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Distinct and Additive Effects of Alcohol and Thiamine deficiency in the developing Brain: Relevance to Fetal Alcohol Spectrum Disorder

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Journal of Behavioral and Brain Science 2024年第6期14卷 161-186页

作者： suzanne M. de la monte Elizabeth Silbermann Ming Tong departments of Pathology (Neuropathology) Neurology and Neurosurgery Brown University Providence RI USA department of Medicine Brown University Providence RI USA Rhode Island Hospital Providence RI USA Women & Infants Hospital Providence RI USA Warren Alpert Medical School of Brown University Providence RI USA Portland VA Medical Center Oregon Health & Science University Portland OR USA

Background: Neurodevelopmental abnormalities in fetal alcohol spectrum disorder (FASD) are linked to brain insulin resistance and oxidative stress. However, the role of thiamine deficiency as a distinct or additive factor in the pathogenesis of the neurodevelopmental and metabolic derangements in FASD has not been determined. Methods: Control and ethanol-exposed human PNET2 cerebellar neuronal cells and rat cerebellar slice cultures were treated with vehicle or pyrithiamine (Pyr) to assess independent and additive effects of thiamine deficiency on ethanol-mediated neurotoxicity, mitochondrial dysfunction, insulin resistance, inhibition of neuronal and glial genes, and oxidative stress. Results: Pyr treatments (0 - 200 µM) caused dose-dependent cell loss (Crystal Violet assay) and reduced mitochondrial function (MTT assay) in PNET2 neuronal cultures. Ethanol alone (100 mM) significantly reduced PNET2 neuronal viability, MTT activity, and ATP production. Over the broad dose range of Pyr treatment, ethanol significantly reduced ATP content and cell number and increased mitochondrial mass (MitoTracker Green). Ex vivo cerebellar slice culture studies revealed ethanol-induced developmental architectural disruption that was substantially worsened by Pyr. The adverse effects of ethanol were linked to increased lipid peroxidation and inhibition of asparatyl-asparaginyl-β-hydroxylase (ASPH) expression. The independent and additive effects of Pyr were associated with increased cytotoxicity, lipid peroxidation, Caspase 3 activation, and Tau accumulation. Conclusions: During development, alcohol exposure and thiamine deficiency exert distinct but overlapping molecular pathologies that ultimately impair the structure and function of cerebellar neurons. While both insults drive cell loss and mitochondrial dysfunction with increased lipid peroxidation, ethanol’s additional inhibitory effects on ASPH reflect impairments in insulin and IGF signaling. In contrast, Pyr’s main adverse e

关键词： Fetal Alcohol Spectrum Disorder Thiamine deficiency Cerebellum Slice Culture Pyrithiamine

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Therapeutic Effects of Myriocin in Experimental Alcohol-Related Neurobehavioral Dysfunction and Frontal Lobe White Matter Biochemical Pathology

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Journal of Behavioral and Brain Science 2022年第2期12卷 23-42页

作者： Camilla Homans Emine B. Yalcin Ming Tong Gina Gallucci David Bautista Natalia Moriel suzanne de la monte Biotechnology Graduate Program Brown University Providence RI USA department of Pathology and laboratory Medicine Warren Alpert Medical School of Brown University Providence RI USA Liver Research Center Department of Medicine Rhode Island Hospital Providence RI USA Warren Alpert Medical School of Brown University Providence RI USA Brown University Providence RI USA department of Pathology and laboratory Medicine Rhode Island Hospital Women and Infants Hospital of Rhode Island Providence VA Medical Center Providence RI USA

Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained deficits in cognition, learning, and memory. Correspondingly, chronic heavy or repeated binge alcohol exposures in humans and experimental models alter myelin lipid composition leading to build-up of ceramides which can be neurotoxic and broadly inhibitory to brain functions. Methods: This study examined the effects of chronic + binge alcohol exposures (8 weeks) and intervention with myriocin, a ceramide inhibitor, on neurobehavioral functions (Open Field, Novel Object Recognition, and Morris Water Maze tests) and frontal lobe white matter myelin lipid biochemical pathology in an adult Long-Evans rat model. Results: The ethanol-exposed group had significant deficits in executive functions with increased indices of anxiety and impairments in spatial learning acquisition. Myriocin partially remediated these effects of ethanol while not impacting behavior in the control group. Ethanol-fed rats had significantly smaller brains with broadly reduced expression of sulfatides and reduced expression of two of the three sphingomyelins detected in frontal white matter. Myriocin partially resolved these effects corresponding with improvements in neurobehavioral function. Conclusion: Therapeutic strategies that support cerebral white matter myelin expression of sulfatide and sphingomyelin may help remediate cognitive-behavioral dysfunction following chronic heavy alcohol consumption in humans.

关键词： Adolescence Alcohol Behavior Binge Drinking Brain Atrophy Myriocin Neurodegeneration Rat Sulfatide White Matter

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The Differential Effects of Chronic Alcohol and Cigarette Smoke Exposures on Cognitive-Behavioral Dysfunction in Long Evans Rats

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Journal of Behavioral and Brain Science 2022年第9期12卷 413-432页

作者： Emine B. Yalcin Büşra Nur delikkaya William Pelit Ming Tong suzanne M. de la monte Sharon Rounds Division of Research Providence VA Medical Center Providence RI USA Liver Research Center Division of Gastroenterology and Department of Medicine Rhode Island Hospital and the Alpert Medical School of Brown University Providence RI USA Chemical Biology and English Brown University Providence RI USA departments of Medicine Neurology and Pathology and Laboratory Medicine Rhode Island Hospital Women & Infants Hospital of Rhode Island Alpert Medical School of Brown University Providence VA Medical Center Providence RI USA departments of Medicine and Pathology and laboratory Medicine Warren Alpert Medical School of Brown University Vascular Research Laboratory Providence VA Medical Center Providence RI USA

Background and Objective: Chronic heavy alcohol consumption and daily cigarette smoking are the most prevalent substance use problems in the U.S., including Veterans. Excessive alcohol use causes neurocognitive and behavioral deficits that can be linked to neurodegeneration. Similarly, preclinical and clinical data suggest that smoking also leads to brain atrophy. This study examines the differential and additive effects of alcohol and cigarette smoke (CS) exposures on cognitive-behavioral function. Methods: A 4-way experimental model of chronic alcohol and CS exposures was generated using 4-week-old male and female Long Evans rats that were pair-fed with Lieber-deCarli isocaloric liquid diets containing 0% or 24% ethanol for 9 weeks. Half of the rats in the control and ethanol groups were exposed to CS for 4 hours/day and 4 days/week for 9 weeks. All rats were subjected to Morris Water Maze, Open Field, and Novel Object Recognition testing in the last experimental week. Results: Chronic alcohol exposure impaired spatial learning as shown by significantly increased latency to locate the platform, and it caused anxiety-like behavior marked by the significantly reduced percentage of entries to the center of the arena. Chronic CS exposure impaired recognition memory as suggested by significantly less time spent at the novel object. Combined exposures to alcohol and CS did not show any significant additive or interactive effect on cognitive-behavioral function. Conclusion: Chronic alcohol exposure was the main driver of spatial learning, while the effect of secondhand CS exposure was not robust. Future studies need to mimic direct CS exposure effects in humans.

关键词： Alcohol Cigarette Smoke Spatial Learning Recognition Memory Anxiety White Matter Rat

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Theobroma cacao improves bone growth by modulating defective ciliogenesis in a mouse model of achondroplasia

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Bone Research 2022年第1期10卷 137-149页

作者： Ludovic Martin Nabil Kaci Catherine Benoist-lasselin Marine Mondoloni suzanne decaudaveine Valentin Estibals Maxence Cornille Léa Loisay Justine Flipo Benoît demuynck Maria de la Luz Cádiz-Gurrea Florent Barbault Salvador Fernández-Arroyo laurent Schibler Antonio Segura-Carretero Emilie Dambroise laurence Legeai-Mallet Universitéde Paris Imagine InstituteLaboratory of Molecular and Physiopathological Bases of OsteochondrodysplasiaINSERM UMR 1163F‑75015ParisFrance Inovarion ParisFrance department of Analytical Chemistry University of GranadaGranadaSpain Research and development of Functional Food Centre(CIDAF) GranadaSpain Universitéde Paris ITODYSCNRSUMR 708615 rue J-A de BaïfParisFrance Biomedical Research Unit Medicine and Surgery DepartmentRovira i Virgili UniversityTarragonaSpain ALLICE Maison Nationale des EleveursParisFrance

A gain-of-function mutation in the fibroblast growth factor receptor 3 gene(FGFR3)results in achondroplasia(ACH),the most frequent form of *** activation of FGFR3 impairs bone formation and elongation and many signal transduction *** of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH,and natural plant compounds are prime drug candidate ***,we found that the phenolic compound(-)-epicatechin,isolated from Theobroma cacao,effectively inhibited FGFR3’s downstream signaling *** analysis in an Fgfr3 mouse model showed that ciliary mRNA expression was modified and influenced significantly by the Indian hedgehog and PKA pathways.(-)-Epicatechin is able to rescue mRNA expression impairments that control both the structural organization of the primary cilium and ciliogenesis-related *** femurs isolated from a mouse model(Fgfr3^(Y367C/+))of ACH,we showed that(-)-epicatechin eliminated bone growth impairment during 6 days of ex vivo *** vivo,we confirmed that daily subcutaneous injections of(-)-epicatechin to Fgfr3^(Y367C/+) mice increased bone elongation and rescued the primary cilium defects observed in *** modification to the primary cilia promoted the typical columnar arrangement of flat proliferative chondrocytes and thus enhanced bone *** results of the present proof-of-principle study support(-)-epicatechin as a potential drug for the treatment of ACH.

关键词： inhibited arrangement eliminated

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Could JC virus provoke metastasis in colon cancer?

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World Journal of Gastroenterology 2014年第42期20卷 15745-15749页

作者： Emanuele Sinagra Dario Raimondo Elena Gallo Mario Stella Mario Cottone Ambrogio Orlando Francesca Rossi Emanuele Orlando Marco Messina Giovanni Tomasello Attilio Ignazio Lo monte Ennio la Rocca Aroldo Gabriele Rizzo Gastroenterology and Endoscopy Unit Fondazione Istituto San Raffaele-G Giglio Contrada Pietra Pollastra Pisciotto course in Surgical Biotechnology and Regenerative Medicine University of Palermo Euro-Mediterranean Institute of Science and Technology (IEMEST) Unit of Pathology Ospedali Riuniti Villa Sofia - Cervello University of Palermo DIBIMIS Unit of Internal Medicine Ospedali Riuniti Villa Sofia - Cervello University of Palermo Oncology Unit Fondazione Istituto San Raffaele-G Giglio Contrada Pietra Pollastra Pisciotto department of Surgical and Oncological Disciplines School of Medicine University of Palermo Unità Operativa di Medicina interna e trapiantologia Ospedale San Raffaele

AIM: To evaluate the prevalence of John Cunningham virus(JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic ***: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 ***: Four out of 19 patients with colon cancer had a positive polymerase chain reaction(PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant(χ2 = 9.55, P = 0.002).CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.

关键词： John Cunningham virus Colon cancer Me-tastasis

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Point-of-care ultrasonography in geriatric medicine: usefulness for approaching infectious endocarditis diagnosis

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Journal of Geriatric Cardiology 2022年第12期19卷 1001-1002页

作者： Pablo Solla Patricia Cancelo Eva López Jesús de la Hera César Morís José Gutiérrez Geriatrics department Geriatrics Clinical Management AreaHospital Monte NarancoOviedoSpain Health Research Institute of Asturias OviedoSpain Cardiology department Cardiac AreaHospital Universitario Central de AsturiasOviedoSpain

Infective endocarditis has a high morbimortality rate,and delay in diagnosis and treatment is associated with a higher prevalence of *** clinical presentation is often atypical in older adults,and even when the classic symptoms are present,they may overlap with those of other conditions,making management more *** present the case of a nonagenarian in whom cardiac-centered point-of-care ultrasound facilitated real-time decision making and the diagnosis of mitral endocarditis.

关键词： diagnosis endocarditis mortality

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Applications of Trichoderma formulations in crop protection

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浙江大学学报(农业与生命科学版) 2004年第4期30卷 410-410页

作者： monte E Rodríguez A Rey M Azpilicueta A Gómez M I de la Via G Grondona I Llobell A Centro Hispano-Luso de Investigaciones Agrarias University of Salamanca Plaza Doctores de la Reina s/n 37007 Salamanca Spain NewBioTechnic S.A. (NBT) Paseo de Bollullos de la Mitación 6. Parque Industrial A-49 (PIBO) 41110 Bollullos de la Mitación Seville Spain IBVF Isla de la Cartuja CSIC/University of Seville Seville Spain

The choice of active Trichoderma strains is important in designing effective and safe biocontrol applications. Many species of Trichoderma have multiple strategies for fungal antagonism and indirect effects on plant health, such as growth promotion, systemic resistance induction and fertility improvements. Some strains are powerful antibiotic producers, and their suitability for use in biocontrol systems must be carefully assessed. However, many other active strains have no antibiotic capacity, and these are likely to be more useful in food production systems since they have not adverse effects on important groups of beneficial soil organisms. We have assessed the performance of selected naturally occurring Trichoderma strains (singly and in combination) and developed TUSAL, a mixture of Trichoderma harzianum and T. viride that has demonstrated to be effective against major pathogens in sugar beet and horticulture. TUSAL, has been bulked up and tested under field conditions, showing positive effects on precocity and root development, and increasing the crop production in field trials carried out in different pathosystems. The environmental impact of TUSAL strains on beneficial organisms in the environment were assessed before release, and molecular detection methods were developed to monitor the presence and performance of strains in the field. In addition, Trichoderma protein extracts with high glucanase and chitinase activities, have also been obtained from wild type strains and their effectiveness as biofungicides was tested in laboratory and field conditions, defining the concentration of protein necessary to produce fungicide effects. The genes coding for protein production were introduced into suitable organisms for large-scale production in the laboratory, never released to the environment. The effect of these novel biofungicide proteins was studied separately and synergistically with Trichoderma conidia, and with minimal doses of chemical fungicides. Suit

关键词： biocontrol TUSAL Trichoderma formulations Trichoderma proteins

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中国早期人类分布的环境制约因素探讨

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第四纪研究 2021年第5期41卷 1342-1356页

作者：丁馨杜雨薇徐欣裴树文 de la Torre Ignacio 高星英国伦敦大学学院考古研究所英国伦敦WC1H 0PY 中国科学院脊椎动物演化与人类起源重点实验室中国科学院古脊椎动物与古人类研究所机构北京100044 中国科学院机构生物演化与环境卓越创新中心北京100044 西班牙国家研究委员会历史研究所西班牙马德里28037 中国科学院大学机构北京100049

在环境因素起制约作用的背景下,随着中国古人类演化与生存能力的进步,其数量和空间分布在不同时间段呈现出不同的特征。为了更好地了解中国早期人类的时空分布特征,本研究以中国境内已发表的2110处旧石器遗址的坐标和年代信息为基础,采... 详细信息

在环境因素起制约作用的背景下,随着中国古人类演化与生存能力的进步,其数量和空间分布在不同时间段呈现出不同的特征。为了更好地了解中国早期人类的时空分布特征,本研究以中国境内已发表的2110处旧石器遗址的坐标和年代信息为基础,采用统计学和空间分析的方法,对遗址的时间分布进行以蒙特卡洛模拟为基础的时间不定性模拟,对遗址的空间分布进行核密度估计和聚类分析;同时,利用环境空间数据集中的海拔、水源、气温和降水信息,对不同时期内各个遗址所在地的环境条件进行统计分析。研究结果表明,在旧石器时代,随着时间的发展,中国境内的遗址数量不断增多,分布范围也逐渐从中部、南部和东部地区向条件较恶劣的北部和西部扩张。其中,600 ka和57 ka为这一变化的两个关键时间点,600 ka之前遗址数量较少,分布也较为局限;在600 ka至57 ka之间,遗址数量缓慢增加,分布范围也在季风区内逐渐扩大;57 ka之后,遗址数量迅速增长,分布遍布中国境内的大部分地区。本文所梳理的中国境内旧石器遗址整体时空分布特征,为进一步解读中国早期人类的环境适应能力,特别是古人类的体质演化和技术进步的环境驱动机制提供参考。

关键词：古人类分布环境因素空间分析统计分析中国

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Plasticity of spermatogonial stem cells

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Asian Journal of Andrology 2015年第3期17卷 355-359页

作者： Paul S Cooke Liz Simon Manjunatha K Nanjappa Theresa I Medrano suzanne E Berry department of Physiological Sciences College of Veterinary Medicine University of Florida Gainesville FL 32608 USA department of Physiology Louisiana State University Health Sciences Center New Orleans LA 70112 USA department of Comparative Biosciences College of Veterinary Medicine University of Illinois at Urbana-Champaign Urbana IL 61802 USA

There have been significant breakthroughs over the past decade in the development and use of pluripotent stem cells as a potential source of cells for applications in regenerative medicine. It is likely that this methodology will begin to play an important role in human clinical medicine in the years to come. This review describes the plasticity of one type of pluripotent cell, spermatogonial stem cells （SSCs）, and their potential therapeutic applications in regenerative medicine and male infertility. Normally, SSCs give rise to sperm when in the testis. However, both human and murine SSCs can give rise to cells with embryonic stem （ES） cell-like characteristics that can be directed to differentiate into tissues of all three embryonic germ layers when placed in an appropriate inductive microenvironment, which is in contrast to other postnatal stem cells. Previous studies have reported that SSCs expressed an intermediate pluripotent phenotype before differentiating into a specific cell type and that extended culture was necessary for this to occur. However, recent studies from our group using a tissue recombination model demonstrated that SSCs differentiated rapidly into another tissue, in this case, prostatic epithelium, without expression of pluripotent ES cell markers before differentiation. These results suggest that SSCs are capable of directly differentiating into other cell types without going through an intermediate ES cell-like stage. Because SSCs do not require reprogramming to achieve a pluripotent state, they are an attractive source of pluripotent cells for use in regenerative medicine.

关键词： pluripotency regenerative medicine spermatogenesis testis

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Effect of Local Wound Infiltration with Ketamine versus dexmedetomidine Added to Bupivacaine on Inflammatory Cytokines, a Randomized Clinical Trial

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Open Journal of Anesthesiology 2022年第8期12卷 261-277页

作者： Fatma A. El Sherif Moaaz Tohamy Mohamed A. M. Mostafa suzanne de la Adlan Sahar Abdel-Baky Mohamed Samar Mansour Mahmoud M. Mohammed Ahmad M. Abd El-Rahman Anethesia ICU and Pain Management South Egypt Cancer Institute Assiut University Assiut Egypt Anesthesia ICU and Pain Management National Cancer Institute Cairo University Cairo Egypt Clinical Pathology South Egypt Cancer Institute Assiut University Assiut Egypt Surgical Oncology South Egypt Cancer Institute Assiut University Assiut Egypt

Background: Ketamine or dexmedetomidine as an adjuvant to bupivacaine in local wound infiltration attenuated postoperative stress response, especially with ketamine in patients undergoing total abdominal hysterectomy. Objectives: Compare effect of local wound infiltration with ketamine or dexmedetomidine added to bupivacaine to bupivacaine alone on inflammatory cytokine response after total abdominal hysterectomy. Methods: Sixty female patients with endometrial carcinoma underwent total abdominal hysterectomy and scheduled to receive local wound infiltration before wound closure either with one of three;40 ml of 0.25% bupivacaine alone (C Group) or with the addition of 2 mg/kg ketamine (K Group) or 2 μg/kg dexmedetomidine (D Group). After extubation, they were followed up for postoperative interleukin 6 (IL6), IL1β, IL10, and TNF-α levels were assessed at baseline, pre-infiltration, 6, and 24 h by blood samples obtained from each patient, hemodynamic variables, analgesic profile and side effects. Results: Inflammatory cytokines response was attenuated in K and D groups, evidenced by decreased mean pro-inflammatory cytokines IL6, TNF-α, and increased anti-inflammatory IL10 at 6 and 24 h postoperatively compared to pre-infiltration levels (p ≤ 0.01) with preservation of IL1β at its preoperative level (p > 0.05). Attenuation was more in K and D groups than in the C group and was highest in the K group with decreased 1st request, total morphine consumption without serious side effect. Conclusion: Local wound infiltration with ketamine or dexmedetomidine added to bupivacaine has a good postoperative analgesic profile and attenuated cytokines inflammatory response more than bupivacaine alone after total abdominal hysterectomy, with highest attenuation in ketamine group.

关键词： Ketamine dexmedetomidine Local Infiltration Cytokines Hysterectomy

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