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REMD Simulations of Full-Length Alpha-Synuclein Together with Ligands Reveal Binding Region and Effect on Amyloid Conversion.

Alpha-synuclein is a key protein involved in the development and progression of Parkinson's disease and other synucleinopathies. The intrins … iction of the binding sites for three tested compounds (fasudil, phthalocyanine tetrasulfonate, and spermine), giving good agreement with data from experiments by other groups. Lots of information about the binding and protein conformational ensemble enabled the suggestion of a putative effect of the ligands on the amyloid-like conversion of alpha-synuclei …

Pharmacological and dietary agents for colorectal cancer chemoprevention: effects on polyamine metabolism (review).

Chemoprevention is the long-term use of different chemical agents, both synthetic and natural, to prevent or delay the onset of disease. Since colorectal cancer has a significant environmental component, it is an ideal disease in which to evaluate the potential benefits of chemopreventive agents. The polyamines, spermine, spermidine and putrescine have been involved in almost all the steps of colorectal tumorigenesis. Consequently, polyamine biosynthesis and catabolism can be considered as promising targets for cancer chemoprevention. A variety of drug formulations have been tested for their e…

Zwitterionic molecularly imprinted polymers for selective capillary microextraction of N1,N12-Diacetylspermine (DiAcSpm) from breast cancer.

N1,N12-diacetylspermine (DiAcSpm), a promising biomarker for cancer diagnosis, presents significant quantification challenges due to the structural homology within the polyamine family. To address this issue, we engineered a molecularly imprinted monolithic (MIM) column functionalized with biomimetic phosphorylcholine (PC) as functional monomer for the selective recognition of DiAcSpm in human urine. The zwitterionic polymer was synthesized via thermally initiated polymerization, with its morphology and pore architecture characterized through scanning electron microscopy (SEM) and brunauer-emm…

Setting up and managing the largest COVID-19 mass vaccination center in Lombardy, Italy.

BACKGROUND: The rapid global spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) was met with the rollout of vaccination campaigns at mass vaccination centers. The Palazzo delle Scintille, Milan, was designated by the Lombardy regional administration as a vaccination site with the target of processing about 9,000 users daily. METHODS: For this observational study, we compared data on vaccinations delivered at the Palazzo delle Scintille with coronavirus disease (COVID-19)-related regional data. RESULTS: Between 25 April 2021 and 28 February 2023, a total of 1,885,822 COVID-1

Self-cleaning antimicrobial surfaces by bio-enabled growth of SnO2 coatings on glass.

Conventional vapor-deposition techniques for coatings require sophisticated equipment and/or high-temperature resistant substrates. Therefore bio-inspired techniques for the fabrication of inorganic coatings have been developed in recent years. Inspired by the biology behind the formation of the intricate skeletons of diatoms orchestrated by a class of cationic polyamines (silaffins) we have used surface-bound spermine, a naturally occurring polyamine, to promote the fast deposition of homogeneous, thin and transparent biomimetic SnO2 coatings on glass surfaces. The bio-enabled SnO2 film is hi…

DAB-APT: a Fluorescence-Based Assay for Determining Aminopropyl Transferase Activity and Inhibition.

Polyamines are polycationic molecules that are crucial in a wide array of cellular functions. Their biosynthesis is mediated by aminopropyl transferases (APTs), promising targets in antimicrobial, antineoplastic and antineurodegenerative therapies. A major limitation, however, is the lack of high-throughput assays to measure their activity. We developed the first fluorescence-based assay, DAB-APT, for measurement of APT activity using 1,2-diacetyl benzene, which forms fluorescent conjugates with putrescine, spermidine and spermine with fluorescence intensity increasing with increasing carbon c…

Polyamines, molecules necessary for cell division, colocalize with peptide growth factors.

The naturally occurring polyamines spermidine and spermine are necessary for cell division and growth. By restaining experiments, using three independent polyamine cytochemical methods, together with peptide immunocytochemistry, we show that substantial amounts of polyamines occur in a number of peptide growth factor-producing cell types. These include submandibular granular convoluted duct cells producing epidermal growth factor (EGF), pancreatic islet cells producing insulin and anterior pituitary cells producing growth hormone (GH). Other cell types in these tissues display only weak or no …

Cerebrospinal fluid polyamines: biochemical markers of malignant childhood brain tumors.

The clinical value of cerebrospinal fluid (CSF) polyamine determinations in childhood medulloblastoma has been suggested. We performed 72 CSF polyamine determinations in 35 children with primary brain tumors. Spermine values were normal and spermidine values were inconsistently elevated. CSF putrescine values, however, were consistently elevated in patients with histologically malignant brain tumors: medulloblastoma, ependymoma, pineal germ cell tumors, primitive neuroectodermal tumors, and brainstem gliomas. Children with supratentorial astrocytomas had normal CSF polyamine values. CSF putres…

6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers.

The combination of increased incidence of drug-resistant strains of bacteria and a lack of novel drugs in development creates an urgency for … scherichia coli and with moderate to excellent antifungal properties. Polyamine 3, which includes a spermine chain, was the most potent of the series - its mechanism of action was attributed to rapid membrane permeabilization and depolarization in both Gram-positive and Gram-negative bacteria.

Comparison of different cationized proteins as biomaterials for nanoparticle-based ocular gene delivery.

Cationized polymers have been proposed as transfection agents for gene therapy. The present work aims to improve the understanding of the po … e nanoparticles based on intermediate molecular weight gelatin cationized with the endogenous amine spermine, which exhibit an adequate toxicological profile, as well as effective association and protection of pDNA or siRNA molecules, thereby resulting in higher transfection efficiency and gene silencing than the other studied formulations.

Nitric oxide inhibits the adenovirus proteinase in vitro and viral infectivity in vivo.

Nitric oxide (NO) is an antiviral effector of the innate immune system, but few of the viral targets of NO have been identified. We now show that NO inhibits adenovirus replication by targeting the adenovirus proteinase (AVP). NO generated from diethylamine NONOate (DEA-NONOate) or spermine NONOate (Sp-NONOate) inhibited the AVP. Inhibition was reversible with dithiothreitol. The equilibrium dissociation constant for reversible binding to the AVP by Sp-NONOate, or Ki, was 0.47 mM, and the first-order rate constant for irreversible inhibition of the AVP by Sp-NONOate, or ki, was 0.0036 s(-1). T…

Polyamines reverse non-steroidal anti-inflammatory drug-induced toxicity in human colorectal cancer cells.

Naproxen, sulindac and salicylate, three NSAIDs (non-steroidal anti-inflammatory drugs), were cytotoxic to human colorectal cancer cells in culture. Toxicity was accompanied by significant depletion of intracellular polyamine content. Inhibition of ornithine decarboxylase (the first enzyme of the polyamine biosynthetic pathway), induction of polyamine oxidase and spermidine/spermine N(1)-acetyltransferase (the enzymes responsible for polyamine catabolism) and induction of polyamine export all contributed to the decreased intracellular polyamine content. Morphological examination of the cells s…

Vitamin C attenuates nitrate tolerance independently of its antioxidant effect.

In LLC-PK1 kidney epithelial cells, a 5-h pretreatment with glyceryl trinitrate (GTN) resulted in substantial desensitization of the intracellular cyclic GMP response to a subsequent 10-min challenge with GTN (1 microM). GTN-tolerant cells were fully sensitive to the spontaneous nitric oxide (NO) donor spermine NONOate, which does not require enzymatic bioactivation. Cyclic GMP stimulation by GTN was up to 3.1-fold higher when vitamin C (1-10 mM) was present during the pretreatment period. In contrast, other oxygen radical scavengers such as tiron or dimethylsulfoxide and the NO scavenger PTIO…

Фосфорилирование-дефосфорилирование ядерных белков во время инфекции (Q лихорадка).

Предложение о том, что выражение гена может регулироваться фосфорилацией нехистонных хроматиновых белков, было испытано путем изучения увеличения транскрипции в результате лихорадки Q. Некоторые виды деятельности, связанные с ядерным фосфопротеином печени и фосфатазной деятельностью, были изменены после того, как свиньи-морозки были заражены ожогом Коксиеллы. Протеины нонхистоунового хроматина увеличили активность фосфопротеиновых киназ и дифференцировали фосфорилаты. Добавление сперматозоида также стимулировало ядерные фосфопротеиновые киназы неинфекционной и зараженной печени. Заражение сопр

Совпадение в аннотации оригинала
The proposal that gene expression may be regulated by phosphorylation of nonhistone chromatin proteins was tested by studying increased tran … ad increased phosphoprotein kinase activity and were differentially phosphorylated. The addition of spermine equally stimulated nuclear phosphoprotein kinases of uninfected and infected livers. Increased nuclear phosphatase activity accompanied infection. It was concluded that protein phosphorylations are altered by infection and are central events in regu …

Methyl salicylate-induced arginine catabolism is associated with up-regulation of polyamine and nitric oxide levels and improves chilling tolerance in cherry tomato fruit.

The effects of methyl salicylate (MeSA) on chilling injury (CI) and gene expression levels, enzyme activities, and metabolites related to arginine catabolism in cherry tomato fruit were investigated. Freshly harvested fruits were treated with 0.05 mM MeSA vapor at 20 °C for 12 h and then stored at 2 °C for up to 28 days. MeSA reduced CI and enhanced the accumulation of putrescine, spermidine, and spermine, which was associated with increased gene expression levels and activities of arginase, arginine decarboxylase, and ornithine decarboxylase at most sampling times. MeSA also increased nitric …

Red blood cell polyamines, anaemia and tumour growth in the rat.

In rats with Mat Lylu prostatic carcinoma, significant changes in blood composition and red blood cell (RBC) characteristics were observed. Anaemia, characterised by a decrease in the number of RBC and the reduction of haemoglobin and the iron content in plasma, was correlated with tumour size and the accumulation of spermidine and spermine in the RBC. In large tumours, spermidine levels were increased by 8-fold over normal value. Spleen weight and splenic spermidine concentrations were enhanced in animals with tumours. After splenectomy, the rate of tumour growth decreased by 30%. It is propo…

Ca2+-, phorbol ester-, and cAMP-stimulated enzyme secretion from permeabilized rat pancreatic acini.

Enzyme secretion from the exocrine pancreas is stimulated by receptor-activated breakdown of phosphatidylinositol 4,5-bisphosphate and conse … ects of carbachol, TPA, cAMP, and a combination of both TPA and cAMP are inhibited by the polyamine spermine in permeabilized cells. Spermine has no effect on carbachol-induced enzyme secretion in intact cells. The data suggest that enzyme secretion from pancreatic acinar cells is mediated by cAMP protein kinase A and by Ca2+ phospholipid protein kinase C …

Tarantula (Eurypelma californicum) venom, a multicomponent system.

The venom of the tarantula Eurypelma californicum was analysed biochemically, the components were isolated and characterized. The pH value o … ns ATP, ADP and AMP as well as a component 2' visible in SDS-PAGE as 1.3-kDa band and consisting of spermine and tryptophan; fraction 3 contains ATP and an unknown component 3'; fractions 4-6 also show a 1.3-kDa band in SDS-PAGE, fraction 4 being tyrosylspermine and fractions 5 and 6 containing compounds of spermine and aromatic molecules; fraction 7 conta …

Dual Functions of Polyamines in Shaping Host-Specific Pathogen Dynamics.

Polyamines such as putrescine, spermidine, and spermine play essential roles in most living organisms. They regulate fundamental processes, like cell proliferation, differentiation, growth, gene expression (DNA/RNA stability, transcription, and translation), and signal transduction. As important regulators, polyamines influence development, stress responses, and the progression of health and disease, including cancer and aging. These positively charged molecules have been extensively studied for decades. In humans, polyamines are often researched as potential therapeutic targets for diseases s…

Sequential co-extraction of gut microbial DNA and fecal polyamines enables integrated microbiome-metabolite profiling in an Alzheimer's disease mouse model.

Early, non-invasive biomarkers for Alzheimer's disease (AD) are urgently needed. Impaired polyamine metabolism, regulated by intracellular pathways and the gut microbiota, has been reported in postmortem brains of AD patients. Here, we developed a sequential co-extraction workflow (Method 10) that enables recovery of gut bacterial DNA and fecal free polyamines-putrescine, spermidine, and spermine-from the same small mouse fecal sample, allowing paired microbiome and metabolite profiling. Applying this workflow to an AD knock-in mouse model and age-matched controls at 8, 32, and 56 weeks reveal…