Janus LAAM-loaded electrospun fibrous buccal films for treating opioid use disorder.

The opioid crisis has claimed approximately one million lives in the United States since 1999, underscoring a significant public health concern. This surge in opioid use disorder (OUD) fatalities necessitates improved therapeutic options. Current OUD therapies often require daily clinical visits, leading to poor patient compliance and high costs to the health systems.

Combination Nanomedicine Strategy for Preventing High-Risk Corneal Transplantation Rejection.

High-risk (HR) corneal transplantation presents a formidable challenge, with over 50% of grafts experiencing rejection despite intensive postoperative care involving frequent topical eyedrop administration up to every 2 h, gradually tapering over 6-12 months, and ongoing maintenance dosing. While clinical evidence underscores the potential benefits of inhibiting postoperative angiogenesis, effective antiangiogenesis therapy remains elusive in this context. Here, we engineered controlled-release nanomedicine formulations comprising immunosuppressants (nanoparticles) and antiangiogenesis drugs (nanowafer) and demonstrated that these formulations can prevent HR corneal transplantation rejection for at least 6 months in a clinically relevant rat model.

Nor-LAAM loaded PLGA microparticles for treating opioid use disorder.

The treatment landscape for opioid use disorder (OUD) faces challenges stemming from the limited efficacy of existing medications, poor adherence to prescribed regimens, and a heightened risk of fatal overdose post-treatment cessation. Therefore, there is a pressing need for innovative therapeutic strategies that enhance the effectiveness of interventions and the overall well-being of individuals with OUD. This study explored the therapeutic potential of nor-Levo-α-acetylmethadol (nor-LAAM) to treat OUD.

Nor-LAAM loaded PLGA Microparticles for Treating Opioid Use Disorder.

The treatment landscape for opioid use disorder (OUD) faces challenges stemming from the limited efficacy of existing medications, poor adherence to prescribed regimens, and a heightened risk of fatal overdose post-treatment cessation. Therefore, there is a pressing need for innovative therapeutic strategies that enhance the effectiveness of interventions and the overall well-being of individuals with OUD. This study explored the therapeutic potential of nor-Levo-α-acetylmethadol (nor-LAAM) to treat OUD.

Dexamethasone sodium phosphate loaded nanoparticles for prevention of nitrogen mustard induced corneal injury.

Nitrogen mustard (NM) is a potent vesicating chemical warfare agent that is primarily absorbed through skin, inhalation, or ocular surface. Ocular exposure of NM can cause acute to chronic keratopathy which can eventually lead to blindness. There is a current lack of effective countermeasures against ocular exposure of NM despite their imperative need.

Six-month effective treatment of corneal graft rejection.

Topical corticosteroid eye drop is the mainstay for preventing and treating corneal graft rejection. While the frequent topical corticosteroid use is associated with risk of intraocular pressure (IOP) elevation and poor patient compliance that leads to graft failure and the requirement for a repeated, high-risk corneal transplantation. Here, we developed dexamethasone sodium phosphate (DSP)-loaded dicarboxyl-terminated poly(lactic acid) nanoparticle (PLA DSP-NP) formulations with relatively high drug loading (8 to 10 weight %) and 6 months of sustained intraocular DSP delivery in rats with a single dosing.

Nano-in-Nano Dendrimer Gel Particles for Efficient Topical Delivery of Antiglaucoma Drugs into the Eye.

Low bioavailability of topically applied drugs remains a significant challenge for long-term glaucoma therapy. To enhance drug delivery efficiency, we developed dendrimer gel particles that collectively exhibit structural benefits of dendrimer, hydrogel, and particles, using the inverse emulsion method coupled with the highly efficient aza-Michael addition reaction (IEaMA). This hierarchical approach would maximize the utility of the structural features of existing ocular drug delivery systems.

Dystrophic muscle distribution in late-stage muscular dystrophy.

There is scant information about the comprehensive distribution of dystrophic muscles in muscular dystrophy. Despite different clinical presentations of muscular dystrophy, a recent multi-center study concluded that phenotypic distribution of dystrophic muscles is independent of clinical phenotype and suggested that there is a common pattern of involved muscles. To evaluate this possibility, the present case report used cadaveric dissection to determine the whole-body distribution of fat-infiltrated, dystrophic muscles from a 72-year-old white male cadaver with adult-onset, late-stage muscular dystrophy.

Infiltration of Benign Meningioma into Sagittal Sinus and Subsequent Metastasis to Lung: Case Report and Literature Review.

Background: Meningioma is an intracranial tumor frequently encountered in the neurosurgical setting. Extracranial disease is a rare occurrence, with a reported incidence in 0.1% of cases.

Paleopathology of Spleens in South American Mummies.

This study analyzed 19 naturally mummified pre-Columbian individuals excavated from desert regions of southern Peru and northern Chile. In the majority of autopsies of mummies, the spleen cannot be identified due to rapid autolysis and decomposition; therefore, our aim was to identify, in the cases in which the spleen was found, any normal and abnormal structures from mummified spleen tissues. The research consisted of gross and microscopic examinations of the spleen.

The incorporation of growth factor and chondroitinase ABC into an electrospun scaffold to promote axon regrowth following spinal cord injury.

Spinal cord injury results in tissue necrosis in and around the lesion site, commonly leading to the formation of a fluid-filled cyst. This pathological end point represents a physical gap that impedes axonal regeneration. To overcome the obstacle of the cavity, we have explored the extent to which axonal substrates can be bioengineered through electrospinning, a process that uses an electrical field to produce fine fibres of synthetic or biological molecules.

Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells.

Transcription factors (TF) often bind in heterodimeric complexes with each TF recognizing a specific neighboring cis element in the regulatory region of the genome. Comprehension of this DNA motif grammar is opaque, yet recent developments have allowed the interrogation of genome-wide TF binding sites. We reasoned that within this data novel motif grammars could be identified that controlled distinct biological programs.

Two pole air gap electrospinning: Fabrication of highly aligned, three-dimensional scaffolds for nerve reconstruction.

We describe the structural and functional properties of three-dimensional (3D) nerve guides fabricated from poly-ε-caprolactone (PCL) using the air gap electrospinning process. This process makes it possible to deposit nano-to-micron diameter fibers into linear bundles that are aligned in parallel with the long axis of a cylindrical construct. By varying starting electrospinning conditions it is possible to modulate scaffold material properties and void space volume.

FTY720 reduces inflammation and promotes functional recovery after spinal cord injury.

A robust and complex inflammatory cascade is known to be a prominent component of secondary injury following spinal cord injury (SCI). Specifically, the concept of trauma-induced autoimmunity has linked the lymphocyte population with neural tissue injury and neurologic deficit. FTY720, a sphingosine receptor modulator that sequesters lymphocytes in secondary lymphoid organs, has been shown to be effective in the treatment of a variety of experimental autoimmune disorders.

Evaluating neuronal and glial growth on electrospun polarized matrices: bridging the gap in percussive spinal cord injuries.

One of the many obstacles to spinal cord repair following trauma is the formation of a cyst that impedes axonal regeneration. Accordingly, we examined the potential use of electrospinning to engineer an implantable polarized matrix for axonal guidance. Polydioxanone, a resorbable material, was electrospun to fabricate matrices possessing either aligned or randomly oriented fibers.

Macrophage-specific transgenic expression of cholesteryl ester hydrolase significantly reduces atherosclerosis and lesion necrosis in Ldlr mice.

Accumulation of cholesteryl esters (CEs) in macrophage foam cells, central to atherosclerotic plaque formation, occurs as a result of imbalance between the cholesterol influx and efflux pathways. While the uptake, or influx, of modified lipoproteins is largely unregulated, extracellular acceptor-mediated free cholesterol (FC) efflux is rate limited by the intracellular hydrolysis of CE. We previously identified and cloned a neutral CE hydrolase (CEH) from human macrophages and demonstrated its role in cellular CE mobilization.

Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: inhibition of tumor angiogenesis with extensive tumor necrosis.

Purpose: Toward improved glioblastoma multiforme treatment, we determined whether celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, could enhance glioblastoma radiosensitivity by inducing tumor necrosis and inhibiting tumor angiogenesis.

Methods And Materials: U-87MG cells treated with celecoxib, irradiation, or both were assayed for clonogenic survival and angiogenic factor protein analysis (angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor [VEGF]). In vivo, survival of mice intracranially implanted with U-87MG cells and treated with celecoxib and/or irradiation was monitored.

Glucocorticoid and mineralocorticoid cross-talk with progesterone receptor to induce focal adhesion and growth inhibition in breast cancer cells.

Progesterone receptor (PR), glucocorticoid receptor, and mineralocorticoid receptor belong to a subfamily of nuclear receptor superfamily with similar sequence and structural characteristics. Many reports have documented glucocorticoid-like effects of progesterone in various tissues. This study addresses the issue of cross-talk between corticosteroids and PR using PR-transfected MDA-MB-231 cells ABC28 and vector-transfected control cells CTC15.

Distinct molecular pathways mediate progesterone-induced growth inhibition and focal adhesion.

We have reported previously that reactivation of progesterone receptor (PR) expression in estrogen receptor (ER)- and PR-negative MDA-MB-231 breast cancer cells enabled progesterone to inhibit cell growth and invasiveness, and to induce remarkable focal adhesions. The present study addressed molecular mechanisms that mediate these anticancer effects of progesterone in the PR-transfected breast cancer cells ABC28. In response to progesterone treatment are the marked up-regulation of cyclin-dependent kinase inhibitor protein p21WAF1/CIP1 and decreased expression of cyclin A, cyclin B1, and cyclin D1 that are required for G1 progression and during cell mitosis.