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

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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

Predicting colorectal adenomatous polyps in patients with chronic liver disease: A novel nomogram

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World Journal of Gastroenterology 2025年第2期31卷 71-84页

作者： Yu-Qin Li Wen-Tao Kuai Lin Chen Ming-Hui Zeng Xue-Mei Tao Jia-Xin Han Yue-Kui Wang Lian-Xin Xu Li-Ying Ge Yong-Gang Liu Shuang Li Liang Xu Yu-Qiang Mi clinical School of the Second People’s Hospital Tianjin Medical UniversityTianjin 300192China department of Hepatology Tianjin Second People’s HospitalTianjin 300192China department of Pathology Clinical School of the Second People’s HospitalTianjin 300110China Endoscopy Center Tianjin Second People’s HospitalTianjin 300192China

BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for *** To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were *** data including laboratory results,colonoscopy findings,and pathology reports were *** variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic *** performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve *** The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin *** novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation *** curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of *** The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.

关键词： Metabolic dysfunction associated steatotic liver disease Fatty liver Chronic liver disease Colorectal adenomas Hepatitis Risk factors

Therapeutic potential of stem cells in subarachnoid hemorrhage

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Neural Regeneration Research 2025年第4期20卷 936-945页

作者： Hideki Kanamaru Hidenori Suzuki department of Neurosurgery Mie University Graduate School of MedicineTsuJapan

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and *** the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm *** may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient *** complications such as brain volume loss and chronic hydrocephalus can further impact *** the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective *** cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable *** review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

关键词： delayed cerebral ischemia early brain injury matricellular protein neurogenesis stem cell therapy subarachnoid hemorrhage

Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study

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World Journal of Gastroenterology 2025年第2期31卷 102-112页

作者： Thanaboon Chaemsupaphan Aviv Pudipeddi Hui-Yu Lin Sudarshan Paramsothy Viraj C Kariyawasam Melissa Kermeen Rupert W Leong department of Gastroenterology and Liver Services Concord Repatriation General HospitalSydney 2139New South WalesAustralia Faculty of medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Faculty of medicine and Health University of SydneySydney 2139New South WalesAustralia department of Gastroenterology Tan Tock Seng HospitalSingapore 308433Singapore Faculty of medicine and Health Sciences Macquarie UniversitySydney 2139New South WalesAustralia department of Gastroenterology and Hepatology Blacktown HospitalSydney 2148New South WalesAustralia Blacktown clinical School Western Sydney UniversitySydney 2148New South WalesAustralia

BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and *** is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is *** To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance *** This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to *** in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving *** evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine *** There were 62 UC participants with mean age of 43.4 years and 42%were *** participants received vedolizumab as maintenance therapy with 67.7%withdrew *** serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies ***-tients with clinical remission had higher trough concentrations at week *** quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving *** A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be *** thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remi

关键词： Pharmacokinetic Vedolizumab Thiopurine Ulcerative colitis Trough concentration Antibody Inflammatory bowel diseases

Relevance of low viral load in haemodialysed patients with chronic hepatitis C virus infection

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World Journal of Gastroenterology 2015年第18期21卷 5496-5504页

作者： Jan Sperl Sona Frankova Renata Senkerikova Magdalena Neroldova Vaclav Hejda Miroslava Volfova Dusan Merta Ondrej Viklicky Julius Spicak Milan Jirsa department of Hepatogastroenterology Institute for Clinical and Experimental Medicine Laboratory of experimental Hepatology Institute for Clinical and Experimental Medicine department of Internal medicine Division of Gastroenterology and Hepatology Charles University Medical School and Teaching Hospital Hepato-gastroenterology 50012 Hradec Kralove Czech Republic department of Anesthesiology Resuscitation and Intensive Care Institute for Clinical and Experimental Medicine department of Nephrology Institute for Clinical and Experimental Medicine

AIM: To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype ***: The sustained virological response(SVR) rate, IL28 B genotype, IFNL4 genotype, initial viral load(IVL) and other pretreatment variables in 39 endstage renal disease patients(ESRD) on maintenance haemodialysis(HD) infected with hepatitis C virus(HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment nave and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a(Peg IFN-α) weekly and a reduced dose of ribavirin(RBV) was administered to 23/39 patients with an initial haemoglobin level > 10 g/d L. Control group patients were given standard doses of Peg IFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ2 testcompared the *** regression was used to determine significant predictors of *** values for continuous variables were obtained from Receiver Operating Characteristic ***:The distribution of IL28B rs12979860 CC,CT and TT genotypes in the ESRD group was 28.2%,64.1%and 7.7%,respectively,and 19.3%,62.4%and18.3%in the *** IFNL4 genotype was in almost absolute linkage disequlibrium with *** proportion of patients with a low IVL(<600000 IU/m L)was significantly higher in the ESRD group than in the controls(28/39,71.8%vs 51/109,46.8%,P=0.009),as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group(10/11,90.9%vs 18/28,64.3%,P=0.0035).This difference was not found in the controls(7/22,31.8%vs 44/87,50.6%,P=0.9).The overall SVR rate was 64.1%(25/39)in the ESRD group and 50.5%(55/109)in the control group(P=0.19).11/11(100%)and 19/22(86.4%)IL28B CC patients achieved SVR in the

关键词： End-stage renal disease Hepatitis C virus genotype 1 Interferon alpha IFNL4 Ribavirin

Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Sports medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

Glucagon-like peptide-2 modulates the nitrergic neurotransmission in strips from the mouse gastric fundus

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World Journal of Gastroenterology 2017年第40期23卷 7211-7220页

作者： Rachele Garella Eglantina Idrizaj Chiara Traini Roberta Squecco Maria Giuliana Vannucchi Maria Caterina Baccari department of experimental and clinical medicine Section of Physiology University of Florence department of experimental and clinical medicine Histology and Embryology Research Unit University of Florence

AIM To investigate whether glucagon-like peptide-2(GLP-2) influences the neurally-induced responses in gastric strips from mice, since no data are available. METHODS For functional experiments, gastric fundal strips were mounted in organ baths containing Krebs-Henseleit solution. Mechanical responses were recorded via forcedisplacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparationwas threaded. The effects of GLP-2(2 and 20 nmol/L) were evaluated on the neurally-induced contractile and relaxant responses elicited by EFS. Neuronal nitric oxide synthase(n NOS) enzyme was evaluated by *** In the functional experiments, electrical field stimulation(EFS, 4-16 Hz) induced tetrodotoxin(TTX)-sensitive contractile responses, which were reduced in amplitude by GLP-2(P 0.05). The direct smooth muscle response to methacholine was not influenced by GLP-2(P > 0.05). In the presence of guanethidine and carbachol, the addition of GLP-2 to the bath medium evoked TTX-sensitive relaxant responses that were unaffected by L-NNA(P > 0.05). EFS induced a fast NO-mediated relaxation, whose amplitude was enhanced in the presence of the hormone(P < 0.05). Immunohistochemical experiments showed a significant increase(P < 0.05) in n NOS immunoreactivity in the nerve structures after GLP-2 exposure. CONCLUSION The results demonstrate that in gastric fundal strips, GLP-2 influences the amplitude of neurally-induced responses through the modulation of the nitrergic neurotransmission and increases n NOS expression.

关键词： Immunohistochemistry Gastric motility Glucagon-like peptide-2 Neuronal nitric oxide synthase Non-adrenergic non-cholinergic neurotransmission

How dopamine tunes parvalbumin interneurons in the hippocampus:new experimental observations in Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1405-1406页

作者： Livia La Barbera Paraskevi Krashia Annalisa Nobili department of medicine and Surgery UniversitàCampus Bio-Medico di RomaViaÁlvaro del PortilloRomeItaly department of experimental Neurosciences IRCCS Santa Lucia FoundationVia del Fosso di FioranoRomeItaly department of Science and Technology for Sustainable Development and One Health UniversitàCampus Bio-Medico di RomaViaÁlvaro del PortilloRomeItaly

Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc *** is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.

关键词： Alzheimer alterations dopamine

Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2982-2997页

作者： Hongli Li Jianhua Huang Di Zhao Lemei Zhu Zheyu Zhang Min Yi Weijun Peng department of Integrated Traditional Chinese&Western medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina National clinical Research Center for Metabolic Diseases ChangshaHunan ProvinceChina Hunan Academy of Chinese medicine ChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina

Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut *** aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease *** do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of ***-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 ***,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 *** findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.

关键词： Alzheimer’s disease APP/PS1 mice brain-kidney axis gut microbiota heart-brain axis liver-brain axis lung-brain axis microbiota-gut-brain axis peripheral organ metabolism spleen-brain axis