Desosomes and desimicelles - a novel vesicular and micellar system for enhanced oral delivery of poorly soluble drug: Optimization of in vitro characteristics and in vivo performance.

This study introduces two innovative nanocarrier systems to improve oral drug delivery. Desosomes and desimicelles combine Deep eutectic solvent (DES) with vesicular or micellar nanosystems, respectively. These novel nanosystems integrate the DES solubilization potency for administering drugs with low aqueous solubility and the vesicular and micellar systems to bypass physiological barriers and improve poor drug bioavailability.

Myosin inhibitor reverses hypertrophic cardiomyopathy in genotypically diverse pediatric iPSC-cardiomyocytes to mirror variant correction.

Pathogenic variants in MYH7 and MYBPC3 account for the majority of hypertrophic cardiomyopathy (HCM). Targeted drugs like myosin ATPase inhibitors have not been evaluated in children. We generate patient and variant-corrected iPSC-cardiomyocytes (CMs) from pediatric HCM patients harboring single variants in MYH7 (V606M; R453C), MYBPC3 (G148R) or digenic variants (MYBPC3 P955fs, TNNI3 A157V).

Fexofenadine-loaded chitosan coated solid lipid nanoparticles (SLNs): A potential oral therapy for ulcerative colitis.

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.

Systematic characterization of regulatory variants of blood pressure genes.

High blood pressure (BP) is the major risk factor for cardiovascular disease. Genome-wide association studies have identified genetic variants for BP, but functional insights into causality and related molecular mechanisms lag behind. We functionally characterize 4,608 genetic variants in linkage with 135 BP loci in vascular smooth muscle cells and cardiomyocytes by massively parallel reporter assays.

Regulatory functional role of NLRP3 inflammasome during Mycoplasma hyopneumoniae infection in swine.

Mycoplasma hyopneumoniae causes enzootic pneumonia, a highly contagious respiratory disease in swine that causes significant economic losses worldwide. It is unknown whether the nucleotide oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome regulates the immune response in swine during M. hyopneumoniae infection.

Nanostructured lipid carriers for enhanced and schistosomicidal activity of praziquantel: effect of charge.

WHO considers praziquantel (PZQ) as the drug of choice for treatment of infection but this requires high dose due to poor solubility and first pass metabolism. The aim of this work was to optimize nanostructured lipid carriers (NLCs) for enhanced PZQ oral delivery. The optimization involved testing the effect of surface charge of NLCs.

Regions of bovine adenovirus-3 IVa2 involved in nuclear/nucleolar localization and interaction with pV.

Bovine adenovirus-3 (BAdV-3) is a non enveloped, icosahedral DNA virus containing a genome of 34446 bps. The intermediate region of BAdV-3 encodes pIX and IVa2 proteins. Here, we report the characterization of BAdV-3 IVa2.

The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning.

Background: What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL).

Porcine Adenovirus Type 3 E3 Encodes a Structural Protein Essential for Capsid Stability and Production of Infectious Progeny Virions.

The adenovirus E3 region encodes proteins that are not essential for viral replication The porcine adenovirus type 3 (PAdV-3) E3 region encodes three proteins, including 13.7K. Here, we report that 13.

Domains of bovine adenovirus-3 protein 22K involved in interacting with viral protein 52K and cellular importins α-5/α-7.

The L6 region of bovine adenovirus-3 (BAdV-3) encodes unspliced and spliced proteins named 22K and 33K, respectively. Earlier, anti-22K sera detected two proteins of 42- and 37-kDa in infected cells and 42-kDa protein in transfected cells. Here, we demonstrate that 22K protein localizes to the nucleus of BAdV-3 infected or transfected cells.

Establishment and evaluation of the goose embryo epithelial (GEE) cell line as a new model for propagation of avian viruses.

In this study, we report the establishment and characterization of a new epithelial cell line, goose embryonated epithelial cell line (GEE), derived from embryonic goose tissue. The purified GEE cell line can efficiently grow over 65 passages in the M199 medium supplemented with 10% fetal bovine serum at 37°C. Immunofluorescence assay was used to identify purified GEE cells as epithelial cell line by detecting expression of the Keratin-18 and -19.

Development and validation of immortalized bovine mammary epithelial cell line as an in vitro model for the study of mammary gland functions.

This study aimed to develop a bovine mammary epithelial (BME) cell line model, which provides a possibility to determine functional properties of the bovine mammary gland. The primary cell culture was derived from bovine mammary gland tissues and processed enzymatically to obtain cell colonies with epithelial-like morphology. The cultures of BME cells were purified and optimally cultured at 37 °C in DMEM/F12 medium supplemented with 10% fetal bovine serum.

An equine herpesvirus type 1 (EHV-1) vector expressing Rift Valley fever virus (RVFV) Gn and Gc induces neutralizing antibodies in sheep.

Rift Valley fever virus (RVFV) is an arthropod-borne bunyavirus that can cause serious and fatal disease in humans and animals. RVFV is a negative-sense RNA virus of the Phlebovirus genus in the Bunyaviridae family. The main envelope RVFV glycoproteins, Gn and Gc, are encoded on the M segment of RVFV and known inducers of protective immunity.

Establishment and characterization of duck embryo epithelial (DEE) cell line and its use as a new approach toward DHAV-1 propagation and vaccine development.

The primary cell culture was derived from duck embryonic tissue, digested with collagenase type I. The existence of cell colonies with epithelial-like morphology, named duck embryo epithelial (DEE), were purified and optimally maintained at 37°C in M199 medium supplemented with 5% fetal bovine serum. The purified cells were identified as epithelial cell line by detecting Keratin-18 expression using immunofluorescence assay.

Major histocompatibility complex class I downregulation induced by equine herpesvirus type 1 pUL56 is through dynamin-dependent endocytosis.

Unlabelled: Equine herpesvirus type 1 (EHV-1) downregulates cell surface expression of major histocompatibility complex class I (MHC-I) in infected cells. We have previously shown that pUL56 encoded by the EHV-1 ORF1 gene regulates the process (G. Ma, S.

Ubiquitination and degradation of the ORF34 gene product of equine herpesvirus type 1 (EHV-1) at late times of infection.

The equine herpesvirus type 1 (EHV-1) open reading frame 34 (ORF34) is predicted to encode a polypeptide of 161 amino acids. We show that an ORF34 deletion mutant exhibited a significant growth defect in equine peripheral blood mononuclear cells taken directly ex vivo during early but not late times of infection. ORF34 protein (pORF34)-specific antibodies specifically reacted with a 28-kDa early polypeptide present in the cytosol of infected cells.

Equine herpesvirus type 1 (EHV-1) open reading frame 59 encodes an early protein that is localized to the cytosol and required for efficient virus growth.

Equine herpesvirus type 1 (EHV-1) ORF59 is predicted to encode a protein consisting of 180 amino acids. To determine whether ORF59 in fact encodes a protein, sequences encoding an HA epitope (YPYDVPDYA) was inserted at the carboxyterminus of the ORF59 protein in EHV-1 strain Ab4. Using anti-HA monoclonal antibodies, a 21-kDa band was specifically detected by western blot analysis in lysates of cells infected with a recombinant EHV-1 from strain Ab4 that carries the pORF59-HA but not in cells infected with parental Ab4.

Recombinant equine herpesvirus 1 (EHV-1) vaccine protects pigs against challenge with influenza A(H1N1)pmd09.

Swine influenza virus (SIV) is not only an important respiratory pathogen in pigs but also a threat to human health. The pandemic influenza A(H1N1)pdm09 virus likely originated in swine through reassortment between a North American triple reassortant and Eurasian avian-like SIV. The North American triple reassortant virus harbors genes from avian, human and swine influenza viruses.

Equine herpesvirus type 4 UL56 and UL49.5 proteins downregulate cell surface major histocompatibility complex class I expression independently of each other.

Major histocompatibility complex class I (MHC-I) molecules are critically important in the host defense against various pathogens through presentation of viral peptides to cytotoxic T lymphocytes (CTLs), a process resulting in the destruction of virus-infected cells. Herpesviruses interfere with CTL-mediated elimination of infected cells by various mechanisms, including inhibition of peptide transport and loading, perturbation of MHC-I trafficking, and rerouting and proteolysis of cell surface MHC-I. In this study, we show that equine herpesvirus type 4 (EHV-4) modulates MHC-I cell surface expression through two different mechanisms.

An equine herpesvirus type 1 (EHV-1) expressing VP2 and VP5 of serotype 8 bluetongue virus (BTV-8) induces protection in a murine infection model.

Bluetongue virus (BTV) can infect most species of domestic and wild ruminants causing substantial morbidity and mortality and, consequently, high economic losses. In 2006, an epizootic of BTV serotype 8 (BTV-8) started in northern Europe that caused significant disease in cattle and sheep before comprehensive vaccination was introduced two years later. Here, we evaluate the potential of equine herpesvirus type 1 (EHV-1), an alphaherpesvirus, as a novel vectored DIVA (differentiating infected from vaccinated animals) vaccine expressing VP2 of BTV-8 alone or in combination with VP5.

An equine herpesvirus 1 (EHV-1) vectored H1 vaccine protects against challenge with swine-origin influenza virus H1N1.

In 2009, a novel swine-origin H1N1 influenza A virus (S-OIV), antigenically and genetically divergent from seasonal H1N1, caused a flu pandemic in humans. Development of an effective vaccine to limit transmission of S-OIV in animal reservoir hosts and from reservoir hosts to humans and animals is necessary. In the present study, we constructed and evaluated a vectored vaccine expressing the H1 hemagglutinin of a recent S-OIV isolate using equine herpesvirus 1 (EHV-1) as the delivery vehicle.

Acute coronary syndrome in young adults from oman: results from the gulf registry of acute coronary events.

Objective: To assess the prevalence, risk factors, presenting features, and in-hospital outcomes of acute coronary syndrome (ACS) patients ≤40 years of age from Oman.

Methods: Data were analyzed from 1579 consecutive ACS patients from Oman during May, 2006 to June, 2007, as part of Gulf RACE (Registry of Acute Coronary Events). ACS patients ≤40 years of age were compared with patients >40 years of age.