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| 1 | ALDH2 contributes to melatonin-induced protection against APP/PS1 mutation-prompted cardiac anomalies through cGAS-STING-TBK1-mediated regulation of mitophagy显示文摘Ample clinical evidence suggests a high incidence of cardiovascular events in Alzheimer’s disease(AD),although neither precise etiology nor effective treatment is available.This study was designed to evaluate cardiac function in AD patients and APP/PS1 mutant mice,along with circulating levels of melatonin,mitochondrial aldehyde dehydrogenase(ALDH2)and autophagy.AD patients and APP/PS1 mice displayed cognitive and myocardial deficits,low levels of circulating melatonin,ALDH2 activity,and autophagy,ultrastructural,geometric(cardiac atrophy and interstitial fibrosis)and functional(reduced fractional shortening and cardiomyocyte contraction)anomalies,mitochondrial injury,cytosolic mtDNA buildup,apoptosis,and suppressed autophagy and mitophagy.APP/PS1 mutation downregulated cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)levels and TBK1 phosphorylation,while promoting Aβaccumulation.Treatment with melatonin overtly ameliorated unfavorable APP/PS1-induced changes in cardiac geometry and function,apoptosis,mitochondrial integrity,cytosolic mtDNA accumulation(using both immunocytochemistry and qPCR),mitophagy,and cGAS-STING-TBK1 signaling,although these benefits were absent in APP/PS1/ALDH2−/−mice.In vitro evidence indicated that melatonin attenuated APP/PS1-induced suppression of mitophagy and cardiomyocyte function,and the effect was negated by the nonselective melatonin receptor blocker luzindole,inhibitors or RNA interference of cGAS,STING,TBK1,and autophagy.Our data collectively established a correlation among cardiac dysfunction,low levels of melatonin,ALDH2 activity,and autophagy in AD patients,with compelling support in APP/PS1 mice,in which melatonin rescued myopathic changes by promoting cGAS-STING-TBK1 signaling and mitophagy via an ALDH2-dependent mechanism. | Shuyi Wang Lin Wang Xing Qin Subat Turdi Dongdong Sun Bruce Culver Russel JReiter Xiaoming Wang Hao Zhou Jun Ren | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 9 |
| 2 | Mitochondrial aldehyde dehydrogenase(ALDH2)rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer’s disease via inhibition of ACSL4-dependent ferroptosis显示文摘Alzheimer’s disease(AD)is associated with high incidence of cardiovascular events but the mechanism remains elusive.Our previous study reveals a tight correlation between cardiac dysfunction and low mitochondrial aldehyde dehydrogenase(ALDH2)activity in elderly AD patients.In the present study we investigated the effect of ALDH2 overexpression on cardiac function in APP/PS1 mouse model of AD.Global ALDH2 transgenic mice were crossed with APP/PS1 mutant mice to generate the ALDH2-APP/PS1 mutant mice.Cognitive function,cardiac contractile,and morphological properties were assessed.We showed that APP/PS1 mice displayed significant cognitive deficit in Morris water maze test,myocardial ultrastructural,geometric(cardiac atrophy,interstitial fibrosis)and functional(reduced fractional shortening and cardiomyocyte contraction)anomalies along with oxidative stress,apoptosis,and inflammation in myocardium.ALDH2 transgene significantly attenuated or mitigated these anomalies.We also noted the markedly elevated levels of lipid peroxidation,the essential lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4(ACSL4),the transcriptional regulator for ACLS4 special protein 1(SP1)and ferroptosis,evidenced by elevated NCOA4,decreased GPx4,and SLC7A11 in myocardium of APP/PS1 mutant mice;these effects were nullified by ALDH2 transgene.In cardiomyocytes isolated from WT mice and in H9C2 myoblasts in vitro,application of Aβ(20μM)decreased cell survival,compromised cardiomyocyte contractile function,and induced lipid peroxidation;ALDH2 transgene or activator Alda-1 rescued Aβ-induced deteriorating effects.ALDH2-induced protection against Aβ-induced lipid peroxidation was mimicked by the SP1 inhibitor tolfenamic acid(TA)or the ACSL4 inhibitor triacsin C(TC),and mitigated by the lipid peroxidation inducer 5-hydroxyeicosatetraenoic acid(5-HETE)or the ferroptosis inducer erastin.These results demonstrate an essential role for ALDH2 in AD-induced cardiac anomalies through regulation of lipid peroxidation and ferroptosis. | Zhi-yun Zhu Yan-dong Liu Yan Gong Wei Jin Elena Topchiy Subat Turdi Yue-feng Gao Bruce Culver Shu-yi Wang Wei Ge Wen-liang Zha Jun Ren Zhao-hui Pei Xing Qin | 2022 | Acta Pharmacologica Sinica2022，43，1： | 6 |
| 3 | Review of primary sclerosing cholangitis with increased IgG4 levels显示文摘Primary sclerosing cholangitis(PSC) is a chronic progressive liver disease. Subtypes of PSC have been described, most recently PSC with elevated serum and/or tissue IgG4 subclass. We aim to summarise the clinical phenotype,disease associations, differential diagnosis, response to therapy and pathogenic mechanisms underlying PSC-high IgG4 subtype. We reviewed Pub Med,MEDLINE and Embase with the search terms 'primary sclerosing cholangitis','IgG4', and 'IgG4-related sclerosing cholangitis(IgG4-SC)'. Elevated serum IgG4 are found in up-to one-quarter, and abundant IgG4-plasma cell infiltrates in the liver and bile ducts are found in up-to one-fifth of PSC patients. This group have a distinct clinical phenotype, with some studies reporting a more aggressive course of liver and associated inflammatory bowel disease, compared to PSCnormal IgG4 and the disease mimic IgG4-SC. Distinguishing PSC-high IgG4 from IgG4-SC remains challenging, requiring careful assessment of clinical features,organ involvement and tissue morphology. Calculation of serum IgG4:IgG1 ratios and use of a novel IgG4:IgG RNA ratio have been reported to have excellent specificity to distinguish IgG4-SC and PSC-high IgG4 but require validation in larger cohorts. A role for corticosteroid therapy in PSC-high IgG4 remains unanswered, with concerns of increased toxicity and lack of outcome data. The immunological drivers underlying prominent IgG4 antibodies in PSC are incompletely defined. An association with PSC-high IgG4 and HLA class-II haplotypes(B*07, DRB1*15), T-helper2 and T-regulatory cytokines(IL4, IL10,IL13) and chemokines(CCL1, CCR8) have been described. PSC-high IgG4 have a distinct clinical phenotype and need careful discrimination from IgG4-SC,although response to immunosuppressive treatments and long-term outcome remains unresolved. The presence of IgG4 likely represents chronic activation to persistent antigenic exposure in genetically predisposed individuals. | Charis D Manganis Roger W Chapman Emma L Culver | 2020 | World Journal of Gastroenterology2020，26，23： | 5 |
| 4 | Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis显示文摘 | Phil A Hart Terumi Kamisawa William R Brugge Jae Bock Chung Emma L Culver László Czakó Luca Frulloni Vay Liang W Go Thomas M Gress Myung-Hwan Kim Shigeyuki Kawa Kyu Taek Lee Markus M Lerch Wei-Chih Liao Matthias L?hr Kazuichi Okazaki Ji Kon Ryu Nicolas Sc | 2013 | Gut2013，，12： | 2 |
| 5 | T lymphocyte-directed gene therapy for ADA-SCID:initial trial results after 4 years显示文摘 | Blaese R M Culver K W Miller A D | 1995 | Science1995，270，5235： | 2 |
| 6 | Evolving role of magnetic resonance techniques in primary sclerosing cholangitis显示文摘Development of non-invasive methods to risk-stratify patients and predict clinical endpoints have been identified as one of the key research priorities in primary sclerosing cholangitis(PSC). In addition to serum and histological biomarkers, there has been much recent interest in developing imaging biomarkers that can predict disease course and clinical outcomes in PSC.Magnetic resonance imaging/magnetic resonance cholangiopancreatography(MRI/MRCP) continue to play a central role in the diagnosis and follow-up of PSC patients. Magnetic resonance(MR) techniques have undergone significant advancement over the last three decades both in MR data acquisition and interpretation. The progression from a qualitative to quantitative approach in MR acquisition techniques and data interpretation, offers the opportunity for the development of objective and reproducible imaging biomarkers that can potentially be incorporated as an additional endpoint in clinical trials. This review article will discuss how the role of MR techniques have evolved over the last three decades from emerging as an alternative diagnostic tool to endoscopic retrograde cholangiopancreatography, to being instrumental in the ongoing search for imaging biomarker of disease stage, progression and prognosis in PSC. | Emmanuel A Selvaraj Emma L Culver Helen Bungay Adam Bailey Roger W Chapman Michael Pavlides | 2019 | World Journal of Gastroenterology2019，25，6： | 2 |
| 7 | The Planktonic Index of Biotic Integrity (P-IBI): An approach for assessing lake ecosystem health显示文摘 | Douglas D. Kane Steven I. Gordon Mohiuddin Munawar Murray N. Charlton David A. Culver | 2009 | Ecological Indicators2009，，6： | 2 |
| 8 | The nationwide nosocomial infection rate: a new need for vital statistics显示文摘 | Haley R Culver D White J | 1985 | Am J Epidemiol1985，121，： | 2 |
| 9 | Virus-host interaction: induction of chlorotic and necrotic responses in plants by tabacco mosaic virus显示文摘 | Culver J N Lindbeck A G C Dawson W O | 1991 | Annual Review of Phytopathology1991，29，： | 1 |
| 10 | T lymphocyte-directed gene therapy for ADA--SCID:initial trial results after 4 years显示文摘 | Blaese R M Culver K W Miller A D | 1995 | Science1995，270，： | 1 |
| 11 | Tobacco mosaic virus assembly and disassembly: determinants in pathogenicity and resistance 显示文摘 | Culver JN | 2002 | Annu Rev Phytopathol2002，40，9： | 1 |
| 12 | A concise review of pulmonary sarcoidosis显示文摘 | Baughman RP Culver DA Judson MA | 2011 | Am J Respir Crit Care Med2011，183，5： | 1 |
| 13 | Essential elementsof genetic cancer risk assessment, counseling, and testing:updated recommendations of the National Society of GeneticCounselors 显示文摘 | Riley BD Culver JO Skrzynia C | 2012 | J Genet Couns2012，21，2： | 1 |
| 14 | Dietary iron deficiency induces ventricular dilation, mitochondrial ultrastructural aberrations and cytochrome c release: involvement of nitric oxide synthase and protein tyrosine nitration 显示文摘 | Dong F Zhang X Culver B | 2005 | Clin Sci (Lond)2005，109，3： | 1 |
| 15 | Extensive cervical lymphadenitis due to Mycobacterium avium-intracellulare显示文摘 | Kinsella J P Culver K Jeffrey R B | 1987 | Pediatr Infect Dis J1987，6，： | 1 |
| 16 | Surgical site infection (SSI) rates in the United States, 1992-1998: the National Nosocomial Infections Surveillance System basic SSI risk index 显示文摘 | Gaynes RP Culver DH Horan TC | 2001 | Clin Infect Dis2001，33，2： | 1 |
| 17 | The relationship of bloodand urine-boron to boron exposure in borax-workers and the usefulness of urine-boron as an exposure maker显示文摘 | Dwight Culver B Petex T Shen Thomas H T | 1994 | Environmental Health Perspectives1994，102，7： | 1 |
| 18 | Major trends in the microbial etioliogy of nosocomial infections显示文摘 | Schaberg DR Culver DH Gaynes RP | 1991 | Am J Med1991，91，3： | 1 |
| 19 | Diffusion-weighted MR imaging of female pelvic tumors ; a pictorial review显示文摘 | Whitaker CS Coady A Culver L | 2009 | Radiographies2009，29，3： | 1 |
| 20 | Coping and distress a mong women under treatment for early stage 'breast cancer : compa ring African Americans, Hispanics and non Hispanics whites显示文摘 | Culver J L Arena P L Antoni M H | 2002 | Psychooncology2002，11，6： | 1 |
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