Multi-omics characterization of improved cognitive functions in Parkinson’s disease patients after the combined metabolic activator treatment:a randomized, double-blinded, placebo-controlled phase II trial

Parkinson’s disease is primarily marked by mitochondrial dysfunction and metabolic abnormalities. We recently reported that the combined metabolic activators improved the immunohistochemical parameters and behavioural functions in Parkinson’s disease and Alzheimer’s disease animal models and the cognitive functions in Alzheimer’s disease patients. These metabolic activators serve as the precursors of nicotinamide adenine dinucleotide and glutathione, and they can be used to activate mitochondrial metabolism and eventually treat mitochondrial dysfunction. Here, we designed a randomized, double-blinded, placebo-controlled phase II study in Parkinson’s disease patients with 84 days combined metabolic activator administration. A single dose of combined metabolic activator contains L-serine (12.35 g), N-acetyl-L-cysteine (2.55 g), nicotinamide riboside (1 g) and L-carnitine tartrate (3.73 g). Patients were administered either one dose of combined metabolic activator or a placebo daily for the initial 28 days, followed by twice-daily dosing for the next 56 days. The main goal of the study was to evaluate the clinical impact on motor functions using the Unified Parkinson’s Disease Rating Scale and to determine the safety and tolerability of combined metabolic activator. A secondary objective was to assess cognitive functions utilizing the Montreal Cognitive Assessment and to analyse brain activity through functional MRI. We also performed comprehensive plasma metabolomics and proteomics analysis for detailed characterization of Parkinson’s disease patients who participated in the study. Although no improvement in motor functions was observed, cognitive function was shown to be significantly improved (P &lt; 0.0000) in Parkinson’s disease patients treated with the combined metabolic activator group over 84 days, whereas no such improvement was noted in the placebo group (P &gt; 0.05). Moreover, a significant reduction (P = 0.001) in Montreal Cognitive Assessment scores was observed in the combined metabolic activator group, with no decline (P &gt; 0.05) in the placebo group among severe Parkinson’s disease patients with lower baseline Montreal Cognitive Assessment scores. We showed that improvement in cognition was associated with critical brain network alterations based on functional MRI analysis, especially relevant to areas with cognitive functions in the brain. Finally, through a comprehensive multi-omics analysis, we elucidated the molecular mechanisms underlying cognitive improvements observed in Parkinson’s disease patients. Our results show that combined metabolic activator administration leads to enhanced cognitive function and improved metabolic health in Parkinson’s disease patients as recently shown in Alzheimer’s disease patients.</p

Literature analysis on asparagus roots and review of its functional characterizations

Asparagus root (AR) is utilized globally as a traditional herbal medicine because it contains various bioactive compounds, such as polyphenols, flavonoids, saponins, and minerals. The composition profiles of AR are strongly affected by its botanical and geographical origins. Although minerals and heavy metals are minor constituents of AR, they play a crucial role in determining its quality and efficacy. A comprehensive classification of AR, its phytochemistry, and its pharmacology were reviewed and interpreted herein. Potentially eligible articles (in English) were identified through an electronic search of the Web of Science database (2010–2022) and Google (2001–2022). We used the primary search term “Asparagus roots” combined with the words “pharmacology,” “bioactive compounds,” “physicochemical properties,” and “health benefits” to find the relevant literature. We screened the titles, keywords, and abstracts of the publications obtained from the database. A full copy of the article was obtained for further assessment if deemed appropriate. Different asparagus species might potentially be used as herbal medicines and functional foods. Phytochemical studies have revealed the presence of various bioactive compounds as valuable secondary metabolites. The dominant class of bioactive compounds in AR is flavonoids. Furthermore, AR displayed significant pharmacological effects, such as antioxidant, antimicrobial, antiviral, anticancer, anti-inflammatory, and antidiabetic effects, as shown in animal and human studies. This review provides a valuable resource to enable a thorough assessment of the profile of Asparagus root as a functional ingredient for the pharmaceutical and food industries. In addition, it is anticipated that this review will provide information to healthcare professionals seeking alternative sources of critical bioactive compounds

Additive Antinociceptive Effects of a Combination of Vitamin C and Vitamin E after Peripheral Nerve Injury

Accumulating evidence indicates that increased generation of reactive oxygen species (ROS) contributes to the development of exaggerated pain hypersensitivity during persistent pain. In the present study, we investigated the antinociceptive efficacy of the antioxidants vitamin C and vitamin E in mouse models of inflammatory and neuropathic pain. We show that systemic administration of a combination of vitamins C and E inhibited the early behavioral responses to formalin injection and the neuropathic pain behavior after peripheral nerve injury, but not the inflammatory pain behavior induced by Complete Freund's Adjuvant. In contrast, vitamin C or vitamin E given alone failed to affect the nociceptive behavior in all tested models. The attenuated neuropathic pain behavior induced by the vitamin C and E combination was paralleled by a reduced p38 phosphorylation in the spinal cord and in dorsal root ganglia, and was also observed after intrathecal injection of the vitamins. Moreover, the vitamin C and E combination ameliorated the allodynia induced by an intrathecally delivered ROS donor. Our results suggest that administration of vitamins C and E in combination may exert synergistic antinociceptive effects, and further indicate that ROS essentially contribute to nociceptive processing in special pain states

A highly sensitive bio-barcode immunoassay for multi-residue detection of organophosphate pesticides based on fluorescence anti-quenching

Balancing the risks and benefits of organophosphate pesticides (OPs) on human and environmental health relies partly on their accurate measurement. A highly sensitive fluorescence anti-quenching multi-residue bio-barcode immunoassay was developed to detect OPs (triazophos, parathion, and chlorpyrifos) in apples, turnips, cabbages, and rice. Gold nanoparticles were functionalized with monoclonal antibodies against the tested OPs. DNA oligonucleotides were complementarily hybridized with an RNA fluorescent label for signal amplification. The detection signals were generated by DNA-RNA hybridization and ribonuclease H dissociation of the fluorophore. The resulting fluorescence signal enables multiplexed quantification of triazophos, parathion, and chlorpyrifos residues over the concentration range of 0.01–25, 0.01–50, and 0.1–50 ng/mL with limits of detection of 0.014, 0.011, and 0.126 ng/mL, respectively. The mean recovery ranged between 80.3% and 110.8% with relative standard deviations of 7.3%–17.6%, which correlate well with results obtained by LC-MS/MS. The proposed bio-barcode immunoassay is stable, reproducible and reliable, and is able to detect low residual levels of multi-residue OPs in agricultural products.This work was supported by the Central Public Interest Scientific Institution Basal Research Fund for the Chinese Academy of Agricultural Sciences (Grant No.: Y2021PT05), National Institute of Environmental Health Science Superfund Research Program (Grant No.: P42 ES004699), National Academy of Sciences (Subaward No.: 2000009144), and Ningbo Innovation Project for Agro-Products Quality and Safety (Grant No.: 2019CXGC007).Peer reviewe

Neuroprotective effects of agmatine in antineoplastic drugs induced neurotoxicity: In vitro study

Aims: The effects of agmatine, an endogenous substance known to have a neuroprotective effect against neurotoxicity has been investigated

P.1.g.090 Effects of escitalopram and ceftriaxone on body mass changes in a rat depression model

A space $X$ has a $\mathbb{Q}$-diagonal if $X^2\setminus \Delta$ has a$\mathcal{K}(\mathbb{Q})$-directed compact cover. We show that any compactspace with a $\mathbb{Q}$-diagonal is metrizable, hence any Tychonorff spacewith a $\mathbb{Q}$-diagonal is cosmic. These give a positive answer to Problem4.2 and Problem 4.8 in \cite{COT11} raised by Cascales, Orihuela and Tkachuk