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Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams Department of Biology University of PisaPisaItaly Department of clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

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Neuroprotective potential for mitigating ischemia-reperfusion-induced damage

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Neural Regeneration Research 2025年第8期20卷 2199-2217页

作者： Zi Ye Runqing Liu Hangxing Wang Aizhen Zuo Cen Jin Nan Wang Huiqi Sun Luqian Feng Hua Yang The clinical Medical College Guizhou Medical UniversityGuiyangGuizhou ProvinceChina division of Infectious Diseases Department of Internal MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina School of Medical Imaging Guizhou Medical UniversityGuiyangGuizhou ProvinceChina division of Gastroenterology First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina The Second clinical Medical College Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurosurgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion *** studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion ***,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional *** this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and *** therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box *** review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins *** review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk *** Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug ***,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.

关键词： apoptosis autophagy blood-brain barrier dietary supplements drug hormones inflammation neuroprotection oxidative stress prognosis pyroptosis reperfusion injury risk factors RNA therapeutics

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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li Department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden Department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden Department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA Department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

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Cross-subcarrier precoder design for massive MIMO-OFDM downlink with symplectic optimization

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Science China(Information Sciences) 2025年

作者： Yu-Xuan ZHANG An-An LU Xiang-Gen XIA Xi-Qi GAO National Mobile Communications Research Laboratory Southeast University Purple Mountain laboratories Department of Electrical and Computer Engineering University of Delaware

We propose a cross-subcarrier precoder design(CSPD) for massive multiple-input multiple-output(MIMO) orthogonal frequency division multiplexing(OFDM) downlink. This work aims to significantly improve the channel estimation and signal detection performance by enhancing the smoothness of the frequency domain effective channel. This is accomplished by designing a few vectors known as the transform domain precoding vectors(TDPVs), which are then transformed into the frequency domain to generate the precoders for a set of subcarriers. To combat the effect of channel aging, the TDPVs are optimized under imperfect channel state information(CSI). The optimal precoder structure is derived by maximizing an upper bound of the ergodic weighted sum-rate(WSR) and utilizing the a posteriori beam-based statistical channel model(BSCM). To avoid the large-dimensional matrix inversion, we propose an algorithm with symplectic optimization. Simulation results indicate that the proposed cross-subcarrier precoder design significantly outperforms conventional methods.

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Acquired sensorineural hearing loss,oxidative stress,and microRNAs

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Neural Regeneration Research 2025年第9期20卷 2513-2519页

作者： Desmond A.Nunez Ru C.Guo division of Otolaryngology–Head&Neck Surgery Department of SurgeryFaculty of MedicineThe University of British ColumbiaVancouverBCCanada division of Otolaryngology–Head&Neck Surgery Gordon&Leslie Diamond Health Care CentreVancouver General HospitalVancouverBCCanada Faculty of Medicine–The University of British Columbia VancouverBCCanada

Hearing loss is the third leading cause of human ***-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health ***-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing *** etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental *** stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing *** non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic *** hair cell death is a central histopathological finding in sensorineural hearing *** these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing *** EMBASE,Ovid MEDLINE,Web of Science Core Collection,and *** databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical *** red clinical trials known to the senior author we re also assessed.A total of 222studies were thus *** excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text *** resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative *** miR-34a and miR-29b levels increase with age in *** miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT

关键词： hearing loss hypoxia microRNAs oxidative stress sensorineural

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Hepatitis C virus and type 2 diabetes

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World Journal of Gastroenterology 2009年第13期15卷 1537-1547页

作者： Francesco Negro Mahnaz Alaei division of Gastroenterology Hepatology and Clinical PathologyUniversity Hospitals division of clinical Pathology University Hospitals

This review focuses on the relationship between hepatitis C virus(HCV) infection and glucose metabolism ***-sectional and longitudinal studies have shown that the chronic HCV infection is associated with an increased risk of developing insulin resistance(IR) and type 2 diabetes(T2D).The direct effect of HCV on the insulin signaling has been analyzed in experimental *** currently available data should be considered as preliminary,HCV seems to affect glucose metabolism via mechanisms that involve cellular pathways that have been implicated in the host innate immune *** and T2D not only accelerate the histological and clinical progression of chronic hepatitis C,but also reduce the early and sustained virological response to interferon-alpha-based ***,a detailed knowledge of the mechanisms underlying the HCV-associated glucose metabolism derangements is warranted,in order to improve the clinical management of chronic hepatitis C patients.

关键词： Hepatitis C Fibrosis Insulin resistance Insulin signaling Type 2 diabetes

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Endothelial progenitor cells, potential biomarkers for diagnosis and prognosis of ischemic stroke: protocol for an observational case-control study

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Neural Regeneration Research 2020年第7期15卷 1300-1307页

作者： Kamini Rakkar Othman Othman Nikola Sprigg Philip Bath Ulvi Bayraktutan Stroke Division of Clinical Neuroscience University of Nottingham Clinical Sciences Building City Hospital

Ischemic stroke is a devastating,life altering event which can severely reduce patient quality of *** years of research there have been minimal therapeutic *** progenitor cells(EPCs),stem cells involved in both vasculogenesis and angiogenesis,may be a potential therapeutic *** a stroke,EPCs migrate to the site of ischemic injury to repair cerebrovascular damage,and their numbers and functional capacity may determine patients'*** study aims to determine whether the number of circulating EPCs and their functional aspects may be used as biomarkers to identify the type(cortical or lacunar)and/or severity of ischemic *** study will also investigate if there are any differences in these characteristics between healthy volunteers over and under 65 years of age.100 stroke patients(50 lacunar and 50 cortical strokes)will be recruited in this prospective,observational case-controlled *** samples will be taken from stroke patients at baseline(within 48 hours of stroke)and days 7,30 *** will be counted with flow *** plasma levels of pro-and anti-angiogenic factors and inflammatory cytokines will also be *** endothelial cells will be cultured to be used in tube formation,migration and proliferation functional *** outcome is disability or dependence on day 90 after stroke,assessed by the modified Rankin *** outcomes are changes in circulating EPC numbers and/or functional capacity between patient and healthy volunteers,between patient subgroups and between elderly and young healthy *** started in February 2017,167 participants have been *** will end in November *** Midlands-Coventry&Warwickshire Research Ethics Committee approved this study(REC number:16/WM/0304)on September8,*** version:*** Bayraktutan Dunhill Medical Trust EPC Study was registered in ***(NCT02980354)on November 15,*** st

关键词： ageing biomarkers cortical stroke endothelial progenitor cells ischemic stroke lacunar stroke observational study stem cells

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A rapid and sensitive liquid chromatography-tandem mass spectrometric assay for duloxetine in human plasma:Its pharmacokinetic application

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Journal of Pharmaceutical Analysis 2013年第1期3卷 36-44页

作者： Ramakrishna Gajula Rambabu Maddela Vasu Babu Ravi Jaswanth Kumar Inamadugu Nageswara Rao Pilli Wellquest clinical Research laboratories

This paper describes a simple, rapid and sensitive liquid chromatography tandem mass spectrometry assay for the determination of duloxetine in human plasma. A duloxetine stable labeled isotope （duloxetine ds） was used as an internal standard. Analyte and the internal standard were extracted from 100 btL of human plasma via solid phase extraction technique using Oasis HLB cartridges. The chromatographic separation was achieved on a Cl8 column by using a mixture of acetonitrile 5 mM ammonium acetate buffer （83：17, v/v） as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear （r2≥0.99） over the concentration range of 0.05 101 ng/mL. Multiple-reaction monitoring mode （MRM） was used for quantification of ion transitions at rn/z 298.3/154.1 and 303.3/159.1 for the drug and the internal standard, respectively. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.

关键词： Duloxetine in humanplasma Solid-phase extraction(SPE) Liquidchromatography-tandem mass spectro-metry Method validation Pharmacokinetic studies

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Scavenger receptor BI: A multi-purpose player in cholesterol and steroid metabolism

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World Journal of Gastroenterology 2010年第47期16卷 591-5924页

作者： Menno Hoekstra Theo JC Van Berkel Miranda Van Eck division of Biopharmaceutics Leiden/Amsterdam Center for Drug Research Gorlaeus Laboratories

Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a

关键词： Scavenger receptor class B type Ⅰ Highdensity lipoprotein Cholesterol Lipoprotein metabolism Liver Macrophages Adrenal gland Platelets Steroido- genesis

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Altered thermal sensitivity in facial skin in chronic whiplash-associated disorders

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International Journal of Oral Science 2013年第3期5卷 150-154页

作者： Birgitta Hggman-Henrikson Ewa Lampa Erik Nordh Department of Odontology Clinical Oral Physiology Umea University Department of Pharmacology and clinical Neurosciences Division of Clinical Neurophysiology Ume University

There is a close functional relationship between the jaw and neck regions and it has been suggested that trigeminal sensory impairment can follow whiplash *** of manageable routines for valid assessment of the facial sensory capacity is thus needed for comprehensive evaluations of patients exposed to such *** present study investigated facial thermal thresholds in patients with chronic whiplash-associated disorders（WADs）with both a qualitative method and quantitative sensory testing（QST）.Ten women with pain and dysfunction following a whiplash injury were compared to 10 healthy age-matched *** detection thresholds were assessed by qualitative chair-side testing and by QST according to the *** test sites in the facial skin（overlying each trigeminal branch bilaterally,and the midpoint of the chin）were *** detection warm and cold thresholds were defined as the mean values of 10 individual *** the WAD patients,the qualitative assessment demonstrated both reduced and increased sensitivity compared to the healthy,whereas QST systematically showed significantly higher detection thresholds（i.e.,decreased sensitivity）for both cold and warm *** the individuals who were assessed as having increased sensitivity in the qualitative assessment,the QST displayed either normal or higher thresholds,i.e.,decreased *** results suggest that QST is more sensitive for detecting thermal sensory disturbances in the face than a qualitative *** impaired thermal sensitivity among the patients corroborates the notion of altered thermal detection capacity induced by WAD-related pain.

关键词： jaw neck quantitative sensory testing thermal thresholds trigeminal whiplash injury

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