Suppression of annexin A1 and its receptor reduces herpes simplex virus 1 lethality in mice.

Herpes simplex virus 1 (HSV-1)-induced encephalitis is the most common cause of sporadic, fatal encephalitis in humans. HSV-1 has at least 10 different envelope glycoproteins, which can promote virus infection. The ligands for most of the envelope glycoproteins and the significance of these ligands in virus-induced encephalitis remain elusive.

Stroke propensity in the Th3+/ mouse model of β-thalassemia intermedia.

β-thalassemia is associated with multiple hematological and cerebrovascular symptoms linked to a hypercoagulable state that has not been fully replicated in animal models for the development of stroke treatments. Herein we compared the physiological properties and responses to transient cerebral hypoxia-ischemia (tHI) between six-month-old wildtype and heterozygous Th3/+ mice, a model of non-transfusion-dependent β-thalassemia intermedia (β-TI). We found that Th3/+ mice developed microcytic anemia, splenomegaly, higher platelet counts, and increased platelet-erythrocyte plus erythrocyte-leukocyte aggregates.

Simultaneous determination of NO released inside and outside cells at the single-cell level using CE-LIF.

A simple, fast and reliable method based on capillary electrophoresis (CE) coupled with laser-induced fluorescence (LIF) detection was developed for the simultaneous analysis of NO released both inside and outside cells at the single-cell level closer to physiological conditions. After pre-capillary dual-labeling derivatization with a group of cells, single cells were injected into the separation capillary and lysed. The subsequent separation and detection of NO derivatives were achieved within 4.

Simultaneous Quantitation of Intra- and Extracellular Nitric Oxide in Single Macrophage RAW 264.7 Cells by Capillary Electrophoresis with Laser-Induced Fluorescence Detection.

Single-cell analysis contributes to the understanding of cellular heterogeneity and behaviors. Nitric oxide (NO) is an important intracellular and intercellular signaling molecule, and the functions of NO are closely related to the balance between intra- and extracellular NO levels. In this manuscript, a convenient and reliable method based on a dual-labeling strategy using capillary electrophoresis (CE) separation with laser-induced fluorescence (LIF) detection has been presented for quantifying intra- and extracellular NO simultaneously in single cells.

Early neutrophil infiltration is critical for inflammation-sensitized hypoxic-ischemic brain injury in newborns.

Neutrophils are the most abundant leukocytes and usually the first immune cell-type recruited to a site of infection or tissue damage. In asphyxiated neonates, elevated peripheral neutrophil counts are associated with poorer neurological outcomes. Induced neutropenia provides brain protection in animal models of neonatal hypoxic-ischemic (HI) injury, but the anti-neutrophil serum used in past studies heavily cross-reacts with monocytes, thus complicating the interpretation of results.

Bortezomib induces HSV-1 lethality in mice with neutrophil deficiency.

Bortezomib suppressing NF-κB activity is an effective therapy for patients with myeloma or lymphoma. However, this drug can cause adverse effects, neutropenia, and recurrent infections of herpes viruses. Among herpes viruses, HSV-1 can reactivate to induce mortality.

Effect of substituents on Stokes shift of BODIPY and its application in designing bioimaging probes.

BODIPY-based probes have excellent fluorescence properties. However, small Stokes shifts approximately 5-15 nm greatly affect their detection sensitivity. In this study, we compared the Stokes shifts of reported BODIPY-based probes with various of substituents, and found that the phenyl groups on the specific position of BODIPY core could expand the Stokes shift of BODIPY-based probes, and methoxy groups on these phenyl substituents could enhance such effects.

Suppression of interleukin-6 increases enterovirus A71 lethality in mice.

Background: Enterovirus A71 (EV-A71) infection can induce fatal encephalitis in young children. Clinical reports show that interleukin-6 (IL-6) levels in the serum and cerebrospinal fluid of infected patients with brainstem encephalitis are significantly elevated. We used a murine model to address the significance of endogenous IL-6 in EV-A71 infection.

A cell surface specific two-photon fluorescent probe for monitoring intercellular transmission of hydrogen sulfide.

Hydrogen sulfide (HS) is a new endogenously generated gasotransmitter and has implicated in many physiologies and pathologies closely related to its intracellular and intercellular signaling transduction. Although many fluorescent probes have been exploited to track and quantify HS in living systems, none of them could be used for monitoring intercellular transmission of HS. Herein, we developed a cell surface specific HS probe, 4-azido-6-sulfo-N-hexadecyl-1,8-naphthalimide, sodium salt (ASNHN-N), trying to investigate the behaviors of extracellular release of HS.

Simultaneous monitoring of intra- and extracellular nitric oxide in living cells by means of dual-color fluorescence imaging.

A dual-color fluorescence imaging method for simultaneous monitoring of intra- and extracellular nitric oxide (NO) was developed. Assisted by confocal laser scanning microscope, the intra- and extracellular NO can be successfully visualized by using two selected probes, 4,4-difluoro-8-(3,4-diaminophenyl)-3,5-bis(4-methoxyphenyl)-4-bora-3a,4a-diaza-s-indacene (p-MOPB) and disodium 2,6-disulfonate-1,3-dimethyl-5-hexadecyl-8-(3,4-diaminophenyl)-4,4'-difluoro-4-bora-3a,4a-diaza-s-indacene (DSDMHDAB), which display distinct membrane permeability and show different colors of fluorescence after reaction with NO. Results indicated that intra- and extracellular NO could be fluorometrically detected without mutual interference.

Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice.

Unlabelled: Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R.

An Amphiphilic Fluorescent Probe Designed for Extracellular Visualization of Nitric Oxide Released from Living Cells.

Nitric oxide (NO) is an intracellular and intercellular messenger involved in numerous physiological and pathophysiological processes. Small-molecule fluorescent probes coupled with fluorescence microscopy provide excellent tools for real-time detection of NO in situ. However, most probes are designed for imaging intracellular NO, which cannot reflect the release behavior of endogenously produced NO.

In vivo reactivation of latent herpes simplex virus 1 in mice can occur in the brain before occurring in the trigeminal ganglion.

Unlabelled: Herpes simplex virus 1 (HSV-1) establishes latency in neurons of the brains and sensory ganglia of humans and experimentally infected mice. The latent virus can reactivate to cause recurrent infection. Both primary and recurrent infections can induce diseases, such as encephalitis.

Tranylcypromine reduces herpes simplex virus 1 infection in mice.

Herpes simplex virus 1 (HSV-1) infects the majority of the human population and establishes latency by maintaining viral genomes in neurons of sensory ganglia. Latent virus can undergo reactivation to cause recurrent infection. Both primary and recurrent infections can cause devastating diseases, including encephalitis and corneal blindness.

Factors affecting herpes simplex virus reactivation from the explanted mouse brain.

The majority of encephalitis induced by herpes simplex virus type I (HSV-1) is due to viral reactivation from latency, but few studies have investigated the factors influencing viral reactivation in the brain due to the lack of a sensitive assay. We have established an ex vivo explant assay, which induced efficient viral reactivation in the dissociated mouse brain. Applying this assay, we investigated the infection of four HSV-1 strains with varying degrees of neurovirulence in three mouse strains with different levels of susceptibility to HSV-1 infection.

Suppression of transcription factor early growth response 1 reduces herpes simplex virus 1-induced corneal disease in mice.

Herpes simplex virus 1 replication initiates angiogenesis and inflammation in the cornea. This can result in herpetic stromal keratitis (HSK), which is a leading cause of infection-induced corneal blindness. Host cellular factors mediate the progression of HSK, but little is known about these cellular factors and their mechanisms of action.

Beta interferon plus gamma interferon efficiently reduces acyclovir-resistant herpes simplex virus infection in mice in a T-cell-independent manner.

Acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) causes severe diseases in immunocompromised patients, so identification of new therapies is needed. Interferons (IFNs) are used to treat several other viral infections in the clinic, and IFN-beta and IFN-gamma are known to cooperatively reduce wild-type HSV-1 replication in the corneas of immunocompetent mice. Because IFN-gamma has been shown to exert an antiviral effect mostly through T cells, whether combined IFN treatment can still inhibit ACV-resistant HSV-1 replication, especially in immunocompromised hosts, is unknown.

Suppression of transcription factor early growth response 1 reduces herpes simplex virus lethality in mice.

Herpes simplex virus type 1 (HSV-1) infection is the most common cause of sporadic, fatal encephalitis, but current understanding of how the virus interacts with cellular factors to regulate disease progression is limited. Here, we show that HSV-1 infection induced the expression of the cellular transcription factor early growth response 1 (Egr-1) in a human neuronal cell line. Egr-1 increased viral replication by activating promoters of viral productive cycle genes through binding to its corresponding sequences in the viral promoters.

Efficient reactivation of latent herpes simplex virus from mouse central nervous system tissues.

For decades, numerous ex vivo studies have documented that latent herpes simplex virus (HSV) reactivates efficiently from ganglia, but rarely from the central nervous systems (CNS), of mice when assayed by mincing tissues before explant culture, despite the presence of viral genomes in both sites. Here we show that 88% of mouse brain stems reactivated latent virus when they were dissociated into cell suspensions before ex vivo explant culture. The efficient reactivation of HSV from the mouse CNS was demonstrated with more than one viral strain, viral serotype, and mouse strain, further indicating that the CNS can be an authentic latency site for HSV with the potential to cause recurrent disease.