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NF-κB Inducing Kinase Attenuates Colorectal Cancer by Regulating Noncanonical NF-κB Mediated Colonic Epithelial Cell Regeneration

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Cellular and Molecular Gastroenterology and Hepatology 2024年第3期18卷 101356-101356页

作者： Morrison, Holly A. Eden, Kristin Trusiano, Brie Rothschild, Daniel E. Qin, Yufeng Wade, Paul A. Rowe, Audrey J. Mounzer, Christina Stephens, Morgan C. Hanson, Katherine M. Brown, Stephan L. Holl, Eda K. Allen, Irving C. Virginia Tech Virginia Maryland College of Veterinary Medicine Department of Biomedical Science and Pathobiology Blacksburg VA United States Virginia Tech Department of Basic Science Education Virginia Tech Carilion School of Medicine Roanoke VA United States National Institute of Environmental Health Sciences Research Triangle Park North Carolina United States Via College of Osteopathic Medicine Department of Cell Biology and Physiology Spartanburg SC United States Duke University Department of Surgery Durham North Carolina United States Graduate Program in Translational Biology Medicine and Health Virginia Polytechnic Institute and State University Roanoke VA United States

Background & Aims: Dysregulated colonic epithelial cell (CEC) proliferation is a critical feature in the development of colorectal cancer. We show that NF-κB-inducing kinase (NIK) attenuates colorectal cancer through coordinating CEC regeneration/differentiation via noncanonical NF-κB signaling that is unique from canonical NF-kB signaling. Methods: Initial studies evaluated crypt morphology/functionality, organoid generation, transcriptome profiles, and the microbiome. Inflammation and inflammation-induced tumorigenesis were initiated in whole-body NIK knockout mice (Nik^-/-) and conditional-knockout mice following administration of azoxymethane and dextran sulfate sodium. Results: Human transcriptomic data revealed dysregulated noncanonical NF-kB signaling. In vitro studies evaluating Nik^-/- crypts and organoids derived from mature, nondividing CECs, and colonic stem cells exhibited increased accumulation and stunted growth, respectively. Transcriptomic analysis of Nik^-/- cells revealed gene expression signatures associated with altered differentiation-regeneration. When assessed in vivo, Nik^-/- mice exhibited more severe colitis with dextran sulfate sodium administration and an altered microbiome characterized by increased colitogenic microbiota. In the inflammation-induced tumorigenesis model, we observed both increased tumor burdens and inflammation in mice where NIK is knocked out in CECs (Nik^ΔCEC). Interestingly, this was not recapitulated when NIK was conditionally knocked out in myeloid cells (Nik^ΔMYE). Surprisingly, conditional knockout of the canonical pathway in myeloid cells (RelA^ΔMYE) revealed decreased tumor burden and inflammation and no significant changes when conditionally knocked out in CECs (RelA^ΔCEC). Conclusions: Dysregulated noncanonical NF-κB signaling is associated with the development of colorectal cancer in a tissue-dependent manner and defines a critic

关键词： Colitis-Associated Tumorigenesis Differentiation Epithelial Cells Organoids

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Housing Temperature Impacts the Systemic and Tissue-Specific Molecular Responses to Cancer in Mice

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Journal of Cachexia, Sarcopenia and Muscle 2025年第2期16卷 e13781页

作者： Irazoki, Andrea Frank, Emma Pham, Tang Cam Phung Braun, Jessica L. Ehrlich, Amy M. Haid, Mark Riols, Fabien Hansen, Camilla Hartmann Friis Jørgensen, Anne-Sofie Rydal Andersen, Nicoline Resen Hidalgo-Corbacho, Laura Meneses-Valdes, Roberto Ali, Mona Sadek Raun, Steffen Henning Modvig, Johanne Louise Gallero, Samantha Larsen, Steen Gerhart-Hines, Zach Jensen, Thomas Elbenhardt Rohm, Maria Treebak, Jonas T. Fajardo, Val Andrew Sylow, Lykke Department of Biomedical Sciences Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark Department of Kinesiology Faculty of Applied Health Sciences Cairns Family Health and Bioscience Research Complex Brock University Niagara Region ON Canada Novo Nordisk Foundation Center for Basic Metabolic Research Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark Metabolism & Proteomics Core Helmholtz Center Munich German Research Center for Environmental Health Neuherberg Germany Section of Experimental Animal Models Department of Veterinary and Animal Sciences University of Copenhagen Copenhagen Denmark Department of Nutrition Exercise and Sport University of Copenhagen Copenhagen Denmark Clinical Research Centre Medical University of Bialystok Bialystok Poland Institute of Sports Medicine Copenhagen Department of Orthopedic Surgery M Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen Denmark Institute for Diabetes and Cancer Helmholtz Center Munich Neuherberg Germany Joint Heidelberg-IDC Translational Diabetes Program Inner Medicine 1 Heidelberg University Hospital Heidelberg Germany German Center for Diabetes Research (DZD) Neuherberg Germany

Background: Cancer cachexia, affecting up to 80% of patients with cancer, is characterized by muscle and fat loss with functional decline. Preclinical research seeks to uncover the molecular mechanisms underlying cachexia to identify potential targets. Housing laboratory mice at ambient temperature induces cold stress, triggering thermogenic activity and metabolic adaptations. Yet, the impact of housing temperature on preclinical cachexia remains unknown. Methods: Colon 26 carcinoma (C26)-bearing and PBS-inoculated (Ctrl) mice were housed at standard (ST;20°C–22°C) or thermoneutral temperature (TN;28°C–32°C). They were monitored for body weight, composition, food intake and systemic factors. Upon necropsy, tissues were weighed and used for evaluation of ex vivo force and respiration, or snap frozen for biochemical assays. Results: C26 mice lost 7.5% body weight (p = 0.0001 vs. Ctrls), accounted by decreased fat mass (−35%, p < 0.0001 vs. Ctrls), showing mild cachexia irrespective of housing temperature. All C26 mice exhibited reduced force (−40%, p < 0.0001 vs. Ctrls) and increased atrogene expression (3-fold, p < 0.003 vs. Ctrls). Cancer altered white adipose tissue (WAT)'s functional gene signature (49%, p < 0.05 vs. Ctrls), whereas housing temperature reduced brown adipose tissue (BAT)'s (−78%, p < 0.05 vs. ST Ctrl). Thermogenic capacity measured by Ucp1 expression decreased upon cancer in both WAT and BAT (−93% and −63%, p < 0.0044 vs. Ctrls). Cancer-driven glucose intolerance was noted at ST (26%, p = 0.0192 vs. ST Ctrl), but restored at TN (−23%, p = 0.005 vs. ST C26). Circulating FGF21, GDF-15 and IL-6 increased in all C26 mice (4-fold, p < 0.009 vs. Ctrls), with a greater effect on IL-6 at TN (76%, p = 0.0018 vs. ST C26). Tumour and WAT Il6 mRNA levels remained unchanged, while cancer induced skeletal muscle (SkM) Il6 (2-fold, p = 0.0016 vs. Ctrls) at both temperatures. BAT Il6 was only induced in C26 mice at TN (116%, p = 0.0087 vs. ST C26). At the bioenerg

关键词： bioenergetics cancer cachexia cold-induced stress thermogenic tissues thermoneutrality

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Uncovering chromatin accessibility and cancer diagnostic potential via cell-free DNA utilization

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Science Bulletin 2024年第19期69卷 2987-2992页

作者： Jie Li Jiahui Chen Xin Sun Heli Yang Keyong Sun Chang Liu Yongwang Wang Mengyue Xu Xin Ji Ji Zhang Xiaojiang Wu Anqiang Wang Biao Fan Xiaolu Zhang Yue Wu Peilin Cui Junya Peng Yupei Zhao Wenming Wu Honghao Yu Zhaode Bu Jiafu Ji Xun Lan Department of Basic Medical Sciences School of MedicineTsinghua UniversityBeijing 100084China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Center of Gastrointestinal CancerPeking University Cancer Hospital&InstituteBeijing 100142China Guangxi Key Laboratory of Drug Discovery and Optimization Guilin Medical UniversityGuilin 541001China Department of General Surgery Peking Union Medical College HospitalPeking Union Medical CollegeBeijing 100730China Department of Internal Medicine International Medical Services(IMS)Beijing Tiantan Hospital of Capital Medical UniversityBeijing 100070China Institute of Clinical Medicine Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China MOE Key Laboratory of Bioinformatics Tsinghua UniversityBeijing 100084China Peking-Tsinghua-NIBS Joint Graduate Program Tsinghua UniversityBeijing 100084China Tsinghua-Peking Joint Center for Life Sciences Tsinghua UniversityBeijing 100084China Department of Anesthesiology Affiliated Hospital of Guilin Medical UniversityGuilin 541000China Key Laboratory of Medical Biotechnology and Translational Medicine Guilin Medical UniversityGuilin 541001China State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Department of Gastric Surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhou 310022China The Islands Healthcare Complex-Macao Medical Center of Peking Union Medical College Hospital Macao 999078China

Gene expression patterns of tumor cells can be inferred from features of circulating cell-free DNA(cfDNA),such as histone modifications and fragmentation patterns at ***,the direct relationship between cfDNA patterns and tumor-specific chromatin accessibility has not yet been experimentally established,limiting its current application to cancer diagnosis alone.

关键词： diagnosis cancer alone

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Computational investigation of turmeric phytochemicals targeting PTR1 enzyme of Leishmania species

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Heliyon 2024年第6期10卷

作者： Ullah, Wasia Wu, Wen-Feng Malak, Nosheen Nasreen, Nasreen Swelum, Ayman A. Marcelino, Liliana Aguilar Niaz, Sadaf Khan, Adil Ben Said, Mourad Chen, Chien-Chin Department of Zoology Abdul Wali Khan University Mardan Mardan 23200 Pakistan Department of Radiology Ditmanson Medical Foundation Chia-Yi Christian Hospital 600 Chiayi Taiwan Department of Animal Production College of Food and Agriculture Sciences King Saud University Riyadh 1451 Saudi Arabia National Center for Disciplinary Research in Animal Health and Safety (INIFAP) Km 11 Federal Road Cuernavaca-Cuautla Morelos Jiutepec 62550 Mexico Department of Zoology Bacha Khan University Charsadda Charsadda 24420 Pakistan Department of Biology Mount Allison University Sackville E4L 1G7 NB Canada Laboratory of Microbiology National School of Veterinary Medicine of Sidi Thabet University of Manouba Manouba 2010 Tunisia Department of Basic Sciences Higher Institute of Biotechnology of Sidi Thabet University of Manouba Manouba 2010 Tunisia Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan 701 Taiwan Department of Pathology Ditmanson Medical Foundation Chia-Yi Christian Hospital 600 Chiayi Taiwan Department of Cosmetic Science Chia Nan University of Pharmacy and Science Tainan 717 Taiwan Ph.D. Program in Translational Medicine Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung 40227 Taiwan

In this study, we used in silico techniques to identify available parasite treatments, representing a promising therapeutic avenue. Building upon our computational initiatives aimed at discovering natural inhibitors for various target enzymes from parasites causing neglected tropical diseases (NTDs), we present novel findings on three turmeric-derived phytochemicals as inhibitors of Leishmania pteridine reductase I (PTR1) through in silico methodologies. PTR1, a crucial enzyme in the unique folate metabolism of trypanosomatid parasites, holds established therapeutic significance. Employing MOE software, a molecular docking analysis assesses the efficacy of turmeric phytochemicals against Leishmania PTR1. Validation of the docking protocol is confirmed with an RMSD value of 2. Post-docking, compounds displaying notable interactions with critical residues and binding affinities ranging between −6 and −8 kcal/mol are selected for interaction pattern exploration. Testing twelve turmeric phytochemicals, including curcumin, zingiberene, curcumol, curcumenol, eugenol, bisdemethoxycurcumin, tetrahydrocurcumin, tryethylcurcumin, turmerones, turmerin, demethoxycurcumin, and turmeronols, revealed binding affinities ranging from −5.5 to −8 kcal/mol. Notably, curcumin, demethoxycurcumin, and bisdemethoxycurcumin exhibit binding affinities within −6.5 to −8 kcal/mol and establish substantial interactions with catalytic residues. These phytochemicals hold promise as lead structures for rational drug design targeting Leishmania spp. PTR in future applications. This work underscores the potential of these identified phytochemicals in the development of more effective inhibitors, demonstrating their relevance in addressing neglected tropical diseases caused by parasites. © 2024 The Authors

关键词： Binding affinities Enzyme inhibition In silico techniques Leishmania pteridine reductase I (PTR1) Molecular docking analysis Neglected tropical diseases Parasite treatments Rational drug design Therapeutic potential Turmeric-derived phytochemicals

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Oxidative Stress and Natural Antioxidants: Back and Forth in the Neurological Mechanisms of Alzheimer’s Disease

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Journal of Alzheimer's Disease 2023年第3期96卷 877-912页

作者： Mani, Shalini Dubey, Rajni Lai, I-Chun Babu, M. Arockia Tyagi, Sakshi Swargiary, Geeta Mody, Deepansh Singh, Manisha Agarwal, Shriya Iqbal, Danish Kumar, Sanjay Hamed, Munerah Sachdeva, Punya Almutary, Abdulmajeed G. Albadrani, Hind Muteb Ojha, Shreesh Singh, Sandeep Kumar Jha, Niraj Kumar Centre for Emerging Diseases Department of Biotechnology Jaypee Institute of Information Technology UP Noida India Division of Cardiology Department of Internal Medicine Taipei Medical University Hospital Taipei Taiwan School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Division of Radiation Oncology Department of Oncology Taipei Veterans General Hospital Taipei Taiwan The Ph.D. Program for Translational Medicine College of Medical Science and Technology Taipei Medical University Academia Sinica Taipei Taiwan Institute of Pharmaceutical Research GLA University Mathura India Department of Molecular Sciences Macquarie University Sydney Australia Department of Health Information Management College of Applied Medical Sciences Buraydah Private Colleges Buraydah Saudi Arabia Department of Life Sciences School of Basic Sciences and Research (SBSR) Sharda University Uttar Pradesh Greater Noida India Department of Pathology Faculty of Medicine Umm Al-Qura University Makkah Saudi Arabia GloNeuro Vishwakarma Road Noida India Department of Biomedical Sciences College of Health Sciences Abu Dhabi University Abu Dhabi United Arab Emirates Department of Clinical Laboratory Sciences College of Applied Medical Sciences Imam Abdulrahman Bin Faisal University Eastern Province Dammam Saudi Arabia Department of Pharmacology and Therapeutics College of Medicine and Health Sciences United Arab Emirates University Abu Dhabi United Arab Emirates Indian Scientific Education and Technology Foundation Lucknow India Department of Biotechnology School of Engineering & Technology (SET) Sharda University Uttar Pradesh Greater Noida India School of Bioengineering and Biosciences Lovely Professional University Punjab Phagwara India Department of Biotechnology School of Applied & Life Sciences (SALS) Uttaranchal University Uttarakhand Dehradun India Department of Biotechnology Engineering and Food Technology Chandigarh University Mohali India

Alzheimer’s disease (AD) is characterized by the progressive degeneration of neuronal cells. With the increase in aged population, there is a prevalence of irreversible neurodegenerative changes, causing a significant mental, social, and economic burden globally. The factors contributing to AD are multidimensional, highly complex, and not completely understood. However, it is widely known that aging, neuroinflammation, and excessive production of reactive oxygen species (ROS), along with other free radicals, substantially contribute to oxidative stress and cell death, which are inextricably linked. While oxidative stress is undeniably important in AD, limiting free radicals and ROS levels is an intriguing and potential strategy for deferring the process of neurodegeneration and alleviating associated symptoms. Therapeutic compounds from natural sources have recently become increasingly accepted and have been effectively studied for AD treatment. These phytocompounds are widely available and a multitude of holistic therapeutic efficiencies for treating AD owing to their antioxidant, anti-inflammatory, and biological activities. Some of these compounds also function by stimulating cholinergic neurotransmission, facilitating the suppression of beta-site amyloid precursor protein-cleaving enzyme 1, α-synuclein, and monoamine oxidase proteins, and deterring the occurrence of AD. Additionally, various phenolic, flavonoid, and terpenoid phytocompounds have been extensively described as potential palliative agents for AD progression. Preclinical studies have shown their involvement in modulating the cellular redox balance and minimizing ROS formation, displaying them as antioxidant agents with neuroprotective abilities. This review emphasizes the mechanistic role of natural products in the treatment of AD and discusses the various pathological hypotheses proposed for AD. © 2023 – IOS Press. All rights reserved.

关键词： Alzheimer’s disease antioxidants neuroprotection oxidative stress therapeutics vitamins

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Toxoplasma gondii infection in small ruminants from Khyber Pakhtunkhwa, Pakistan: Seroprevalence, spatial distribution and associated risk factors

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Veterinary Parasitology: Regional Studies and Reports 2024年 47卷 100979页

作者： Khattak, Irfan Usman, Tahir Swelum, Ayman A. Nasreen, Nasreen Khan, Adil Haider, Jamila Muhammad, Javed Chen, Chien-Chin Ben Said, Mourad College of Veterinary and Animal Husbandry Abdul Wali Khan University Mardan Khyber Pakhtunkhwa Pakistan Department of Animal Production College of Food and Agriculture Sciences King Saud University Riyadh 11451 Saudi Arabia Department of Zoology Khyber Pakhtunkhwa Abdul Wali Khan University Mardan 2320 Pakistan Department of Zoology Khyber Pakhtunkhwa Bacha Khan University Charsadda Pakistan Department of Biology Mount Allison University Sackville E4L1E4 NB Canada Department of Microbiology Shaheed Benazir Women University Peshawar Khyber Pakhtunkhwa Pakistan Department of Microbiology University of Haripur Khyber Pakhtunkhwa Pakistan Department of Pathology Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi 600 Taiwan Department of Cosmetic Science Chia Nan University of Pharmacy and Science Tainan 717 Taiwan Ph.D. Program in Translational Medicine Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung 402 Taiwan Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan 701 Taiwan Laboratory of Microbiology National School of Veterinary Medicine of Sidi Thabet University of Manouba Manouba 2010 Tunisia Department of Basic Sciences Higher Institute of Biotechnology of Sidi Thabet University of Manouba Manouba 2010 Tunisia

The primary aim of this investigation was to assess the occurrence of Toxoplasma gondii infection among sheep and goats in five districts within the southern region of Khyber Pakhtunkhwa province, Pakistan. Additionally, the study aimed to pinpoint potential factors associated with the spread of this infection. Serum samples were gathered from a total of 3505 small ruminants, comprising 1810 sheep and 1695 goats. These samples were then subjected to testing for anti-Toxoplasma antibodies using the Toxo-Latex slide Agglutination test. Concurrently, a predetermined questionnaire was employed to gather data on possible risk factors. The collected data underwent bivariate frequency analysis and multivariable logistic regression analyses. The findings revealed that 20.08% of the examined animals had positive results for anti-Toxoplasma antibodies. Notably, the prevalence of T. gondii was notably higher among sheep, with 21.8% of the sheep testing positive, as opposed to the 18% of tested goats (P = 0.007). The seroprevalence percentages were comparable across the five districts for both types of animals. For goats, the prevalence ranged from 16.8% to 20.1%, while for sheep, it ranged from 20.2% to 24%. Among the younger population (≤1 year), the seroprevalence was statistically lower at 17.7% compared to the older population (>1 year) at 23.1% (P < 0.001). Female animals demonstrated a higher prevalence (21.9%) in contrast to their male counterparts (17.8%) (P = 0.002). Animals reared for breeding and milking purposes displayed a greater seroprevalence (23.9%) compared to those intended for sale (17.7%) (P < 0.001). Furthermore, animals kept under a transhumant production system displayed the lowest prevalence (18.9%), followed by sedentary (21.7%) and nomadic (31.2%) herds (P < 0.001). The outcomes of this study highlight the importance of implementing management interventions to curtail T. gondii infection among animals within the Khyber Pakhtunkhwa province of Pakista

关键词： Epidemiological investigation Pakistan Risk factors Seroprevalence Small ruminants Toxoplasma gondii

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Contribution of Common Sulfur-Containing Substrates to Hydrogen Sulfide Production By Human Gut Microbiota Using anIn VitroModel Standardized For Bacterial Counts

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Gut Microbes Reports 2024年第1期1卷

作者： Levi M. Teigen Thomas Kaiser-Powers Michael Matson Baila Elkin Amanda J. Kabage Matthew Hamilton Byron P Vaughn Michael J. Sadowsky Christopher Staley Alexander Khoruts a Department of Food Science and Nutrition University of Minnesota St. Paul MN USA b Division of Basic and Translational Research Department of Surgery University of Minnesota Minneapolis MN USA c Division of Gastroenterology Hepatology and Nutrition Department of Medicine University of Minnesota Minneapolis MN USA d Medical School University of Minnesota Minneapolis MN USA e Microbiota Therapeutics Program University of Minnesota Minneapolis MN USA f Department of Soil Water and Climate and Department of Plant and Microbial Biology University of Minnesota Minneapolis MN USA

ABSTRACTHydrogen sulfide (H2S) produced by human gut microbiota is highly toxic and implicated in pathogenesis of gastrointestinal tract disorders. Sulfur-containing amino acid (SAA) degradation is a major contributor to its production, but SAA degradation pathways have not been extensively *** vitromodel systems of fecal H2S production offer a basic method to help elucidate SAA degradation pathways, but the approach is not standardized. To address this, we used fecal microbiota separated from feces and standardized for bacterial counts to measure H2S production potential in response to different substrates in healthy controls (n= 6) with repeated sampling (three samples per participant). H2S production was highest with cysteine (mean = 16.7 ppm) compared to sodium sulfate (0.7 ppm) and taurine (0.8 ppm). Sodium-sulfate-driven H2S production negatively correlated withRuminococcus(Spearman’sρ= −0.5) and cysteine-driven H2S production negatively correlated withFirmicutes(Spearman’sρ= −0.5). These findings, using a protocol controlling for confounding variables such as bacterial counts, validate previous findings of cysteine as a primary driver of H2S production. Finally, the inclusion of samples from two patients with UC allowed for the illustration of the potential of this approach to identify functional differences in specific disease states.

关键词： Microbiome hydrogen sulfide cysteine sulfate taurine

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ENIGMA-Meditation: Worldwide Consortium for Neuroscientific Investigations of Meditation Practices

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Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 2025年第4期10卷 425-436页

作者： Ganesan, Saampras Barrios, Fernando A. Batta, Ishaan Bauer, Clemens C.C. Braver, Todd S. Brewer, Judson A. Brown, Kirk Warren Cahn, Rael Cain, Joshua A. Calhoun, Vince D. Cao, Lei Chetelat, Gaël Ching, Christopher R.K. Creswell, J. David Dagnino, Paulina Clara Davanger, Svend Davidson, Richard J. Deco, Gustavo Dutcher, Janine M. Escrichs, Anira Eyler, Lisa T. Fani, Negar Farb, Norman A.S. Fialoke, Suruchi Fresco, David M. Garg, Rahul Garland, Eric L. Goldin, Philippe Hafeman, Danella M. Jahanshad, Neda Kang, Yoona Khalsa, Sahib S. Kirlic, Namik Lazar, Sara W. Lutz, Antoine McDermott, Timothy J. Pagnoni, Giuseppe Piguet, Camille Prakash, Ruchika S. Rahrig, Hadley Reggente, Nicco Saccaro, Luigi F. Sacchet, Matthew D. Siegle, Greg J. Tang, Yi-Yuan Thomopoulos, Sophia I. Thompson, Paul M. Torske, Alyssa Treves, Isaac N. Tripathi, Vaibhav Tsuchiyagaito, Aki Turner, Matthew D. Vago, David R. Valk, Sofie Zeidan, Fadel Zalesky, Andrew Turner, Jessica A. King, Anthony P. Department of Biomedical Engineering The University of Melbourne Carlton VIC Australia Contemplative Studies Centre Melbourne School of Psychological Sciences The University of Melbourne Melbourne VIC Australia Systems Lab of Neuroscience Neuropsychiatry and Neuroengineering The University of Melbourne Parkville VIC Australia Universidad Nacional Autónoma de México Instituto de Neurobiolgía México Querétaro Mexico Center for Translational Research in Neuroimaging and Data Science: Georgia State University Georgia Institute of Technology and Emory University Atlanta GA United States Department of Psychology Northeastern University Boston Massachusetts Brain and Cognitive Science McGovern Institute for Brain Research Massachusetts Institute of Technology Cambridge Massachusetts Department of Psychological and Brain Sciences Washington University St. Louis Missouri Department of Behavioral and Social Sciences Brown University School of Public Health Providence Rhode Island Department of Psychology Carnegie Mellon University Pittsburgh PA United States University of Southern California Department of Psychiatry & Behavioral Sciences Los Angeles California University of Southern California Center for Mindfulness Science Los Angeles California Institute for Advanced Consciousness Studies Santa Monica California Department of Psychiatry and Behavioral Health The Ohio State University College of Medicine Columbus OH United States Normandie University Université de Caen Normandie INSERM U1237 Neuropresage Team Cyceron Caen France Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute Keck School of Medicine of the University of Southern California Los Angeles California Desert-Pacific Mental Illness Research Education and Clinical Center VA San Diego Healthcare System San Diego California Computational Neuroscience Group Center for Brain and Cognition Department of Information and Communication Technologies Universitat Pompeu Fa

Meditation is a family of ancient and contemporary contemplative mind-body practices that can modulate psychological processes, awareness, and mental states. Over the last 40 years, clinical science has manualized meditation practices and designed various meditation interventions that have shown therapeutic efficacy for disorders including depression, pain, addiction, and anxiety. Over the past decade, neuroimaging has been used to examine the neuroscientific basis of meditation practices, effects, states, and outcomes for clinical and nonclinical populations. However, the generalizability and replicability of current neuroscientific models of meditation have not yet been established, because they are largely based on small datasets entrenched with heterogeneity along several domains of meditation (e.g., practice types, meditation experience, clinical disorder targeted), experimental design, and neuroimaging methods (e.g., preprocessing, analysis, task-based, resting-state, structural magnetic resonance imaging). These limitations have precluded a nuanced and rigorous neuroscientific phenotyping of meditation practices and their potential benefits. Here, we present ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)–Meditation, the first worldwide collaborative consortium for neuroscientific investigations of meditation practices. ENIGMA-Meditation will enable systematic meta- and mega-analyses of globally distributed neuroimaging datasets of meditation using shared, standardized neuroimaging methods and tools to improve statistical power and generalizability. Through this powerful collaborative framework, existing neuroscientific accounts of meditation practices can be extended to generate novel and rigorous neuroscientific insights that account for multidomain heterogeneity. ENIGMA-Meditation will inform neuroscientific mechanisms that underlie therapeutic action of meditation practices on psychological and cognitive attributes, thereby advancing the f

关键词： Consortium ENIGMA Magnetic resonance imaging (MRI) Meditation Mindfulness Neuroimaging

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Novel electrospun poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits for repair of peripheral nerve injury

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Neural Regeneration research 2019年第9期14卷 1617-1625页

作者： Chun-Ming Yen Chiung-Chyi Shen Yi-Chin Yang Bai-Shuan Liu Hsu-Tung Lee Meei-Ling Sheu Meng-Hsiun Tsai Wen-Yu Cheng Department of Neurosurgery Neurological InstituteTaichung Veterans General HospitalTaichungTaiwanChina Ph.D.Program in Translational Medicine National Chung Hsing UniversityTaichungTaiwanChina Department of Physical Therapy Hungkuang UniversityTaichungTaiwanChina Basic Medical Education Center Central Taiwan University of Science and TechnologyTaichungTaiwanChina Department of Medical Imaging and Radiological Sciences Central Taiwan University of Science and TechnologyTaichungTaiwanChina Institute of Biomedical Sciences National Chung Hsing UniversityTaichungTaiwanChina Department of Medical Research Taichung Veterans General HospitalTaichungTaiwanChina Rong Hsing Research Center for Translational Medicine National Chung Hsing UniversityTaichungTaiwanChina Department of Management Information System National Chung Hsing UniversityTaichungTaiwanChina

Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits(biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy.S-100(Schwann cell marker) and CD4(inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China(La-1031218) on October 2, 2014.

关键词： poly(ε-caprolactone) type Ⅰ collagen electrospinning sciatic nerve nerve conduit immunohistostaining walking track analysis peripheral nerve injury

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Repurposing nitric oxide donating drugs in cancer therapy through immune modulation

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Journal of Experimental and Clinical Cancer research 2023年第1期42卷 22-22页

作者： Li, Chung-Yen Anuraga, Gangga Chang, Chih-Peng Weng, Tzu-Yang Hsu, Hui-Ping Ta, Hoang Dang Khoa Su, Pei-Fang Chiu, Pin-Hsuan Yang, Shiang-Jie Chen, Feng-Wei Ye, Pei-Hsuan Wang, Chih-Yang Lai, Ming-Derg College of Medicine Institute of basic medical sciences National Cheng Kung University Tainan Taiwan PhD Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei Taiwan Department of Statistics Faculty of Science and Technology Universitas PGRI Adi Buana Surabaya Indonesia Department of Microbiology and Immunology College of Medicine National Cheng Kung University Tainan Taiwan Department of Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan Department of Statistics National Cheng Kung University Tainan Taiwan The Center for Quantitative Sciences Clinical Medicine Research Center National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan Department of Biochemistry and Molecular Biology College of Medicine National Cheng Kung University Tainan Taiwan TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan

Background: Nitric oxide-releasing drugs are used for cardiovascular diseases;however, their effects on the tumor immune microenvironment are less clear. Therefore, this study explored the impact of nitric oxide donors on tumor progression in immune-competent mice. Methods: The effects of three different nitric oxide-releasing compounds (SNAP, SNP, and ISMN) on tumor growth were studied in tumor-bearing mouse models. Three mouse tumor models were used: B16F1 melanoma and LL2 lung carcinoma in C57BL/6 mice, CT26 colon cancer in BALB/c mice, and LL2 lung carcinoma in NOD/SCID mice. After nitric oxide treatment, splenic cytokines and lymphocytes were analyzed by cytokine array and flow cytometry, and tumor-infiltrating lymphocytes in the TME were analyzed using flow cytometry and single-cell RNA sequencing. Results: Low doses of three exogenous nitric oxide donors inhibited tumor growth in two immunocompetent mouse models but not in NOD/SCID immunodeficient mice. Low-dose nitric oxide donors increase the levels of splenic cytokines IFN-γ and TNF-α but decrease the levels of cytokines IL-6 and IL-10, suggesting an alteration in Th2 cells. Nitric oxide donors increased the number of CD8⁺ T cells with activation gene signatures, as indicated by single-cell RNA sequencing. Flow cytometry analysis confirmed an increase in infiltrating CD8⁺ T cells and dendritic cells. The antitumor effect of nitric oxide donors was abolished by depletion of CD8⁺ T cells, indicating the requirement for CD8⁺ T cells. Tumor inhibition correlated with a decrease in a subtype of protumor macrophages and an increase in a subset of Arg1-positive macrophages expressing antitumor gene signatures. The increase in this subset of macrophages was confirmed by flow cytometry analysis. Finally, the combination of low-dose nitric oxide donor and cisplatin induced an additive cancer therapeutic effect in two immunocompetent animal models. The enhanced therapeutic

关键词： Cancer CD8+ cytotoxic T cells Immune Macrophages Nitric oxide donor Single-cell RNA-seq SNAP

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