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BIOCELL 2022年第8期46卷 1861-1865页

作者： MASASHI KAWAMI RYOKO YUMOTO MIKIHISA TAKANO graduate school of biomedical and Health sciences Hiroshima UniversityHiroshima7348553Japan

A number of drugs induce pulmonary injury and subsequently lead to serious lung diseases such as pulmonary fibrosis as the adverse drug reactions.However,an effective preventive approach against drug-induced pulmonary fibrosis has not been established due to poor understanding of common preventive targets in a variety of drugs showing pulmonary toxicity.Epithelial-mesenchymal transition(EMT),a cellular phenotypic change of the epithelial to mesenchymal state,contributes to the development of pulmonary fibrosis through the conversion of damaged alveolar epithelium into myofibroblasts.As several drugs with pulmonary toxicity have been reported to induce EMT,EMT serves as a bridge between the drugs and pulmonary fibrosis.Accumulated evidence supports the potential of EMT as a preventive target against drug-induced pulmonary fibrosis.Additionally,since there are mechanistic differences between the main pharmacological effect and EMT induced by the drug,prevention based on EMT suppression would be possible and would contribute to continuous clinical treatment with the drug to avoid EMT-mediated serious pulmonary fibrosis.Furthermore,targeting EMT seems to be adequate for exerting a preventive effect since EMT in damaged alveolar epithelial cells occurs prior to the development of the pathophysiological state of the whole lung in a bleomycin-induced lung injury rat model.This viewpoint deals with the benefits and perspectives of preventive approaches against druginduced pulmonary fibrosis through the suppression of EMT,which has rarely been addressed.

关键词： Drug-induced lung injury Epithelial-mesenchymal transition Pulmonary fibrosis α-smooth muscle actin

Heparin-induced thrombocytopenia occurring early after living donor liver transplantation:a case report

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Emergency and Critical Care Medicine 2023年第4期3卷 198-202页

作者： Naoya Iwasaki Motohiro Sekino Takanobu Hara Akihiko Soyama Masaaki Hidaka Yusuke Kasai Miki Suzumura Hiroshi Araki Rintaro Yano Sojiro Matsumoto Taiga Ichinomiya Ushio Higashijima Susumu Eguchi Tetsuya Har Department of Anesthesiology and Intensive Care Medicine Nagasaki University Graduate School of Biomedical SciencesNagasakiJapan Department of Surgery Nagasaki University Graduate School of Biomedical SciencesNagasakiJapan

Background:Thrombocytopenia commonly occurs early after liver transplantation.Heparin,usually administered as anticoagulant ther-apy for thrombosis,a common complication after liver transplantation,may cause heparin-induced thrombocytopenia.Heparin-induced thrombocytopenia is a rare but life-threatening complication,and its diagnosis after liver transplantation is challenging.Case presentation:We report a case of heparin-induced thrombocytopenia after living donor liver transplantation with a good out-come because of early diagnosis and discontinuation of heparin.After liver transplantation,the platelet count usually reaches a nadir on postoperative days 3–5 and gradually recovers.In contrast,heparin-induced thrombocytopenia typically occurs 5–10 days after heparin administration;therefore,if heparin is started intraoperatively,then thrombocytopenia will occur on postoperative days 5–10.Conclusion:Monitoring the trend and timing of thrombocytopenia and detailed examination for thrombosis may help confirm the diag-nosis of heparin-induced thrombocytopenia in the early stage after liver transplantation.

关键词： Case report Heparin Heparin-induced thrombocytopenia Liver transplantation Thrombocytopenia Thrombosis

You had me at PELO:a"Ribosome Rescuer"induces NLR inflammasome assembly

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Cellular & Molecular Immunology 2024年第1期21卷 1-2页

作者： Zoie Magri Alexander Poltorak graduate Program in Immunology Tufts Graduate School of Biomedical Sciences136 Harrison AvenueBostonMA02111USA Department of Immunology Tufts University School of MedicineBostonMA02111USA

Pyroptosis,an inflammatory form of programmed cell death,eliminates a niche where pathogens replicate,providing overall benefits to a host.When left uncontrolled,pyroptosis can lead to severe pathology.Overactive pyroptotic activation has been implicated in neuroinflammation,cardiovascular disease,acute respiratory distress syndrome(ARDS),and many other diseases[1,2,3].Because of its multiple and permanent consequences,pyroptosis is a highly regulated signaling pathway.Major regulators of pyroptosis are NLR inflammasomes,which are activated by various“danger”signals such as ATP.

关键词： inflam NLR distress

Differential effects of physical activity and sleep duration on cognitive function in young adults

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Journal of Sport and Health Science 2018年第2期7卷 227-236页

作者： Kazuko Kato Kunihiro Iwamoto Naoko Kawano Yukihiro Noda Norio Ozaki Akiko Noda Department of biomedical sciences Chubu University Graduate School of Life and Health Sciences Department of Psychiatry Nagoya University Graduate School of Medicine Institutes of Innovation for Future Society Nagoya University Division of Clinical sciences and Neuropsychopharmacology Graduate School of PharmacyMeijo University

Purpose: Although exercise and sleep duration habits are associated with cognitive function, their beneficial effects on cognitive function remain unclear. We aimed to examine the effect of sleep duration and daily physical activity on cognitive function, elucidating the neural mechanisms using near-infrared spectroscopy(NIRS).Methods: A total of 23 healthy young adults(age 22.0 ± 2.2 years) participated in this study. Exercise amount was assessed using a uniaxial accelerometer. We evaluated total sleep time(TST) and sleep efficiency by actigraphy. Cognitive function was tested using the N-back task, the Wisconsin Card Sorting Test(WCST), and the Continuous Performance Test—Identical Pairs(CPT-IP), and the cortical oxygenated hemoglobin levels during a word fluency task were measured with NIRS.Results: Exercise amount was significantly correlated with reaction time on 0- and 1-back tasks(r = —0.602, p = 0.002; r = —0.446, p = 0.033,respectively), whereas TST was significantly correlated with % corrects on the 2-back task(r = 0.486, p = 0.019). Multiple regression analysis,including exercise amount, TST, and sleep efficiency, revealed that exercise amount was the most significant factor for reaction time on 0- and 1-back tasks(b = —0.634, p = 0.002; b = —0.454, p = 0.031, respectively), and TST was the most significant factor for % corrects on the 2-back task(b = 0.542, p = 0.014). The parameter measured by WCST and CPT-IP was not significantly correlated with TST or exercise amount. Exercise amount, but not TST, was significantly correlated with the mean area under the NIRS curve in the prefrontal area(r = 0.492, p = 0.017).Conclusion: Exercise amount and TST had differential effects on working memory and cortical activation in the prefrontal area. Daily physical activity and appropriate sleep duration may play an important role in working memory.

关键词：持续时间认知功能成年人睡觉物理微分多重回归分析性能测试

Enzymatic remodeling of heparan sulfate:a therapeutic strategy for systemic and localized amyloidoses?

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Neural Regeneration Research 2016年第3期11卷 408-409页

作者： Kazuchika Nishitsuji Hiroyuki Saito Kenji Uchimura Department of Molecular Pathology Institute of Biomedical SciencesTokushima University Graduate School Department of Molecular Physical Pharmaceutics Institute of Biomedical SciencesTokushima University Graduate School Department of Biochemistry Nagoya University Graduate School of Medicine

In 1854,Rudolf Virchow introduced the term＂amyloid＂to indicate white waxy deposits that stained positive for iodine and that were found in many organs of patients with chronic inflammatory diseases.He observed that these deposits stained pale blue after treatment with iodine and became dark blue or black after subsequent addition of sulfuric acid,in a similar manner to that of cellulose or carbohydrate.

关键词： heparan amyloid remodeling carbohydrate stained subsequent Virchow organs iodine cellulose

Hemi-hepatectomy in pediatric patients using two-surgeon technique and a liver hanging maneuver

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World Journal of Gastroenterology 2011年第10期17卷 1354-1357页

作者： Kyoko Mochizuki Susumu Eguchi Ryuichiro Hirose Taiichiro Kosaka Mitsuhisa Takatsuki Takashi Kanematsu Department of Surgery Nagasaki University Graduate School of Biomedical Sciences

AIM: To evaluate the efficacy of the two-surgeon technique with the liver hanging maneuver (LHM) for hepatectomies in pediatric patients with hepatoblastoma. METHODS: Three pediatric patients with hepatoblastoma were enrolled in this study. Two underwent right hemi-hepatectomies and one underwent a left hemihepatectomy using the two-surgeon technique by means of saline-linked electric cautery (SLC) and the Cavitron Ultrasonic Surgical Aspirator (CUSA; Valleylab, Boulder, CO) and the LHM. RESULTS: The mean operative time during the parenchymal transections was 50 min and the mean blood loss was 235 g. There was no bile leakage from the cut surface after surgery. No macroscopic or microscopic-positive margins were observed in the hepatic transections. CONCLUSION: The two-surgeon technique using SLC and CUSA with the LHM is applicable to even pediatric patients with hepatoblastoma.

关键词：肝切除外科技术医生患者挂机切除术儿科

Lim kinase,a bi-functional effector in injury-induced structural plasticity of synapses

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Neural Regeneration Research 2016年第7期11卷 1029-1032页

作者： Weiwei Wang Ellen Townes-Anderson Department of Pharmacology Physiology and NeuroscienceNew Jersey Medical SchoolGraduate School of Biomedical SciencesRutgers Biomedical and Health SciencesRutgersThe State University of New Jersey

The structural plasticity of synaptic terminals contributes to normal nervous system function but also to neural degeneration, in the form of terminal retraction, and regeneration, due to process growth. Synaptic morphological change is mediated through the actin cytoskeleton, which is enriched in axonal and dendritic terminals. Whereas the three RhoGTPases, RhoA, Cdc42 and Rac, function as upstream signaling nodes sensitive to extracellular stimuli, LIMK-cofilin activity serves as a common downstream effector to up-regulate actin turnover, which is necessary for both polymerization and depolymerization. The dual effects of LIMK activity make LIMK a potential target of therapeutic intervention for iniury-induced synaptic plasticity, as LIMK inhibition can stabilize actin cytoskeleton and preserve existing structure. This therapeutic benefit of LIMK inhibition has been demonstrated in animal models of injury-induced axon retraction and neuritic sprouting by rod photoreceptors. A better understanding of the regulation of LIMK-cofilin activity and the interaction with the microtubular cytoskeleton may open new ways to promote synaptic regeneration that can benefit neuronal degenerative disease.

关键词： LIMK cofilin RhoGTPases actin turnover structural plasticity synaptic degeneration andregeneration

Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance

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World Journal of Diabetes 2017年第3期8卷 97-103页

作者： Tomoki Abe Katsuya Hirasaka Takeshi Nikawa Department of Nutritional Physiology Institute of Biomedical Sciences Tokushima University Graduate School graduate school of Fisheries Science and Environmental Studies Nagasaki University

Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance(IR). Macrophages infiltrate the adipose tissue(AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4(TLR4) and induce inflammatory responses in AT macrophages(ATMs). The inflammatory cytokines that are released from activated ATMs promote IR in peripheral organs, such as the liver, skeletal muscle and AT. Therefore, ATM activation is a therapeutic target for IR in obesity. The ubiquitin ligase Casitas b-lineage lymphoma-b(Cbl-b) appears to potently suppress macrophage migration and activation. Cbl-b is highly expressed in leukocytes and negatively regulates signals associated with migration and activation. Cbl-b deficiency enhances ATM accumulation and IR in aging- and diet-induced obese mice. Cbl-b inhibits migration-related signals and SFA-induced TLR4 signaling in ATMs. Thus, targeting Cbl-b may be a potential therapeutic strategy to reduce the IR induced by ATM activation. In this review, we summarize the regulatory functions of Cbl-b in ATMs.

关键词： Casitas b 系 lymphoma-b 胰岛素抵抗巨噬细胞肥胖像使用费的受体 4

Expression of alpha smooth muscle actin in living donor liver transplant recipients

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World Journal of Gastroenterology 2014年第22期20卷 7067-7074页

作者： Masataka Hirabaru Kyoko Mochizuki Mitsuhisa Takatsuki Akihiko Soyama Taiichiro Kosaka Tamotsu Kuroki Isao Shimokawa Susmu Eguchi Department of Surgery Nagasaki University Graduate School of Biomedical SciencesNagasaki 852-8501Japan Department of Investigative Pathology Nagasaki University Graduate School of Biomedical SciencesNagasaki 852-8501Japan

Recently,there have been reports from liver biopsies that showed the progression of liver fibrosis in liver transplant patients after the cessation of immunosuppression.Herein,we focused on activated hepatic stellate cells expressing alpha smooth muscle actin(α-SMA)to understand the correlation between immunosuppressant medication and liver fibrosis.The study enrolled two pediatric patients who underwent living donor liver transplantation and ceased immunosuppressant therapy.The number ofα-SMA-positive cells in the specimens obtained by liver biopsy from these two patients showed a three-fold increase compared with the number from four transplanted pediatric patients who were continuing immunosuppressant therapy.In addition,theα-SMA-positive area evaluated using the WinRooF image processing software program continued toincrease over time in three adult transplanted patients with liver fibrosis,and theα-SMA-positive area was increasing even during the pre-fibrotic stage in these adult cases,according to a retrospective review.Therefore,α-SMA could be a useful marker for the detection of early stage fibrosis.

关键词： Living donor liver transplantation Liver fibrosis

In-vivo evaluation of molybdenum as bioabsorbable stent candidate

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Bioactive Materials 2022年第8期7卷 262-271页

作者： Malgorzata Sikora-Jasinska Lea M.Morath Maria P.Kwesiga Margaret E.Plank Alexia L.Nelson Alexander A.Oliver Martin L.Bocks Roger J.Guillory II Jeremy Goldman Department of biomedical Engineering Michigan Technological UniversityUSA Department of biomedical Engineering and Physiology Mayo Clinic Graduate School of Biomedical SciencesUSA Case Western Reserve University school of Medicine UH Rainbow Babies&Children’s HospitalClevelandOHUSA

Biodegradable stents have tremendous theoretical potential as an alternative to bare metal stents and drug-eluting stents for the treatment of obstructive coronary artery disease.Any bioresorbable or biodegradable scaffold material needs to possess optimal mechanical properties and uniform degradation behavior that avoids local and systemic toxicity.Recently,molybdenum(Mo)has been investigated as a potential novel biodegradable material for this purpose.With its proven moderate degradation rate and excellent mechanical properties,Mo may represent an ideal source material for clinical cardiac and vascular applications.The present study was performed to evaluate the mechanical performance of metallic Mo in vitro and the biodegradation properties in vivo.The results demonstrated favorable mechanical behavior and a uniform degradation profile as desired for a new generation ultra-thin degradable endovascular stent material.Moreover,Mo implants in mouse arteries avoided the typical cellular response that contributes to restenosis.There was minimal neointimal hyperplasia over 6 months,an absence of excessive smooth muscle cell(SMC)proliferation or inflammation near the implant,and avoidance of significant harm to regenerating endothelial cells(EC).Qualitative inspection of kidney sections showed a potentially pathological remodeling of kidney Bowman’s capsule and glomeruli,indicative of impaired filtering function and development of kidney disease,although quantifications of these morphological changes were not statistically significant.Together,the results suggest that the products of Mo corrosion may exert beneficial or inert effects on the activities of inflammatory and arterial cells,while exerting potentially toxic effects in the kidneys that warrant further investigation.

关键词： Biodegradable stent Molybdenum Biocompatibility Degradation