Elucidating the structure and functions of Resolvin D6 isomers on nerve regeneration with a distinctive trigeminal transcriptome.

Innervation sustains cornea integrity. Pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) regenerated damaged nerves by stimulating the synthesis of a new stereoisomer of Resolvin D6 (RvD6si). Here, we resolved the structure of this lipid isolated from mouse tears after injured corneas were treated with PEDF + DHA.

Age-related changes in brain phospholipids and bioactive lipids in the APP knock-in mouse model of Alzheimer's disease.

Sustained brain chronic inflammation in Alzheimer's disease (AD) includes glial cell activation, an increase in cytokines and chemokines, and lipid mediators (LMs), concomitant with decreased pro-homeostatic mediators. The inflammatory response at the onset of pathology engages activation of pro-resolving, pro-homeostatic LMs followed by a gradual decrease. We used an APP knock-in (App KI) AD mouse that accumulates β-amyloid (Aβ) and presents cognitive deficits (at 2 and 6 months of age, respectively) to investigate LMs, their precursors, biosynthetic enzymes and receptors, glial activation, and inflammatory proteins in the cerebral cortex and hippocampus at 2-, 4-, 8- and 18-month-old in comparison with wild-type (WT) mice.

ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable in society, triggering a public health crisis and economic collapse around the world. Effective treatments to mitigate this viral infection are needed. Since the eye is a route of virus entrance, we use an in vivo rat model of corneal inflammation as well as human corneal epithelial cells (HCEC) in culture challenged with IFNγ as models of the eye surface to study this issue.

Elovanoids downregulate SARS-CoV-2 cell-entry, canonical mediators and enhance protective signaling in human alveolar cells.

The pro-homeostatic lipid mediators elovanoids (ELVs) attenuate cell binding and entrance of the SARS-CoV-2 receptor-binding domain (RBD) as well as of the SARS-CoV-2 virus in human primary alveoli cells in culture. We uncovered that very-long-chain polyunsaturated fatty acid precursors (VLC-PUFA, n-3) activate ELV biosynthesis in lung cells. Both ELVs and their precursors reduce the binding to RBD.

Peroxisomal Multifunctional Protein 2 Deficiency Perturbs Lipid Homeostasis in the Retina and Causes Visual Dysfunction in Mice.

Patients lacking multifunctional protein 2 (MFP2), the central enzyme of the peroxisomal β-oxidation pathway, develop retinopathy. This pathway is involved in the metabolism of very long chain (VLCFAs) and polyunsaturated (PUFAs) fatty acids, which are enriched in the photoreceptor outer segments (POS). The molecular mechanisms underlying the retinopathy remain, however, elusive.

Anti-inflammatory genes in PBMCs post-spontaneous intracerebral hemorrhage.

Background: Neuroinflammation is important in the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and peripheral inflammatory cells play a role in the clinical evolution and outcome.

Methodology: Blood samples from ICH patients ( = 20) were collected at admission for 5 consecutive days for peripheral blood mononuclear cells (PBMCs). Frozen PBMCs were used for real-time PCR using Taqman probes (NFKB1, SOD1, PPARG, IL10, NFE2L2, and REL) and normalized to GAPDH.

Neuroanatomy and neurochemistry of rat cornea: Changes with age.

Purpose: To characterize the entire rat corneal nerve architecture, the changes that occur with aging, and its sensory, sympathetic, and parasympathetic fiber distribution.

Methods: Sprague-Dawley rats (aged 1 day to 2 years old) of both sexes were euthanized, and the whole corneas were immunostained with protein gene product 9.5 (PGP9.

Bioavailability and spatial distribution of fatty acids in the rat retina after dietary omega-3 supplementation.

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector.

Chlorhexidine gluconate bathing in children with cancer or those undergoing hematopoietic stem cell transplantation: A double-blinded randomized controlled trial from the Children's Oncology Group.

Background: To the authors' knowledge, information regarding whether daily bathing with chlorhexidine gluconate (CHG) reduces central line-associated bloodstream infection (CLABSI) in pediatric oncology patients and those undergoing hematopoietic stem cell transplantation (HCT) is limited.

Methods: In the current multicenter, randomized, double-blind, placebo-controlled trial, patients aged ≥2 months and <22 years with cancer or those undergoing allogeneic HCT were randomized 1:1 to once-daily bathing with 2% CHG-impregnated cloths or control cloths for 90 days. The primary outcome was CLABSI.

In vivo immune cell dynamics in the human cornea.

In vivo confocal microscopy (IVCM) allows the evaluation of the living human cornea at the cellular level. The non-invasive nature of this technique longitudinal, repeated examinations of the same tissue over time. Image analysis of two-dimensional time-lapse sequences of presumed immune cells with and without visible dendrites at the corneal sub-basal nerve plexus in the eyes of healthy individuals was performed.

Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable in society, triggering a public health crisis and economic tall around the world. Effective treatments to mitigate this virus infection are needed. Since the eye is a route of virus entrance, we use an rat model of corneal inflammation as well as human corneal epithelial cells in culture challenged with IFNγ to study this issue.

Docosanoid signaling modulates corneal nerve regeneration: effect on tear secretion, wound healing, and neuropathic pain.

The cornea is densely innervated, mainly by sensory nerves of the ophthalmic branch of the trigeminal ganglia (TG). These nerves are important to maintain corneal homeostasis, and nerve damage can lead to a decrease in wound healing, an increase in corneal ulceration and dry eye disease (DED), and neuropathic pain. Pathologies, such as diabetes, aging, viral and bacterial infection, as well as prolonged use of contact lenses and surgeries to correct vision can produce nerve damage.

DHA modulates MANF and TREM2 abundance, enhances neurogenesis, reduces infarct size, and improves neurological function after experimental ischemic stroke.

Aims: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secretory neurotrophic factor protein that promotes repair after neuronal injury. The microglia cell surface receptor (triggering receptor expressed on myeloid cells-2; TREM2) regulates the production of pro- and antiinflammatory mediators after stroke. Here, we study MANF and TREM2 expression after middle cerebral artery occlusion (MCAo) and explore if docosahexaenoic acid (DHA) treatment exerts a potentiating effect.

A novel pipeline of 2-(benzenesulfonamide)-N-(4-hydroxyphenyl) acetamide analgesics that lack hepatotoxicity and retain antipyresis.

Although acetaminophen (ApAP) is one of the most commonly used medicines worldwide, hepatotoxicity is a risk with overdose or in patients with compromised liver function. ApAP overdose is the most common cause of acute fulminant hepatic failure. Oxidation of ApAP to N-acetyl-p-benzoquinone imine (NAPQI) is the mechanism for hepatotoxicity.

Assessment of risk factors, and racial and ethnic differences in hepatocellular carcinoma.

Despite improved screening and surveillance guidelines, significant race/ethnicity-specific disparities in hepatocellular carcinoma (HCC) continue to exist and disproportionately affect minority and disadvantaged populations. This trend indicates that social determinants, genetic, and environmental factors are driving the epidemic at the population level. Race and geography had independent associations with risk of mortality among patients with HCC.

Combined effects of gender affirmation and economic hardship on vulnerability to HIV: a qualitative analysis among U.S. adult transgender women.

Background: Transgender women ("trans women"), particularly African-American and Latina trans women, have disproportionately high prevalence of HIV in the United States (U.S.).

Chordae Willisii Within the Transverse Sinus: Morphologic Study.

Objective: Some have suggested that trabeculae within the transverse sinuses (chordae Willisii) might restrict flow and potentially contribute to thrombus organization. In addition, these structures might be encountered with endovascular procedures within the transverse sinus and are now readily seen on imaging. Therefore as anatomic studies of these structures are scant, the current study aimed to better elucidate these structures within the transverse sinus via a morphologic study in cadavers.

Novel RvD6 stereoisomer induces corneal nerve regeneration and wound healing post-injury by modulating trigeminal transcriptomic signature.

The high-density corneal innervation plays a pivotal role in sustaining the integrity of the ocular surface. We have previously demonstrated that pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) promotes corneal nerve regeneration; here, we report the mechanism involved and the discovery of a stereospecific Resolvin D6-isomer (RvD6si) that drives the process. RvD6si promotes corneal wound healing and functional recovery by restoring corneal innervation after injury.

MicroRNA Regulatory Network as Biomarkers of Late Seizure in Patients with Spontaneous Intracerebral Hemorrhage.

Approximately 15% of patients experience seizures after spontaneous intracerebral hemorrhage (ICH). The pathogenesis of seizures post-ICH is not well-known; however, iron deposition-related neuronal injury following hemoglobin breakdown may contribute. Profiling known miRNAs to identify biomarkers for post-ICH late seizures, we found 64 differentially expressed miRNA: 32 upregulated and 32 downregulated in seizure vs.

Membrane-type frizzled-related protein regulates lipidome and transcription for photoreceptor function.

Molecular decision-makers of photoreceptor (PRC) membrane organization and gene regulation are critical to understanding sight and retinal degenerations that lead to blindness. Using Mfrp mice, which develop PRC degeneration, we uncovered that membrane-type frizzled-related protein (MFRP) participates in docosahexaenoic acid (DHA, 22:6) enrichment in a manner similar to adiponectin receptor 1 (AdipoR1). Untargeted imaging mass spectrometry demonstrates cell-specific reduction of phospholipids containing 22:6 and very long-chain polyunsaturated fatty acids (VLC-PUFAs) in Adipor1 and Mfrp retinas.