Isolating Primary Melanocyte-like Cells from the Mouse Heart

We identified a novel population of melanocyte-like cells (also known as cardiac melanocytes) in the hearts of mice and humans that contribute to atrial ...

Optimized Griess Reaction for UV-Vis and Naked-eye Determination of Anti-malarial Primaquine

Primaquine (PMQ), an important anti-malarial drug, has been recommended by the World Health Organization (WHO) for the treatment of life-threatening ...

University of Pennsylvania 

Guangzhou University of Chinese Medicine

Living in a prediabetes state significantly increases a patient's risk for both diabetes and cardiovascular disease. Tianqi capsule, containing 10 Chinese herbal medicines, is used in China for the treatment of type 2 diabetes mellitus (T2DM).

Chinese herbal medicine Tianqi reduces progression from impaired glucose tolerance to diabetes: a double-blind, randomized, placebo-controlled, multicenter trial.

Inhibitory neurotransmission in amygdala is important for fear learning and memory. However, mechanisms that control the inhibitory activity in amygdala are not well understood. We provide evidence that neuregulin 1 (NRG1) and its receptor ErbB4 tyrosine kinase are critical for maintaining GABAergic activity in amygdala. Neutralizing endogenous NRG1, inhibition, or genetic ablation of ErbB4, which was expressed in a majority of palvalbumin (PV)+ neurons in amygdala, reduced GABAergic transmission and inhibited tone-cued fear conditioning. Specific ablation of ErbB4 in PV+ neurons reduced eIPSC/eEPSC ratios and impaired fear conditioning. Notably, expression of ErbB4 in amygdala was sufficient to diminish synaptic dysfunction and fear conditioning deficits in PV-ErbB4-/- mice. These observations indicated that NRG1 signaling maintains high GABAergic activity in amygdala and, thus, regulates fear memory. Considering that both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study sheds light on potential pathophysiological mechanisms of this disorder. 

Maintenance of GABAergic activity by neuregulin 1-ErbB4 in amygdala for fear memory.

Zika virus (ZIKV) infection is a public health emergency and host innate immunity is essential for the control of virus infection. The NLRP3 inflammasome plays a key role in host innate immune responses by activating caspase-1 to facilitate interleukin-1β (IL-1β) secretion. Here we report that ZIKV stimulates IL-1β secretion in infected patients, human PBMCs and macrophages, mice, and mice BMDCs. The knockdown of NLRP3 in cells and knockout of NLRP3 in mice inhibit ZIKV-mediated IL-1β secretion, indicating an essential role for NLRP3 in ZIKV-induced IL-1β activation. Moreover, ZIKV NS5 protein is required for NLRP3 activation and IL-1β secretion by binding with NLRP3 to facilitate the inflammasome complex assembly. Finally, ZIKV infection in mice activates IL-1β secretion, leading to inflammatory responses in the mice brain, spleen, liver, and kidney. Thus we reveal a mechanism by which ZIKV induces inflammatory responses by facilitating NLRP3 inflammasome complex assembly and IL-1β activation.

Zika virus infection induces host inflammatory responses by facilitating NLRP3 inflammasome assembly and interleukin-1β secretion.

Hydroxyl radical (•OH) is the most reactive oxygen species involved in many environmental and biological processes. The development of simple and reliable methods to quantitatively determine hydroxyl radicals is desired. Herein, a colorimetric strategy based on a modified Griess test has been presented. The detection started with the nitrite release from nitroimidazoles (nIm) upon its specific reaction with •OH radicals and subsequently nitrite quantification by Griess reagent. The result showed that this nitroimidazole modified Griess test (nIm-Griess) was successfully adapted for the measurement of •OH radicals generated by Fenton reaction, water radiolysis, as well as the activation of two antimalarials artemisinin (Art) and dihydroartemisinin (DHA).

A novel strategy for colorimetric detection of hydroxyl radicals based on a modified Griess test.

Puerarin (PU) has emerged as a promising herb-derived anti-Parkinsonism compound. However, the undesirable water solubility as well as the unwanted bioavailability of PU limit its application. Therefore, this study aimed to develop and characterize PU nanocrystals (PU-NCs) with enhanced oral bioavailability and improved brain accumulation for the treatment of Parkinson's disease (PD). The fabricated PU-NCs were approximately spherical, with a mean size of 83.05 ± 1.96 nm, a PDI of 0.047 ± 0.009, a drug loading of 72.7%, and a rapid dissolution rate in vitro. Molecular dynamics simulation of PU and Pluronic F68 demonstrated the interaction energy and binding energy of -88.1 kJ/mol and -40.201 ± 0.685 kJ/mol, respectively, indicating a spontaneous binding with van der Waals interactions. In addition, the cellular uptake and permeability of PU-NCs were significantly enhanced as compared to PU alone ( p < 0.01). Moreover, PU-NCs exerted a significant neuroprotective effect against the cellular damage induced by the 1-methyl-4-phenylpyridinium ion (MPP). Besides, PU-NCs demonstrated no obvious toxic effects on zebrafish, as evidenced by the unaltered morphology, hatching, survival rate, body length, and heart rate. Fluorescence resonance energy transfer (FRET) imaging revealed that intact nanocrystals were found in the intestine and brain of adult zebrafish gavaged with DiO/DiI/PU-NCs. Increased values of C and AUC were observed in the plasma of rats following oral administration of PU-NCs compared to PU suspension. Likewise, brain accumulation of PU-NCs was higher than that of PU suspension. Furthermore, PU-NCs attenuated dopamine depletion, ameliorated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral deficits, and enhanced the levels of dopamine and its metabolites. Taken altogether, this study provides evidence that PU-NCs could be exploited as a potential oral delivery system to treat PD, by improving the poor bioavailability of PU and enhancing their delivery into the brain.

Oral Delivery of Puerarin Nanocrystals To Improve Brain Accumulation and Anti-Parkinsonian Efficacy.

Dengue virus (DENV) infection causes serious clinical symptoms, including Dengue hemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Vascular permeability change is the main feature of the diseases, and the abnormal expression of pro-inflammation cytokines is the important cause of vascular permeability change. However, the mechanism underlying vascular permeability induced by DENV is not fully elucidated. Here we reveal a distinct mechanism by which DENV infection promotes the NLRP3 inflammasome activation and interleukin-1 beta (IL-1β) release to induce endothelial permeability and vascular leakage in mice. DENV M protein interacts with NLRP3 to facilitate the NLRP3 inflammasome assemble and activation, which lead to the induction of pro-inflammation cytokine IL-1β activation and release. Notably, M can induce vascular leakage in mice tissues through activating NLRP3 inflammasome and IL-1β. More importantly, inflammatory cell infiltration and tissue injuries are induced by M in WT mice tissues, but they are not affected by M in NLRP3 knock-out (NLRP3) mice tissues, and Evans blue intensities in WT mice tissues are significantly higher as compared with NLRP3 mice tissues, demonstrating an essential role of NLRP3 in M-induced vascular leakages in mice. Therefore, we propose that upon DENV infection, M interacts with NLRP3 to facilitate the inflammasome activation and IL-1β secretion, which lead to induction of endothelial permeability and vascular leakage in mice tissues. The important role of the DENV-M-NLRP3-IL-1β axis in the induction of vascular leakage provides new insights into the mechanisms underlying DENV pathogenesis and DENV-associated DHF and DSS development. Dengue virus (DENV) is a mosquito-borne pathogen and its infection is prevalent in over 100 tropical and sub-tropical countries or regions with approximately 2.5 billion people at risk. DENV infection induces a spectrum of clinical symptoms ranging from classical dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Therefore, it is important to understand the mechanisms underlying DENV pathogenesis. In this study, the authors reveal that the DENV membrane protein (M) interacts with the host NLRP3 protein to promote the NLRP3 inflammasome activation, which leads to the activation and release of pro-inflammation cytokine, interleukin-1 beta (IL-1β). More importantly, the authors demonstrate that M protein can induce vascular permeability and vascular leakage and NLRP3 is required for M-induced vascular leakage in mice tissues. Collectively, this study reveals a distinct mechanism underlying DENV pathogeneses and provides new insights into the development of therapeutic agent for DENV-associated diseases.

Fang Liu

Penn Cardiovascular Institute,
Perelman School of Medicine,
Penn Cardiovascular Institute, Perelman School of Medicine

University of Pennsylvania

Isolating Primary Melanocyte-like Cells from the Mouse Heart

Optimized Griess Reaction for UV-Vis and Naked-eye Determination of Anti-malarial Primaquine

Fang Liu

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University of Pennsylvania

Isolating Primary Melanocyte-like Cells from the Mouse Heart

Optimized Griess Reaction for UV-Vis and Naked-eye Determination of Anti-malarial Primaquine

Penn Cardiovascular Institute,
Perelman School of Medicine,
Penn Cardiovascular Institute, Perelman School of Medicine