18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response

Chacko, Ann‐Marie; Watanabe, Sumio; Herr, Keira Joann; Kalimuddin, Shirin; Tham, Jing Yang; Ong, Joanne; Reolo, Marie Jennifer; Serrano, Raymond; Cheung, Yin Bun; Low, Jenny; Vasudevan, Subhash G.

doi:10.1172/jci.insight.93474

Cited by 25 publications

(15 citation statements)

References 48 publications

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“…In addition, the HMGB1 inhibitor glycyrrhizin was also used to further demonstrate that berberine plays a neuroprotective role through the HMGB1/TLR4 signaling pathway. 18 F-FDG is an inflammation biomarker for imaging dengue virus infection and assessing treatment response during therapeutic intervention trials, which has been reported in atherosclerosis [35,36]. A previous study found that imaging with 18 F-FDG/PET enabled the detection and quantification of ischemia-induced metabolic deficits and provided a sensitive and reliable means of assessing cerebral ischemic lesions compared with conventional Fig.…”

Section: Discussionmentioning

confidence: 99%

Berberine attenuates ischemia–reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation

Zhu

Guo

et al. 2018

Acta Pharmacol Sin

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Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO). Male mice were administered berberine (25, 50 mg/kg/d, intragastric; i.g.), glycyrrhizin (50 mg/kg/d, intraperitoneal), or berberine (50 mg/ kg/d, i.g.) plus glycyrrhizin (50 mg/kg/d, intraperitoneal) for 14 consecutive days before tMCAO. The neurological deficit scores were evaluated at 24 h after tMCAO, and then the mice were killed to obtain the brain samples. We showed that pretreatment with berberine dose-dependently decreased the infarct size, neurological deficits, hispathological changes, brain edema, and inflammatory mediators in serum and ischemic cortical tissue. We revealed that pretreatment with berberine significantly enhanced uptake of 18 F-fluorodeoxyglucose of ischemic hemisphere comparing with the vehicle group at 24 h after stroke. Furthermore, pretreatment with berberine dose-dependently suppressed the nuclear-to cytosolic translocation of high-mobility group box1 (HMGB1) protein, the cytosolic-to nuclear translocation of nuclear factor kappa B (NF-κB) and decreased the expression of TLR4 in ischemic cortical tissue. Moreover, co-administration of glycyrrhizin and berberine exerted more potent suppression on the HMGB1/TLR4/NF-κB pathway than berberine or glycyrrhizin administered alone. These results demonstrate that berberine protects the brain from ischemia-reperfusion injury and the mechanism may rely on its anti-inflammatory effects mediated by suppressing the activation of HMGB1/TLR4/NF-κB signaling.

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Section: Discussionmentioning

confidence: 99%

Berberine attenuates ischemia–reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation

Zhu

Guo

et al. 2018

Acta Pharmacol Sin

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“…7B). Data for one mouse from the wild-type virusinfected group were excluded from subsequent analysis because of its unusual early death on day 2 after infection (27). The increased mortality of the mice infected with T164S mutant virus corresponded to an overall higher viremia with a 2.1-fold (P = 0.073) and 4.5-fold (P = 0.004) higher serum viral load compared to mice infected with wild-type virus on days 3 and 4 after infection, respectively (fig.…”

Section: T164s Mutant Virus Induces More Severe Disease In Ag129 Mice Compared To Wild-type Virusmentioning

confidence: 99%

A T164S mutation in the dengue virus NS1 protein is associated with greater disease severity in mice

et al. 2019

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Dengue viruses cause severe and sudden human epidemics worldwide. The secreted form of the nonstructural protein 1 (sNS1) of dengue virus causes vascular leakage, a hallmark of severe dengue disease. Here, we reverse engineered the T164S mutation of NS1, associated with the severity of dengue epidemics in the Americas, into a dengue virus serotype 2 mildly infectious strain. The T164S mutant virus decreased infectious virus production and increased sNS1 production in mammalian cell lines and human peripheral blood mononuclear cells (PBMCs) without affecting viral RNA replication. Gene expression profiling of 268 inflammation-associated human genes revealed up-regulation of genes induced in response to vascular leakage. Infection of the mosquito vector Aedes aegypti with the T164S mutant virus resulted in increased viral load in the mosquito midgut and higher sNS1 production compared to wild-type virus infection. Infection of type 1 and 2 interferon receptor–deficient AG129 mice with the T164S mutant virus resulted in severe disease coupled with increased complement activation, tissue inflammation, and more rapid mortality compared to AG129 mice infected with wild-type virus. Molecular dynamics simulations predicted that mutant sNS1 formed stable dimers similar to the wild-type protein, whereas the hexameric mutant sNS1 was predicted to be unstable. Immunoaffinity-purified sNS1 from T164S mutant virus–infected mammalian cells was associated with different lipid classes compared to wild-type sNS1. Treatment of human PBMCs with sNS1 purified from T164S mutant virus resulted in a twofold higher production of proinflammatory cytokines, suggesting a mechanism for how mutant sNS1 may cause more severe dengue disease.

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“…In part to further address clinical endpoints that require large sample size as used in dengue trials, an alternative robust biomarker, fluorodeoxyglucose (FDG), was recently examined in preclinical animal models. The goal was that drug efficacy could be directly correlated with reduction in FDG signals that were reflective of virus-induced inflammation by using positron emission tomography (PET) imaging (Chacko et al 2017). If the observations from the preclinical study translates to human cases, then it is conceivable that smaller Phase II trials can be rapidly conducted to triage a pipeline of drugs from various consortia.…”

Section: Chu Family Foundation Awards (Amy Patick)mentioning

confidence: 99%

ISAR News

2017

Antiviral Research

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18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response

Cited by 25 publications

References 48 publications

Berberine attenuates ischemia–reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation

Berberine attenuates ischemia–reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation

A T164S mutation in the dengue virus NS1 protein is associated with greater disease severity in mice

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