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International Journal of Molecular... Nov 2023Polyamines (Pas) are short molecules that exhibit two or three amine groups that are positively charged at a physiological pH. These small molecules are present in high... (Review)
Review
Polyamines (Pas) are short molecules that exhibit two or three amine groups that are positively charged at a physiological pH. These small molecules are present in high concentrations in a wide variety of organisms and tissues, suggesting that they play an important role in cellular physiology. Polyamines include spermine, spermidine, and putrescine, which play important roles in age-related diseases that have not been completely elucidated. Aging is a natural process, defined as the time-related deterioration of the physiological functions; it is considered a risk factor for degenerative diseases such as cardiovascular, neurodegenerative, and musculoskeletal diseases; arthritis; and even cancer. In this review, we provide a new perspective on the participation of Pas in the cellular and molecular processes related to age-related diseases, focusing our attention on important degenerative diseases such as Alzheimerߣs disease, Parkinsonߣs disease, osteoarthritis, sarcopenia, and osteoporosis. This new perspective leads us to propose that Pas function as novel biomarkers for age-related diseases, with the main purpose of achieving new molecular alternatives for healthier aging.
Topics: Polyamines; Spermidine; Spermine; Putrescine
PubMed: 38003659
DOI: 10.3390/ijms242216469 -
Oral Health & Preventive Dentistry Nov 2022To determine the salivary flow rate and subsequent dilution of toothpaste and assess the pH of oral fluids during toothbrushing with toothpastes of various pHs. (Clinical Trial)
Clinical Trial
PURPOSE
To determine the salivary flow rate and subsequent dilution of toothpaste and assess the pH of oral fluids during toothbrushing with toothpastes of various pHs.
MATERIALS AND METHODS
The study was conducted as an in-vivo trial involving 30 healthy volunteers. The participants took part in a series of trials distributed over four appointments. After a screening check, in which the participants' stimulated and unstimulated salivary flow rate and buffering capacities were determined, four test series involving toothbrushing were conducted. Participants brushed their teeth using a manual toothbrush for 2 min: once without toothpaste and three times using toothpastes of varying pHs. The salivary flow rate and subsequent dilution of the toothpaste was determined. Additionally, the pH of the collected oral fluid was analysed.
RESULTS
Brushing teeth with toothpaste caused a statistically significant increase in salivary flow rate (median/IQR in ml/min) (Elmex Kariesschutz 3.29/1.36, Colgate Total Original 3.23/1.08, Elmex Sensitive Professional 3.18/1.39) when compared to brushing teeth using a manual toothbrush without toothpaste (1.85/0.78) (p < 0.05). The variation in pH of the oral fluid samples was dictated primarily by the pH of the toothpaste used.
CONCLUSION
The salivary flow rate when brushing using toothpaste was similar across all tested toothpastes, independent of pH, and had an average median of 3.23 ml/min. The dilution of 1 g of toothpaste during a standard toothbrushing procedure of 2 min is therefore approximately at a ratio of one part toothpaste to 6.5 parts saliva.
Topics: Humans; Diamines; Fluorides; Toothbrushing; Toothpastes
PubMed: 36416604
DOI: 10.3290/j.ohpd.b3601691 -
The Journal of Biological Chemistry Dec 2020Mitochondrial DNA (mtDNA) encodes proteins and RNAs that support the functions of mitochondria and thereby numerous physiological processes. Mutations of mtDNA can cause... (Review)
Review
Mitochondrial DNA (mtDNA) encodes proteins and RNAs that support the functions of mitochondria and thereby numerous physiological processes. Mutations of mtDNA can cause mitochondrial diseases and are implicated in aging. The mtDNA within cells is organized into nucleoids within the mitochondrial matrix, but how mtDNA nucleoids are formed and regulated within cells remains incompletely resolved. Visualization of mtDNA within cells is a powerful means by which mechanistic insight can be gained. Manipulation of the amount and sequence of mtDNA within cells is important experimentally and for developing therapeutic interventions to treat mitochondrial disease. This review details recent developments and opportunities for improvements in the experimental tools and techniques that can be used to visualize, quantify, and manipulate the properties of mtDNA within cells.
Topics: Antibodies; Benzothiazoles; DNA, Mitochondrial; Diamines; Humans; In Situ Hybridization, Fluorescence; Microscopy, Confocal; Mitochondria; Quinolines; Urea
PubMed: 33454000
DOI: 10.1074/jbc.REV120.015101 -
Nature Communications Aug 2022Molecular conformations induced by the rotation about single bonds play a crucial role in chemical transformations. Revealing the relationship between the conformations...
Molecular conformations induced by the rotation about single bonds play a crucial role in chemical transformations. Revealing the relationship between the conformations of chiral catalysts and the enantiodiscrimination is a formidable challenge due to the great difficulty in isolating the conformers. Herein, we report a chiral catalytic system composed of an achiral catalytically active unit and an axially chiral 1,1'-bi-2-naphthol (BINOL) unit which are connected via a C-O single bond. The two conformers of the catalyst induced by the rotation about the C-O bond, are determined via single-crystal X-ray diffraction and found to respectively lead to the formation of highly important axially chiral 1,1'-binaphthyl-2,2'-diamine (BINAM) and 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN) derivatives in high yields (up to 98%), with excellent enantioselectivities (up to 98:2 e.r.) and opposite absolute configurations. The results highlight the importance of conformational dynamics of chiral catalysts in asymmetric catalysis.
Topics: Catalysis; Crystallography, X-Ray; Diamines; Molecular Conformation
PubMed: 35961985
DOI: 10.1038/s41467-022-32432-8 -
Angewandte Chemie (International Ed. in... Aug 2020Vicinal diamines are ubiquitous materials in organic and medicinal chemistry. The direct coupling of olefins and amines would be an ideal approach to construct these...
Vicinal diamines are ubiquitous materials in organic and medicinal chemistry. The direct coupling of olefins and amines would be an ideal approach to construct these motifs. However, alkene diamination remains a long-standing challenge in organic synthesis, especially when using two different amine components. We report a general strategy for the direct and selective assembly of vicinal 1,2-diamines using readily available olefin and amine building blocks. This mild and straightforward approach involves in situ formation and photoinduced activation of N-chloroamines to give aminium radicals that enable efficient alkene aminochlorination. Owing to the ambiphilic nature of the β-chloroamines produced, conversion into tetra-alkyl aziridinium ions was possible, thus enabling diamination by regioselective ring-opening with primary or secondary amines. This strategy streamlines the preparation of vicinal diamines from multistep sequences to a single chemical transformation.
PubMed: 32432808
DOI: 10.1002/anie.202005652 -
Chimia Apr 2020Polyoxophosphates are ubiquitous in nature and play important roles in biological systems and in the environment. Pyrophosphate (PPi), an important member of this... (Review)
Review
Polyoxophosphates are ubiquitous in nature and play important roles in biological systems and in the environment. Pyrophosphate (PPi), an important member of this family, is produced in over 200 biochemical reactions and is a marker in clinical diagnosis. In addition to its endogenous role, PPi alias E450 is currently used as preservative, emulsifier or taste intensifier in foodstuff. Despite this widespread occurrence and biological importance, it is rather surprising that robust chemical systems that detect selectively and sensitively PPi in challenging matrices are still lacking. This mini review focuses on metal-salen complexes as reaction-based fluorescent sensors for the selective detection of PPi and other phosphates. The mode of detection is based on a novel disassembly approach in which the metal ion is sequestered by the target analyte from the complex and the metal-free ligand hydrolyses spontaneously into its fluorescent subunits. Optimizations of the probe and applications for PPi detection in cells and foodstuff are described.
Topics: Ethylenediamines; Fluorescent Dyes; Metals; Phosphates
PubMed: 32331542
DOI: 10.2533/chimia.2020.252 -
Plant, Cell & Environment Jun 2020Biomarker metabolites are of increasing interest in crops since they open avenues for precision agriculture, whereby nutritional needs and stresses can be monitored... (Review)
Review
Biomarker metabolites are of increasing interest in crops since they open avenues for precision agriculture, whereby nutritional needs and stresses can be monitored optimally. Putrescine has the potential to be a useful biomarker to reveal potassium (K ) deficiency. In fact, although this diamine has also been observed to increase during other stresses such as drought, cold or heavy metals, respective changes are comparably low. Due to its multifaceted biochemical properties, several roles for putrescine under K deficiency have been suggested, such as cation balance, antioxidant, reactive oxygen species mediated signalling, osmolyte or pH regulator. However, the specific association of putrescine build-up with low K availability in plants remains poorly understood, and possible regulatory roles must be consistent with putrescine concentration found in plant tissues. We hypothesize that the massive increase of putrescine upon K starvation plays an adaptive role. A distinction of putrescine function from that of other polyamines (spermine, spermidine) may be based either on its specificity or (which is probably more relevant under K deficiency) on a very high attainable concentration of putrescine, which far exceeds those for spermidine and spermine. putrescine and its catabolites appear to possess a strong potential in controlling cellular K and Ca , and mitochondria and chloroplasts bioenergetics under K stress.
Topics: Biological Transport; Biomarkers; Chloroplasts; Potassium; Putrescine; Stress, Physiological
PubMed: 32017122
DOI: 10.1111/pce.13740 -
Journal of Nuclear Medicine : Official... Jul 2022
Topics: Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Glutamate Carboxypeptidase II; Positron Emission Tomography Computed Tomography
PubMed: 35772954
DOI: 10.2967/jnumed.121.264374 -
Journal of Medicinal Chemistry Aug 2022Neuronal Kv7 channels represent important pharmacological targets for hyperexcitability disorders including epilepsy. Retigabine is the prototype Kv7 activator...
Neuronal Kv7 channels represent important pharmacological targets for hyperexcitability disorders including epilepsy. Retigabine is the prototype Kv7 activator clinically approved for seizure treatment; however, severe side effects associated with long-term use have led to its market discontinuation. Building upon the recently described cryoEM structure of Kv7.2 complexed with retigabine and on previous structure-activity relationship studies, a small library of retigabine analogues has been designed, synthesized, and characterized for their Kv7 opening ability using both fluorescence- and electrophysiology-based assays. Among all tested compounds, emerged as a potent and photochemically stable neuronal Kv7 channel activator. Compared to retigabine, compound displayed a higher brain/plasma distribution ratio, a longer elimination half-life, and more potent and effective anticonvulsant effects in an acute seizure model in mice. Collectively, these data highlight compound as a promising lead compound for the development of novel Kv7 activators for the treatment of hyperexcitability diseases.
Topics: Animals; Anticonvulsants; Carbamates; KCNQ2 Potassium Channel; KCNQ3 Potassium Channel; Mice; Phenylenediamines; Seizures
PubMed: 35972998
DOI: 10.1021/acs.jmedchem.2c00911 -
Seminars in Cancer Biology Dec 2020The anaphase promoting complex/ cyclosome (APC/C), is an evolutionarily conserved protein complex essential for cellular division due to its role in regulating the... (Review)
Review
The anaphase promoting complex/ cyclosome (APC/C), is an evolutionarily conserved protein complex essential for cellular division due to its role in regulating the mitotic transition from metaphase to anaphase. In this review, we highlight recent work that has shed light on our understanding of the role of APC/C coactivators, Cdh1 and Cdc20, in cancer initiation and development. We summarize the current state of knowledge regarding APC/C structure and function, as well as the distinct ways Cdh1 and Cdc20 are dysregulated in human cancer. We also discuss APC/C inhibitors, novel approaches for targeting the APC/C as a cancer therapy, and areas for future work.
Topics: Anaphase-Promoting Complex-Cyclosome; Antigens, CD; Antineoplastic Agents; Carbamates; Cdc20 Proteins; Cdh1 Proteins; Diamines; Genomic Instability; Humans; Molecular Targeted Therapy; Neoplasms
PubMed: 32165320
DOI: 10.1016/j.semcancer.2020.03.001