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Therapeutic targeting of hepatocellular carcinoma cells with antrocinol, a novel, dual-specificity, small-molecule inhibitor of the KRAS and ERK oncogenic signaling pathways

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Chemico-Biological Interactions 2023年第1期370卷 110329页

作者： Hsu, Chia-Hung Weng, Pei-Wei Chen, Ming-Yao Yeh, Chi-Tai Setiawan, Syahru Agung Yadav, Vijesh Kumar Wu, Alexander T.H. Tzeng, David T.W. Gong, Jian-Xian Yang, Zhen Tzeng, Yew-Min Department of Emergency Medicine Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Graduate Institute of Injury Prevention and Control College of Public Health Taipei Medical University Taipei City 11031 Taiwan Department of Emergency Medicine School of Medicine Taipei Medical University Taipei 11031 Taiwan Department of Orthopaedics School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Department of Orthopaedics Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Shuang Ho Hospital New Taipei City 23561 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Continuing Education Program of Food Biotechnology Applications College of Science and Engineering National Taitung University Taitung 95092 Taiwan International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan Ph.D. Program of Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan School of Life Sciences The Chinese University of Hong Kong 999077 Hong Kong Lifebit London EC2A 2AP United Kingdom Laboratory of Chemical Genomics School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School Shenzhen 518055 China State Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education and Beijing National Laboratory for Molecular Science College of Chemistry and Molecular Engineering Peking University Beijing 100871 China Shenzhen Bay Laboratory Shenzhen 518055 China Department of Applied Science National Taitung University Taitung

Until recently, sorafenib has been the only treatment approved by the U.S. Food and Drug Administration for patients with advanced hepatocellular carcinoma (HCC). Some patients, however, exhibit resistance to this treatment and subsequently experience cancer progression, recurrence, or death. Therefore, identifying a new alternative treatment for patients with little or no response to sorafenib treatment is vital. In this study, we explored the therapeutic potential and underlying molecular mechanism of antrocinol ((3aS,4R,6aS,10aR)-4-(hydroxymethyl)-7,7-dimethyldecahydro-1H-naphtho[1,8a-c]furan-1-one) in patients with HCC. The results indicated that antrocinol was more therapeutically effective than antrocin, Stivarga, and sorafenib against HCC cell lines. Antrocinol also substantially suppressed the expression of KRAS-GTP, p-MEK1/2, p-ERK1/2, and p-AKT in the Huh7 cell line. Additionally, antrocinol-induced apoptosis in the Huh7 cell line, inhibited the formation of tumorspheres, and suppressed the expression of cancer stem cell markers CD133, KLF4, CD44, OCT4, SOX2, and c-Myc. Animal studies revealed that antrocinol alone considerably suppressed tumor growth in nonobese diabetic/severe combined immunodeficient mice inoculated with Huh7 tumorspheres. It also synergistically enhanced the anticancer effect of sorafenib, resulting in enhanced suppression of tumor growth (p < 0.001) and tumorsphere formation (p < 0.001). In tumor samples resected from mice treated with antrocinol alone or in combination with sorafenib, immunohistochemical analysis revealed an increase in BAX expression and a decrease in ERK and AKT protein expression. To the best of our knowledge, this is the first report of the anti-HCC activity of antrocinol. With its higher therapeutic efficacy than that of sorafenib, antrocinol is a candidate drug for patients with HCC who demonstrate little or no response to sorafenib treatment. © 2022 Elsevier B.V.

关键词： Antrocinol Cancer stemness Hepatocellular carcinoma KRAS/AKT/ERK axis Sorafenib

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YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome

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Biomedicine and Pharmacotherapy 2023年第1期159卷 114302-114302页

作者： Chen, Xiao-Yue Chen, Kuan-Yuan Feng, Po-Hao Lee, Kang-Yun Fang, Yu-Ting Chen, You-Yin Lo, Yu-Chun Bhavsar, Pankaj K. Chung, Kian Fan Chuang, Hsiao-Chi Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan School of Respiratory Therapy College of Medicine Taipei Medical University Taipei Taiwan National Heart and Lung Institute Imperial College London London United Kingdom Division of Pulmonary Medicine Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Division of Pulmonary Medicine Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Biomedical Engineering National Yang Ming Chiao Tung University Taipei Taiwan The Ph.D. Program for Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan Industrial Ph.D. Program of Biomedical Science and Engineering National Yang Ming Chiao Tung University Taipei Taiwan Cell Physiology and Molecular Image Research Center Wan Fang Hospital Taipei Medical University Taipei Taiwan

Acute respiratory distress syndrome (ARDS) contributes to higher mortality worldwide. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have immunomodulatory and regenerative potential. However, the effects of hUC-MSCs as an ARDS treatment remain unclear. We investigated the role of hUC-MSCs in the differentiation of type II alveolar epithelial cells (AECII) by regulating Yes-associated protein (YAP) in ARDS. Male C57BL/6JNarl mice were intratracheally (i.t.) administered lipopolysaccharide (LPS) to induce an ARDS model, followed by a single intravenous (i.v.) dose of hUC-MSCs. hUC-MSCs improved pulmonary function, decreased inflammation on day 3, and mitigated lung injury by reducing the lung injury score and increasing lung aeration (%) in mice on day 7 (p < 0.05). hUC-MSCs inactivated YAP on AECII and facilitated cell differentiation by decreasing Pro-surfactant protein C (Pro-SPC) and galectin 3 (LGALS3) while increasing podoplanin (T1α) in lungs of mice (p < 0.05). In AECII MLE-12 cells, both coculture with hUC-MSCs after LPS exposure and the YAP inhibitor, verteporfin, reduced Pro-SPC and LGALS3, whereas the YAP inhibitor increased T1α expression (p < 0.05). In conclusion, hUC-MSCs ameliorated lung injury of ARDS and regulated YAP to facilitate AECII differentiation. © 2023 The Authors

关键词： Alveoli Inflammation Pneumocytes Regeneration Stem cells

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Physical and toxicological profiles of human IAPP amyloids and plaques

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science Bulletin 2019年第1期64卷 26-35页

作者： Aleksandr Kakinen Yunxiang Sun Ibrahim Javed Ava Faridi Emily H.Pilkington Pouya Faridi Anthony W.Purcell Ruhong Zhou Feng Ding Sijie Lin Pu Chun Ke Thomas P.Davis ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical Sciences Monash University Department of Physics and Astronomy Clemson University College of Environmental Science and Engineering Shanghai Institute of Pollution Control and Ecological Security Biomedical Multidisciplinary Innovation Research Institute Shanghai East Hospital Tongji University Infection and Immunity Program & Department of Biochemistry and Molecular Biology Biomedicine Discovery Institute Monash University IBM Thomas J.Watson Research Center Department of Chemistry Columbia University

Although much has been learned about the fibrillization kinetics, structure and toxicity of amyloid proteins, the properties of amyloid fibrils beyond the saturation phase are often perceived as chemically and biologically inert, despite evidence suggesting otherwise. To fill this knowledge gap, we examined the physical and biological characteristics of human islet amyloid polypeptide(IAPP) fibrils that were aged up to two months. Not only did aging decrease the toxicity of IAPP fibrils, but the fibrils also sequestered fresh IAPP and suppressed their toxicity in an embryonic zebrafish model. The mechanical properties of IAPP fibrils in different aging stages were probed by atomic force microscopy and sonication, which displayed comparable stiffness but age-dependent fragmentation, followed by self-assembly of such fragments into the largest lamellar amyloid structures reported to date. The dynamic structural and toxicity profiles of amyloid fibrils and plaques suggest that they play active, long-term roles in cell degeneration and may be a therapeutic target for amyloid diseases.

关键词： IAPP Amyloid Plaque Self assembly Toxicity

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Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates (vol 16, pg 671, 2017)

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NATURE MATERIALS 2021年第7期20卷 1038-1038页

作者： Dolo, Joshua C. Veiseh, Omid Vegas, Arturo J. Tam, Hok Hei Farah, Shady Ma, Minglin Li, Jie Bader, Andrew Chiu, Alan Sadraei, Atieh Aresta-Dasilva, Stephanie Grin, Marissa Jhunjhunwala, Siddharth Webber, Matthew Siebert, Sean Tang, Katherine Chen, Michael Langan, Erin Dholakia, Nimit Thakrar, Raj Qi, Meirigeng Oberholzer, Jose Greiner, Dale L. Langer, Robert Anderson, Daniel G. David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology 500 Main Street Cambridge Massachusetts 02139 USA Department of Anesthesiology Boston Children’s Hospital 300 Longwood Avenue Boston Massachusetts 02115 USA Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge Massachusetts 02139 USA Division of Health Science Technology Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge Massachusetts 02139 USA Institute for Medical Engineering and Science Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge Massachusetts 02139 USA Division of Transplantation Department of Surgery University of Illinois at Chicago Chicago Illinois 60607 USA Program in Molecular Medicine University of Massachusetts Medical School Worcester Massachusetts 01605 USA

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Neurorestorative properties of 2-butoxytetrahydrofuran from Holothuria scabra via activation of stress resistance and detoxification in a 6-OHDA-induced C. elegans model of Parkinson's disease

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Biomedicine and Pharmacotherapy 2025年 188卷 118158-118158页

作者： Promtang, Sukrit Sanguanphun, Tanatcha Chalorak, Pawanrat Rodma, Darunee Sunan, Rungsarit Pe, Laurence S. Niamnont, Nakorn Chompoopong, Supin Sobhon, Prasert Meemon, Krai Molecular Medicine Program Multidisciplinary Unit Faculty of Science Mahidol University Ratchathewi Bangkok 10400 Thailand Division of Basic and Medical Sciences Faculty of Allied Health Sciences Pathumthani University Pathum Thani Mueang Pathum Thani 12000 Thailand Department of Anatomy Faculty of Science Mahidol University Ratchathewi Bangkok 10400 Thailand Department of Radiological Technology and Medical Physics Faculty of Allied Health Sciences Chulalongkorn University Pathumwan Bangkok 10330 Thailand Research Center for Neuroscience Institute of Molecular Biosciences Mahidol University Salaya Nakhon Pathom 73170 Thailand Department of Chemistry Faculty of Science King Mongkut's University of Technology Thonburi Bang Mod Bangkok 10140 Thailand Department of Anatomy Faculty of Medicine Siriraj Hospital Mahidol University Bangkoknoi Bangkok 10700 Thailand Center for Neuroscience Faculty of Science Mahidol University Ratchathewi Bangkok 10400 Thailand

Holothuria scabra (H. scabra), a marine organism traditionally known for its health benefits, has been utilized in both food and medicine. Our previous studies indicated that 2-butoxytetrahydrofuran (2-BTHF), which is isolated from H. scabra, possesses the potential to alleviate amyloid-β and α-synuclein accumulations associated with Alzheimer's and Parkinson's diseases (AD and PD), respectively. However, the mechanisms through which 2-BTHF mitigates PD-related neurotoxicity remain unclear. In this study, we investigated the effects of 2-BTHF on a 6-hydroxydopamine (6-OHDA)-induced Caenorhabditis elegans (C. elegans) model. Our results demonstrated that 2-BTHF recovered dopaminergic (DAergic) neurons from degeneration and restored dopamine-related behaviors. Furthermore, 2-BTHF reduced reactive oxygen species (ROS) production, preserved mitochondrial fluorescence, and decreased both mitochondrial and cytoplasmic unfolded protein responses (UPR^mt and UPR^cyto) activation. Transcriptome sequencing analysis revealed the critical roles of various systems, including the immune system, nervous system, glutathione (GSH) metabolism, xenobiotics, terpenoids, energy metabolism, cell growth and death, and aging-related longevity pathways. Additionally, 2-BTHF showed potential interactions with stress resistance and detoxification transcription factors, promoting the nuclear translocation of DAF-16 and SKN-1, which in turn activated their targets, including SOD-3, CTL-2, GCS-1, and GST-4. Moreover, 2-BTHF increased total GSH levels and reduced the ced-3-related cascade. This study demonstrates that 2-BTHF holds promise as a therapeutic agent for treating 6-OHDA-induced DAergic neurodegeneration in the C. elegans model. © 2025 The Authors

关键词： 2-butoxytetrahydrofuran 6-OHDA Caenorhabditis elegans Detoxification Holothuria scabra Stress resistance

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MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice

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molecular therapy. Nucleic acids 2023年 32卷 144-160页

作者： Tai-Heng Chen Shih-Hsin Chang Yu-Fu Wu Ya-Ping Yen Fang-Yu Hsu Yen-Chung Chen Yang Ming Ho-Chiang Hsu Yi-Ching Su Sheng-Tang Wong Jui-Hung Hung Shih-Hwa Chiou Yuh-Jyh Jong Jun-An Chen PhD Program in Translational Medicine Kaohsiung Medical University Kaohsiung 80708 and Academia Sinica Taipei 11529 Taiwan. Institute of Molecular Biology Academia Sinica Taipei 11529 Taiwan. Department of Pediatrics Kaohsiung Medical University Kaohsiung 80708 Taiwan. School of Post-Baccalaureate Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Neuroscience Program of Academia Sinica Academia Sinica Taipei 11529 Taiwan. Department of Computer Science National Yang Ming Chiao Tung University Hsinchu 30093 Taiwan. Institute of Pharmacology School of Medicine National Yang Ming Chiao Tung University Taipei 11221 Taiwan. Innovative Cellular Therapy Center Department of Medical Research Taipei Veterans General Hospital Taipei 11217 Taiwan. Department of Laboratory Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Translational Research Center of Neuromuscular Diseases Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung 80708 Taiwan. Graduate Institute of Clinical Medicine College of Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung 80708 Taiwan. Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu 30093 Taiwan.

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the selective loss of spinal motor neurons (MNs) and concomitant muscle weakness. Mutation of is known to cause SMA, and restoring SMN protein levels via antisense oligonucleotide treatment is effective for ameliorating symptoms. However, this approach is hindered by exorbitant costs, invasive procedures, and poor treatment responses of some patients. Here, we seek to circumvent these hurdles by identifying reliable biomarkers that could predict treatment efficacy. We uncovered that MiR34 exhibits consistent downregulation during SMA progression in both human and rodent contexts. Importantly, family-knockout mice display axon swelling and reduced neuromuscular junction (NMJ) endplates, recapitulating SMA pathology. Introducing MiR34a via scAAV9 improved the motor ability of SMNΔ7 mice, possibly by restoring NMJ endplate size. Finally, we observed a consistent decreasing trend in MiR34 family expression in the cerebrospinal fluid (CSF) of type I SMA patients during the loading phase of nusinersen treatment. Baseline CSF MiR34 levels before nusinersen injection proved predictive of patient motor skills 1 year later. Thus, we propose that MiR34 may serve as a biomarker of SMA since it is associated with the pathology and can help evaluate the therapeutic effects of nusinersen.

关键词： ASO MT: Non-coding RNAs MiR34 SMA biomarker microRNA nusinersen spinal muscular atrophy

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TextAI 3.0 (Multimodal): multimodal sentiment analysis using attention-enabled ensemble-based deep learning in hyperbolic space

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International Journal of Information technology (Singapore) 2025年 1-16页

作者： Singh, Jaskaran Sanga, Prabhav Khanna, Narendra N. Laird, John R. Singh, Inder M. Kalra, Mannudeep K. Mantella, Laura E. Johri, Amer M. Faa, Gavino Tiwari, Ekta Singh, Rajesh Abbas, Mohamed Saba, Luca Suri, Jasjit S. Stroke Monitoring and Diagnostic Division AtheroPoint™ Roseville 95661 CA United States Bharati Vidyapeeth’s College of Engineering New Delhi India Department of Cardiology Indraprastha APOLLO Hospitals New Delhi 110001 India Department of Neurology and Stroke Program University of Maryland School of Medicine Baltimore United States Department of Radiology Harvard Medical School Boston 02115 MA United States Department of Biomedical and Molecular Sciences Queen’s University Kingston ON Canada Division of Cardiology Department of Medicine Queen’s University Kingston ON Canada Department of Pathology University of Cagliari Cagliari Italy Department of Computer Science Visvesvaraya National Institute of Technology (VNIT) Nagpur 440010 India Department of Research and Innovation Uttaranchal Institute of Technology Uttaranchal University Dehradun 248007 India Central Labs King Khalid University P.O. Box 960 AlQura’a Abha Saudi Arabia Electrical Engineering Department College of Engineering King Khalid University Abha 61421 Saudi Arabia Department of Neurology University of Cagliari Cagliari Italy Department of ECE Idaho State University Pocatello 83209 ID United States Department of CE Graphic Era Deemed to Be University Dehradun 248002 India University Center for Research and Development Chandigarh University Mohali India Symbiosis Institute of Technology Symbiosis International (Deemed University) Nagpur Campus Pune India Department of Innovation Global Biomedical Technologies Inc. Roseville 95661 CA United States

The rising prevalence of depression presents a significant global health challenge, underscoring the need for effective early detection through sentiment analysis. Traditional multimodal sentiment analysis methods, which rely on Euclidean space for data representation, often fail to capture the complex hierarchical relationships and non-linear structures inherent in multimodal data. To address this limitation, we propose a novel multimodal architecture that operates in hyperbolic space and incorporates attention-based ensemble learning to enhance feature representation and model performance. We developed and evaluated ten AI models—five utilizing Euclidean space and five leveraging hyperbolic space—on the Spoken Language Understanding Evaluation (SLUE) benchmark dataset. The models were assessed using cross-validation techniques to ensure robustness, and statistical analyses were conducted to validate the findings. Our results indicate that hyperbolic-based multimodal models achieve a 2.32% improvement in accuracy compared to their Euclidean counterparts, while the integration of self-attention mechanisms further contributes an average accuracy gain of 0.96%. Additionally, we observed a 3.76% decline in performance when reducing the training-to-test data ratio from 90:10 to 50:50, highlighting the importance of data distribution in model training. These findings confirm that attention-enhanced multimodal models in hyperbolic space offer superior representations for sentiment analysis. © Bharati Vidyapeeth's Institute of Computer Applications and Management 2025.

关键词： Attention-enabled Deep learning Euclidean space Hyperbolic space Multimodal Sentiment analysis

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Designer three-dimensional electronic bands in asymmetric transition metal dichalcogenide heterostructures

arXiv

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arXiv 2025年

作者： Clark, Oliver J. Azhar, Anugrah Chambers, Ben A. McEwen, Daniel Vu, Thi-Hai-Yen Bhuiyan, Tofajjol M.H. Belosludov, Rodion V. Bostwick, Aaron Jozwiak, Chris Rotenberg, Eli Lee, Seng Huat Mao, Zhiqiang Balakrishnan, Geetha Mazzola, Federico Harmer, Sarah L. Fuhrer, Michael S. Bahramy, M. Saeed Edmonds, Mark T. School of Physics and Astronomy Monash University ClaytonVIC Australia Department of Physics and Astronomy University of Manchester Oxford Road ManchesterM13 9PY United Kingdom Physics Study Program Faculty of Science and Technology Syarif Hidayatullah State Islamic University Tangerang Selatan Jakarta15412 Indonesia Flinders Microscopy and Microanalysis Flinders University Bedford ParkSA5042 Australia ARC Centre for Future Low Energy Electronics Technologies Monash University ClaytonVIC Australia Institute for Materials Research Tohoku University Sendai980-8577 Japan Advanced Light Source Lawrence Berkeley National Laboratory BerkeleyCA94720 United States Department of Physics Pennsylvania State University University ParkPA16802 United States 2D Crystal Consortium Materials Research Institute Pennsylvania State University University ParkPA16802 United States Department of Physics University of Warwick CoventryCV4 7AL United Kingdom Department of Molecular Sciences and Nanosystems Ca Foscari University of Venice VeniceIT-30172 Italy CNR-SPIN UOS Napoli Complesso Universitario di Monte Sant’Angelo Via Cinthia Napoli80126 Italy Institute for Nanoscale Science and Technology Flinders University Bedford ParkSA5042 Australia ANFF-VIC Technology Fellow Melbourne Centre for Nanofabrication Victorian Node of the Australian National Fabrication Facility ClaytonVIC3168 Australia

Van der Waals materials enable the construction of atomically sharp interfaces between compounds with distinct crystal and electronic properties [1]. This is dramatically exploited in moiré systems, where a lattice mismatch or twist between monolayers generates an emergent in-plane periodicity, giving rise to electronic properties absent in the constituent materials [2, 3]. In contrast, vertical superlattices—formed by stacking dissimilar van der Waals materials in the out-of-plane direction on the nanometer scale—remain largely unexplored, despite their potential to realize analogous emergent phenomena in three dimensions [4]. Here, we employ angle-resolved photoemission spectroscopy and density functional theory to investigate six-to-eight layer transition metal dichalcogenide (TMD) heterostructures. We find that even a single superlattice unit, i.e. a pair of stacked few-layer materials, exhibits emergent bands that closely resemble the hallmark three-dimensional electronic structure of many-layer TMDs, while simultaneously exhibiting an orbital- and momentum-dependent delocalization through the entire heterostructure due to its asymmetric architecture. We demonstrate how non-trivial band topology and unique TMD fermiologies are readily stabilized through these mechanisms, thus providing direct evidence for the novel electronic states possible through vertical superlattice engineering. These findings establish asymmetric heterostructures as platforms to invoke and control unprecedented combinations of the diverse quantum phases native to many-layer TMDs. Copyright © 2025, The Authors. All rights reserved.

关键词： Van der Waals forces

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Theoretical study of quantum size effects in thin Al(100), Al(110), and Al(111) films

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Physical Review B 2019年第20期99卷 205401-205401页

作者： Duc-Long Nguyen Ching-Ming Wei Mei-Yin Chou Institute of Atomic and Molecular Sciences Academia Sinica Taipei 10617 Taiwan Department of Physics National Central University Taoyuan City 32001 Taiwan Molecular Science and Technology Program Taiwan International Graduate Program Academia Sinica Taipei 11529 Taiwan School of Physics Georgia Institute of Technology Atlanta Georgia 30332-0430 USA

We have carried out first-principles calculations for Al(100), Al(110), and Al(111) films up to 30 monolayers to study the oscillatory quantum size effects (QSEs) exhibited in the surface energy, work function, electron-phonon coupling constants, and superconductivity transition temperature Tc. Significant oscillatory QSEs on these physical properties are reported. These oscillations are correlated with the thickness dependence of the energies of confined electrons, which can be properly modeled by an energy-dependent phase shift of the electronic wave function upon reflection at the interface. The oscillations in the surface energy and work function for Al(111) and Al(110) films as a function of film thickness can be well fitted by a damped sinusoidal function with the periodicity determined by one Fermi wave vector along the [111] direction or a combination of three Fermi wave vectors along the [110] direction. A quantitative description of these QSE requires the full consideration of the crystal band structure.

关键词： Superconductivity Surface & interfacial phenomena Thin films First-principles calculations

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Predictive analysis between cytokine profile and Aβ42, p-Tau, and p-Tau/Aβ42 levels in the cerebrospinal fluid of older adults with and without cognitive impairment

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Alzheimer's & Dementia 2023年第S14期19卷

作者： Ivonne Carolina Bolaños Burgos Pedro Henrique Oliveira Aquino Julia Mendes Ribeiro Rafael Souza de Andrade Gabriela Tomé Oliveira Engelmann Erika de Oliveira Hansen Natália Silva Dias Andréa Teixeira Carvalho Debora Miranda Sr. Marco Aurelo Romano-Silva Luiz Armando Cunha de Marco Bernardo de Mattos Viana Maria Aparecida Camargos Bicalho Adult Health Sciences Applied Program Faculdade de Medicina Universidade Federal de Minas Gerais Belo Horizonte Brazil National Institute of Science and Technology Neurotec R (INCT-MM) Belo Horizonte Brazil Correspondece Undergraduate medicine Faculdade de Medicina Belo Horizonte Brazil Center of Technology in Molecular Medicine Belo Horizonte Brazil Molecular Medicine Program Faculdade de Medicina Belo Horizonte Brazil Jenny de Andrade Faria Institute– Reference Center for the Elderly Hospital das Clínicas Universidade Federal de Minas Gerais Belo Horizonte Brazil Older Adult Psychiatry and Psychology Extension Program (PROEPSI) Faculdade de Medicina Belo Horizonte Brazil Universidade Federal de Minas Gerais Belo Horizonte Brazil René Rachou Institute Oswaldo Cruz Foundation (Fiocruz) Belo Horizonte Brazil National Institute of Science and Technology Neurotec R (INCT-MM) Faculdade de Medicina Universidade Federal de Minas Gerais Belo Horizonte Brazil Molecular Medicine Program Faculdade de Medicina Universidade Federal de Minas Gerais Belo Horizonte Brazil National Institute of Science and Technology Neurotec R (INCT-MM) Faculdade de Medicina Belo Horizonte Brazil Elderly Psychiatry and Psychology Extension Program (PROEPSI) Faculdade de Medicina Universidade Federal de Minas Gerais Belo Horizonte Brazil Department of Clinical Medicine Faculdade de Medicina Universidade Federal de Minas Gerais Belo Horizonte Brazil

Background The immune system activation observed in Alzheimer’s disease (AD) pathology contributes to its pathogenesis. It is proposed that ongoing interactions between β-amyloid plaques, Tau protein, and neuroinflammatory mediators such as cytokines contribute to the maintenance of the inflammatory state in the brain. The aim was to evaluate whether cytokine profiles can predict variations in Aβ42, pTau, and pTau/Aβ42 cerebrospinal fluid (CSF) levels in older adults with and without objective cognitive impairment. Methods Eighty older adults were recruited, with a clinical diagnosis of AD dementia (36), with Mild Cognitive Impairment (MCI) (24), and without objective cognitive impairment (20). CSF levels of Aβ42, pTau, and 27 cytokines were assessed by the Luminex xMAP technique. Significant associations between Aβ42, p-Tau, and p-Tau/Aβ42 CSF levels and cytokines were explored in multiple linear regression analyses adjusted for age, education, and APOE ε4 carrier status. Results We found that Granulocyte and Macrophage colony-stimulating factors (GM-CSF) (β = -.375; p = .010) and IL-6 (β = -.370; p = .014) had a negative significant association with Aβ42, while IL-8 (β = .452; p = .002) and IL-4 (β = .488; p = .001) had positive significant association and higher magnitude of effect on Aβ42. For pTau, age (β = .240; p = .029), IL-2 (β = .314; p = .012) and ε4 allele (β = 0.349; p = .002) had a positive significant association. The variable with the greatest magnitude of the effect was the presence of the ε4 allele. For the p-Tau/Aβ42 ratio, G-CSF (β = .423; p = .003) and GM-CSF (β = .317; p = .019) had a significant positive association, while for IL-8 (β = -.554; p = .001) and IL-12 (β = -.334; p = .019) the association was significantly negative. IL-8 had the greatest magnitude of effect on p-Tau/Aβ42 ratio values. Conclusion The higher levels of IL-4 and the IL-8 associated to a higher Aβ42 suggest their role at the beginning of the disease. On the other hand,

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