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Multiplexed bioluminescence imaging of cancer cell response to hypoxia and inflammation in the caudal-artery injection model of bone metastasis during zoledronic acid treatment

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 69-80页

作者： misa minegishi Takahiro Kuchimaru Kenji Nakagawa Tatsuhiro Isozaki Satoshi Fujimori Tetsuya Kadonosono Shinae Kizaka-Kondoh School of Life Science and Technology Tokyo Institute of TechnologyKanagawa 226-8501Japan Center for Molecular Medicine Jichi Medical UniversityTochigi 329-0498Japan.

Aim:Therapeutic agents suppressing bone remodeling have been clinically approved to delay metastatic progression and skeletal-related events in patients with bone metastasis.However,therapeutic agents including zoledronic acid(ZA)are insufficient to regress established bone metastasis.Therefore,new treatment strategies are desired,and unraveling the status of cancer cells during bone metastatic progression will help develop therapeutic strategies.Methods:We developed a unique multiplexed reporter system for bioluminescent imaging(MRS-BLI)using three luciferase reporter genes.This system allows for the noninvasive and quantitative monitoring of tumor growth and activities of nuclear factor-kappa B(NF-κB)and hypoxia-inducible factor(HIF),which are the key transcriptional factors in response to inflammation and hypoxia,respectively.PC-3/MRS-BLI,a human prostate cancer cell line that stably retains the MRS-BLI reporter genes,was applied to the caudal-artery injection model of bone metastasis to observe the status of cancer cells during bone metastasis development and ZA treatment(<1 month).Results:MRS-BLI reveals key events during the bone metastasis development:NF-κB and HIF are activated in cancer cells after migration to the bone marrow and are transiently reduced,followed by rapid activation before proliferation begins.ZA treatment suppresses the growth of metastasized cancer cells by suppressing NF-κB and HIF activities that may be indirectly induced by osteoclast activation.Conclusion:By visualizing the NF-κB and HIF activities of PC-3/MRS-BLI in bone,MRS-BLI has enabled new discoveries regarding the regulation of bone metastases.Further analysis of the progression of bone metastases using MRS-BLI may provide important information for developing new therapeutic strategies.

关键词： Bone metastasis multiplexed bioluminescence imaging zoledronic acid nuclear factor-kappa B hypoxia inducible factor

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Asymmetric expression of CA2 and CA13 linked to calcification in the bilateral mandibular condyles cause crossed beaks in chickens

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Journal of Integrative Agriculture 2024年第7期23卷 2379-2390页

作者： Lei Shi Yanyan Sun Yunlei Li Hao Bai Jingwei Yuan Hui Ma Yuanmei Wang Panlin Wang Aixin Ni Linlin Jiang Pingzhuang Ge Shixiong Bian Yunhe Zong Jinmeng Zhao Adamu misa Hailai HTesfay Jilan Chen State Key Laboratory of Animal Biotech Breeding/Key Laboratory of Animal(Poultry)Genetics Breeding and Reproduction of Ministry of Agriculture and Rural Affairs/Institute of Animal Sciences Chinese Academy of Agricultural SciencesBeijing 100193China College of Animal Science and Technology Hebei Agricultural UniversityBaoding 071001China Joint International Research Laboratory of Agriculture and Agri-Product Safety Ministry of Education/Institutes of Agricultural Science and Technology DevelopmentYangzhou UniversityYangzhou 225009China

Crossed beak is a complex mode of inheritance with prevalence ranging from 0.2 to 7.4%in at least 12 chicken strains worldwide.To reveal the intrinsic factors causing crossed beaks,genes expression patterns in bilateral mandibular condyle between affected and normal birds were characterized by RNA sequencing analysis in the present studies.Crossed beak was induced by short length of unilateral mandibular ramus,and a total of 110 differentially expressed genes were up-or down-regulated in the affected(short)mandibular condyle side as compared to the normal side.Carbonic anhydrase 2(CA2)and Carbonic anhydrase 13(CA13)were enriched in the carbonate dehydratase activity,and high-expressed in mandibular condyle and osteoblasts(P<0.05).However,both were low-expressed in short mandibular condyle side of affected birds(P<0.05).The carbonate dehydratase inhibitor experiments confirmed that there is positive association between the calcification and carbonic anhydrase isoenzymes.Quantitative analysis with cetylpyridinium chloride showed a decrease in calcification when the cells were transfected with an anti-CA13 shRNA.Our research suggested that CA2 and CA13 are down-calcified in shortside mandibular condyle,and caused mandibular ramus to grow slowly.CA2 and CA13 have the critical role in crossed beaks by regulating calcification of mandibular condyle.

关键词： chicken crossed beak carbonic anhydrase calcification CA2 CA13

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Treatment of portosystemic shunt-borne hepatic encephalopathy in a 97-year-old woman using balloon-occluded retrograde transvenous obliteration:A case report

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World Journal of Clinical Cases 2023年第4期11卷 945-951页

作者： Akihiro Nishi Tsuneaki Kenzaka misa Sogi Shuichiro Nakaminato Takahiro Suzuki General Medicine Awa Regional Medical CenterTateyama 2940014ChibaJapan Division of Community Medicine and Career Development Kobe University Graduate School of MedicineKobe 6500017HyogoJapan Department of Radiology Kameda Medical CenterKamogawa 2968602ChibaJapan

BACKGROUND Hyperammonemia and hepatic encephalopathy are common in patients with portosystemic shunts.Surgical shunt occlusion has been standard treatment,although recently the less invasive balloon-occluded retrograde transvenous obliteration(B-RTO)has gained increasing attention.Thus far,there have been no reports on the treatment of portosystemic shunts with B-RTO in patients aged over 90 years.In this study,we present a case of hepatic encephalopathy caused by shunting of the left common iliac and inferior mesenteric veins,successfully treated with B-RTO.CASE SUMMARY A 97-year-old woman with no history of liver disease was admitted to our hospital because of disturbance of consciousness.She had no jaundice,spider angioma,palmar erythema,hepatosplenomegaly,or asterixis.Her blood tests showed hyperammonemia,and abdominal contrast-enhanced computed tomography revealed a portosystemic shunt running between the left common iliac vein and the inferior mesenteric vein.She was diagnosed with hepatic encephalopathy secondary to a portosystemic shunt.The patient did not improve with conservative treatment:Lactulose,rifaximin,and a low-protein diet.B-RTO was performed,which resulted in shunt closure and improvement in hyperammonemia and disturbance of consciousness.Moreover,there was no abdominal pain or elevated levels of liver enzymes due to complications.The patient was discharged without further consciousness disturbance.CONCLUSION Portosystemic shunt-borne hepatic encephalopathy must be considered in the differential diagnosis for consciousness disturbance,including abnormal behavior and speech.

关键词： Hepatic encephalopathy Hyperammonemia Portosystemic shunt Balloon-occluded retrograde transvenous obliteration Elderly Case report

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Determination of convergence of underground gas storage caverns using non-invasive methodology based on land surface subsidence measurement

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Journal of Rock Mechanics and Geotechnical Engineering 2023年第8期15卷 1944-1950页

作者： Rafal misa Anton Sroka Mateusz Dudek Krzysztof Tajdus Stefan Meyer Instytut Mechaniki Górotworu PAN ul.Reymonta 2730-059KrakówPoland Salzgewinnungsgesellschaft Westfalen mbH&Co.KG(SGW) AhausGermany

Undergroundgas storage caverns aremonitoredfor environmental safety in termsof equipmentandpotential emissions,particularly methane emissions from the underground and above-ground parts of the storage facility.Periodical measurements of land surface deformations and costly echometric measurements of convergence of individual storage facilities are carried out.The aims of environmental monitoring are:(1)to eliminate potential hazards in the shortest time,(2)assess the overall impact of intensive operation of storage facilities on the environment,(3)developmonitoringmethods relevant to environmental protection,and(4)take actions in case of failure.The paper presents a solution to the problem of determination of the convergence of underground caverns in a salt rock mass based on the results of land surface subsidence measurements carried out using the Gauss-Markov equalization algorithm.Themethod makes it possible for ongoing control of cavern volume convergence after each subsidence measurement on the ground surface and determining the actual impact of the use frequency(injection-mediumconsumption)on the convergence in time.The presentedmethodology is universal and verified on caverns located in a salt rockmass.The Gauss-Markov inversion model is the first used in this area,hence its application is significant.

关键词： Underground storage Salt cavern Convergence Subsidence Surface deformation

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Effect of different starch sources in a raw meat-based diet on fecal microbiome in dogs housed in a shelter

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Animal Nutrition 2020年第3期6卷 353-361页

作者： misa Sandri Sandy Sgorlon Elisa Scarsella Bruno Stefanon Department of AgriFood Environmental and Animal ScienceUniversity of UdineUdine33100Italy

A dietary intervention study was assessed to determine if different sources of starch in homemade diets could significantly modify fecal microbiome of dogs.Twenty-seven adult dogs were enrolled and fed a diet based on a mixture of rice and pasta with fresh raw meat(CD).After 90 d,8 dogs continued to receive CD diet,10 dogs received a diet made of a raw meat and a complementary food with rice as the main source of starch(B1),and 9 dogs were fed a diet with the same raw meat and a complementary food with potato as the main source of starch(B2).Samples of feces were collected from each dog in the mornings at the beginning of the study and after 15 d and analyzed for pH,ammonia N(N-NH3)and total N,short chain fatty acids(SCFA)and lactic acid.Relative abundance of fecal microbiota was assessed by sequencing and annotating the V3-V4 regions of the 16S rRNA.Total starch intake was similar between diets but differed in the in vitro rate digestion and in the resistant starch,which was higher in B2 than in B1 and CD diets.Dogs fed B2 diet showed lower(P<0.05)N-NH3 and pH but higher(P<0.05)molar proportion of lactic acid.Linear discriminant analysis of the genera relative abundances indicated a significant(P<0.01)increase of SMB53 genus at the end of the study in B1 diet and of Megamonas genus in B1 and B2 diets in comparison to CD diet.These results suggest that changes of starch source in a raw meat-based diet have limited effects on fecal microbiome in healthy dogs,but underline a high variability of microbiota among dogs.

关键词： Diets Starch fraction Microbiome Nutrition Canis lupus familiaris

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Systemic interleukin-9 in inflammatory bowel disease: Association with mucosal healing in ulcerative colitis

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World Journal of Gastroenterology 2017年第22期23卷 4039-4046页

作者： Malgorzata Matusiewicz Katarzyna Neubauer Iwona Bednarz-misa Sabina Gorska Malgorzata Krzystek-Korpacka Department of Medical Biochemistry Wroclaw Medical University Department of Gastroenterology and Hepatology Wroclaw Medical University Laboratory of Medical Microbiology Ludwik Hirszfeld Institute of Immunology and Experimental TherapyPolish Academy of Sciences

AIM To evaluate circulating IL9 in inflammatory bowel disease and disease-associated anemia/cachexia and assess its potential as a mucosal healing marker.METHODS Serum IL9 as well as other cytokines(IL1β, IL6, IL13, IFNγ, TNFα, and VEGF-A) were determined in 293 individuals: 97 patients with Crohn's disease(CD) and 74 with ulcerative colitis(UC) and in 122 apparently healthy controls. The clinical activity of CD and UC was expressed in terms of the Crohn's Disease Activity Index(CDAI) and the Mayo Scoring System(MDAI), respectively, and the severity of bowel inflammation in UC patients was assessed using Mayo endoscopic score. Cytokine concentrations were measured by a flow cytometry-based method using Luminex x MAP? technology. Highsensitive C-reactive protein concentrations(hs CRP) were determined in CD and UC patients using the enhanced immunoturbidimetric method.RESULTS Systemic IL9 was significantly lower in healthy individuals [9 pg/m L(95%CI: 8.2-10)] than in patients with inflammatory bowel disease(IBD): both inactive [14.3 pg/m L(11.9-19.9)] and active [27.6 pg/m L(24.5-32), P < 0.0001]. Cytokine concentrations were significantly higher in active CD [27.4 pg/m L(23.4-32.2)] and in active UC [32.7 pg/m L(27-38.9)] compared to inactive diseases [15.9 pg/m L(10.8-23.4) in CD and 19.4 pg/m L(13.9-27.1) in UC, P = 0.001]. IL9 correlated weakly with CDAI(ρ = 0.32, P = 0.003) and MDAI(ρ = 0.35, P = 0.002) and strongly with endoscopic inflammation in UC(ρ = 0.74, P < 0.0001). As a negative marker of mucosal healing(MH), IL9 had an accuracy superior to hs CRP and IL6 [97%(P < 0.0001), 67%(P = 0.071), and 55%(P = 0.525), respectively]. IL9 was significantly higher in cachectic IBD patients [30.25 pg/m L(24.4-37.5) vs 21.88 pg/m L(18-26.5), P = 0.026] and negatively correlated with hemoglobin concentrations(ρ =-0.27, P < 0.001). Multiple regression showed IL1β and IL13 to be the independent predictors of circulating IL9 in healthy individuals, IFNγ or IL6 in active and inactive UC, respectively, and IL13 and VEGF-A

关键词： Interleukin 9 Mucosal 愈合 Biomarker 煽动性的肠疾病 Crohns 疾病 Ulcerative 大肠炎极度瘦弱贫血症

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Gene expression of CCL8 and CXCL10 in peripheral blood leukocytes during early pregnancy in cows

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Journal of Animal Science and Biotechnology 2018年第4期9卷 813-823页

作者： Ryosuke Sakumoto Kosuke Iga Ken-Go Hayashi Shiori Fujii Hiroko Kanahara misa Hosoe Tadashi Furusawa Division of Animal Breeding and Reproduction Research Institute of Livestock and Grassland Science National Agriculture and Food Research Organization (NARO) Division of Livestock and Forage Research Tohoku Agricultural Research CenterNARO Division of Animal Sciences Institute of Agrobiological SciencesNARO

Background: The aim of the present study was to evaluate CCL8 and CXCL10 expression and its regulatory mechanism in peripheral blood leukocytes(PBLs) at the time of maternal recognition in cows. Blood samples were collected on 14, 15, 16, 17 and 18 d after artificial insemination(AI). Based on the day of return of estrus, cows were divided into three groups, pregnant(n = 5), early embryonic mortality(EEM; n = 5) and late embryonic mortality(LEM; n = 5). The gene expression levels in PBLs were assessed with quantitative real-time reverse transcription PCR.Results: The expression of CCL8 and CXCL10 mRNA in PBLs gradually increased from 14 to 18 d of pregnant cows and significant differences were observed on 18 d(P < 0.05), whereas no significant changes were observed both in EEM and LEM cows. Interferon-stimulated protein 15 k Da(ISG15), myxovirus-resistance gene(MX) 1 and MX2 mRNA expression in PBLs increased from 14 to 18 d which was significant on 18 d of pregnant cows as well as in LEM cows(P < 0.05), but no changes were observed in EEM cows. To determine whether the expression of CCL8 and CXCL10 in PBLs was regulated by pregnancy-related substances or not, expression level was assessed after exposure to interferon-τ(IFNT) and CCL16. Monocytes, granulocytes and lymphocytes were obtained using density-gradient centrifugation and flow cytometry. The addition of IFNT(100 ng/mL) and CCL16(100 ng/mL) to cultured PBLs increased the expression of CCL8 and CXCL10 mRNA(P < 0.05). The expression of ISG15, MX1 and MX2 mRNA in PBLs was also stimulated by IFNT and CCL16(P < 0.05).Conclusions: The expression of CCL8 and CXCL10 genes increased in PBLs during early pregnancy. Since IFNT stimulated CCL8 and CXCL10 expression in cultured PBLs, the increase of CCL8 and CXCL10 might be pregnancy-dependent events.The expression of both CCL8 and CXCL10 in PBLs was stimulated by CCL16 as wel as IFNT, suggesting a chemokine interaction that at least includes CCL8, CXCL10 and CCL16, and may play a role in regulating maternal recognitio

关键词： CCL8 Cow CXCL10 Leukocytes Pregnancy

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The Gap Between Early Adopters and Early Majority in the Diffusion of Environmentally Friendly Farming

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Journal of Sociology Study 2014年第12期4卷 1060-1070页

作者： misa Aoki Nara Women's University Japan

As an increasing number of people have become interested in healthy and environmentally friendly farm products, the diffusion process of sustainable farming has been widely discussed. However, few studies have empirically investigated the differences between early adopters and early majority in diffusion of environmentally friendly farming. The purpose of this study is to examine the existence of the gap between early adopters and the early majority in the diffusion of environmentally friendly certified farm production by focusing on the case in which a frequent buyers program (FBP) was introduced for locally certified crops in the farmers markets of Japan. Though there were no differences in the characteristics of the two groups, early adopters initiated such production through governmental information provision and expected more profit than the adopters that followed. It was also found that non‐economic reasons and information on stable markets for the certified products were crucial for both adopter groups.

关键词：可持续农业扩散过程环境友好型早期大众差距环保认证环保农业

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这个寒冬不下雪

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作者： misa

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Coping Process in Children with Food Allergies Developing during Early Childhood

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Health 2020年第1期12卷 38-62页

作者： misa Suzuki Yuko Tomari Faculty of Nursing Seisen University Shiga Japan Faculty of Nursing Osaka Medical University Osaka Japan

This study aimed to clarify the coping process in children who developed food allergies in early childhood and evaluate the nursing support required to enable the acquisition of independent care behaviors in children with food allergies. Semi structured interviews were conducted on 24 children (aged 11 - 15 years) with food allergies using the modified grounded theory approach. The 11 categories were identified as coping mechanisms that these children used to deal with their early childhood food allergies. The coping process in children with food allergies involved transition from a stage of viewing their allergy with fear to a stage of considering the allergy as manageable and thus tackling allergens in their own way in the Life model. The process required obtaining peace of mind with support from others. In addition to emphasizing the threat of food allergies and risk aversion behaviors to these children, it is important that nurses also communicate viable proposals for alternative behaviors for the prohibited actions. The results also suggest that children in school age or older require support to help them recognize food allergy-related issues as problem-oriented coping tasks from the viewpoint of both Medical and Life models.

关键词： Food Allergies Coping Care Behavior Modified Grounded Theory Approach

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