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Polyphenols-gut microbiota interplay and brain neuromodulation

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Neural Regeneration Research 2018年第12期13卷 2055-2059页

作者： stefania filosa Francesco Di Meo stefania Crispi Institute of Biosciences and Bioresources National Research Council National Research Council via P. Castellino Naples Italy Istituto di Ricovero e Cura a Carattere Scientifico Neuromed Pozzilli Italy

Increasing evidence suggests that food ingested polyphenols can have beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury. Moreover, polyphenols have been reported to promote cognitive functions. Biotransformation of polyphenols is needed to obtain metabolites active in brain and it occurs through their processing by gut microbiota. Polyphenols metabolites could directly act as neurotransmitters crossing the blood-brain barrier or indirectly by modulating the cerebrovascular system. The microbiota-gut-brain axis is considered a neuroendocrine system that acts bidirectionally and plays an important role in stress responses. The metabolites produced by microbiota metabolism can modulate gut bacterial composition and brain biochemistry acting as neurotransmitters in the central nervous system. Gut microbiota composition can be influenced by dietary ingestion of natural bioactive molecules such as probiotics, prebiotics and polyphenol. Microbiota composition can be altered by dietary changes and gastrointestinal dysfunctions are observed in neurodegenerative diseases. In addition, several pieces of evidence support the idea that alterations in gut microbiota and enteric neuroimmune system could contribute to onset and progression of these age-related disorders. The impact of polyphenols on microbiota composition strengthens the idea that maintaining a healthy microbiome by modulating diet is essential for having a healthy brain across the lifespan. Moreover, it is emerging that they could be used as novel therapeutics to prevent brain from neurodegeneration.

关键词： polyphenols gut-microbiota gut-brain axis metagenomic neurodegeneration neurotransmitters prebiotics probiotics

Control of embryonic stem cell metastability by L-proline catabolism

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分子细胞生物学报:英文版 2011年第2期3卷 108-122页

作者： Laura Casalino stefania Comes Giuseppina Lambazzi Benedetta De Stefano stefania filosa Sandro De Falco Dario De Cesare Gabriella Minchiotti Eduardo Jorge Patriarca Stem Cell Fate Laboratory Institute of Genetics and Biophysics“A.Buzzati-Traverso”CNRNaplesItaly

The molecular mechanisms controlling mouse embryonic stem cell(ESC)metastability,*** capacity to fluctuate between different states of pluripotency,are not fully *** developed and used a novel automation platform,the Cellmaker,to screen a library of metabolites on two ESC-based phenotypic assays(*** and colony phenotype)and identified two metabolically related amino acids,namely L-proline(L-Pro)and L-ornithine(L-Orn),as key regulators of ESC *** compounds,but mainly L-Pro,force ESCs toward a novel epiblast stem cell(EpiSC)-like state,in a dose-and time-dependent *** EpiSCs,L-Pro-induced cells(PiCs)contribute to chimeric embryos and rely on leukemia inhibitor factor(LIF)to ***,PiCs revert to ESCs or differentiate randomly upon removal of either L-Pro or LIF,***,PiC generation depends on both L-Pro metabolism(uptake and oxidation)and Fgf5 induction,and is strongly counteracted by antioxidants,mainly L-ascorbic acid(vitamin C,Vc).ESCs↔PiCs phenotypic transition thus represents a previously undefined dynamic equilibrium between pluripotent states,which can be unbalanced either toward an EpiSC-like or an ESC phenotype by L-Pro/L-Orn or Vc treatments,*** together,our data provide evidence that ESC metastability can be regulated at a metabolic level.

关键词： embryonic stem cells L-proline vitamin C colony phenotype pluripotent states metastability

海南汉族、黎族人葡萄糖-6-磷酸脱氢酶缺乏症的基因突变型分析及一种新的G6PD基因突变型的鉴定

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中华医学遗传学杂志 2001年第2期18卷 105-109页

作者：蔡望伟 stefania filosa Giuseppe Martini 周玉英周代锋蔡兰洁邝宇海南医学院生物化学教研室海口570102 Instituto Internazionale di Geneticae Biofisica

目的　阐明海南汉族、黎族人群中葡萄糖 - 6 -磷酸脱氢酶缺乏症的分子基础。方法　用聚合酶链反应、限制性内切酶消化筛查了 1388G→ A、136 0 C→ T、10 2 4C→ T、5 92 C→ T、5 17T→ C、493A→ G、487G→ A、392 G→ T和 95 A→ G突... 详细信息

目的　阐明海南汉族、黎族人群中葡萄糖 - 6 -磷酸脱氢酶缺乏症的分子基础。方法　用聚合酶链反应、限制性内切酶消化筛查了 1388G→ A、136 0 C→ T、10 2 4C→ T、5 92 C→ T、5 17T→ C、493A→ G、487G→ A、392 G→ T和 95 A→ G突变 ;用单链构象多态性分析筛查其它突变 ;用核苷酸顺序分析鉴定具有SSCP异常区带样品的突变。结果　在 5 9例汉族 G6 PD缺乏症患者中 ,发现 1388G→ A 14例 (2 3.7% )、871G→ A 3例 (5 .1% )、835 A→ T 1例 (1.7% )、5 17T→ C 1例 (1.7% )、392 G→ T 3例 (5 .1% )和 95 A→ G 4例 (6 .8% ) ;在 32例黎族 G6 PD缺乏症患者中 ,发现 1388G→ A6例 (18.8% )、871G→ A3例 (9.4% )和95 A→ G2例 (6 .3% ) ;在 1例汉族患者中发现了一种新的 G6 PD基因突变—— 835 A→ G突变 ,此突变导致第 2 79位的苏氨酸被丙氨酸取代 ,将此突变型命名为 G6 PD-海口 ,其酶活性约是正常的 10 % ,比 835 A→ T突变的活性低 ,后者的酶活性约是正常的 40 %。分析人 G6 PD的三维结构模型表明 ,第 2 79位苏氨酸残基的羟基是维持 G6 PD亚基相互作用的基团。结论　海南汉族、黎族人群中具有共同的常见 G6 PD基因突变型 ;与中国其它地区人群的 G6 PD基因突变谱比较 ,结果表明某些 G6 PD基因突变广?

关键词：葡萄糖-6-磷酸脱氢酶葡萄糖-6-磷酸脱氢酶缺乏症聚合酶链反应基因突变

中国黎族人红视蛋白和绿视蛋白基因外显子3DNA多态的初步研究

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中国黎族人红视蛋白和绿视蛋白基因外显子3DNA多态的初步研究

海南汉族、黎族人葡萄糖-6-磷酸脱氢酶缺乏症的基因突变

“科技增强国力，青年开创未来——携手走向辉煌的新世纪”中国科协第三届青年学术年会

作者：蔡望伟 Giuseppe Martini stefania filosa 海南医学院生物化学教研室

红视蛋白和绿视蛋白是人视锥细胞的感红光色素和感绿光色素的载体蛋白,对于维持红色及绿色视觉起着极其重要的作用。它们的基因定位于X-染色体长臂2区8带(Xq28),两个基因呈头尾相对排列,均由6个外显子和5个内含子组成,核苷酸顺序有98%...

红视蛋白和绿视蛋白是人视锥细胞的感红光色素和感绿光色素的载体蛋白,对于维持红色及绿色视觉起着极其重要的作用。它们的基因定位于X-染色体长臂2区8带(Xq28),两个基因呈头尾相对排列,均由6个外显子和5个内含子组成,核苷酸顺序有98%的同源性。红绿色觉正常的人可有一个或多个红视蛋白基因和绿视蛋白基因。据文献报道,红视蛋白基因及绿视蛋白基因存在一些DNA多态,对于研究红视

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海南医学院学报 2003年第1期9卷 4-7页

作者：蔡望伟周代锋蔡兰洁邝宇周玉英 filosa stefania Martini Giuseppe 海南医学院生物化学教研室海口571101 Istituto Internazionale di Genetica e Biofisica

目的:阐明海南汉族、黎族人群中葡萄糖-6-磷酸脱氢酶缺乏症的分子基础。方法:用聚合酶链反应、限制性内切酶消化筛查了1388G→A、1376G→T、1360C→T、1024C→T、592C→T、517T→C、493A→G、487G→A、392G→T和95A→G突变;用单链构象... 详细信息

目的:阐明海南汉族、黎族人群中葡萄糖-6-磷酸脱氢酶缺乏症的分子基础。方法:用聚合酶链反应、限制性内切酶消化筛查了1388G→A、1376G→T、1360C→T、1024C→T、592C→T、517T→C、493A→G、487G→A、392G→T和95A→G突变;用单链构象多态性分析筛查其它突变;用核苷酸顺序分析鉴定具有SSCP异常区带样品的突变。结果:在59例汉族G6PD缺乏症患者中,发现1388G→A14例(23.7%)、1376G→T19例(32.2%)、871G→A3例(5.1%)、835A→T1例(1.7%)、517T→C1例(1.7%)、392G→T3例(5.1%)、95A→G4例(6.8%);在32例黎族G6PD缺乏症患者中,发现1388G→A6例(18.8%)、1376G→T18例(56.2%)、871G→A3例(9.4%)、95A→G2例(6.3%);结论:海南汉族、黎族人群中具有共同的常见G6PD基因突变型,提示一些G6PD基因突变是中国南方人群的遗传特征。

关键词：葡萄糖-6-磷酸脱氢酶葡萄糖-6-磷酸脱氢酶缺乏症聚合酶链反应黎族汉族

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一种新的G6PD基因突变型的鉴定

海南医学院学报 2003年第1期9卷 1-3,7页

作者：蔡望伟周代锋蔡兰洁邝宇周玉英 filosa stefania Martini Giuseppe 海南医学院生物化学教研室海口571101 Istituto Internazionale di Genetica e Biofisica

目的:鉴定1例葡萄糖-6-磷酸脱氢酶缺乏症患者的基因突变。方法:用聚合酶链反应、限制性内切酶筛查葡萄糖-6-磷酸酶基因1388G→A、1376G→T、1360C→T、1024C→T、592C→T、517T→C、493A→G,487G→A、392G→T、95A→G突变,用单链构象多... 详细信息

目的:鉴定1例葡萄糖-6-磷酸脱氢酶缺乏症患者的基因突变。方法:用聚合酶链反应、限制性内切酶筛查葡萄糖-6-磷酸酶基因1388G→A、1376G→T、1360C→T、1024C→T、592C→T、517T→C、493A→G,487G→A、392G→T、95A→G突变,用单链构象多态性筛查葡萄糖-6-磷酸脱氢酶基因的所有外显子,用核苷酸序列测定确定基因突变。结果:该患者未存在1388G→A、1376G→T、1360C→T、1024C→T、592C→T、517T→C、493A→G、487G→A、392G→T、95A→G突变,但在外显子8发现了一种新的G6PD基因突变———835A→G突变,此突变导致第279位的苏氨酸被丙氨酸取代,将其命名为G6PD-海口,其酶活性约是正常的10%,比835A→T突变型的活性低,后者的酶活性约是正常的40%;分析人G6PD的三维结构模型表明,第279位苏氨酸残基的羟基对于维持G6PD亚基的相互作用具有非常重要的作用。结论:835A→G突变是一种新的G6PD基因突变型,G6PD的第279位苏氨酸残基的羟基是维持G6PD亚基相互作用及酶活性的必需基团。

关键词：葡萄糖-6-磷酸脱氢酶葡萄糖-6-磷酸脱氢酶缺乏症聚合酶链反应三雏结构模型

海南汉族、黎族人群葡萄糖-6-磷酸脱氢酶基因的1376G→T突变

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中华医学遗传学杂志 2000年第5期17卷 326-328页

作者：蔡望伟蔡兰洁周代锋邝宇周玉英 filosa stefania Martini Giuseppe 海南医学院生物化学教研室海口570102 Istituto Internazionale di Geneticae Biofisica

目的　了解海南汉族、黎族人群 G6 PD缺乏症患者的 G6 PD基因 1376 G→T突变。方法　用盐提取法提取 G6 PD缺乏症患者白细胞的 DNA,用等位基因特异聚合酶链反应检测 1376 G→ T突变。结果在分析的 5 9例汉族患者和 32例黎族患者中 ,19... 详细信息

目的　了解海南汉族、黎族人群 G6 PD缺乏症患者的 G6 PD基因 1376 G→T突变。方法　用盐提取法提取 G6 PD缺乏症患者白细胞的 DNA,用等位基因特异聚合酶链反应检测 1376 G→ T突变。结果在分析的 5 9例汉族患者和 32例黎族患者中 ,19例汉族患者和 18例黎族患者有 G6 PD基因 1376 G→ T突变 ,该突变在汉族、黎族患者中所占的比例分别为 32 .2 %和 5 6 .2 %。结论　 G6 PD基因 1376 G→T是引起海南黎族、汉族人 G6 PD缺乏症的主要突变之一 ;根据中国不同民族的聚类分析图 ,该结果提示 1376 G→ T突变可能在黎族人形成之前已经出现。研究不同民族的 G6 PD基因突变 ,对于阐明各民族的起源、迁移。

关键词：葡萄糖-6-磷酸脱氢酶缺乏症基因突变 G6PD基因

Calcium-sensitive protein MLC1 as a possible modulator of the astrocyte functional state

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Neural Regeneration Research 2025年第7期20卷 2008-2010页

作者： Elena Ambrosini Angela Lanciotti Maria stefania Brignone Department of Neuroscience Istituto Superiore di SanitàRomeItaly

Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult *** maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.

关键词： alterations modulator maintain

Application of ultrasonography-elastography score to suspect porto-sinusoidal vascular disease in patients with portal vein thrombosis

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 20-24页

作者： stefania Gioia Adriano De Santis Giulia d’Amati Silvia Nardelli Alessandra Spagnoli Arianna Di Rocco Lorenzo Ridola Oliviero Riggio Department of Translational and Precision Medicine Sapienza University of RomeRomeItaly Department of Radiological Oncologicaland Pathological SciencesSapienza University of RomeRomeItaly Department of Public Health and Infectious Diseases Sapienza University of RomeRomeItaly

Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal *** PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be *** these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be *** this setting ultrasonography may be valuable in differential *** aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing ***:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT ***,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.

关键词： Non-cirrhotic portal hypertension Porto-sinusoidal vascular disease Chronic portal vein thrombosis Liver stiffness Portal hypertension Acoustic radiation force impulse