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Biochemical and Biophysical Research... Apr 2024Nicotinamide adenine dinucleotide (NAD) is the fundamental molecule that performs numerous biological reactions and is crucial for maintaining cellular homeostasis.... (Review)
Review
Nicotinamide adenine dinucleotide (NAD) is the fundamental molecule that performs numerous biological reactions and is crucial for maintaining cellular homeostasis. Studies have found that NAD decreases with age in certain tissues, and age-related NAD depletion affects physiological functions and contributes to various aging-related diseases. Supplementation of NAD precursor significantly elevates NAD levels in murine tissues, effectively mitigates metabolic syndrome, enhances cardiovascular health, protects against neurodegeneration, and boosts muscular strength. Despite the versatile therapeutic functions of NAD in animal studies, the efficacy of NAD precursors in clinical studies have been limited compared with that in the pre-clinical study. Clinical studies have demonstrated that NAD precursor treatment efficiently increases NAD levels in various tissues, though their clinical proficiency is insufficient to ameliorate the diseases. However, the latest studies regarding NAD precursors and their metabolism highlight the significant role of gut microbiota. The studies found that orally administered NAD intermediates interact with the gut microbiome. These findings provide compelling evidence for future trials to further explore the involvement of gut microbiota in NAD metabolism. Also, the reduced form of NAD precursor shows their potential to raise NAD, though preclinical studies have yet to discover their efficacy. This review sheds light on NAD therapeutic efficiency in preclinical and clinical studies and the effect of the gut microbiota on NAD metabolism.
Topics: Mice; Animals; NAD; Dietary Supplements; Aging; Niacinamide; Nicotinamide Mononucleotide
PubMed: 38340651
DOI: 10.1016/j.bbrc.2024.149590 -
Journal of Cerebral Blood Flow and... Nov 2023Nicotinamide adenine dinucleotide (NAD) is a redox cofactor critical for oxidative phosphorylation. Nicotinamide (NAM) and nicotinamide riboside (NR) are NAD precursors...
Nicotinamide adenine dinucleotide (NAD) is a redox cofactor critical for oxidative phosphorylation. Nicotinamide (NAM) and nicotinamide riboside (NR) are NAD precursors widely used as nutritional supplements to augment oxidative phosphorylation. Indeed, NAD precursors have been reported to improve outcomes in ischemic stroke when administered as a rescue therapy after stroke onset. However, we have also reported that enhanced reliance on oxidative phosphorylation before ischemia onset might worsen outcomes. To address the paradox, we examined how NAD precursors modulate the outcome of middle cerebral artery occlusion in mice, when administered either 20 minutes after reperfusion or daily for three days before ischemia onset. A single post-ischemic dose of NAM or NR indeed improved tissue and neurologic outcomes examined at 72 hours. In contrast, pre-ischemic treatment for three days enlarged the infarcts and worsened neurological deficits. As a possible explanation for the diametric outcomes, a single dose of NAM or NR augmented tissue AMPK, PGC1α, SIRT1, and ATP in both naïve and ischemic brains, while the multiple-dose paradigm failed to do so. Our data suggest that NAD precursor supplements may sensitize the brain to subsequent ischemic events, despite their neuroprotective effect when administered after ischemia onset.
Topics: Mice; Animals; NAD; Dietary Supplements; Brain; Stroke; Ischemia
PubMed: 37434361
DOI: 10.1177/0271678X231156500 -
The Journal of Steroid Biochemistry and... Feb 2024Prostate cancer (PC) is dependent on androgen receptor (AR) activation by testosterone and 5α-dihydrotestosterone (DHT). Intratumoral androgen accumulation and...
Prostate cancer (PC) is dependent on androgen receptor (AR) activation by testosterone and 5α-dihydrotestosterone (DHT). Intratumoral androgen accumulation and activation despite systemic androgen deprivation therapy underlies the development of castration-resistant PC (CRPC), but the precise pathways involved remain controversial. Here we investigated the differential contributions of de novo androgen biosynthesis and androgen precursor conversion to androgen accumulation. Steroid flux analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed on (CR)PC cell lines and fresh patient PC tissue slices after incubation with classic and alternative biosynthesis intermediates, alongside quantitative PCR analysis for steroidogenic enzyme expression. Activity of CYP17A1 was undetectable in all PC cell lines and patient PC tissue slices. Instead, steroid flux analysis confirmed the generation of testosterone and DHT from adrenal precursors and reactivation of androgen metabolites. Precursor steroids upstream of DHEA were converted down the first steps of the alternative DHT biosynthesis pathway, but did not proceed through to active androgen generation. Comprehensive steroid flux analysis of (CR)PC cells provides strong evidence against intratumoral de novo androgen biosynthesis and demonstrates that androgen precursor steroids downstream of CYP17A1 activities constitute the major source of intracrine androgen generation.
Topics: Male; Humans; Prostatic Neoplasms; Androgens; Androgen Antagonists; Chromatography, Liquid; Tandem Mass Spectrometry; Testosterone; Dihydrotestosterone; Receptors, Androgen; Steroids; Cell Line, Tumor; Steroid 17-alpha-Hydroxylase
PubMed: 38104728
DOI: 10.1016/j.jsbmb.2023.106446 -
Inorganic Chemistry Oct 2023Currently, two approaches dominate the large-scale production of MoS: liquid-phase exfoliation, referred to as the top-down approach, and bottom-up colloidal synthesis...
Currently, two approaches dominate the large-scale production of MoS: liquid-phase exfoliation, referred to as the top-down approach, and bottom-up colloidal synthesis from molecular precursors. Known colloidal synthesis approaches utilize toxic precursors. Here, an alternative green route for the bottom-up synthesis of MoS nanoflakes (NFs) is described. The NFs were synthesized by colloidal synthesis using [Mo(CHCOO)] and a series of sulfur (S)-precursors including thioacetamide (TAA), 3-mercaptopropionic acid (3-MPA), l-cysteine (L-CYS), mercaptosuccinic acid (MSA), 11-mercaptoundecanoic acid (MUA), 1-dodecanethiol (DDTH), and di--butyl disulfide (DTBD). While TAA, an S-precursor most commonly used for MoS NF preparation, is a known carcinogen, the other investigated S-precursors have low or no known toxicity. High-resolution scanning transmission electron microscopy (HR-STEM) and grazing incidence wide-angle X-ray scattering (GIWAXS) confirmed that in all cases, the syntheses yielded single-layer MoS NFs with lateral sizes smaller than 15 nm and a well-defined crystal structure. Electronic absorption and Raman spectra showed characteristic features associated with the MoS monolayers. The evolution of the absorption spectra of the growth solution during the syntheses reveals how the kinetics of the NF formation is affected by the S-precursor as well as the nature of the coordinating ligands.
PubMed: 37751900
DOI: 10.1021/acs.inorgchem.3c02420 -
Chemosphere Oct 2023Sulfate radical (SO)-based advanced oxidation processes (AOPs) have become promising alternatives in environmental remediation due to the higher redox potential... (Review)
Review
Sulfate radical (SO)-based advanced oxidation processes (AOPs) have become promising alternatives in environmental remediation due to the higher redox potential (2.6-3.1 V) and longer half-life period (30-40 μs) of sulfate radicals compared with many other radicals such as hydroxyl radicals (•OH). The generation and mechanisms of SO and the applications of SO-AOPs have been examined extensively, while those using sulfite as activation precursor and their comparisons among various activation precursors have rarely reviewed comprehensively. In this article, the latest progresses in SO-AOPs were comprehensively reviewed and commented on. First of all, the generation of SO was summarized via the two activation methods using various oxidant precursors, and the generation mechanisms were also presented, which provides a reference for guiding researchers to better select two precursors. Secondly, the reaction mechanisms of SO were reviewed for organic pollutant degradation, and the reactivity was systematically compared between SO and •OH. Thirdly, methods for SO detection were reviewed which include quantitative and qualitative ones, over which current controversies were discussed. Fourthly, the applications of SO-AOPs in various environmental remediation were summarized, and the advantages, challenges, and prospects were also commented. At last, future research needs for SO-AOPs were also proposed consequently. This review could lead to better understanding and applications of SO-AOPs in environmental remediations.
Topics: Water Pollutants, Chemical; Sulfates; Oxidation-Reduction; Hydroxyl Radical
PubMed: 37506891
DOI: 10.1016/j.chemosphere.2023.139659 -
Frontiers in Aging Neuroscience 2023Dementias and mild cognitive impairment (MCI) are associated with variously combined changes in the neurotransmitter system and signaling, from neurotransmitter...
Several dementia subtypes and mild cognitive impairment share brain reduction of neurotransmitter precursor amino acids, impaired energy metabolism, and lipid hyperoxidation.
OBJECTIVE
Dementias and mild cognitive impairment (MCI) are associated with variously combined changes in the neurotransmitter system and signaling, from neurotransmitter synthesis to synaptic binding. The study tested the hypothesis that different dementia subtypes and MCI may share similar reductions of brain availability in amino acid precursors (AAPs) of neurotransmitter synthesis and concomitant similar impairment in energy production and increase of oxidative stress, i.e., two important metabolic alterations that impact neurotransmission.
MATERIALS AND METHODS
Sixty-five demented patients (Alzheimer's disease, AD, = 44; frontotemporal disease, FTD, = 13; vascular disease, VaD, = 8), 10 subjects with MCI and 15 control subjects (CTRL) were recruited for this study. Cerebrospinal fluid (CSF) and plasma levels of AAPs, energy substrates (lactate, pyruvate), and an oxidative stress marker (malondialdehyde, MDA) were measured in all participants.
RESULTS
Demented patients and subjects with MCI were similar for age, anthropometric parameters, biohumoral variables, insulin resistance (HOMA index model), and CSF neuropathology markers. Compared to age-matched CTRL, both demented patients and MCI subjects showed low CSF AAP tyrosine (precursor of dopamine and catecholamines), tryptophan (precursor of serotonin), methionine (precursor of acetylcholine) limited to AD and FTD, and phenylalanine (an essential amino acid largely used for protein synthesis) ( = 0.03 to <0.0001). No significant differences were found among dementia subtypes or between each dementia subtype and MCI subjects. In addition, demented patients and MCI subjects, compared to CTRL, had similar increases in CSF and plasma levels of pyruvate (CSF: = 0.023 to <0.0001; plasma: < 0.002 to <0.0001) and MDA (CSF: < 0.035 to 0.002; plasma: < 0.0001). Only in AD patients was the CSF level of lactate higher than in CTRL ( = 0.003). Lactate/pyruvate ratios were lower in all experimental groups than in CTRL.
CONCLUSION
AD, FTD, and VaD dementia patients and MCI subjects may share similar deficits in AAPs, partly in energy substrates, and similar increases in oxidative stress. These metabolic alterations may be due to AAP overconsumption following high brain protein turnover (leading to phenylalanine reductions), altered mitochondrial structure and function, and an excess of free radical production. All these metabolic alterations may have a negative impact on synaptic plasticity and activity.
PubMed: 37655338
DOI: 10.3389/fnagi.2023.1237469 -
Small (Weinheim An Der Bergstrasse,... Jan 2024Carbon dots (CDs) are a newly discovered type of fluorescent material that has gained significant attention due to their exceptional optical properties,... (Review)
Review
Carbon dots (CDs) are a newly discovered type of fluorescent material that has gained significant attention due to their exceptional optical properties, biocompatibility, and other remarkable characteristics. However, single CDs have some drawbacks such as self-quenching, low quantum yield (QY), and poor stability. To address these issues, researchers have turned to organosilicon, which is known for its green, economical, and abundant properties. Organosilicon is widely used in various fields including optics, electronics, and biology. By utilizing organosilicon as a synthetic precursor, the biocompatibility, QY, and resistance to self-quenching of CDs can be improved. Meanwhile, the combination of organosilicon with CDs enables the functionalization of CDs, which significantly expands their original application scenarios. This paper comprehensively analyzes organosilicon in two main categories: precursors for CD synthesis and matrix materials for compounding with CDs. The role of organosilicon in these categories is thoroughly reviewed. In addition, the paper presents various applications of organosilicon compounded CDs, including detection and sensing, anti-counterfeiting, optoelectronic applications, and biological applications. Finally, the paper briefly discusses current development challenges and future directions in the field.
PubMed: 37661362
DOI: 10.1002/smll.202305933 -
Frontiers in Neuroscience 2023Neural precursors generate neurons in the embryonic brain and in restricted niches of the adult brain in a process called neurogenesis. The precise control of cell... (Review)
Review
Neural precursors generate neurons in the embryonic brain and in restricted niches of the adult brain in a process called neurogenesis. The precise control of cell proliferation and differentiation in time and space required for neurogenesis depends on sophisticated orchestration of gene transcription in neural precursor cells. Much progress has been made in understanding the transcriptional regulation of neurogenesis, which relies on dose- and context-dependent expression of specific transcription factors that regulate the maintenance and proliferation of neural progenitors, followed by their differentiation into lineage-specified cells. Here, we review some of the most widely studied neurogenic transcription factors in the embryonic cortex and neurogenic niches in the adult brain. We compare functions of these transcription factors in embryonic and adult neurogenesis, highlighting biochemical, developmental, and cell biological properties. Our goal is to present an overview of transcriptional regulation underlying neurogenesis in the developing cerebral cortex and in the adult brain.
PubMed: 37588515
DOI: 10.3389/fnins.2023.1217596 -
ACS Biomaterials Science & Engineering Oct 2023The discovery of chiral carbon dots (Ch-CDs) has opened up an exciting new research direction in the field of carbon dots. It not only retains the chirality of the... (Review)
Review
The discovery of chiral carbon dots (Ch-CDs) has opened up an exciting new research direction in the field of carbon dots. It not only retains the chirality of the precursor and exhibits highly symmetric chiral optical properties but also has properties such as chemical stability, antibacterial and antitumor properties, and good biocompatibility of carbon dots. Based on these advantages, the application of Ch-CDs in the biomedical field has attracted significant interest among researchers. However, a comprehensive review of the selection of precursors for Ch-CDs, preparation methods, and applications in biomedical fields is still lacking. Here, we summarize their precursor selection and preparation methods based on recent reports on Ch-CDs and provide the first comprehensive review for specific applications in biomedical engineering, such as biosensing, bioimaging, drug carriers, antibacterial and antibiofilm, and enzyme activity modulation. Finally, we discuss application prospects and challenges that need to be overcome. We hope this review will provide valuable guidance for researchers to prepare novel Ch-CDs and facilitate their application in biomedical engineering.
Topics: Quantum Dots; Carbon; Drug Carriers; Biomedical Engineering; Anti-Bacterial Agents
PubMed: 37735749
DOI: 10.1021/acsbiomaterials.3c00918 -
Scandinavian Journal of Gastroenterology 2023is the leading cause of zoonotic gastroenteritis. The other emerging group of spp. are part of human oral commensal, represented by (CC), which has been recently... (Review)
Review
BACKGROUND
is the leading cause of zoonotic gastroenteritis. The other emerging group of spp. are part of human oral commensal, represented by (CC), which has been recently linked to non-oral conditions. Although long-term gastrointestinal (GI) complications from these two groups of have been previously reviewed individually, overall impact of infection on GI carcinogenesis and their inflammatory precursor lesions has not been assessed collectively.
AIMS
To evaluate the available evidence concerning the association between infection/colonization and inflammatory bowel disease (IBD), reflux esophagitis/metaplasia colorectal cancer (CRC) and esophageal cancer (EC).
METHODS
We performed a comprehensive literature search of PubMed for relevant original publications and systematic reviews/meta-analyses of epidemiological and clinical studies. In addition, we gathered additional information concerning microbiological data, animal models and mechanistic data from studies.
RESULTS
Both retrospective and prospective studies on IBD showed relatively consistent increased risk associated with infection. Despite lack of supporting prospective studies, retrospective studies based on tissue/fecal microbiome revealed consistent enrichment of in CRC samples. Studies on EC precursor lesions (esophagitis and metaplasia) were generally supportive for the association with while inconsistent observations on EC. Studies on both IBD and EC precursors suggested the predominant role of CC, but studies on CRC were not informative of species.
CONCLUSIONS
There is sufficient evidence calling for concerted effort in unveiling direct and indirect connection of this organism to colorectal and esophageal cancer in humans.
Topics: Animals; Humans; Campylobacter Infections; Retrospective Studies; Prospective Studies; Campylobacter; Inflammatory Bowel Diseases; Gastrointestinal Diseases; Esophageal Neoplasms; Esophagitis, Peptic; Metaplasia
PubMed: 37366241
DOI: 10.1080/00365521.2023.2228954