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Alpha-synuclein in mitochondrial dysfunction:opportunities or obstacles

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Neural Regeneration Research 2025年第1期20卷 197-198页

作者： Shermali Gunawardena Department of Biological Sciences The State University of New York at BuffaloBuffaloNYUSA

Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still *** notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is *** date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.

关键词： dysfunction homeostasis Alpha

Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

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Biomedical and Environmental Sciences 1991年第1期4卷 93-103页

作者： STEPHEN S.HECHT STEVEN G.CARMELLA SHARON E.MURPHY Dana Road American Health Foundation ValhallaDana Road American Health Foundation ValhallaDana Road American Health Foundation Valhalla New York 10595New York 10595 New York 10595

The carcinogenic tobacco-specific nitrosamines N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) form hemoglobin adducts in laboratory animals and humans. These adducts release 4-hydroxy-l-(3-pyridyl)-l-butanone (HPB) upon mild base hydrolysis. HPB released from human hemoglobin can be quantified by gas chromatography-mass spectrometry. It is the only available biochemical marker for determination of exposure to, and metabolic activation of, carcinogens present only in tobacco. Levels of HPB were highest in snuff-dippers, followed by smokers and nonsmokers. Large interindividual variations in adduct levels were observed. The relationship between HPB levels in globin and DNA of rats treated with NNK has been investigated in order to aid in interpretation of the data from humans. These studies have provided the initial database for understanding the metabolic activation of tobacco-specific nitrosamines in humans.

关键词： Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

Exploiting fly models to investigate rare human neurological disorders

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Neural Regeneration Research 2025年第1期20卷 21-28页

作者： Tomomi Tanaka Hyung-Lok Chung Department of Neurology Houston Methodist Research InstituteHoustonTXUSA Department of Neurology Weill Cornell Medical CollegeNew YorkNYUSA

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological *** attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted *** investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary *** tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological *** boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug *** can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical *** this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic *** discuss rare diseases associated with both neuron-expressed and glial-expressed *** cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal *** we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell ***-of-fun

关键词： ACOX1 Drosophila melanogaster glia lipid metabolism model organisms neuroinflammation neurologic disorders neuron rare disease VLCFA

A new guideline for diagnosis and treatment of syncope in children and adolescents that stimulates further thought and discussion

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Science Bulletin 2018年第23期63卷 1527-1528页

作者： Julian M.Stewart Physiology and Medicine Center for HypotensionThe New York Medical CollegeValhallaNY 10595USA

A new guideline for diagnosis and treatment of syncope in children and adolescents was published by Chinese Pediatric Cardiology Society (CPCS)[1].This guideline admirably outlines a differential diagnosis of syncope in the Chinese population,placing appropriate emphasis on vasovagal syncope (VVS,simple faint), the most common *** authors appropriately discuss other more ominous causes of syncope such as cardiogenic syncope and neurogenic orthostatic *** particular,cardiogemc syncope can have lethal consequences if not promptly treated.

关键词： Children Adolescent syncope CPCS

Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

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Biomedical and Environmental Sciences 1991年第Z1期 93-103页

作者： STEPHEN S.HECHT,STEVEN G.CARMELLA,SHARON E.MURPHY Dana Road American Health Foundation valhalla Dana Road American Health Foundation valhalla Dana Road American Health Foundation valhalla new york 10595 new york 10595 new york 10595

The carcinogenic tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) form hemoglobin adducts in laboratory animals and humans. These adducts release 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) upon mild base hydrolysis. HPB released from human hemoglobin can be quantified by gas chromatography-mass spectrometry. It is the only available biochemical marker for determination of exposure to, and metabolic activation of, carcinogens present only in tobacco. Levels of HPB were highest in snuff-dippers, followed by smokers and nonsmokers. Large interindividual variations in adduct levels were observed. The relationship between HPB levels in globin and DNA of rats treated with NNK has been investigated in order to aid in interpretation of the data from humans. These studies have provided the initial database for understanding the metabolic activation of tobacco-specific nitrosamines in humans.

关键词： Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

SX-fraction:Promise for novel treatment of type 2 diabetes

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World Journal of Diabetes 2020年第12期11卷 572-583页

作者： Sensuke Konno Department of Urology New York Medical CollegeValhallaNY 10595United States

SX-fraction(SXF)is a bioactive glycoprotein with anti-diabetic and hypoglycemic activities that have been documented in several *** have reviewed those studies herein and also explored the possible mechanism of its hypoglycemic *** early animal studies of SXF using diabetic mice showed the significant reduction in the three diabetic parameters,serum glucose,insulin,and triglyceride,suggesting its anti-diabetic *** limited clinical studies also showed that SXF led to the significant reduction in the fasting blood glucose levels of type 2 diabetic patients within 2 wk or a month,suggesting its hypoglycemic *** explore the hypoglycemic mechanism of SXF,its possible effects on the insulin signal transduction pathway was examined in ***,activities of insulin receptor,insulin receptor substrate 1,and protein kinase B,which are essential elements playing a key regulatory role in the signal pathway,were studied using skeletal muscle L6 *** status of these three parameters were examined under a high glucose(35 mmol/L)milieu with SXF and assessed using the enzyme-linked immunosorbent *** studies revealed that all three parameters(insulin receptor,insulin receptor substrate 1,and protein kinase B)were inactivated by high glucose,indicating a disruption of the signal ***,such an inactivation was reversed or re-activated by SXF to successfully carry out the sequential signaling *** fact,a measurement of glucose uptake in cells showed that SXF did increase a glucose uptake while high glucose decreased ***,SXF has anti-diabetic and hypoglycemic activities through activation of the insulin signal pathway and appears to be a safe,natural agent for lowering the serum glucose levels in type 2 diabetic patents and improving their diabetic conditions.

关键词： SX-fraction Diabetes Anti-diabetic Hypoglycemic Insulin signal pathway

Re:Association between intestinal neoplasms and celiac disease-beyond celiac disease and more

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 746-747页

作者： Kenji Okumura Department of Surgery Westchester Medical Center/New York Medical CollegeValhallaNY 10595United States

The association between celiac disease and enteropathy-associated T cell lymphoma has been *** pathogenesis of the development of malignant neoplasms remains *** addition to celiac disease,we believe that other underl... 详细信息

关键词： Celiac disease Entropathy-associated T cell lymphoma c-MYC JAK-STAT

Effect of external and internal cues on core muscle activation during the Sahrmann five-level core stability test

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World Journal of Methodology 2025年第1期15卷 95-104页

作者： Skyla Stifter Jessie McCaffrey Tyler Nichols Ayse Ozcan Edeer Justine Ward Physical Therapy Dominican University New YorkOrangeburgNY 10962United States

BACKGROUND Pain in the back or pelvis or fear of back pain may affect the timing or cocontraction of the core *** both static and dynamic movements,the Sahrmann core stability test provides an assessment of core muscle activation and a person's ability to stabilize the lumbopelvic *** cues and images can be used to increase the activation of these *** attain optimal movement patterns,it will be necessary to determine what cueing will give the most effective results for core *** To investigate the effects of external and internal cues on core muscle activation during the Sahrmann five-level core stability *** Total 68 participants(21.83±3.47 years)were randomly allocated to an external(n=35)or internal cue group(n=33).Participants performed the Sahrmann fivelevel core stability test without a cue as baseline and the five-level stability exercises with an internal or external *** cue group received a pressure biofeedback unit(PBU),and the internal cue group received an audio cue.A Delsys Trigno^(TM)surface electromyography unit was used for muscle activation from the rectus abdominis,external oblique,and transverse abdominis/internal oblique *** Linear mixed effects model analysis showed that cueing had a significant effect on core muscle activation(P=0.001);however,there was no significant difference between cue types(internal or external)(P=0.130).CONCLUSION Both external and internal cueing have significant effects on core muscle activation during the Sahrmann five-level core stability test and the PBU does not create higher muscle activation than internal cueing.

关键词： External cue Internal cue Muscle activation Core muscles Lumbopelvic stability Pressure biofeedback unit

Trends and outcomes of liver transplantation among older recipients in the United States

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World Journal of Transplantation 2022年第8期12卷 259-267页

作者： Kenji Okumura Joon Sub Lee Abhay Dhand Hiroshi Sogawa Gregory Veillette Devon John Ryosuke Misawa Roxana Bodin David C Wolf Thomas Diflo Seigo Nishida Department of Surgery Westchester Medical Center/New York Medical CollegeValhallaNY 10595United States

BACKGROUND The average age of recipients and donors of liver transplantation(LT)is *** there has been a change in the indications for LT over the years,data regarding the trends and outcomes of LT in the older population is *** To assess the clinical characteristics,age-related trends,and outcomes of LT among the older population in the United *** We analyzed data from the United Network for Organ Sharing database between *** sample was split into younger group(18-64 years old)and older group(≥65 years old).RESULTS Between 1987-2019,155758 LT were performed in the United *** this period there was a rise in median age of the recipients and percentage of LT recipients who were older than 65 years increased(P<0.05)with the highest incidence of LT among older population seen in 2019(1920,23%).Common primary etiologies of liver disease leading to LT in older patients when compared to the younger group,were non-alcoholic steatohepatitis(16.4%vs 5.9%),hepatocellular carcinoma(14.9%vs 6.9%),acute liver failure(2.5%vs 5.2%),hepatitis C cirrhosis(HCV)(19.2%vs 25.6%)and acute alcoholic hepatitis(0.13%vs 0.35%).In older recipient group female sex and Asian race were higher,while model for end-stage liver disease(MELD)score and rates of preoperative mechanical ventilation were lower(P<0.01).Median age of donor,female sex,body mass index(BMI),donor HCV positive status,and donor risk index(DRI)were significantly higher in older group(P<0.01).In univariable analysis,there was no difference in post-transplant length of hospitalization,one-year,three-year and five-year graft survivals between the two *** multivariable Cox-Hazard regression analysis,older group had an increased risk of graft failure during the five-year post-transplant period(hazard ratio:1.27,P<0.001).Other risk factors for graft failure among recipients were male sex,African American race,re-transplantation,presence of diabetes,mechanical ventilation at th

关键词： Liver transplant Elderly Outcomes Hepatocellular carcinoma Nonalcohol steatohepatitis