charge suppression, and internal field distortion under a high external field (−100 kV/mm) due to newly-generated deep charge trapping sites. This crystalline modification strategy is attractive for future development of many engineering insulating polymers

A novel glycyrrhizin acid-coated stent reduces neointimal formation in a rabbit iliac artery model

Introduction: Most drug-eluting stents (DESs) inhibit intimal hyperplasia but impair re-endothelialization. This study aimed to evaluate in vivo strut coverage and neointimal growth in a new glycyrrhizin acid (GA)-eluting stent.Methods: New Zealand White rabbits (n = 20) with atherosclerotic plaques were randomly divided into three groups based on implanted iliac artery stents: bare-metal stents (BMSs), rapamycin-eluting stents, and GA-eluting stents. After the in vivo intravascular ultrasound (IVUS) assessment at 28 days, the vessels were harvested for scanning electron microscopy (SEM) and histology. After 4 weeks of follow-up, the stent and external elastic lamina (EEL) areas were compared among the groups.Results: The rapamycin- or GA-eluting stents significantly reduced the neointimal area compared with BMSs, though GA-eluting stents had the lowest reduction. There were more uncovered struts for rapamycin-eluting stents than those for GA-eluting stents and bare-metal stents. The endothelial nitric oxide synthase (eNOS) expression in GA-eluting stents was much higher than that in BMSs and rapamycin-eluting stents, even though the endothelial coverage between struts was equivalent between BMSs and GA-eluting stents. Moreover, GA-eluting stents markedly promoted re-endothelialization and improved arterial healing compared to rapamycin-eluting stents in a rabbit atherosclerotic model.Conclusion: In conclusion, the novel GA-coated stent used in this study inhibited intimal hyperplasia and promoted re-endothelialization

An updated analysis of opioids increasing the risk of fractures.

OBJECTIVE:To assess the relationship between opioid therapy for chronic noncancer pain and fracture risk by a meta-analysis of cohort studies and case-control studies. METHODS:The included cohort studies and case-control studies were identified by searching the PubMed and EMBASE databases from their inception until May 24, 2019. The outcome of interest was a fracture. This information was independently screened by two authors. When the heterogeneity among studies was significant, a random effects model was used to determine the overall combined risk estimate. RESULTS:In total, 12 cohort studies and 6 case-control studies were included. We used the Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included literature, and 14 of the studies were considered high-quality studies. The overall relative risk of opioid therapy and fractures was 1.78 (95% confidence interval (CI) 1.53-2.07). Subgroup analyses revealed sources of heterogeneity, sensitivity analysis was stable, and no publication bias was observed. CONCLUSIONS:The meta-analysis showed that the use of opioids significantly increased the risk of fracture

Opioids contribute to fracture risk: a meta-analysis of 8 cohort studies.

To evaluate the association between chronic opioid use for non-cancer pain and fracture risk by conducting a meta-analysis of cohort studies.Cohort studies were identified by searching PubMed and EMBASE from their inception to July 2014. A fracture was considered an endpoint. The information was extracted by two authors independently. When the heterogeneity was significant, a random-effects model was used to calculate the overall pooled risk estimates.Eight cohort studies were included in the final meta-analysis. On the basis of the Newcastle-Ottawa Scale (NOS), six studies were considered to be of high quality. The overall combined relative risk for the use of opioids and fractures was 1.88 (95% confidence interval [CI] 1.51-2.34). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed.This meta-analysis of cohort studies demonstrates that opioids significantly increase the risk of fractures

Human Norovirus NS3 Has RNA Helicase and Chaperoning Activities.

RNA-remodeling proteins, including RNA helicases and chaperones, act to remodel RNA structures and/or protein-RNA interactions and are required for all processes involving RNAs. Although many viruses encode RNA helicases and chaperones, their in vitro activities and their roles in infected cells largely remain elusive. Noroviruses are a diverse group of positive-strand RNA viruses in the family Caliciviridae and constitute a significant and potentially fatal threat to human health. Here, we report that the protein NS3 encoded by human norovirus has both ATP-dependent RNA helicase activity that unwinds RNA helices and ATP-independent RNA-chaperoning activity that can remodel structured RNAs and facilitate strand annealing. Moreover, NS3 can facilitate viral RNA synthesis in vitro by norovirus polymerase. NS3 may therefore play an important role in norovirus RNA replication. Lastly, we demonstrate that the RNA-remodeling activity of NS3 is inhibited by guanidine hydrochloride, an FDA-approved compound, and, more importantly, that it reduces the replication of the norovirus replicon in cultured human cells. Altogether, these findings are the first to demonstrate the presence of RNA-remodeling activities encoded by Caliciviridae and highlight the functional significance of NS3 in the noroviral life cycle.IMPORTANCE Noroviruses are a diverse group of positive-strand RNA viruses, which annually cause hundreds of millions of human infections and over 200,000 deaths worldwide. For RNA viruses, cellular or virus-encoded RNA helicases and/or chaperones have long been considered to play pivotal roles in viral life cycles. However, neither RNA helicase nor chaperoning activity has been demonstrated to be associated with any norovirus-encoded proteins, and it is also unknown whether norovirus replication requires the participation of any viral or cellular RNA helicases/chaperones. We found that a norovirus protein, NS3, not only has ATP-dependent helicase activity, but also acts as an ATP-independent RNA chaperone. Also, NS3 can facilitate in vitro viral RNA synthesis, suggesting the important role of NS3 in norovirus replication. Moreover, NS3 activities can be inhibited by an FDA-approved compound, which also suppresses norovirus replicon replication in human cells, raising the possibility that NS3 could be a target for antinoroviral drug development