Результаты поиска

Inhalable solid lipid nanoparticles for intracellular tuberculosis infection therapy: macrophage-targeting and pH-sensitive properties.

Mycobacterium tuberculosis (MTB) is one of the most threatening pathogens for its latent infection in macrophages. The intracellular MTB isolated itself from drugs and could spread via macrophages. Therefore, a mannose-modified macrophage-targeting solid lipid nanoparticle, MAN-IC-SLN, loading the pH-sensitive prodrug of isoniazid (INH), was designed to treat the latent tuberculosis infection. The surface of SLNs was modified by a synthesized 6-octadecylimino-hexane-1,2,3,4,5-pentanol (MAN-SA) to target macrophages, and the modified SLNs showed a higher cell uptake in macrophages (97.2%) than

Factor analysis of proton MR spectroscopic imaging data in HIV infection: metabolite-derived factors help identify infection and dementia.

PURPOSE: To develop a relevant pathophysiologic model of human immunodeficiency virus (HIV)-associated dementia by studying regional variations in metabolite levels measured with magnetic resonance (MR) spectroscopic imaging and their relationship to immunologic measures and cognitive dysfunction. MATERIALS AND METHODS: This was a HIPAA-compliant, institutional review board-approved study involving written informed consent. Distributions of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) concentrations in 94 subjects (20 seronegative controls and 74 HIV-positive subjects; 34 of the

Gonadotrophin receptor blocking antibodies measured by the use of cell lines stably expressing human gonadotrophin receptors are not detectable in women with 46,XX premature ovarian failure.

BACKGROUND: Premature ovarian failure (POF) is defined by cessation of ovarian function after puberty and before the age of 40. The syndrome is characterized by amenorrhoea, oestrogen deficiency and elevated levels of gonadotrophins. Autoimmunity has been proposed as a mechanism for some cases of destruction or malfunction of ovarian follicles. POF is often associated with type I and type II polyglandular autoimmune syndromes. It has also been postulated that receptors such as the LH and FSH receptors might become targets for blocking antibodies and such antibodies could be a cause of ovarian

Epitopes for thyroid-stimulating antibodies in Graves' sera: a possible link of heterogeneity to differences in response to antithyroid drug treatment.

To evaluate the extent and clinical relevance of epitope heterogeneity for stimulating TSH receptor antibodies (TSHRAbs), we measured the activity of IgG preparations from 66 untreated patients with Graves' disease using Chinese hamster ovary (CHO) cells transfected with wild-type human TSHR and two TSHR chimeras with residues 9-165 (Mc1 + 2) or 90-165 (Mc2) substituted by equivalent residues of the LH/CG receptor. IgG from 68% of patients lose all of the stimulating TSHRAb activity with the chimeras; IgG from 27% lose most of the activity. Thus, we show that 95% of patients have stimulating T

Novel hybrid 1,4-naphthoquinone-endoperoxide antimalarial hits: Synthesis, stereoisomeric separation, and biological evaluation.

Hybrid molecules, chemical entities with two or more pharmacophore domains, are widely investigated for their antiparasitic potential. First … rum W2 and K1 chloroquine-resistant strains for their antiplasmodial activity and against HepG2 and CHO cells for their cytotoxicity. Antiplasmodial activity was better than those obtained for reference compound chloroquine for 15 compounds on PfW2 strain and 8 compounds on PfK1 strain. Hit compounds were identified among stereoisomer mixtures (12, IC50PfW2 …

Safety Assessment of Antrodia cinnamomea Cultured in Red Quinoa and Barley: Genotoxicity in Mice and 90-Day Feeding Toxicity in Rats.

Antrodia cinnamomea (AC) is a medicinal mushroom native to Taiwan. This study evaluated the genotoxicity and toxicity of red quinoa and barley-based solid-state fermented AC mycelium (RQBACM). The safety of RQBACM was evaluated via a 90-day repeated-dose oral toxicity study in rats and a battery of genotoxicity assays, including the Ames, CHO-K1 chromosomal aberration, and in vivo micronucleus tests. RQBACM exhibited no mutagenicity in the Ames test, regardless of S9 metabolic activation, nor did it induce chromosomal aberrations in CHO-K1 cells. In mice, no significant changes in reticulocyte

Injectable, In Situ Self-cross-linking, Self-healing Poly(l-glutamic acid)/Polyethylene Glycol Hydrogels for Cartilage Tissue Engineering.

Injectable hydrogels have drawn much attention in the field of tissue engineering because of advantages such as simple operation, strong plasticity, and good biocompatibility and biodegradability. Herein, we propose the novel design of injectable hydrogels via a Schiff base cross-linking reaction between adipic dihydrazide (ADH)-modified poly(l-glutamic acid) (PLGA-ADH) and benzaldehyde-terminated poly(ethylene glycol) (PEG-CHO). The effects of the mass fraction and the molar ratio of -CHO/-NH2 on the gelation time, mechanical properties, equilibrium swelling, and in vitro degradation of the h

Immune Activity of BCG Infected Mouse Macrophages Treated with a Novel Recombinant Mouse Lactoferrin.

Lactoferrin has been investigated for its adjuvant action to boost the BCG vaccine. Previous studies demonstrated that lactoferrin (LF) enhanced efficacy of the Bacillus Calmette-Guérin (BCG) vaccine to protect mice against the virulent Erdman Mycobacterium tuberculosis challenge. The studies here investigate the hypothesis that a novel CHO-derived recombinant mouse LF can modify cytokine production and antigen presentation molecules on macrophages. The mouse LF (rmLF) was examined for effects on bone marrow derived macrophage (BMM) activities when cultured with BCG. Comparisons were made to C

Assessment of in vitro toxicity of chloronitramide anion (CNAM).

In 2024, the chloronitramide anion (CNAM) was identified as a degradation product of inorganic chloramines, more than 40 years since its exi … ata. Additional in vitro testing further suggests that CNAM induces substantial oxidative stress in CHO cells, whereas mitochondrial dysfunction and DNA damage were not significant under the tested conditions.

Oil-in-ionic liquid nanoemulsion-based intranasal delivery system for influenza split-virus vaccine.

Effective antigen delivery and immune stimulation in nasal mucosa determine the success of mucosal immunity. Here, an oil-in-ionic liquid (o/IL) nanoemulsion formulated with choline and niacin IL ([Cho][Nic]), squalene, and Tween 80 surfactant is explored as a vaccine delivery system for intranasal mucosal immunization. Compared to the o/w emulsion counterpart without the ILs, the o/IL manoemulsion showed a reduced and more uniform size of approximately 168 nm and significantly improved stability. Studies in mice model showed that when was used as an intranasal vaccine delivery system for infl

Molecular characterization of the AdeI mutant of Chinese hamster ovary cells: a cellular model of adenylosuccinate lyase deficiency.

Adenylosuccinate lyase (ADSL, E. C. 4.3.2.2) carries out two non-sequential steps in de novo AMP synthesis, the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazolecarboxamide ribotide (AICAR) and the conversion of succinyl AMP (AMPS) to AMP. In humans, mutations in ADSL lead to an inborn error of metabolism originally characterized by developmental delay, often with autistic features. There is no effective treatment for ADSL deficiency. Hypotheses regarding the pathogenesis include toxicity of high levels of SAICAR, AMPS, or their metabolites, deficiency of the

Neisseria meningitidis lipid A mutant LPSs function as LPS antagonists in humans by inhibiting TLR 4-dependent cytokine production.

Lipopolysaccharide is a major constituent of the outer membrane of Gram-negative bacteria and important in the induction of pro-inflammatory responses. Recently, novel LPS species derived from Neisseria meningitidis H44/76 by insertional inactivation of the lpxL1 and lpxL2 genes have been created with a lipid A portion consisting of five (penta-acylated lpxL1) or four (tetra-acylated lpxL2) fatty acids connected to the glucosamine backbone instead of six fatty acids in the wild-type LPS. We show that these mutant LPS-types are poor inducers of cytokines (tumor-necrosis factor-α, IL-1β, IL-10,

The phenothiazine drugs inhibit hERG potassium channels.

Cardiovascular adverse effects from phenothiazine drugs are common. The most serious consequences of treatment, arrhythmias and sudden death … ne) on hERG channel expressed in chinese hamster ovary (CHO) cells. HERG channels were expressed in CHO cells, and ion currents were measured using the patch-clamp technique. Thioridazine, perphenazine, trifluoperazine, and chlorpromazine blocked hERG potassium channels with the following IC(50) values: IC(50) values were 224 +/- 42 nM for thioridazine, 100 …

Agonist-induced desensitization and phosphorylation of m1-muscarinic receptors.

Pre-stimulation of Chinese hamster ovary (CHO) cells expressing the human m1-muscarinic receptor (CHO-m1 cells) with a maximally effective concentration of the muscarinic agonist methacholine resulted in desensitization of Ins(1,4,5)P3 accumulation, apparent as a approximately 4-fold shift in the agonist dose-response curve. Agonist-induced desensitization was rapid (detectable by 10 s) and concentration dependent (EC50=8.2+/-2.2 microM) and resulted in a complete loss of receptor reserve for the agonist-stimulated Ins(1,4, 5)P3 response. An investigation of the possible mechanisms involved in

AgNPs loaded adenine-modified chitosan composite POSS-PEG hybrid hydrogel with enhanced antibacterial and cell proliferation properties for promotion of infected wound healing.

Wound healing is a dynamic and complex process, it's urgent to develop new wound dressings with excellent performance to promote wound healing at the different stages. Here, a novel composite hydrogel dressing composed by silver nanoparticles (AgNPs) impregnated adenine-modified chitosan (CS-A) and octafunctionalized polyhedral oligomeric silsesquioxane (POSS) of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) solution was presented to solve the problem of wound infection. Modification of chitosan with adenine, not only can improve the water solubility of chitosan, but also introduc

Development and comparison of 68Ga/18F/64Cu-labeled nanobody tracers probing Claudin18.2.

Claudin 18.2 (CLDN18.2) is an emerging target for the treatment of gastric cancers. We aim to develop tracers to image the expression of CLDN18.2. A humanized nanobody targeting CLDN18.2 (clone hu19V3) was produced and labeled with 68Ga, 64Cu, and 18F. The tracers were investigated in subcutaneous and metastatic models established using two different mouse types (nude and Balb/c mice) and two different cell lines (CHO-CLDN18.2 and CT26-CLDN18.2). Gastric cancer patient-derived xenograft (PDX) models were further established for validation experiments. Three novel CLDN18.2-targeted tracers (i.e

Совпадение в полном тексте источника
… Histopathological staining studies showed positive expression of CLDN18.2 on the CHO cells, reflecting the stable expression of the protein in in vivo conditions ( Figures 3 B and 3C). The above data together indicated the in vivo targeting ability and specificity of [ 68 Ga]Ga-NOTA-hu19V3. …

Serial 1H-MRS in GM2 gangliosidoses.

GM2 gangliosidoses are a group of neuronal storage disorders caused by deficiency in the lysosomal enzyme hexosaminidase A. Clinically, the disease is marked by a relentless encephalopathy. Proton magnetic resonance spectroscopy (1H-MRS) provides in-vivo measurement of various brain metabolites including N-acetyl aspartate+N-acetyl aspartate glutamate (NAA), myo-inositol (mI), choline (Cho) and creatine (Cr). The NAA represents neuronal integrity while elevation in the mI reflects abnormal inflammation and gliosis in the brain tissue. An elevation in the Cho levels suggest cell membrane breakd

Characterization of low-glycosylated forms of soluble human urokinase receptor expressed in Drosophila Schneider 2 cells after deletion of glycosylation-sites.

The urokinase-type plasminogen activator receptor (uPAR) is a glycolipid-anchored membrane protein that is thought to play an active role du … ce reveals that S2-produced suPAR exhibits binding properties similar to those of suPAR produced by CHO cells. By site-directed mutagenesis we have furthermore removed the five potential N-linked glycosylation-sites either individually or in various combinations and studied the effect thereof on secretion and ligand-binding. Only suPAR completely deprived o …

Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model.

The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involvi

Variable Clinical Appearance of the Kir2.1 Rare Variants in Russian Patients with Long QT Syndrome.

BACKGROUND: The KCNJ2 gene encodes inward rectifier Kir2.1 channels, maintaining resting potential and cell excitability. Presumably, clinical phenotypes of mutation carriers correlate with ion permeability defects. Loss-of-function mutations lead to QTc prolongation with variable dysmorphic features, whereas gain-of-function mutations cause short QT syndrome and/or atrial fibrillation. METHODS: We screened 210 probands with Long QT syndrome for mutations in the KCNJ2 gene. The electrophysiological study was performed for the p.Val93Ile variant in the transfected CHO-K1 cells. RESULTS: We fo