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Cellular response against cytosolic leakage of mitochondrial DNA: insights into the pathology of Parkinson’s disease

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Neural Regeneration Research 2022年第12期17卷 2682-2684页

作者： akiko Sakai Hideaki Matsui Department of Neuroscience of Disease Brain Research InstituteNiigata UniversityNiigataJapan

Mitochondria are important organelles for cellular metabolism and homeostasis,and their abnormalities are implicated in various *** mitochondria originate from protobacterium,their components are easily recognized by pathogen sensors called pattern-recognition receptors as foreign substances in the *** is prominent for mitochondrial DNA(mtDNA)which has different properties from nuclear DNA,such as low,if any,methylation status,vulnerability to oxidation due to the proximity to the oxidative phosphorylation machinery,and its circular *** studies indicate that perturbations in mitochondrial function and homeostasis cause mtDNA to leak into the cytoplasm,where it triggers the innate immune response(West and Shadel,2017).Although inflammatory response is a cellular strategy to resist viral infections,it can also lead to undesirable outcomes by damaging own cells and tissues.

关键词： homeostasis metabolism insight

Polydendrocytes in development and myelin repair

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Neuroscience Bulletin 2013年第2期29卷 165-176页

作者： Hao Zuo akiko Nishiyama Department of Physiology and Neurobiology University of Connecticut University of Connecticut Stem cell Institute

Polydendrocytes （NG2 cells） are a distinct type of glia that populate the developing and adult central nervous systems （CNS）. In the adult CNS, they retain mitotic activity and represent the largest proliferating cell popula- tion. Genetic and epigenetic mechanisms regulate the fate of polydendrocytes, which give rise to both oligo- dendrocytes and astrocytes. In addition, polydendrocytes actively differentiate into myelin-forming oligodendro- cytes in response to demyelination. This review summarizes the current knowledge regarding polydendrocyte development, which provides an important basis for understanding the mechanisms that lead to the remyelina- tion of demyelinated lesions.

关键词： polydendrocytes NG2 cells oligodendrocytes myelin cell fate

Involvement of insulin receptor substrates in cognitive impairment and Alzheimer’s disease

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Neural Regeneration Research 2019年第8期14卷 1330-1334页

作者： Daisuke Tanokashira Wataru Fukuokaya akiko Taguchi Department of Integrative Aging Neuroscience National Center for Geriatrics and Gerontology Obu Aichi Japan Division of Neurology Endocrinology and Metabolism Faculty of Medicine University of Miyazaki Miyazaki Japan

Type 2 diabetes一associated with impaired insulin/insulin-like growth factor-1 (IGF1) signaling (IIS)一is a risk factor for cognitive impairment and dementia including Alzheimer's disease (AD). The insulin receptor substrate (IRS) proteins are major components of IIS, which transmit upstream signals via the insulin receptor and/or IGF1 receptor to multiple intracellular signaling pathways, including AKT/protein kinase B and extracellular-signal-regulated kinase cascades. Of the four IRS proteins in mammals, IRS1 and IRS2 play key roles in regulating growth and survival, metabolism, and aging. Meanwhile, the roles of IRS1 and IRS2 in the central nervous system with respect to cognitive abilities remain to be clarified. In contrast to IRS2 in peripheral tissues, inactivation of neural IRS2 exerts beneficial effects, resulting in the reduction of amyloid p accumulation and premature mortality in AD mouse models. On the other hand, the increased phosphorylation of IRS 1 at several serine sites is observed in the brains from patients with AD and animal models of AD or cognitive impairment induced by type 2 diabetes. However, these serine sites are also activated in a mouse model of type 2 diabetes, in which the diabetes drug metformin improves memory impairment. Because IRS1 and IRS2 signaling pathways are regulated through complex mechanisms including positive and negative feedback loops, whether the elevated phosphorylation of IRS1 at specific serine sites found in AD brains is a primary response to cognitive dysfunction remains unknown. Here, we examine the associations between IRS 1 /1 RS2-mediated signaling in the central nervous system and cognitive decline.

关键词： type 2 diabetes insulin/insulin^like growth factor-1 insulin receptor substrate Alzheimer's disease aging serine phosphorylation metformin neuroprotective effects high-fat-diet

The promises and challenges of research on plant-insect-microbe interactions

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Insect Science 2017年第6期24卷 904-909页

作者： Jean-Christophe Simon Arjen Biere akiko Sugio UMR 1349 Institut de Genetique Environnement et Protection des Plantes INRA Agrocampus Ouest Universite Rennes 1 Domaine de la Motte Le Rheu Cedex France Department of Terrestrial Ecology Netherlands Institute of Ecology NIOO-KNA W Wageningen the Netherlands

Ecological interactions are of paramount importance for the functioning and health of ecosystems. Phytophagous insects are part of complex ecological networks involving abiotic factors, host plants, natural enemies, and benefi- cial organisms （McLean et al., 2016）. Insects and plants are also associated durably or transitorily with a wealth of microbes including pathogens, commensals and beneficial partners from a vast array of microbial taxa （Sugio et al., 2015）. In recent years, evidence has accumulated that microbes directly or indirectly influence plant-insect interactions at individual, population and community levels.

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Metachronous gastric cancer after successful Helicobacter pylori eradication

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World Journal of Gastroenterology 2014年第33期20卷 11552-11559页

作者： akiko Shiotani Ken Haruma David Y Graham Department of Internal Medicine Kawasaki Medical School Kurashiki 701-0192 Japan Department of Medicine Michael E DeBakey VAMC and Baylor College of Medicine Houston TX 77030 United States

The high incidence of gastric cancer in Japan initially resulted in establishment of a country-wide gastric cancer screening program to detect early and treatable cancers. In 2013 countrywide Helicobacter pylori(H. pylori) eradication was approved coupled with endoscopy to assess for the presence of chronic gastritis. Current data support the notion that cure of the infection in those with non-atrophic gastritis will prevent development of gastric cancer. However, while progression to more severe damage is halted in those who have already developed, atrophic gastritis/gastric atrophy remain at risk for subsequent development of gastric cancer. That risk is directly related to the extent and severity of atrophic gastritis. Methods to stratify cancer risk include those based on endoscopic assessment of the atrophic border, histologic grading, and non-invasive methods based on serologic testing of pepsinogen levels. Continued surveillance is required because those with atrophic gastritis/gastric atrophy retain considerable gastric cancer risk even after H. pylori eradication. Those who have already experienced a resectable early gastric cancer are among those at highest risk as metachronous lesions are frequent even after H. pylorieradication. We review the role of H. pylori and effect of H. pylori eradication indicating the incidence and the predictive factors on development of metachronous cancer after endoscopic therapy of early gastric cancer. Studies to refine risk markers to stratify for risk, surveillance methods, intervals, and duration after successful H. pylori eradication, and whether adjuvant therapy would change risk are needed.

关键词： Atrophic gastritis Pepsinogen miRNA Intestinal metaplasia Cancer prevention

A potential new tool to enhance translational success rate in stroke research by backcrossing techniques in transgenic mice

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Neural Regeneration Research 2023年第1期18卷 107-108页

作者： Takayuki Nakagomi Hideaki Nishie Toshinori Sawano akiko Nakano-Doi Institute for Advanced Medical Sciences Hyogo College of MedicineHyogoJapan Department of Therapeutic Progress in Brain Diseases Hyogo College of MedicineHyogoJapan Department of Biomedical Sciences Ritsumeikan UniversityShigaJapan

Ischemic stroke is a leading disease of the central nervous system,frequently coupled to severe damage and dysfunction in *** models mimicking human stroke provide useful tools for studying the pathomechanisms(e.g.,inflammation,neuroprotection,and neural regeneration),the treatment efficiency of various materials(e.g.,bioactive molecules or drugs),and transplantation usefulness by various cell types[e.g.,neural stem/progenitor cells(NSPCs),and mesenchymal or hematopoietic stem cells]under ischemic stroke.

关键词： inflammation damage neural

Clinical features of acute esophageal mucosal lesions and reflux esophagitis Los Angeles classification grade D: A retrospective study

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World Journal of Gastrointestinal Surgery 2023年第3期15卷 408-419页

作者： Chikamasa Ichita akiko Sasaki Sayuri Shimizu Department of Gastroenterology Medicine Center Shonan Kamakura General HospitalKamakura 247-8533KanagawaJapan Department of Health Data Science Yokohama City UniversityYokohama 236–0027KanagawaJapan

BACKGROUND Acute esophageal mucosal lesions(AEMLs)are an underrecognized and largely unexplored *** findings are similar,and a higher percentage of AEML could be misdiagnosed as reflux esophagitis Los Angeles classification grade D(RE-D).These diseases could have different pathologies and require different *** To compare AEML and RE-D to confirm that the two diseases are different from each other and to clarify the clinical features of *** We selected emergency endoscopic cases of upper gastrointestinal bleeding with circumferential esophageal mucosal injury and classified them into AEML and RE-D groups according to the mucosal injury’s shape on the oral *** examined patient background,blood sampling data,comorbidities at onset,endoscopic characteristics,and outcomes in each *** Among the emergency cases,the AEML and RE-D groups had 105(3.1%)and 48(1.4%)cases,*** variables exhibited significantly different results,indicating that these two diseases are *** clinical features of AEML consisted of more comorbidities[risk ratio(RR):3.10;95%confidence interval(CI):1.68–5.71;P<0.001]and less endoscopic hemostasis compared with RE-D(RR:0.25;95%CI:0.10–0.63;P<0.001).Mortality during hospitalization was higher in the AEML group(RR:3.43;95%CI:0.82–14.40;P=0.094),and stenosis developed only in the AEML *** AEML and RE-D were clearly distinct diseases with different clinical *** may be more common than assumed,and the potential for its presence should be taken into account in cases of upper gastrointestinal bleeding with comorbidities.

关键词： Acute esophageal mucosal lesion Comorbidities Esophageal reflux Black esophagus Acute necrotizing esophagitis

Ambipolar device simulation based on the drift-diffusion model in ion-gated transition metal dichalcogenide transistors

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npj Computational Materials 2020年第1期6卷 1446-1454页

作者： akiko Ueda Yijin Zhang Nobuyuki Sano Hiroshi Imamura Yoshihiro Iwasa National Institute of Advanced Industrial Science and Technology(AIST) Spintronics Research CenterTsukuba 305-8568Japan Department of Electrical Engineering Columbia UniversityNew YorkNYUSA The Institute of Scientific and Industrial Research Osaka UniversityOsaka 067-0047Japan Max Planck Institute for Solid State Research 70569 StuttgartGermany Institute of Applied Physics University of TsukubaTsukuba 305-8573Japan Department of Applied Physics and Quantum-Phase Electronics(QPEC)Center The University of TokyoTokyo 113-8656Japan RIKEN Center for Emergent Matter Science(CEMS)Wako 351-0198Japan

Ionic gating is known as a powerful tool for investigation of electronic functionalities stemming from low voltage transistor operation to gate-induced electronic phase control including ***-dimensional(2D)material is one of the archetypal channel materials which exhibit a variety of gate-induced ***,the device simulations on such iongated transistor devices have never been reported,despite its importance for the future design of device *** this paper,we developed a drift-diffusion(DD)model on a 2D material,WSe2 monolayer,attached with an ionic liquid,and succeeded in simulating the transport properties,potential profile,carrier density distributions in the transistor configuration.

关键词： transistor bipolar diffusion

Biomarkers of skin toxicity induced by anti-epidermal growthfactor receptor antibody treatment in colorectal cancer

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World Journal of Gastroenterology 2016年第2期22卷 887-894页

作者： akiko Kubo Hironobu Hashimoto Naoki Takahashi Yasuhide Yamada Division of Pharmacy National Cancer Center HospitalTokyo 104-0045Japan Gastrointestinal Oncology Division National Cancer Center HospitalTokyo 104-0045Japan

Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer(the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing(EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients.

关键词： Colorectal cancer Skin toxicity Epidermalgrowth factor receptor Epidermal growth factorreceptor polymorphism Ligand