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Transduction of liver metastases after intravenous injection of Ad5/35 or Ad35 vectors with and without factor X-binding protein pretreatment.

Inefficient tumor transduction with targeted adenoviral vectors is largely due to unspecific virus sequestration by blood components, including coagulation factor X, and Kupffer cell scavenging. In this study, we show that preinjection of snake venom factor X-binding protein (X-bp) reduces hepatocyte transduction and increases the circulation time in blood of an intravenously injected, fiber-chimeric Ad5/35 vector. X-bp pretreatment resulted in improved Ad5/35 transduction of liver metastases and increased the antitumor efficacy of an Ad5/35-based oncolytic adenovirus. Furthermore, we demonstr

Engineering galactoside acetyltransferase for enhanced hesperetin-7-O-glucoside bioavailability.

Flavonoid glycosides exhibit compromised bioavailability due to low membrane permeability. To address this limitation, we acetylated flavonoids through enzymatic reactions to increase bioavailability. This study first reported that Hesperetin-7-O-glucoside (Hes-7-G) was acetylated by galactoside acetyltransferase (GAT), and the apparent permeability (Papp) of the Caco-2 monolayer was increased by 69%, indicating the acetylated Hes-7-G application potential to improve bioavailability. Subsequently, we designed GAT mutants through comprehensive computational and experimental methods to improve t

Cooperative mechanisms of β-ketoacyl-ACP synthase III and acyl carrier protein in branched-chain fatty acid biosynthesis in Cutibacterium acnes.

The branched-chain fatty acids (BCFAs) synthesized by Cutibacterium acnes contribute to its membrane fluidity and adaptation to anaerobic environments. We investigated the structural and functional characteristics of β-ketoacyl-ACP synthase III (CaKAS III) and its cofactor, acyl carrier protein (CaACP) that are key components of BCFA synthesis. Structural analysis revealed that W228 and V233 in CaKAS III regulate branched-chain substrate accommodation. Docking and molecular dynamics (MD) simulations demonstrated that isovaleryl-CoA is stably accommodated in the CaKAS III cavity but does not re

Biocatalytic system for comparatively assessing the functional association of monolignol cytochrome P450 monooxygenases with their redox partners.

Lignin is a complex heterogenous polymer derived from oxidative radical polymerization of three monolignols, i.e., p-coumaryl alcohol, coniferyl alcohol and sinapyl alcohol. These lignin monomeric precursors structurally differ in their methoxy groups of the benzene rings. In phenylpropanoid-monolignol biosynthetic pathway, the endoplasmic reticulum (ER)-resident cytochrome P450 monooxygenases, cinnamate 4-hydroxylase, coumaroyl ester 3'-hydroxylase and ferulate 5-hydroxylase, establish the key structural characteristics of monolignols. The catalysis of cytochrome P450 monooxygenase requires r

Neuroprotective effects of hydrogen sulfide on sodium azide-induced oxidative stress in PC12 cells.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, responsible for >50% of all dementia cases. Sodium azide (NaN3) inhibits cytochrome oxidase by irreversibly binding to the heme cofactor and selectively reducing the complex IV activity, which is present in post‑mortem AD brains. Previous data demonstrated that hydrogen sulfide (H2S), the third endogenous gaseous mediator, exerted protective effects against neuronal damage. Therefore, it was hypothesized that H2S may be able to scavenge excess reactive oxygen species (ROS), thereby protecting against oxidative stress and c

Living Donor Kidney Transplantation in Atypical Hemolytic Uremic Syndrome: A Case Series.

BACKGROUND: The development of complement inhibitors has greatly improved the outcome of patients with atypical hemolytic uremic syndrome (a … nts carried a pathogenic or likely pathogenic variant in genes encoding complement factor H, C3, or membrane cofactor protein, giving a high risk for aHUS recurrence. Median follow-up after transplantation was 25 (range, 7-68) months. One patient had aHUS recurrence 68 days after transplantation, which was successfully treated with eculizumab. 3 patients were treated for r …

Thrombotic microangiopathy in renal allografts: the diagnostic challenge.

PURPOSE OF REVIEW: The diagnosis of thrombotic microangiopathy (TMA) is complex and often difficult. This review provides an approach to the diagnosis with emphasis on recent relevant developments. RECENT FINDINGS: There is increasing evidence that most cases of recurrent TMA in renal allografts are secondary to mutations in genes encoding complement regulatory factors and complement components, such as factor H, factor I, membrane cofactor protein, C3, and others. Genetic work-up for these potential complement abnormalities is now available and recommended. Another important cause for recurr…

A case of atypical hemolytic uremic syndrome due to anti-factor H antibody in a patient presenting with a factor XII deficiency identified two novel mutations.

A 9-year-old boy with pallor and macrohematuria showed hemolytic anemia, thrombocytopenia and renal failure. There was no history of diarrhe … d. Factor H (FH) and factor I (IF) levels were normal and we did not detect mutations of FH, IF and membrane cofactor protein. Further investigation revealed the presence of anti-FH antibody in the patient's plasma and a deficiency of coagulation factor XII. Analysis of the patient's coagulation system displayed <3% functional activity of factor XII, whereas levels of othe …

Ограничительный анализ связанных с отосклерозом вариантов CD46.

Отосклероз является первичным расстройством костной реконструкции зоотической капсулы человека и ассоциируется с стойкой вирусной инфекцией кори. Человеческий клеточный рецептор вируса кори — мембранный кофакторный белок (MCP, CD46), который имеет 14 хорошо описываемых сплетений. Уникальный CD46 - экспресс-образец зоотической капсулы и таблички для ног может определить подверженность стойкой инфекции корью. С помощью гистопатологических и молекулярных биологических методов был проанализирован в общей сложности 51 удалённый хирургическим путем анкилотические стопки ног. Были извлечены нуклеинов

Совпадение в аннотации оригинала
Otosclerosis is a primary bone remodeling disorder of the human otic capsule and is associated with persistent measles virus infection. The human cellular receptor of measles virus is the membrane cofactor protein (MCP, CD46), which has 14 well-described splicing variants. Unique CD46 expression pattern of the otic capsule and the stapes footplate may determ…

CD46 in meningococcal disease.

The human-specific bacterial pathogen Neisseria meningitidis is a major cause of sepsis and/or meningitis. The pili of N. meningitidis interact with CD46, a human cell-surface protein involved in regulation of complement activation. Transgenic mice expressing human CD46 were susceptible to meningococcal disease, because bacteria crossed the blood-brain barrier in these mice. Development of disease was more efficient with piliated bacteria after intranasal, but not intraperitoneal, challenge of CD46 transgenic mice, suggesting that human CD46 facilitates pilus-dependent interactions at the epit

Antioxidant and neuroprotective effects of ubiquinol diacetate: Insights from SH-SY5Y cell line and Caenorhabditis elegans models of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra and the presence of misfolded α-synuclein in the brain. Mitochondrial dysfunction and oxidative stress are factors contributing to the death of these neurons. Coenzyme Q10 (CoQ10) serve as an antioxidant and cofactor for mitochondrial enzymes, and its deficiency can exacerbate neurodegenerative processes in PD. However, the clinical efficacy of CoQ10 is limited by its low bioavailability and instability. Ubiquinol diacetate (CoQ10 Ac), an esterified form of

Chimeric oncolytic Ad5/3 virus replicates and lyses ovarian cancer cells through desmoglein-2 cell entry receptor.

Despite new therapies, the estimated 229 875 women living with ovarian cancer have a 5-year survival rate of 47.6%. This cavity-localized cancer lends itself to local administration of modalities, such as the oncolytic adenovirus (Ad) Ad5/3-D24-granulocyte-macrophage colony-stimulating factor virus (ONCOS-102). Its repeated administration to a patient with chemotherapy-refractory ovarian cancer induced CD8+ antitumor immune responses with the overall survival reaching 40 months. Here we probe the dominant receptor used by ONCOS-102 in four established epithelial ovarian cancer cell lines. Ad3

CD46 facilitates entry and dissemination of human cytomegalovirus.

Human cytomegalovirus (CMV) causes a wide array of disease to diverse populations of immune-compromised individuals. Thus, a more comprehensive understanding of how CMV enters numerous host cell types is necessary to further delineate the complex nature of CMV pathogenesis and to develop targeted therapeutics. To that end, we establish a vaccination strategy utilizing membrane vesicles derived from epithelial cells to generate a library of monoclonal antibodies (mAbs) targeting cell surface proteins in their native conformation. A high-throughput inhibition assay is employed to screen these an

Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune bullous disease caused by autoantibodies against BP180 in the epidermal basement membrane. Autoantibody-mediated complement activation is an important process in BP pathogenesis. CD46, a crucial complement regulatory protein in the complement activation, has been reported to be involved in several autoimmune diseases. In the present study, we investigated whether CD46 plays a role in BP development. We found that sCD46 expression was significantly increased in the serum and blister fluids of BP patients and correlated with the levels of anti-BP180 NC16A

SUN2 Overexpression Deforms Nuclear Shape and Inhibits HIV.

UNLABELLED: In a previous screen of putative interferon-stimulated genes, SUN2 was shown to inhibit HIV-1 infection in an uncharacterized manner. SUN2 is an inner nuclear membrane protein belonging to the linker of nucleoskeleton and cytoskeleton complex. We have analyzed here the role of SUN2 in HIV infection. We report that in contrast to what was initially thought, SUN2 is not induced by type I interferon, and that SUN2 silencing does not modulate HIV infection. However, SUN2 overexpression in cell lines and in primary monocyte-derived dendritic cells inhibits the replication of HIV but not

Ndt80 Orchestrates Copper Stress Responses and Mitochondrial Homeostasis in Candida albicans.

Copper is a crucial cofactor that sustains multiple cellular electron-transfer reactions, making it an essential element for life. However, cytotoxic levels of copper can cause structural damage and cell death through the production of reactive oxygen species (ROS) and nonspecific attacks on proteins. Moreover, immune cells, including neutrophils and macrophages, accumulate copper to induce oxidative bursts that kill engulfed pathogens. Therefore, a well-regulated copper homeostasis system is required for the human commensal fungus Candida albicans to thrive in extreme host environments. Remar

Glutathione Metabolism and the Novel Role of Mitochondrial GSH in Retinal Degeneration.

Glutathione (GSH) is present ubiquitously, and its role as a crucial cellular antioxidant in tissues, including the retina, is well established. GSH's antioxidant function arises from its ability to scavenge reactive oxygen species or to serve as an essential cofactor for GSH S-transferases and peroxidases. This review summarizes the general functions, retinal distribution, disorders linked to GSH deficiency, and the emerging role for mitochondrial GSH (mGSH) in retinal function. Though synthesized only in the cytosol, the presence of GSH in multiple cell organelles suggests the requirement fo

A novel mutation in LMBRD1 causes the cblF defect of vitamin B(12) metabolism in a Turkish patient.

In the cblF defect of vitamin B(12) (cobalamin) metabolism, cobalamin is trapped in lysosomes. Consequently, cobalamin coenzyme synthesis is blocked, and cofactors for methionine synthase and methylmalonyl-coenzyme A (CoA) mutase are deficient. We recently identified LMBRD1 as the causative gene located on chromosome 6q13 and showed that 18 out of 24 alleles in unrelated patients carried the deletion c.1056delG (p.L352fsX18) (Rutsch et al. (Nat Genet 41:234-239, 2009). LMBRD1 encodes the lysosomal membrane protein LMBD1, which presumably facilitates lysosomal cobalamin export. Our patient is t

The human gephyrin (GPHN) gene: structure, chromosome localization and expression in non-neuronal cells.

Gephyrin was first described as a peripheral membrane protein of 93 kDa anchoring the glycine receptor (GlyR) to subsynaptic microtubules and cytoskeleton. Analysis of knock-out mice demonstrated that gephyrin has additional functions in GABA(A) receptor localization at the synapse and in the biosynthetic pathway of the molybdenum cofactor (Moco). Here we describe a human non-neuronal gephyrin cDNA and the exon/intron organization of the human gephyrin gene. We found the coding region to consist of 27 exons and to span approximately 800 kb on the long arm of chromosome 14. This structure is al

Renal elimination of magnesium as a parameter of bioavailability of oral magnesium therapy.

Magnesium is an important cation in human physiology, especially in the regulation of membrane proteins, as a cofactor for various enzyme systems and in neuromuscular transmission. Magnesium deficiency leads to severe impairment in muscle function, particularly in cardiovascular diseases. Classical bioavailability studies with magnesium cannot be carried out for several reasons. As the magnesium concentration in plasma is extraordinarily well regulated, renal elimination proves to be the best method to determine the absorption of orally administered magnesium. Magnesium pools must first be fil