PRO-VESICULAR (PV)-BASED GEL FOR THE TOPICAL DELIVERY OF NAPROXEN: PREPARATION, CHARACTERIZATION AND IN VIVO EVALUATION

ObjectiveThe objective of the present investigation was to develop and characterize a vesicular drug carrier system (Proliposomes) for topical delivery of naproxen to overcome the gastrointestinal complications occurred when taken by oral route. Methods Proliposomes were prepared by film deposition on carrier method and characterized for size, entrapment efficiency, surface morphology, drug content, percentage yield. Proliposomal gels were prepared by using 1percent carbopol as a polymer and gels were evaluated for PH, viscosity, in-vitro, ex-vivo, pharmacodynmic studies and stability studies. The size and surface morphology were studied using optical microscope and scanning electron microscope.Results     The maximum entrapment efficiency of reconstituted liposomes was 96percent whereas drug content in Proliposomes was found to be more than 90percent. FTIR studies showed no possible interaction between drug and excipients. In-vitro and ex-vivo studies shows that liposomes not only enhance the penetration of drug molecules but also help to localize the drug within the skin indicating sustain release of drug. In-vivo studies concluded that proliposomal gel shows greater percentage of inhibition of paw oedema when compared to marketed gel.ConclusionIt was found that Proliposomes exhibited more stability as compared to liposomes. Hence Proliposomes drug delivery system was better choice for sustained release of drug through topical drug delivery.Key words: Naproxen, liposomes, Proliposomes, sustained release, transdermal delivery

The First Korean Case of Cutaneous Lung Tissue Heterotopia

Cutaneous lung tissue heterotopia is a very rare disorder where mature lung tissues develop in the skin. This is only the second known report of cutaneous lung tissue heterotopia, with the first by Singer et al. in 1998. A newborn infant had a hemangioma-like, freely movable mass connected to the anterior aspect of the sternal manubrium. Pathologic findings showed mature lung tissues with bronchi, bronchioles, and alveoli through the dermis and subcutis, and it was diagnosed as cutaneous lung tissue heterotopia. Cutaneous lung tissue heterotopia is hypervascular, so grossly it looks like a hemangioma. It can be differentiated from pulmonary sequestration, teratoma, bronchogenic cyst, and branchial cleft cyst by histology and the location of the mass. We describe the clinical, radiologic, and pathologic findings of a cutaneous lung tissue heterotopia, the first reported in Korea

PepMLM: Target Sequence-Conditioned Generation of Peptide Binders via Masked Language Modeling

Target proteins that lack accessible binding pockets and conformational stability have posed increasing challenges for drug development. Induced proximity strategies, such as PROTACs and molecular glues, have thus gained attention as pharmacological alternatives, but still require small molecule docking at binding pockets for targeted protein degradation (TPD). The computational design of protein-based binders presents unique opportunities to access undruggable targets, but have often relied on stable 3D structures or predictions for effective binder generation. Recently, we have leveraged the expressive latent spaces of protein language models (pLMs) for the prioritization of peptide binders from sequence alone, which we have then fused to E3 ubiquitin ligase domains, creating a CRISPR-analogous TPD system for target proteins. However, our methods rely on training discriminator models for ranking heuristically or unconditionally-derived guide peptides for their target binding capability. In this work, we introduce PepMLM, a purely target sequence-conditioned de novo generator of linear peptide binders. By employing a novel masking strategy that uniquely positions cognate peptide sequences at the terminus of target protein sequences, PepMLM tasks the state-of-the-art ESM-2 pLM to fully reconstruct the binder region, achieving low perplexities matching or improving upon previously-validated peptide-protein sequence pairs. After successful in silico benchmarking with AlphaFold-Multimer, we experimentally verify PepMLM's efficacy via fusion of model-derived peptides to E3 ubiquitin ligase domains, demonstrating endogenous degradation of target substrates in cellular models. In total, PepMLM enables the generative design of candidate binders to any target protein, without the requirement of target structure, empowering downstream programmable proteome editing applications

Engineered immunogens to elicit antibodies against conserved coronavirus epitopes

Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine

Comparative analysis of mangrove species and seedlings in a Riverine Region of Ogoniland, Nigeria

The comparative study of mangrove species and seedlings with respect to their density and relative abundance were carried out in the mangrove back swamp in Gokana Local Government Area, Rivers State, Nigeria. Four transects each with length and width of 100 m and 10 m respectively were set up with more than 1 km from each other. Each station was subdivided into four subplots of 2 5 m x 1.0 m. Data collection was based on identification, enumeration and recording. Density of species and seedlings were analysis using number of stem wood per hectare while relative abundance was expressed in percentage. Mangrove species density was highest in Plots 4 and lowest in Plot 1. Rhizophora racemosa had highest relative abundance in Plots 1 (62.07%) and 2 (4 1.08%). R. mangle had highest relative abundance (4 1.67%) in Plots 3, while in Plots 4, R. mangle, A. aureum and P. reclinata recorded 26.56% each. Mangrove seedlings were: Plot 1(1.35%), (Plot 2) 2.02%, Plot 3 (93.67%) and Plot 4 (2.96%). The bulk density of seedlings in Plots 3 was attributed to high population of matured stand which enhanced constant production of propagates. Critical attention and artificial regeneration should therefore be given to waterfronts to facilitate sustainable growth and development of species and seedlings at the water front and the entire ecosystem.Keywords: Nigerian mangroves, composition, abundance, Rhizophora racemosa, Niger Delt

Distribution and diversity of mangrove species in Gokana Local Government Area, Rivers State, Nigeria

Analysis of mangrove species distribution and diversity were carried out in Gokana Local Government Area, Rivers State, Nigeria. four transects (100 m x 10 m) with a distance of about 2 km from each other were set up at the mangrove back swamp starting from the waterfront towards upland. Each was divided into four equal plots of 25 m x 10 m. Data collection was based on identification and enumeration of the species. Distribution of the species as classified by Morisita’s index showed a uniform dispersion (id <1) in all plots. Simpson’s diversity index showed that species diversity was highest in Plots 4 (0.1272), followed by Plots 3 (0.2068). Plots 1 and 2 were dominated by Rhizophora racemosa (62.07% and 41.17% respectively). Plots 3 were dominated by R. mangle (4 1.67%) while Plots 4 had 26.56% of Acrostichum aureum and 26.56% of Phoenix reclinata. The overlapping mangrove species occurrence (Laguncularia racemosa and R. mangle) at the waterfronts should not alter the phenomenon of zonation for any form of reforestation project to be carried out in the area. Species for planting a specific mangrove area should be decided by environmental condition according to mangrove zonation principle so that reforestation and sustainable rehabilitation in the deteriorated ecosystem will be successfully achieved.Keywords: Nigerian mangroves, biodiversity, distribution, assemblage, Niger Delt

Congenital midline cervical cleft with an underlying bronchogenic like cyst

Congenital midline cervical cleft (CMCC) is an uncommon malformation. We report a case of a baby girl aged 3 days with a CMCC associated with a cyst reported as a bronchogenic cyst (BC). The pathology is not specific. The association of BC and CMCC is extremely rare and only five cases have been found in the literature. We report our case and review the relevant literature